Interview Questions and Answers for Oral Solid Formulations

160+ Pharmaceutical Interview Questions and Answers for Oral Solid Formulations

This page covers most of the interview questions and answers during a technical round in Production Oral Solid Dosage. The interview questions cover questions from basic to advance level of technical aspects. These interview questions and answers will help to crack an interview, enhance your knowledge, and also be helpful for the interviewer who is involved in the recruitment process.

The topics covered here are the Granulation process, the Tablet Compression process, the Coating process, and associated topics. In addition, the interview questions and answers cover various equipment used for the manufacturing process of solid oral formulation such as Compression Machine, Coating Machine, Graduation equipment, and supporting accessories.

You will find it much more enjoyable while going through these interview questions and answers. So enjoy learning, and best of luck with your interview! Happy Learning.

1. What is the granulation end point?

End-point can be defined by the formulator as a target particle size mean or distribution. [Reference: 5]

The agglomerate growth in wet granulation processes depend mainly on rheology of the wet powder mass, as an adequate consistency is necessary for a controllable coalescence and growth of smaller agglomerates into larger agglomerates.[Reference: 6]

2. Method for end point detection for wet granulation process.

i. Banana breaking test or Hand squeeze test

ii. Ampere load method

iii. Measurements of power consumption of the mixer motor

iv. Impeller Torque

v. Binder solution addition and measurement of Loss On Drying (LOD)

vi. Torque value

3. What is the Banana breaking method or Hand squeeze test for determination of granulation end point?

Wear hand gloves, take one handful of wet mass in the palm and press to make a lump. Open the palm and break the lump by pressing the thumb at the center of the lump.

4. What is the principle of metal detectors?

The operation of these metal detectors is based on the principles of electromagnetic induction. Metal detectors contain one or more inductor coils that are used to interact with metallic elements. Metallic contaminant in the product creates a high frequency magnetic field within the detector coil, which in turn activates a reject flap.

5. What is the fail safe mechanism of metal detectors?

When a metal detector gets off because of power failure or inadvertently did not start before the start of the batch, the flap should remain open so that tablets get rejected. It must be challenged at regular intervals (e.g.: start, intermittently and at the end of shift) to make sure they are effective.

6. What are typical standards used for the challenge of metal detectors?

Tablet: Ferrous – 0.3 mm, Non-ferrous – 0.3 mm, Stainless Steel – 0.5 mm, Plain (without metal as a blank)

Capsule: Ferrous – 0.1 mm, Non-ferrous – 0.15 mm, Stainless Steel – 0.2 mm, Plain (without metal as a blank)

7. What is tablet tooling?

Tooling consists of three parts.

i. Upper punch, ii. Lower punch, and iii. Die

8. What is the meaning of one set of tablet tooling?

One set consists of one Upper punch, one Lower punch and a Die.

9. What is a tooling station?

The place where one set accommodates the tablet press.

10. Explain parts of tablet tooling.

Punch terminologies:

image
image 1

Head: Head is the top part of upper and lower punch which contacts the machine’s cams and the pressure rollers apply the pressure to the head to compress the tablets.

Head flat or Dwell Flat: Top flat area of the head. Compression force applied through the upper punch head flat and ejection pressure applied through the head flat of lower punches. Dwell time for compression is determined based on the Head flat hence, it is also called Dwell Flat.

Outside head angle: The area touches the pressure roller during compression operation.

Inside head angle: The part of the punch head helps the upper punch to lift after compression of tablets and helps in pulling down the lower punches after ejection.

Neck: The part between head and barrel. Allow a clear path to the cam.

Barrel: Allows punch to do vertical up and down movement.

Stem: Area from tip end to barrel edge.

Tip: It is the lowest portion of the punch which is responsible for shape, size and profile of the tablet.

Tip face or cup: Outer part of the tip which gives shape to the tablet. The face also will have embossing depending on the need of the tablet requirement.

Tip length: The straight portion of the stem or tip.

Tip straight: The portion of tip towards the face having a higher diameter of the tip.

Tip relief: Tip part other than the tip straight.

Working length: This is the distance from the head flat to bottom of the cup.

Overall length: Length from punch head flat to the tip.

Key or woodruff key: An elevated portion in the middle of the punch barrel. The key with upper punches for shaped tablets to prevent punch rotation when the punch is out of the die.

Types of heads: Domed head and Flat head

Difference between Flat head and Domed headDomed head punches have smaller flat heads.

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The extended head flat offers multiple benefits, including a longer dwell time (the time the head flat spends in contact with the pressure roll) at a given press speed to better compact poorly compressible products. The longer dwell time may even reduce the amount of force required to attain specific tablet hardness.

Whereas, round extended head flats don’t require keyed tooling as oval ones do, and that allows them to be used on multiple makes and models of tablet presses.

Dwell time: It is the time the head flat spends in contact with the pressure roller.

Land: The area between the outer part of the punch cup and the outside edge of the punch tip.

Cup depth: Distance between tip edge to the center point of the cup.

Barrel chamfer: Chamfers at the ends of the punch barrel.

Die terminologies:

image 4

Clearance: pace between die bore diameter and punch tip diameter

Die Bore: It is the cavity of the die where granules are converted into tablets.

Die height or overall length: The height from top to bottom face of the die.

Die chamfer: This is the angle of the die bore at entry point. It guides the upper punch into the die bore.

Die groove and die lock: The radial groove around the die outer diameter requires locking the die into the turret with the help of die lock.

Die taper: Taper is a feature that increases the bore size at the top of the die then nominal bore size. It helps to release air from the die cavity during the compression. The feature helps to reduce tablet defects, such as capping and lamination.

Annealing: This is a heat treatment process to reduce the hardness to make it more workable. The processing done fragile punch tips to decrease the hardness of the punch cups which helps in reducing punch tip fracturing.

11. Describe tablet tooling standards?

There are two types of standards for tablet tooling:

i. US specification provided by Tableting Specification Manual (TSM) (This is the only tooling specifications are the only published standards for the tablet compression industry). The standard is established by the American Pharmacists Association (APhA),

ii. European standard known as the EU, or “Euronorm” standard.

EU, or Euronorm standard tool configurations are not published or governed by an organization or association. The EU standard is the most common tooling configuration used outside the U.S. [Reference: 7]

12. Differences between TSM and EU Tooling Configurations

Tableting Specification Manual (TSM) Tooling ConfigurationsEU Tooling Configurations
Angled top profileDomed head profile
Inside head angle for “B” punches is 37°Inside head angle for “B” punches is 30°
Overall head thickness is greater in both “B” and “D”Overall head thickness is lesser in both “B” and “D”
Overall punch length of the TSM tool is 0.010 inches shorter than the EUOverall punch length of the EU tool is 0.010 inches longer than the TSM
[Reference: 7]

13. What is the type of tablet tooling for a compression machine with die and punch dimension?

There are the following six types of tablet tooling and its dimensions.


Tooling specification
Nominal punch barrel diameter (mm)Nominal punch die diameter (mm)Maximum tablet diameter for round tablet (mm)Maximum tablet diameter for shaped tablet (mm)
TSM or EU B1930.161616
TSM or EU D25.3538.12525
TSM or EU BB19241314
TSM or EU DB25.3530.161919
TSM or EU  BBS19211213
TSM or EU A12.71788
[Reference: 8]

14. What is the choice for material of construction (MoC) of Die and Punch?

i. OHNS (T) Oil Hardened Non shrinking steel (Tungsten) – AISI 01 (American Iron and Steel Institute)

ii. HCHC – High carbon High chromium steel – AISI D3

15. What is the choice for material of construction (MoC) of Turret?

Three piece turret having the center die table of SS 316 and the Upper and lower piece of Spheroidal Graphite Iron (SG Iron) with ELNP (ELECTROLESS NICKEL PLATING) Coating.

16. What is the chemical composition of OHNS steel?

ElementContent (%)
C0.85-1.00
Si0.15-0.35
Mn1.00-1.20
P0.03 Max
S0.03 Max
Cr0.50-0.70
W0.50-0.70

17. How much is the lifespan of the die and punches?

The life span of punches and dies is purely depending on materials of construction (MoC) as well as usage and handling.

OHNS Punches and HCHC Dies: 4 million tablets

HCHC Punches and HCHC Dies: 8 Million tablets Complete hard chrome plating punches and

HCHC dies: 10 Million tablets

18. How to maintain Punches and Dies?

The maintenance of compression tooling becomes easy by following these mentioned steps:

Step 1: Cleaning during every product change over or on a periodic basis. They can be wiped with IPA and dried using a lint free cloth.

Step 2: Periodic evaluation to increase their shelf life. Industry practice is to

Step 3: The regular visual inspection of the tooling should be done after each cleaning to check for physical damages to head, tip, die, and embossing, debossing using Magnifying glass.

Step 4: Periodic inspection of the punch set should be done using measuring tools. Frequency for die and punch inspection should be such that first inspection after procurement should be done after 3 million tablet compression using each tool set and subsequently after each million.

Step 5: Compression punch set should be lubricated to decrease friction and enhance the operational activity of the tablet compression machine. A non-toxic, FDA approved oils and greases should be used for preservation and lubrication purposes. Storage of tooling should be done in the safe and moisture-free place.

19. What should be available in a punch set/ tablet tooling inspection kit?

1Dial gauge compactor stand with a least count of 0.001 inch
2Micrometer Range from 0.25 mm with least count : 0.01 mm
3Punch holding bushes for B type punch and D type of punch
4Punch height gauge
5Die Outer diameter block for all types of die i.e. D, B, BB, DB etc.
6Magnetic V – block
7GO – NO GO gauges
8Magnifying Glass
9Die Pocket Cleaner

20. Explain about the punch set/ tablet tooling inspection program?

i. Height uniformity of the punches

ii. Punch body to punch tip concentricity

iii. Die bore Go / No go status

iv. Other dimensions as per the drawing

v.  Punch tip to die before clearance

vi. Hollow penetration of the punches

vii. Die outdoor diameter consistency

viii. Die height regularity

ix. Die hole GO and NO GO examination

x. Die internal diameter to outer diameter concentricity

21. Issue that may arise after prolonged use for punch set/ tablet tooling.

i. Tablet weight difference          

ii. Tablet hardness difference    

iii. Powder leakage from lower punch or collar formation

iv. Twisting of small size punch tips

22. Commonly used material of construction in the pharmaceutical industry for equipment manufacturing?

i. Commonly used materials of construction in the pharmaceutical industry for product contact parts are Stainless steel 316, 316 L, Toughened glass, Silicon, Food grade Teflon etc.

ii. Commonly used materials of construction in the pharmaceutical industry for non-product contact parts are Stainless steel 304, 304 L, Teflon, Anodized or powder coated aluminum, brass etc.

23. Explain characteristics of different grades of stainless steel material.

Following are the different types of types of Stainless and similar material with its characteristics.

Stainless and similar materialApplication for the different types of environment
Hastelloy C276Excellent corrosion resistance in a wide range of severe environments
316, 316LChemical corrosion
304, Custom 450Medium Corrosion
430, 431, Custom 455Industry polluted air
405, 410, 420, 440Clean air

24. Explain most commonly used stainless steel for pharmaceutical industry and its attributes.

Following most commonly used stainless steel for the pharmaceutical industry and its attributes.

Commonly known namesUNSENAttributes
304S304001.4301Good at general corrosion resistance to acidic as well as caustic material
304LS304031.4307Good at general corrosion resistance to acidic as well as caustic material with low carbon and improved performance
316S316001.4401/ 1.4436Improved corrosion resistance to most acidic as well as caustic material with high temperature or chloride present
316LS316031.4404/ 1.4432Improved corrosion resistance to most acidic as well as caustic material with high temperature or chloride present with low carbon and improved performance

25. How to distinguish SS 202, SS 304 and SS 316 grade stainless steel?

Using molybdenum detection electrolyte kit. To know how to perform the test, Click Here.

26. What is the composition of SS 304, SS 304L, SS 316, and SS 316L?

Following are the composition of SS 304, SS 304L, SS 316, and SS 316L

image 25

27. What is the meaning of Suffix L in SS 316L and SS 304L?

Suffix L for SS 316 and SS 304 represents low carbon content. Standard grade consists of ≤ 0.08 % carbon and low carbon grade consists of ≤ 0.03 % carbon content.

28. What are the different types of stainless steel in terms of material composition?

image 5

29. What is Hastelloy?

Hastelloy is a nickel-molybdenum-chromium superalloy with an addition of tungsten designed to have excellent corrosion resistance in a wide range of severe environments. The high nickel and molybdenum contents make the nickel steel alloy especially resistant to pitting and crevice corrosion in reducing environments while chromium conveys resistance to oxidizing media. The low carbon content minimizes carbide precipitation during welding to maintain corrosion resistance in as-welded structures. This nickel alloy is resistant to the formation of grain boundary precipitates in the weld heat-affected zone, thus making it suitable for most chemical process application in an as welded condition.

Source: megamex.com

30. In what applications is Hastelloy used?

i. Pharmaceutical and food processing equipment

ii. Chemical processing components like heat exchangers, reaction vessels, evaporators, and transfer piping

iii. Sour gas wells

iv. Waste treatment

31. Which are typical in-process control tests for tablets?

Dimensions

Hardness

Friability

Thickness

Disintegration

Weight variation

Content uniformity

Dissolution

Leakage testing for strip and blister packaging

Checking printing matter during packaging

Physical appearance of packs

32. Explain Disintegration time (DT) of different types of tablets?

Disintegration time (DT) of different types of tablets is as follows.

Types of tabletsDisintegration time (DT)
Uncoated15 minutes
Plain coated tablet60 minutes
Enteric coated tablet3 hours
Dispersible tablet3 minutes
Effervescent tablet˂ 3 minutes
Sublingual tablet4 hours
Buccal tablet4 hours
Vaginal tablet60 minutes
Chewable tabletnot required

33. What are the types of hardness testers?

Manual hardness tester

Monsanto tester

image 6

Pfizer tester

image 7

Strong-cobb

image 8

Automatic hardness testers

Erweka tester

image 9

Dr. Schleuniger tester

image 10

34. Which instruments are used for testing tablet dimension?

A. Vernier caliper

image 11

1. Outside jaws: used to measure external length

2. Inside jaws: used to measure internal length

3. Depth probe: used to measure depth

4. Main scale (cm)

5. Main scale (inch)

6. Vernier (cm)

7. Vernier (inch)

8. Retainer: used to block/release movable part

B. Micrometer screw gauge

image 12

35. Which instruments are used for testing of tablet friability?

Roche friabilator is used for testing of tablet friability.

36. Explain the construction of tablet friability tester, testing process and limit.

i. Plastic chamber that revolves at 25 rpm

ii. For testing it operates for 100 revolutions

iii. Dropping the tablets from a Distance of 6 inches in the tester

iv. The tablets are weighed before and after rotation. De-dust tablets after rotation. Perform calculation in percentage weight loss.

v. Limit of friability testing is NMT 1.0 %

37. What is Disintegration Time (DT) Test?

Disintegration time is time taken to break down the tablets into granules or primary powder particles.

38. Explain the tablet disintegration tester parts.

i. Basket rack assembly

ii. A suitable vessel for the immersion liquid

iii. Heater for fluid heating between 35°C and 39°C

iv. Basket in the immersion in fluid at frequency rate between 28 and 32 cpm (Cycle per minute)

v. Distance of up and down not less than 5 cm and not more than 6 cm

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39. What are the common tablet defects at compression stage?

Weight variation

High friability

High or low hardness (resistance to crushing)

Sticking

Picking

Capping

Laminating

Chipping

Mottling

Double press or impression

Cracking

Binding

Edging or Flashing of tablet

Disintegration time abnormality

Black Spot/ particles/ fiber

Improper embossing or debossing

Layer separation

Improper Layers

40. What are the different types of tablet coating defects?

Blistering

Chipping

Cratering

Sticking or Picking

Pitting

Blooming

Blushing

Color Variation

Infilling

Orange Peel or Roughness

Cracking or Splitting

Twinning Erosion

Bridging

41. Definitions of tablet defects at compression stage.

Weight variation: Individual weight of tablet outside of the accepted criteria.

High friability: The condition of tablets being friable. The tendency of tablets to break into smaller pieces or weight loss of powder from the surface of the tablets due to mechanical action such as transportation conditions. When percentage loss is more than 1%, it is considered as high friability.

To view images of tablet defects and to download high resolution poster, CLICK HERE

High or low hardness (resistance to crushing): Individual hardness of tablets is outside the accepted limit (upper limit or lower limit). Hardness limits are determined during the development phase of the product.

Sticking: Sticking is a defect of the tablet wherein the portion tablet surface sticks to the face of the punch or to the die wall during tablet compression activity.

Picking: Picking is a counter part of the sticking. When part of the tablet surface sticks to the punch or to the die wall, the produced tablets are with a pitted surface instead of a smooth surface.

Capping: Capping (or splitting) is a term used to describe the partial or complete separation of the upper or lower segment of the tablet horizontally from the main body of a tablet during ejection from the tablet press.

Laminating: Laminating of tablets means separation of a tablet into two or more different parallel layers.

Chipping: Chipping of tablets is the breaking of tablet edges during manufacturing or handling.

Mottling: Mottling of tablet refers to unequal or nonuniform distribution of color on the tablet surface.

Double press or impression: Double impression is a tablet defect where an embossing or break or score line appears two times on the tablet surface.

Cracking: Cracking of tablets means small fine cracks on the upper and lower central surface of the tablets and sometimes seen on the side wall.

Binding: The term binding is used when tablets stick to the die and do not eject properly out of the die.

Edging or Flashing of tablet: Edging or Flashing means observation of burrs or sharp edges on the edges of tablet.

Disintegration time abnormality – Too fast or too slow disintegration of tablets.

Black Spot/ particles/ fiber – Observation of black spot or particles or fiber which could be indigenous or foreign matter or contaminant.

Improper embossing or debossing: The defect because of improper embossing or debossing of letter, logo or monogram.

Layer separation: Layer separation is the defect of a tablet where layers of tablet get separated. This is usually seen in tablets such as bilayer tablets.

Improper Layers: Improper Layers mainly appear in layered tablets such as bilayer tablets. In this type of defect, the layer does not distinguish sharply.

42. What are the different types of tablet coating defects?

Blistering: Blistering means blistering of a surface film appears when film becomes detached from the tablet’s substrate.

Chipping: Chipping means dented and chipped film mostly on the edges of the tablet.

Cratering: Cratering means volcanic-like cratering happens exposing the tablet surface.

Sticking or Picking: Sticking or picking means sticking of film with each other or with the coating pan resulting in some of the tablet pieces being detached from the core.

Pitting: Pitting is the deformation of the core of the tablet without any visible signs of disruption of the film coating.

Blooming: Blooming is the fading or dulling of a tablet color after it is stored for a prolonged period at a high temperature.

Blushing: Blushing is described as the appearance of white specks or a haziness in the film.

Color Variation: Color variation of tablet film.

Infilling: This refers to the filling of intagliations – i.e., the distinctive words or symbols formed on the tablet.

Orange Peel or Roughness: When film having a rough surface or having a matt surface rather than glossy texture. It appears the same as an orange.

Cracking or Splitting: The cracking defect is observed when the film coating of the tablet cracks in the crown area or splits around the edges.

Twinning: Twinning is when two tablets stick together.

Erosion: Coating gets removed from the surface due to friction between tablets.

Bridging: When coating material fills in the logo or letter, bridging occurs.

43. Explain the remediation for various types of tablet defects.

image

44. What are the different sizes of hard gelatin capsules?

The capsule sizes are 000, 00, 0, 1, 2, 3, 4, and 5 from the largest to the smallest. There are few special sizes of capsules available such as 2el, 1el, 0el, 0el+, 0xel, 00el etc. Details are tabulated below.

image 16
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45. What are the US Mesh size and corresponding micron, mm and inch for commonly used sieves, provide a few examples?

U.S. MeshMicronsInchesMillimeters
367300.26506.730
447600.18794.760
540000.15704.000
633600.13203.360
728300.11102.830
823800.09372.380
1020000.07872.000
1216800.06611.680
1414100.05551.410
1611900.04691.190
1810000.03941.000
208400.03110.841
257070.02800.707
305950.02320.595
355000.01970.500
404000.01650.400
453540.01380.354
502970.01170.297
602500.00980.250
702100.00830.210
801770.0070.177
1001490.00590.149
1201250.00490.125
1401050.00410.105
170880.00350.088
200740.00290.074
230630.00240.063
270530.00210.053
325440.00170.044
400370.00150.037
450320.00130.032
500250.00100.025
550250.00090.023
635200.00080.020
800150.00060.015
1250100.00040.010

Reference: ASTM E11

46. Give examples of sieve size and corresponding number of Apertures per Linear inch.

Sr. No.Sieve SizeNumber of Apertures per Linear Inch
110 #9-11
212#11-13
314#13-15
416#15-17
520#19-21
624#23-25
730#28-32
840#38-42
960#57-63
1080#77-83
11100#97-103

47. What is the aperture size of the screen?

The size of a square opening (length of clear space between individual wires) is called the aperture size of the screen.

48. What is the Mesh number of screens?

Mesh number of screens is defined as the number of aperture or opening per linear inch of the screen.  E.g. A screen having 10 square openings per inch is said to have Mesh no. 10. Higher the mesh number, smaller the aperture size of the screen.

49. What is the broad classification of Granulation techniques?

Granulation technique is broadly classified into two types as follows:

(i) Dry granulation

a. Slugging technique

b. Roller compaction

c. Pneumatic dry granulation

(ii) Wet granulation

a. Steam granulation

b. Reverse wet granulation

c. Moisture-Activated Dry Granulation

d. Thermal adhesion granulation

e. Melt granulation

f. Freeze granulation

g. Foam granulation

50. What are the equipment used during the Wet Granulation Process?

Depending on process, batch size and type of process steps, following equipment are used during the Wet Granulation Process.

Low Shear mixer/ granulator

High Shear mixer/ granulator OR Rapid Mixture granulator

Fluid-Bed granulator/ dryer,

Spray Dryer,

Extruders and Spheronizer

Vibratory sifter

Cutting mills such as Multimill, Co-mill, Pin Mill etc.

Hammer mill

51. What are the equipment used during the Dry Granulation Process?

Depending on process, batch size and type of process steps, following equipment are used during the Dry Granulation Process.

Role com

Low Shear mixer/ granulator

High Shear mixer/ granulator OR Rapid Mixture granulator

Vibratory sifter

Cutting mills such as Multimill, Co-mill, Pin Mill etc.

Roller Compactor Granulator

Compression machine to generate slugs

52. What is the most commonly used testing method to determine powder flow?

There are four commonly used methods for testing powder flow:

(1) Angle of repose

(2) Compressibility index or Hausner ratio

(3) Flow rate through an orifice

(4) Shear cell

Reference: General Chapters: <1174> POWDER FLOW

53. What is Angle of Repose?

Definition of Angle of Repose: The angle of repose is a relatively simple technique for estimating the flow properties of a powder. It is determined by allowing a powder to flow through a funnel and fall freely onto a fixed diameter base. The height and diameter of the resulting cone are measured. For further reading on Angle of Repose and download free excel, click on this link.

54. What is the Compressibility index and what is Hausner Ratio?

Definition of Compressibility index: The Compressibility Index (Carr Compressibility Index) is a measure of the tendency of a powder to be compressed. It is a measure of the powder’s ability to settle, and it permits an assessment of the relative importance of interparticulate interactions.

Definition of Hausner Ratio: The Hausner Ratio is measures that can be used to predict the tendency of a given powder sample to be compressed. Hausner Ratio reflects the importance of interparticulate interactions.

For further reading of Simple methods to determine powder flow property -Angle of repose, Compressibility index and Hausner ratio CLICK on this link. Also get a FREE Excel sheet for calculation.

55. What is the disintegration time of Chewable Tablets?

Disintegration time test is not applicable for chewable tablets.

56. What is the standard number of rotations used for friability test?

100 Revolutions / 4 Minutes, 25 rotations per minute

57. What is the fall height of the tablets in the friabilator during friability testing? 

Fall height of the tablets is in the friabilator is 154.0 – 158.0 mm (156.0 ± 2.0 mm)

58. Which capsule is bigger in size – size ‘0’ or size ‘1’?

‘0’ size

59. How many tablets shall be taken for checking friability?

6.5 g for the tablets with unit mass equal or less than 650 mg. For tablets with unit mass more than 650 mg, it requires 10 tablets.

60. What is the mesh aperture of DT apparatus?

Mesh aperture of DT apparatus is #10. That is 1.8 -2.2 mm.

61. What is the standard frequency of upward and downward movement of a basket-rack assembly in a DT apparatus?

28 – 32 cycles/minute

62. What are the parameters tested during the calibrating DT apparatus?

Parameters covered during the DT apparatus calibration are as follows

(1) Number of strokes per minute (Limit: 29-32 cycles/min)

(2) Temperature by probe and standard thermometer (Limit: 37 ± 1 °C). (3) Distance travelled by basket (Limit: 53 -57 mm)

63. What is the Disintegration time for different types of tablets?

Type of TabletsDisintegration time
Uncoated Tablets15 minutes
Film-coated30 minutes
Other coated tablets60 minutes
Enteric-coated Tablets 
0.1M hydrochloric acidShould not disintegrate in 120 minutes
Phosphate buffer pH 6.8,60 minutes.
Dispersible and Soluble Tabletswithin 3 minutes
Effervescent Tablets5 minutes
Chewable tabletsNot applicable

64. What are the different clean room conditions? Explain it.

There are three conditions of clean rooms – as built, at rest and in-operation.

As built:

image 18

Condition where the installation is complete with all services connected and functioning but with no production equipment, materials, or personnel present.

At rest:

image 19

Condition where the installation is complete with equipment installed and operating in a manner agreed upon by the customer and supplier, but with no personnel present.

In operational:

image 20

This condition relates to carrying out room  classification tests with the normal production process with equipment in operation, and the normal staff present in the room.

Reference: WHO Working document QAS/02.048/Rev.2

65. What are the different types of air locks? Explain it.

There are three types of air locks, Cascade airlock, Sink airlock and Bubble airlock.

image 21

Cascade airlock: high pressure on one side of the airlock and low pressure on the other side.

Bubble Airlock: high pressure inside the airlock and low pressure on both outer sides.

Sink Airlock: low pressure inside the airlock and high pressure on both outer sides.

Reference: WHO Working document QAS/02.048/Rev.2

66. What should be the differential pressure between two adjacent clean room zones?

The most widely accepted pressure differential to achieve containment between the two adjacent zones is 15 Pa, but pressure differentials of between 5 Pa and 20 Pa could be acceptable.

Where the design pressure differential is too low and tolerances are at opposite extremities, a flow reversal can take place. E.g. where a control tolerance of ±3 Pa is specified, the implications of the upper and lower tolerances on containment should be evaluated.

image 22

67. Comparison of pascals to mm of water?

Pascals to Millimeters of water formula

mm H2O =Pa * 0.10197

Pascals (Pa)

Millimeters of water (mm H2O)

PascalsMillimeters of waterPascalsMillimeters of waterPascalsMillimeters of water
1Pa0.10mm H2O16Pa1.63mm H2O31Pa3.16mm H2O
2Pa0.20mm H2O17Pa1.73mm H2O32Pa3.26mm H2O
3Pa0.31mm H2O18Pa1.84mm H2O33Pa3.37mm H2O
4Pa0.41mm H2O19Pa1.94mm H2O34Pa3.47mm H2O
5Pa0.51mm H2O20Pa2.04mm H2O35Pa3.57mm H2O
6Pa0.61mm H2O21Pa2.14mm H2O36Pa3.67mm H2O
7Pa0.71mm H2O22Pa2.24mm H2O37Pa3.77mm H2O
8Pa0.82mm H2O23Pa2.35mm H2O38Pa3.87mm H2O
9Pa0.92mm H2O24Pa2.45mm H2O39Pa3.98mm H2O
10Pa1.02mm H2O25Pa2.55mm H2O40Pa4.08mm H2O
11Pa1.12mm H2O26Pa2.65mm H2O41Pa4.18mm H2O
12Pa1.22mm H2O27Pa2.75mm H2O42Pa4.28mm H2O
13Pa1.33mm H2O28Pa2.86mm H2O43Pa4.38mm H2O
14Pa1.43mm H2O29Pa2.96mm H2O44Pa4.49mm H2O
15Pa1.53mm H2O30Pa3.06mm H2O45Pa4.59mm H2O

68. What is the difference between disintegration and dissolution?

Disintegration is a process of breaking down of granules into small fragments.

Dissolution is the process in which a substance goes into a solution. It is a measure of bioavailability and therapeutic effectiveness. Dissolution is also called drug release.

69. What is the purpose of maintaining pressure gradients between processing areas and service corridors?

Pressure gradients are maintained to avoid cross contamination of products through air.

70. In oral solid manufacturing facility ‘positive’ pressure is maintained in processing area or in service corridors?

Positive pressure is maintained in service corridors with respect to processing rooms.

71. What should be the characteristic of  Finger Bags used for Fluid Bed Dryer (FBD) or Fluid Bed Processor (FBP)?

Antistatic

Waterproof cloth

Able to handle granulation of highly viscous materials, such as extract powder

Non-stick cloth bag

Good permeability

Good boiling effect

Cost-efficient and durable

72. What is generally used material of construction of Finger Bags used for Fluid Bed Dryer (FBD) or Fluid Bed Processor (FBP)

Finger bags are constructed by a combination of Antistatic polymer, Nylon fabric and Cotton fabric. Following materials are also used for Finger bags’ construction.

Antistatic

Epitropic

Polypropylene

Polyester

Stain

73. What are the typically seen micron ratings of Finger Bags used for Fluid Bed Dryer (FBD) or Fluid Bed Processor (FBP)?

Micron Rating: 1, 5, 10, 15, 25, 50, 100

74. What is the formula for calculating friability test results?

Friability (%) = Weight 1 – Weight 2 / Weight 1 X 100

Where,

Weight 1 = Weight of Tablets (Initial / Before Tumbling) & Weight 2 = Weight of Tablets (After Tumbling or friability)

75. What is the limit of friability test results?

Limit: Friability (%) = Not More Than 1.0 %

76. What is Rheology?

Rheology (Greek words rheos meaning flow and logos meaning science) is the study of the flow under the influence of stress. The principle can be applied to solids, liquids, and gases.

77. Explain the types of excipients.

Organoleptic

o Color

o Flavor

o Sweetener

Stabilizers

o Preservative

o Antioxidant

o Emulsifier

o Suspending Agent

Dose Accuracy

o Diluent

o Bulking agent

o Filler

Process Aids

o Binder

o Lubricant

o Glidant

o Anti-adherent

Drug release

o Disintigrant

o Penetration enhancer

o Coating agent

78 What are the types of tablets? Or Classification of Tablets.

Classification of tablets by route of administration

Oral tablets for ingestion

Implantation tablets

Chewable tablets

Tablets used in the oral cavity

Buccal and sublingual tablets

Dental cones

Vaginal tablets

Tablets used to prepare solutions

Effervescent tablets

Dispensing tablets (DT)

Hypodermic tablets (HT)

Tablet triturates (TT)

Troches and lozenges

Classification of tablets by manufacturing process

Compressed tablets

Layered tablets

Sugar coated tablets

Film-coated tablets

Classification of tablets by onset of action

Immediate release tablets

Repeat-action tablets

Delayed-action and enteric coated tablets Controlled release tablets

79. What are the various types of tablets?

Following are various types of tablets.

  • Compressed Tablet (CT)
  • Sugar-Coated Tablets (SCT)
  • Film-Coated Tablets (FCT)
  • Enteric-Coated Tablets (ECT)
  • Multiple Compressed Tablets (MCT)
  • Layered Tablets
  • Press-Coated Tablets
  • Controlled-Release Tablets (CRT)
  • Tablets for Solution (CTS)
  • Effervescent Tablets
  • Compressed Suppositories or Inserts
  • Buccal and Sublingual Tablets
  • Molded Tablets or Tablet Triturates (TT)
  • Dispensing Tablets (DT)
  • Hypodermic Tablets (BT)
  • Compressed Tablets (CT)

80. What are the ingredients used to formulate or manufacture the various types of tablets?

Following are ingredients used to formulate or manufacture the various types of tablets.

  • Active pharmaceutical ingredient
  • Diluents
  • Binders
  • Lubricants
  • Glidants
  • Disintegrants
  • Coloring Agents
  • Flavoring Agents

81. Explain parts of the compression machine.

  • Machine Hopper
  • Feeder System (force feeder/ gravity feeder)
    • Feeder housing
    • Feed pedals
  •  Punches System
    • Upper punch system
    • Lower punch system
  • Die System
  • Turret
  • Machine Cam Tracks
  • Powder Filling Station and Weight Control
  • Compression Rollers (Pre-compression, main-compression)
  • Tablet Press Ejection Cam
  • Take –off blade
  • Discharge Chute
  • Touch Screen Control Panel (HMI/ MMI)
  • Electric Motors, Gears and Belts
  • Lubrication Systems

82. What are the types of tablet press or compression machines?

Broadly, we there are two main types of tableting machines:

  • Single-station tablet press or compression
  • Multi-station tablet press or compression
    • Single rotary machine
    • Double rotary machine

83. What are the types of tablet Coating Machines available in the market?

• Standard Coating Pan

• Perforated Coating Pan

• Fluidized Bed Coater

84. What are the advantages of the tablet coating process?

Following are the advantages of tablet coating:

• It enhances its appearance

• Easy to consume

• Minimizes the unpleasant colour, odour or taste of drug

• Identification

• Helps to reduces drug degradation by protecting it from environmental factors

• Facilitates the packing process

• Functional coating gives functional advantages like extended release, enteric release, prolonged release etc.

85. What are the disadvantages of the tablet coating process?

Following are the disadvantages of tablet coating:

• Cost of operation, resources and material

• Equipment operation and maintenance cost

• May change tablet properties

• Residual solvent toxicity

• Waiting time between processes

• Increase process lead time

• Increase analysis load

86. Explain parts of tablet coating equipment or machine.

Following are the parts of tablet coating equipment or machine

• Perforated coating pan

• Baffles in coating pan

• Spray gun

• Spray pump e.g. Peristalsis pump, Diaphragm pump

• Electric Motors

• Air Handling unit for inlet air

o Inlet air blower

o Air Handling unit housing

o Primary filter (Washable)

o High temperature HEPA filter

o Inlet air temperature sensor

o Differential air pressure sensors across the above filters

• Ducting to supply air and exhaust air

• Control panel with PLC Control and HMI

• Exhaust air blower

• Dust collector or air Scrubber (Wet or Dry)

• Solution preparation tank

87. Explain parts of Fluid bed dryer and Fluid bed processor?

Following are the parts of Fluid bed dryer and Fluid bed equipment

• Plenum

• Product Container with PU wheel trolley

• Inflatable gasket for connection between plenum and Product Container, and Product Container and expansion chamber

• Product temperature sensor

• Inlet air temperature and RH sensor

• Damper for inlet air

• Sample collection port in Product Container

• Glass view in Product Container

• Silicon molded Dutch Woven sieves

• Conidur mesh for mechanism of vortex formation

• Expansion chamber

• Glass view in Expansion chamber

• Finger bag

• Finger bag mounting assembly

• Finger bag shaking assembly

• Inflatable gasket to seal finger bag assembly

• Broken Bag Detector (BBD) sensor OR Solid Flow Monitor (SFM) sensor

• Exhaust blower

• Exhaust filters (10 and 3 µm porosity)

• Explosion flap and Explosion port

• Inlet Air Handling Unit

o Air Handling unit housing

o Primary filter (Washable)

o High temperature HEPA filter

o Dew point sensor

o Differential air pressure sensors across the above filters

o Damper

• CFM or Air flow sensor

• Inlet air duct

• Clean in place system

• Differential pressure sensors, across filters, across finger bag, across product container

• Exhaust air temperature

• Spraying system (for top spray granulation)

88. What is a Tablet Deduster?

Deduster is an equipment used in the pharmaceutical and nutraceutical industry to remove surface dust from the tablets.

89. What are different types of tablet Deduster?

  • Rotary Vibrating Deduster
  • Uphill Deduster
  • Brush Type Deduster
  • Horizontal Deduster
  • Vertical Deduster
    i. Vertical Downward Conveying Deduster
    ii. Vertical Upward Conveying Deduster

90. Explain in detail about different types of Tablet Deduster.

There are different types of tablet dedusters. Each has its advantages and disadvantages.

a. Rotary Vibrating Tablet Deduster

Rotary Vibrating Tablet Deduster depends on rotation and vibration principles.

It has a vibrated helical path with a perforated sieve. As the tablets vibrate and spin along the helical path with a perforated plate, burrs and dust are wiped from their surface. A dust extraction mechanism extracts the dust and the tablets drop into the collection container.

b. Uphill Tablet Deduster

Uphill tablet Dedusting machine depends on the vibration that removes burr and dust as it elevates the tablets. The deduster elevates and dedusts concurrently.

c. Brush Type Tablet Deduster

It consists of a helically wound brush installed within a stainless steel tube (same as screw conveyor) steered by an adjustable speed motor.

The brush pushes the tablets across the tube till they get to the discharge of the deduster at the top or end.

d. Horizontal Tablet Deduster

These types of tablet dedusters use perforated tubes or perforated stainless steel plates that vibrate from one side to another. It is horizontal but slants downwards that the tablets fall as the vibration conveys them over a distance of around 1 meter.

e. Vertical Tablet Deduster

Vertical tablet dedusters are of two types, Downward Conveying Tablet Dedusters and Upward Conveying Tablet Dedusters. The working principle of both types of dedusters are similar.

The dedusters rely on spiral punctured trays on an anchored central column.

91. Which Material is used to make Tablet Dedusters?

Stainless Steel: Stainless steel forms the largest portion of tablet dedusters.

Acrylic: To make the windows.

92. Which Quality Standards should a Tablet Deduster Comply with?

a. Current good manufacturing practices (cGMP) quality standards

b. ISO certification quality standards

c. CCC compliant

d. CE certification

93. How do you select the tablet deduster?

a. Height of compression machine and containers

b. Tablet Size

c. Output

d. Tablet Hardness and Features of Dust

e. Inclusion of Extra Components such as metal detector

94. Explain parts of multimill?

Material Charging Hopper: To load the material to be milled

Milling chamber: Milling of material happens within the chamber with the help of Cutting blades and desired size of particles are passed through specific size screen

Discharge port: Milled material is discharged from this part

Castor wheels: To move the mill from one place to another place

Operating Panel: To operate the equipment

Screen: To produce desired particle size

Cutting blades: To mill the material

95. What is the Material Of Construction (MOC) of multimill parts?

Product contact parts are made up of SS 316 or SS316L

Non-product contact parts are made up of SS 304 Castor wheels are made up of Polyurethane

96. What is the mechanism of size reduction when using multimill?

a. Impact Milling: Particles are reduced in size by high-speed mechanical impact or impact with other particles; also known as milling, pulverizing, or comminuting.

b. Cutting: Particles are reduced in size by mechanical shearing.

c. Screening: Particles are reduced in size by mechanically induced attrition through a screen. This process commonly is referred to as milling or deagglomeration.

97. What are the typical speeds of multimill?

Fast speed: 2880

Medium fast speed: 2160

Medium speed: 1440

Low speed: 720

Note: Nowadays multimill are available with variable frequency drive where speed can be set as per the requirement (Custom speed).

98. What are the typical settings for milling operation using multimill?

Blade direction: Impact forward or Knife forward

Machine speed: Using V belt adjustment or using VFD as per machine design

99. What is Vibro sifter?

Vibro sifter is equipment used for separating particles based upon particle size alone and without any significant particle size reduction. This process commonly is referred to as screening or bolting. Vibration and Gyratory motion plays an important role to facilitate the screening process.

100. What is the principle of Vibro sifter?

Vibro sifters work on the principle of separation. Particles are segregated based upon particle size alone and without any significant particle size reduction. This process commonly is referred to as screening or bolting. Vibration and Gyratory motion plays an important role to facilitate the screening process.

The mechanism on which Vibro Sifter works is the principle of gyratory vibrations. The material is separated based on its particle size. Once the motor gets energized, vibration is caused in the screen/. This makes material travel across the sieves according to its particle size and sieve/ screen size.

Separator subclasses as per SUPAC: Vibratory/ Shaker and Centrifugal.

101. What is the gyratory motion of a vibro sifter and how does it get generated?

In the vibro sifter gyratory motion is obtained from a specially designed gyro motor, which is fitted underneath the vibrating assembly. A specially designed rugged spring completely isolates this assembly from the base with the help of Gyro-motor.

image 23

The motor is fitted with eccentric weights present at its top as well as base to create centrifugal force. This whole assembly is covered by an SS plate.

102. What are other names of vibro sifters?

The vibro sifter machine is also known as:

Vibro Screen

Vibrating Screen

Lab Vibro Sifter

Pharmaceutical Sifter

Vibro Sieve

Vibro Sifter Machine

Powder Sieving Machine

103. What are the salient features or use of vibro sifter?

• Gradation and separation of dry powder, granules, semi solids and liquids

• Main functioning mechanical arrangement is suspended on a spring to prevent vibration on the floor

• Easy assembling and disabling

• Easy to clean

104. What are different parts of vibro sifter?

• Dust cover

• Clamp for assembling of different parts

• Inlet

• Sieve/ screen

• Vibrating motor for Gyratory motion with eccentrically arranged top and bottom hammer

• Caster wheel

• Discharge port

• Spring

105. How to discharge the static electricity which may get generated over the vibro sifter sieve when silicone bonded sieve is used?

Following are the solutions to discharge the static electricity which may get generated over the vibro sifter sieve when silicone bonded screen is used:

i. Using antistatic screen

ii. Use C clamp over the silicone bonded sieve which makes the entire assembly conductive and to provide earthing to the body of the equipment.

106. What is a solution preparation vessel?

The solution preparation vessel is a closed tank used to prepare solution at room temperature or elevated temperature by using electrical heating or steam heating. To mix the solution homogeneously, it consists of stirring to create a vortex inside the solution.

107. What is the use of solution preparation vessels in the pharmaceutical industry?

The solution preparation vessel is used to prepare various types of solutions such as binder solution, coating solution, heating of water, liquid preparations such as syrup, suspension, solutions, etc. The vessel is used to ensure a homogeneous mix.

108. Explain parts of solution preparation vessel and Material of Construction (MOC)?

• Tank – SS316 or SS316L

• Stirrer – SS316 or SS316L

• Thermal Insulation

• Motor

• Variable Frequency Drive

• Control Panel

• Pressure gauge for jacket

• Temperature sensor – Product contact part SS316 or SS316 L

• Discharge valve (Zero dead leg and sanitary type)(Note: Ball valve is not acceptable) – SS316 or SS316L

• Caster wheel for movement (Need based) – Polyurethane

109. What is vortex and how is it helpful for solution preparation?

A circular, spiral, or helical motion in a fluid. A vortex often forms around areas of low pressure and attracts the fluid (and the objects moving within it) toward its center.

Velocity in the vortex is maximum next to the axis and inversely decreases with the radius.

Vortex enhances the desired solubility of pharmaceutical binder solute into the various solvents.

image 24

110. What should be characteristics of the solution preparation vessel?

• Zero dead leg and sanitary design components

• Stationary or mobile use

• Capable to handle wide temperature range (design as per requirement)

• The Internal surfaces of our preparation vessels are flush ground and mirror polished to <0.3 Microns Ra and electro-polished

• Easy to clean

• Adjustable speed of stirrer

• Adjustable temperature

• 21 CFR Part 11 compliant and EU Annex 11 Compliant

• Low maintenance and long service

111. What are the different particle size reduction mechanisms?

Particle size reduction mechanismsDescription
ImpactParticle size reduction by applying an instantaneous force perpendicular to the particle/ agglomerate surface. The force can result from particle-to-particle or particle-to-mill surface collision.
AttritionParticle size reduction by applying a force in a direction parallel to the particle surface.
CompressionParticle size reduction by applying a force slowly (as compared to Impact) to the particle surface in a direction toward the center of the particle.
CuttingParticle size reduction by applying a shearing force to a material.

112. What are the types of Equipment used for Particle Size Reduction/ Separation. Explain its Operating Principles.

Types of EquipmentOperating Principles
Fluid Energy MillingParticles are reduced in size as a result of high-speed particle-to-particle impact and/or attrition; also known as micronizing.
Impact MillingParticles are reduced in size by high-speed mechanical impact or impact with other particles; also known as milling, pulverizing, or comminuting.
CuttingParticles are reduced in size by mechanical shearing.
Compression MillingParticles are reduced in size by compression stress and shear between two surfaces.
ScreeningParticles are reduced in size by mechanically induced attrition through a screen. This process commonly is referred to as milling or deagglomeration.
Tumble MillingParticles are reduced in size by attrition utilizing grinding media.
SeparatingParticles are segregated based upon particle size alone and without any significant particle size reduction. This process commonly is referred to as screening or bolting.

113. Explain Equipment Classifications for Particle Size Reduction/ Separation. Give examples of Equipment for each classification.

Equipment typeSub classification descriptionSub classification
Fluid Energy MillsFluid energy mill subclasses have no moving parts and primarily are distinguished from one another by the configuration and/ or shape of their chambers, nozzles, and classifiers.Tangential Jet Loop/ Oval Opposed Jet Opposed Jet with Dynamic Classifier Fluidized Bed Fixed Target Moving Target High Pressure Homogenizer   E.g. Jet mill
Impact MillsImpact mill subclasses primarily are distinguished from one another by the configuration of the grinding heads, chamber grinding liners (if any), and classifiers.Hammer Air Swept Hammer Conventional Pin/ Disc Cage  E.g. Hammer millPin mill Impact millCage millDisk millBall mill
Cutting MillsAlthough cutting mills may differ from one another in whether the knives are movable or fixed and in the classifier configuration, no cutting mill subclasses have been identified.No sub class  E.g. MultimillComill
Compression MillsAlthough compression mills may differ from one another in whether one or both surfaces are moving, no compression mill subclasses have been identified.No sub class  E.g. Roller mill
Screening MillsScreening mill subclasses primarily are distinguished from one another by the rotating element.Rotating Impeller Rotating Screen Oscillating Bar  E.g. MultimillComill
Tumbling MillsTumbling mill subclasses primarily are distinguished from one another by the grinding media used and by whether the mill is vibrated.Ball Media Rod Media Vibrating  E.g. Ball millTubular Rod Mills
SeparatorsSeparator subclasses primarily are distinguished from one another by the mechanical means used to induce particle movement.  Vibratory/ Shaker Centrifugal  E.g. Vibro sifterUltra Centrifugal Mill

Source: fda.gov

114. What is Blending and Mixing?

Blending and Mixing is the process of reorientation of particles relative to one another in order to achieve uniformity.

115. What are the Operating Principles of different equipment for Blending and Mixing?

Types of EquipmentOperating Principles
Diffusion Blending (Tumble blending)Particles are reoriented in relation to one another when they are placed in random motion and interparticular friction is reduced as the result of bed expansion (usually within a rotating container).
Convection Mixing (also known as paddle or plow mixing)Particles are reoriented in relation to one another as a result of mechanical movement.
Pneumatic MixingParticles are reoriented in relation to one another as a result of the expansion of a powder bed by gas.

116. Equipment Classifications used for Blending and Mixing

Equipment typeSub classification descriptionSub classification
Diffusion Mixers (Tumble)Diffusion mixer subclasses primarily are distinguished by geometric shape and the positioning of the axis of rotation.• V-blenders• Double Cone Blenders• Slant Cone Blenders• Cube Blenders• Bin Blenders• Horizontal/ Vertical/ Drum Blenders• Static Continuous Blenders• Dynamic Continuous Blenders
Convection Mixers  Convection blender subclasses primarily are distinguished by vessel shape and impeller geometry.• Ribbon Blenders• Orbiting Screw Blenders• Planetary Blenders• Forberg Blenders• Horizontal Double Arm Blenders• Horizontal High Intensity Mixers• Vertical High Intensity Mixers• Diffusion Mixers (Tumble) with Intensifier/Agitator
Pneumatic Mixers  Although pneumatic mixers may differ from one another in vessel geometry, air nozzle type, and air nozzle configuration, no pneumatic mixer subclasses have been identified.No sub lass

Source: fda.gov

117. What is Granulation

Granulation is the process of creating granules. The powder morphology is modified through the use of either a liquid that causes particles to bind through capillary forces or dry compaction forces.

The process will result in one or more of the following powder properties:

Enhanced flow;

Increased compressibility;

Densification;

Alteration of physical appearance to more spherical, uniform, or larger particles;

And/or enhanced hydrophilic surface properties.

118. What are the Operating Principles of different Granulation?

Types of GranulationOperating Principles
Dry GranulationDry powder densification and/or agglomeration by direct physical compaction.
Wet High-Shear GranulationPowder densification and/or agglomeration by the incorporation of a granulation fluid into the powder with high-power-per-unit mass, through rotating high-shear forces.
Wet Low-Shear GranulationPowder densification and/or agglomeration by the incorporation of a granulation fluid into the powder with low-power-per-unit mass, through rotating low-shear forces.
Low-Shear Tumble GranulationPowder densification and/or agglomeration by the incorporation of a granulation fluid into the powder with low-power-per-unit mass, through rotation of the container vessel and/or intensifier bar.
Extrusion GranulationPlasticization of solids or wetted mass of solids and granulation fluid with linear shear through a sized orifice using a pressure gradient.
Rotary GranulationSpheronization, agglomeration, and/or densification of a wetted or non-wetted powder or extruded material.   This is accomplished by centrifugal or rotational forces from a central rotating disk, rotating walls, or both. The process may include the incorporation and/or drying of a granulation fluid.
Fluid Bed GranulationPowder densification and/or agglomeration with little or no shear by direct granulation fluid atomization and impingement on solids, while suspended by a controlled gas stream, with simultaneous drying.
Spray Dry GranulationA pumpable granulating liquid containing solids (in solution or suspension) is atomized in a drying chamber and rapidly dried by a controlled gas stream, producing a dry powder.
Hot-melt GranulationAn agglomeration process that utilizes a molten liquid as a binder(s) or granulation matrix in which the active pharmaceutical ingredient (API) is mixed and then cooled down followed by milling into powder. This is usually accomplished in a temperature controlled jacketed high shear granulating tank or using a heated nozzle that sprays the molten binders(s) onto the fluidizing bed of the API and other inactive ingredients.
Melt ExtrusionA process that involves melting and mixing API and an excipient (generally a polymer) using low or high shear kneading screws followed by cooling and then milling into granules. Thermal energy for melting is usually supplied by the electric/water heater placed on the barrel. Materials are either premixed or fed into an extruder separately. Melt extruder subclasses primarily are distinguished by the configuration of the screw. • Single screw extruder • Twin screw extruder

119. Equipment Classifications used for granulation.

Equipment typeSub classification descriptionSub classification
Dry GranulatorDry granulator subclasses primarily are distinguished by the densification force application mechanism.• Slugging • Roller Compaction
Wet High-Shear GranulatorWet high-shear granulator subclasses primarily are distinguished by the geometric positioning of the primary impellers; impellers can be top, bottom, or side driven.• Vertical (Top or Bottom Driven) • Horizontal (Side Driven)
Wet Low-Shear GranulatorWet low-shear granulator subclasses primarily are distinguished by the geometry and design of the shear inducing components; shear can be induced by rotating impeller, reciprocal kneading action, or convection screw action.• Planetary • Kneading • Screw
Low-Shear Tumble GranulatorAlthough low-shear tumble granulators may differ from one another in vessel geometry and type of dispersion or intensifier bar, no low-shear tumble granulator subclasses have been identified.• Slant cone • Double cone • V-blender
Extrusion GranulatorExtrusion granulator subclasses primarily are distinguished by the orientation of extrusion surfaces and driving pressure production mechanism.• Radial or Basket • Axial • Ram • Roller, Gear, or Pelletizer
Rotary GranulatorRotary granulator subclasses primarily are distinguished by their structural architecture. They have either open top architecture, such as a vertical centrifugal spheronizer, or closed top architecture, such as a closed top fluid bed dryer.• Open • Closed
Fluid Bed GranulatorAlthough fluid bed granulators may differ from one another in geometry, operating pressures, and other conditions, no fluid bed granulator subclasses have been identified.No subclass
Spray Dry GranulatorAlthough spray dry granulators may differ from one another in geometry, operating pressures, and other conditions, no spray dry granulator subclasses have been identified.No subclass
Hot-melt GranulatorAlthough, hot-melt granulator may differ from one another in primarily melting the 455 inactive ingredient (particularly the binder or other polymeric matrices), no 456 subclasses have been identified at this time.No subclass

120. What is an integrated unit as per SUPAC?

When a single piece of equipment is capable of performing multiple discrete unit operations (i.e. mixing, granulating, drying), the unit was evaluated solely for its ability to granulate. If multifunctional units were incapable of discrete steps (fluid bed granulator/ drier), the unit was evaluated as an integrated unit.

Source: fda.gov

121. What is Drying?

The removal of a liquid from a solid by evaporation.

122. What are the Operating Principles of different equipment for Drying?

Types of Drying principleDetails of Principles
Direct Heating, Static Solids BedHeat transfer is accomplished by direct contact between the wet solids and hot gases. The vaporized liquid is carried away by the drying gases. There is no relative motion among solid particles. The solids bed exists as a dense bed, with the particles resting upon one another.
Direct Heating, Moving Solids BedHeat transfer is accomplished by direct contact between the wet solids and hot gases. The vaporized liquid is carried away by the drying gases. Solids motion is achieved by either mechanical agitation or gravity force, which slightly expands the bed enough to flow one particle over another.
Direct Heating, Fluidized Solids BedHeat transfer is accomplished by direct contact between the wet solids and hot gases. The vaporized liquid is carried away by the drying gases. The solids are in an expanded condition, with the particles supported by drag forces caused by the gas phase. The solids and gases intermix and behave like a boiling liquid. This process commonly is referred to as fluid bed drying.
Direct Heating, Dilute Solids Bed, Spray DryingHeat transfer is accomplished by direct contact between a highly dispersed liquid and hot gases. The feed liquid may be a solution, slurry, emulsion, gel or paste, provided it is pumpable and capable of being atomized. The fluid is dispersed as fine droplets into a moving stream of hot gases, where they evaporate rapidly before reaching the wall of the drying chamber. The vaporized liquid is carried away by the drying gases. The solids are fully expanded and so widely separated that they exert essentially no influence on one another.
Direct Heating, Dilute Solids Bed, Flash DryingHeat transfer is accomplished by direct contact between wet solids and hot gases. The solid mass is suspended in a finely divided state in a high-velocity and high-temperature gas stream. The vaporized liquid is carried away by the drying gases.
Indirect Conduction, Moving Solids BedHeat transfer to the wet solid is through a retaining wall. The vaporized liquid is removed independently from the heating medium. Solids motion is achieved by either mechanical agitation or gravity force, which slightly expands the bed enough to flow one particle over another.
Indirect Conduction, Static Solids BedHeat transfer to the wet solid is through a retaining wall. The vaporized liquid is removed independently from the heating medium. There is no relative motion among solid particles. The solid bed exists as a dense bed, with the particles resting upon one another.
Indirect Conduction, LyophilizationDrying in which the water vapor sublimes from the product after freezing.
Gas StrippingHeat transfer is a combination of direct and indirect heating. The solid motion is achieved by agitation and the bed is partially fluidized.
Indirect Radiant, Moving Solids BedHeat transfer is accomplished with varying wavelengths of energy. Vaporized liquid is removed independently from the solid bed. The solid’s motion is achieved by mechanical agitation, which slightly expands the bed enough to flow one particle over one another. This process commonly is referred to as microwave drying.

123. Equipment Classifications used for drying.

Equipment typeSub classification descriptionSub classification
Direct Heating, Static Solids BedStatic solids bed subclasses primarily are distinguished by the method of moving the solids into the dryer.• Tray and Truck • Belt
Direct Heating, Moving Solids BedMoving solids bed subclasses primarily are distinguished by the method or technology for moving the solid bed.• Rotating Tray • Horizontal Vibrating Conveyor
Direct Heating, Fluidized Solids Bed (Fluid Bed Dryer)Although fluid bed dryers may differ from one another in geometry, operating pressures, and other conditions, no fluidized solids bed dryer subclasses have been identified.No subclass
Direct Heating, Dilute Solids Bed, Spray DryerAlthough spray dryers may differ from one another in geometry, operating pressures, and other conditions, no spray dryer subclasses have been identified.No subclass
Direct Heating, Dilute Solids Bed, Flash DryerAlthough flash dryers may differ from one another in geometry, operating pressures, and other conditions, no flash dryer subclasses have been identified.No subclass
Indirect Conduction Heating, Moving Solids BedMoving solids bed subclasses primarily are distinguished by the method or technology for moving the solids bed.• Paddle • Rotary (Tumble) • Agitation
Indirect Conduction Heating, Static Solids BedsNo indirect heating, static solids bed shelf dryer subclasses have been identified.No subclass
Indirect Conduction, LyophilizationNo lyophilizer subclasses have been identified.No subclass
Gas StrippingAlthough gas stripping dryers may differ from one another in geometry, shape of agitator, and how fluidizing gas is moved through the bed, no gas stripping dryer subclasses have been identified.No subclass
Indirect Radiant Heating, Moving Solids Bed (Microwave Dryer)Although microwave dryers may differ from one another in vessel geometry and the way microwaves are directed into the solids, no indirect radiant heating, moving solids bed dryer subclasses have been identified.No subclass

Source: fda.gov

124. What is Unit Dosing?

The division of a powder blend into uniform single portions for delivery to patients.

125. What are the Operating Principles of different equipment for Unit Dosing?

Types of Unit Dosing principleDetails of Principles
TablettingThe division of a powder blend in which compression force is applied to form a single unit dose.
EncapsulatingThe division of material into a hard gelatin capsule. Encapsulators should all have the following operating principles in common: rectification (orientation of the hard gelatin capsules), separation of capsule caps from bodies, dosing of fill material/formulation, rejoining of caps and bodies, and ejection of filled capsules.
Powder FillingThe division of a powder blend into a container closure system.

126. Equipment Classifications used for Unit Dosing.

Equipment typeSub classification descriptionSub classification
Tablet PressTablet press subclasses primarily are distinguished from one another by the method that the powder blend is delivered to the die cavity. Tablet presses can deliver powders without mechanical assistance (gravity), with mechanical assistance (power assisted), by rotational forces (centrifugal), and in two different locations where a tablet core is formed and subsequently an outer layer of coating material is applied (compression coating).• Gravity• Power Assisted• Centrifugal• Compression Coating
Tablet PressTablet press subclasses are also distinguished from one another for some special types of tablets where more than one hopper and precise powder feeding mechanism might be necessary.• Multi-tablet press for micro/mini tablet • Multi-layer tablet press (bi-layer, tri-layer)
EncapsulatorEncapsulator subclasses primarily are distinguished from one another by the method that is used for introducing material into the capsule. Encapsulators can deliver materials with a rotating auger, vacuum, vibration of perforated plate, tamping into a bored disk (dosing disk), or cylindrical tubes fitted with pistons (dosator).• Auger• Vacuum• Vibratory• Dosing Disk• Dosator
Powder FillerSubclasses of powder fillers primarily are distinguished by the method used to deliver the predetermined amount for container fill.• Vacuum• Auger

Source: fda.gov

127. What is Coating?

The uniform deposition of a layer of material on or around a solid dosage form.

128. Why is the coating done?

Coating is done for the following reasons:

a. Protect the drug from its surrounding environment (air, moisture, and light), with a view to improving stability.

b. Mask unpleasant taste, odor, or color of the drug.

c. Increase the ease of ingesting the product for the patient.

d. Impart a characteristic appearance to the tablets, which facilitates product identification and aids patient compliance.

e. Provide physical protection to facilitate handling. This includes minimizing dust generation in subsequent unit operations.

f. Reduce the risk of interaction between incompatible components. This would be achieved by coating one or more of the offending ingredients.

g. Modify the release of the drug from the dosage form. This includes delaying, extending, and sustaining drug substance release.

h. Modify the dosage form by depositing the API or drug substance on or around a core tablet, which could be a placebo core tablet or a tablet containing another drug or a fractional quantity of the same drug.

129. What are the major techniques used for coating?

The coating material deposition typically is accomplished through one of six major techniques:

a. Sugar Coating – Deposition of coating material onto the substrate from aqueous solution/suspension of coatings, based predominantly upon sucrose as a raw material.

b. Film Coating – The deposition of polymeric film onto the solid dosage form.

c. Core Enrobing – The gelatin coating of gravity or force fed pre- formed tablets or caplets.

d. Microencapsulation – The deposition of a coating material onto a particle, pellet, granule, or bead core. The substrate in this application ranges in size from submicron to several millimeters. It is this size range that differentiates it from the standard coating described in 1 and 2 above.

e. Compression Coating (also addressed in the Unit Dosing section) – A coating process where a dry coatings blend is applied on a previously compressed core tablet using a tablet compression machine.11 Therefore, this process is also known as a dry coating process that does not involve any water or any other solvent in the coating process.

f. Active/ API coating – Deposition of active pharmaceutical ingredient (API or drug substance) on or around a core tablet utilizing any of the above five coating techniques.

Source: fda.gov

130. What are the Operating Principles of different equipment for coating?

Types of coatingDetails of Principles
Pan CoatingThe uniform deposition of coating material onto the surface of a solid dosage form, or component thereof, while being translated via a rotating vessel.
Gas SuspensionThe application of a coating material onto a solid dosage form, or component thereof, while being entrained in a process gas stream. Alternatively, this may be accomplished simultaneously by spraying the coating material and substrate into a process gas stream.
Vacuum Film CoatingThis technique uses a jacketed pan equipped with a baffle system. Tablets are placed into the sealed pan, an inert gas (i.e., nitrogen) is used to displace the air and then a vacuum is drawn.
Dip CoatingCoating is applied to the substrate by dipping it into the coating material. Drying is accomplished using pan coating equipment.
Electrostatic CoatingA strong electrostatic charge is applied to the surface of the substrate. The coating material containing oppositely charged ionic species is sprayed onto the substrate.
Compression CoatingThe division of a powder blend in which compression force is applied to form a single unit dose.

131. Equipment Classifications used for coating.

Equipment typeSub classification descriptionSub classification
Pan CoatingPan coating subclasses primarily are distinguished by the pan configuration, the pan perforations, and/or the perforated device used to introduce process air for drying purposes. Perforated coating systems include both batch and continuous coating processes.• Non-perforated (conventional) Coating System • Perforated Coating System
Gas SuspensionGas suspension subclasses primarily are distinguished by the method by which the coating is applied to the substrate.• Fluidized Bed with bottom spray mechanism • Fluidized Bed with tangential spray mechanism • Fluidized Bed with top spray mechanism • Fluidized Bed with Wurster column • Spray Congealing/Drying
Vacuum Film CoatingAlthough there may be differences in the jacketed pan, baffle system, or vacuum source, no vacuum film coating subclasses have been identified.No sub class
Dip CoatingBecause of the custom design associated with this class of coating, no dip 1013 coating subclasses or examples have been identified.No sub class
Electrostatic CoatingBecause of the custom design associated with this class of coating, no 1018 electrostatic coating subclasses or examples have been identified.No sub class
Compression CoatingRefer tablet press principle Unit Dosing section of previous post.No sub class

Source: fda.gov

132. What is Printing?

The marking of a capsule or tablet surface for the purpose of product identification.

Printing may be accomplished by either the application of a contrasting colored polymer (ink) onto the surface of a capsule or tablet, or by the use of laser etching. The method of application, provided the ink formulation is not altered, is of no consequence to the physical-chemical properties of the product.

133. What is Drilling?

The drilling or ablating of a hole or holes through the polymeric film coating shell on the surfaces of a solid oral dosage form using a laser.

The polymeric film shell is not soluble in vivo. The hole or holes allow for the modified release of the drug from the core of the dosage form.

134. What are the Operating Principles of different equipment for Printing and Drilling?

Types of Printing/ DrillingDetails of Principles
Ink-Based PrintingThe application of contrasting colored polymer (ink) onto the surface of a tablet or capsule.
Laser EtchingThe application of identifying markings onto the surface of a tablet or capsule using laser-based technology.
DrillingA drilling system typically is a custom built unit consisting of a material handling system to orient and hold the solid dosage form, a laser (or lasers), and optics (lenses, mirrors, deflectors, etc.) to ablate the hole or holes, and controls. The drilling unit may include debris extraction and inspection systems as well. The sorting, orienting, and holding equipment commonly is provided by dosage form printing equipment manufacturers, and is considered ancillary in this use.

135. Equipment Classifications used for Printing and Drilling.

Equipment typeSub classification descriptionSub classification
Ink-Based PrintingInk-based printing subclasses primarily are distinguished by the method by which the marking is applied to a capsule or tablet surface.• Offset • Ink Jet
Laser Etching (Printing)Although laser etching systems may differ from one another, no laser etching subclasses have been identified.No sub class
DrillingThe method of producing the laser pulse that ablates the hole(s) is of no consequence to the physical-chemical properties of the product. Therefore, no dosage form drilling equipment subclasses have been identified.No sub class

Source: fda.gov

136. What is excipient?

The word excipient originates from the Latin excipere, which means to receive; hence, the excipient receives the active substance.

As per European Pharmacopoeia (Ph. Eur.) “An excipient is any component, other than the active substance(s), present in a medicinal product or used in the manufacture of the product. The intended function of an excipient is to act as the carrier (vehicle or basis) or as a component of the carrier of the active substance(s) and, in so doing, to contribute to product attributes such as stability, biopharmaceutical profile, appearance and patient acceptability and to the ease with which the product can be manufactured. Usually, more than one excipient is used in the formulation of a medicinal product.”

147. What are the typical functions of excipients?

Excipients play a role in the formulation as Diluent, Binder, Disintegrant, Glidant, Lubricant, Coatings agent, or Coloring agent. It can further classified depending on its functions in the dosage form, which includes:

(i) Modulating solubility and bioavailability of the drug,

(ii) Enhancing stability of the drug in its dosage forms,

(iii) Maintaining a required polymorphic form,

(iv) Maintaining pH and osmolarity of liquid products,

(v)Antioxidants,

(vi) Preventing aggregation or dissociation agent,

(vii) Modulating the immunogenic response of drug,

(viii) Suspending agent,

(ix) Emulsifier,

(x) Aerosol propellants,

(xi) Base or tablet diluent

138. What is role of Diluents as an excipient?

Diluents are the material which provides bulk to the formulation and enable accurate dosing of potent ingredients.

139. Give a few examples of Diluents as an excipient?

Microcrystalline cellulose, Lactose, dextrin, glucose, sucrose, sorbitol, silicates, calcium and magnesium salts, sodium or potassium chloride, starch, lactose

140. What is the role of Binder as an excipient?

Binders, compression aids, granulating agents are the materials which bind the ingredients together giving form and mechanical strength and form granules for tablet, capsule or relevant formualtions

141. Give a few examples of Binder as an excipient?

Polyvinyl pyrrolidone, starch, gelatin, cellulose derivatives, sugars, sugar alcohols and cellulose derivatives

142. What is the role of Disintegrant as an excipient?

Disintegrant aid in dispersion of the tablet in the gastrointestinal tract, releasing the active ingredient and increasing the surface area for dissolution.

143. Give a few examples of Disintegrant as an excipient?

Starch, sodium starch glycollate, cross – linked polyvinyl pyrrolidone super disintegrants, cellulose derivatives and alginates, and crospovidone.

144. What is role of Glidant as an excipient?

Glidant improves the flow of powders during tablet manufacturing by reducing friction and adhesion between particles. It also used as anti-caking agents.

145. Give a few examples of Glidant as an excipient?

Colloidal anhydrous silicon and other silica compounds, talc, magnesium stearate

146. What is the role of Lubricant as an excipient?

Lubricants are used to prevent sticking of granules from die and punch wall during compression.

147. Give a few examples of Lubricant as an excipient?

Stearic acid and its salts (e.g. magnesium stearate), polyethylene glycol, sodium chloride

148. What is the role of coating agents as an excipient?

Coating agents have various functions such as, protect tablets from the environment (air, light and moisture), increase the mechanical strength, mask taste and smell, aid swallowing, assist in product identification.

It also can be used to modify release of the active ingredient.

149. Give a few examples of coating agents as an excipient?

Sugar, cellulose acetate phthalate etc.

150. What is the role of Colouring agent as an excipient?

Coloring agents improves acceptability to patients, aids identification and prevents counterfeiting. It also increases the stability of light-sensitive drugs.

151. Give a few examples of Colouring agents as an excipient?

Iron oxide, natural pigments, and other synthetic dyes.

152. Explain excipient classification based on objective of addition in dosage form.

Type of excipientObjective in dosage form
Improve organoleptic propertyColor Flavor Sweetener Masking of unpleasant test
StabilizersPreservative Antioxidant Emulsifier Suspending agent Isotonicity agent Maintaining pH and osmolarity
Dosage accuracyDiluent Filler Bulking agent
Process aidsBinder Glidant Lubricant Anti-adherent
Drug releaseDisintigrant Permiability enhancer Release rate limiting agent

153. What is immediate – release dosage form?

This is the dosage form intended to release the drug immediately after administration.

154. What is Delayed – release dosage form?

This is the dosage form where drug is not released until a physical event has occurred, e.g., change in pH etc.

155. What is sustained – release dosage form?

This is the dosage form where drug is released slowly over extended time.

156. What is a soluble tablet?

Soluble tablets are those which dissolve in water before administration.

157. What is a Dispersible tablet?

Tablet is added to water to form a suspension to administer.

158. What is an Effervescent tablet?

Tablet which is added into water. Tablet releases carbon dioxide to form an effervescent solution.

159. What is a Chewable tablet?

To administer the dose, the tablet is chewed and swallowed.

160. What is Chewable gum?

The formulation is chewed and removed from the mouth after a directed time as per the label claim.

161. What are Buccal and sublingual tablets?

The tablet which is placed in the oral cavity for local or systemic action is called Buccal and sublingual.

162. What is an Orally disintegrating tablet?

The tablet which gets dissolved or disintegrated in the mouth without the need for water is called an orally disintegrating tablet.

163. What is Lozenge?

Lozenge is a slowly dissolving tablet designed to be sucked in the mouth.

164. What is Pastille?

Pastille is the tablet consisting of gelatin and glycerine that facilitate dissolving tablets slowly in the mouth.

165. What is a Hard gelatin capsule?

Hard gelatin capsule is a two piece capsule shell that is filled with powder, granulate, tablets, semisolid or liquid in it.

166. What is Soft gelatin capsule (softgel)?

Soft gelatin capsule is a one piece capsule that contains a liquid or semisolid filled in it.

References:

1. WHO GMP Guidelines: Guide to Master Formulae, WHO/FWC/IVB/QSS/VQR, 2011

EU and PIC GMP guidelines: EudraLex Volume 4, Chapter 4: Documentation

PIC/S guidelines: Chapter 4: Documentation

Health Canada GMP guidelines: Good manufacturing practices guide for drug products (GUI-0001), Manufacturing control, C.02.011

U.S. FDA: CFR 21, Chapter I, Subchapter F: Biologics, Part 211 Current Good Manufacturing Practice for Finished Pharmaceuticals; Subpart F–Production and Process Controls, Sec. 211.100 Written procedures; deviations; and Subpart J–Records and Reports; Sec. 211.186 Master production and control records

U.S. FDA: CFR 21, Chapter I, Subchapter F: Biologics; Subchapter C: Drugs General; Part 211 Current Good Manufacturing Practice for Finished Pharmaceuticals; Subpart J– Records and Reports; Sec. 211.188 Batch production and control records.

India: The drugs and cosmetics act, 1940 and The drugs and cosmetics rules, 1945, Schedule M, 12. Documentation and records]

2. PART 314 — APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG, Subpart A – General Provisions Sec. 314.3 Definitions.

3. 21 CFR PART 210: CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL Sec. 210.1 Status of current good manufacturing practice regulations.

5. Wet Granulation:

End-Point Determination and Scale-Up, By Michael Levin, Ph. D., Metropolitan Computing Corporation East Hanover, New Jersey, USA

6. Saudi Pharmaceutical Journal

Volume 20, Issue 1, January 2012, Pages 9-19, Saudi Pharmaceutical Journal, Review article, Upgrading wet granulation monitoring from hand squeeze test to mixing torque rheometry Author links open overlay panel Walid F. Sakr Mohamed A. Ibrahim Fars K. Alanazi Adel A. Sakr

7. natoli.com

8. pacifictools.in

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