1. PHR 303 Pharmaceutical Technology - II
Friday, April 28, 2017
PHR 303 Pharmaceutical Technology - II

2. TO BE INCLUDED IN FINAL SYLLABUS
1. Formulation & Manufacturing of Tablets
2. Common Tableting Problems & Evaluation of Tablets
3. Tablet Coating
1. Sustained Release Drug Delivery Systems
2. Aerosol Science & technology
3. Design & operation of clean rooms
4. Parental products
5. Ophthalmic products
6. Packaging technology
7. Blood products & plasma substitutes

3. TOPICs: Formulation, Manufacturing, Evaluation & Coating of Tablets
Friday, April 28, 2017

4. Tablets may be defined as solid pharmaceutical dosage forms containing drug substances prepared either by compression or molding methods. Although it is possible to manufacture in a wide range of shape, official tablets are defined as circular sizes with either flat or convex faces.

5. Friday, April 28, 2017

6. Advantages of Tablets
1. Large scale manufacturing is feasible in comparison to other dosage forms. Therefore, economy can be achieved. 2. Accuracy of dose is maintained since tablet is a solid unit dosage form. 3. Tailor made release profile can be achieved. 4. Longer expiry period and minimum microbial spillage owing to lower moisture content. 5. As tablet is not a sterile dosage form, stringent environmental conditions are not required in the tablet department.
Fri, Feb

7. …continued
6. Ease of packaging (blister or strip) and easy handling. 7. Ease of product identification because of huge number of shapes and color. 8. Easy to transport in bulk. Emergency supply supplies can be carried by patients. 9. Organoleptic properties (taste, appearance and odour) are best improved by coating of tablet.
Fri, Feb

8. …continued
10. Product identification is easy and markings done with the help of grooved punches and printing with edible ink. 11. Different types of tablets are available like buccal, floating, colon targeting, effervescent, dispersible, soluble, and chewable, etc. 12. In composition to parenterals dosage form, a doctor or a nurse is not required for administration. I.e. self administration is possible. 13. In comparison to capsules, tablets are more tamperproof.
Fri, Feb

9. Disadvantages of tablets
1. Drugs not absorbed or extensively degraded into GI tract cannot be made into tablets 2. It is difficult to convert a high dose poorly compressible API into a tablet of suitable size for human use. 3. Difficult to formulate a drug with poor wettability, slow dissolution into a tablet. 4. Slow onset of action as compared to parenterals, liquid orals and capsules.
Fri, Feb

10. …continued
5. The amount of liquid drug (e.g. Vitamin E, Simethicone) that can be trapped into a tablet is very less. 6. Difficult to swallow for kids, terminally ill and geriatric patients. 7. Patients undergoing radiotherapy cannot swallow tablet.
Fri, Feb

11. Essential qualities of a good tablet
They should be accurate and uniform in weight
The drugs should be uniformly distributed throughout the tablets
The size and shape should be reasonable for easy administration
The tablets should not be too hard that it may not be disintegrate in the stomach
After administration it should disintegrate readily
They should be attractive in appearance
They should not have any manufacturing defects like cracking, capping or discoloration

12. Absorption of drug from tablets

13. Friday, April 28, 2017

14. Compressed tablets- Immediate release tablets
Coated tablets
Sugar coated tablets
Film coated tablets-Enteric coated tablets
Compression Coating & Layered Tablets
Modified release/Sustained release/Controlled release
Fri, Feb

15. Examples Chewable- Antacid tablet Soluble tablets- Aspirin tablet
Effervescent tablets- vitamin C
Mouth dissolving tablets (orally disintegrating tablets)- Loratidin tablets
Fri, Feb

16. Friday, April 28, 2017

17. Classes & Designations of Tablets
Oral Tablets for Ingestion
Compressed Tablets
Multiple Compressed Tablets
Enteric Coated Tablets
Repeat Action Tablets
Delayed Action Tablets
6. Sugar coated Tablets
Film Coated Tablets
Effervescent Tablets
Chewable Tablets
Chocolate Coated Tablets
Tablets Used in the Oral Cavity
Buccal Tablets
Sublingual Tablets
Lozenges or Troches
Dental Cones
Tablets Administered by Other Routes
1. Implantation Tablets
Tablets Used to Prepare Solutions
Hypodermic Tablets
Dispensing Tablets
3. Compressed Tablet Triturates
Tablets Manufactured by Molding
1. Tablet Triturates
2. Hypodermic Tablets
Friday, April 28, 2017

18. Tablet excipients
Compressed tablets usually consist of active medicaments mixed with a number of inert substances known as excipient or additives i.e. all non – drug components of a formula are termed excipients or additives. Although these additives are termed as inert but they have a great influence on stability, bioavailability and the process by which the dosage forms are prepared.
Friday, April 28, 2017

19. Classification of tablet excipients
According to the functions, tablet excipients are classified as follows:
1. Diluent (or filler)
2. Disintegrant
3. Solution binder
4. Dry binder
5. Glidant
6. Lubricant
7. Antiadherent
8. Sorbent
9. Flavor
10. Colorant
Friday, April 28, 2017

20. Examples of substances used as excipients in tablet formulation
Type of Excipient
Example of substances
FIller
Lactose, Sucrose, Glucose, Mannitol, Sorbitol, Calcium phosphate, Calcium carbonate, Cellulose
Disintegrant
Starch, Cellulose, Crosslinked polyvinyl pyrrolidine, Sodium starch glycolate, Sodium CMC
Solution Binder
Gelatin, Polyvinyl pyrrolidine, Cellulose derivatives (hydroxypropylmethyl cellulose, Sucrose, Starch
Dry Binder
Cellulose, Methylcellulose, Polyvinyl pyrrolidine, Polyethylene glycol
Glidant
Silica, Magnesium stearate, Talc
Lubricant
Magnesium stearate, Stearic acid, Polyethylene glycol, Liquid Paraffin
Antiadherent
Magnesium stearate, Talc, Starch, Cellulose
Examples of substances used as excipients in tablet formulation
Friday, April 28, 2017

21. Regardless of why an excipient is selected, they must meet certain criteria in the formulation. These include the following:
1. they must be nontoxic & acceptable to the regulatory agencies in all countries where the product is to be marketed. 2. They must be commercially available in an acceptable grade in all countries where the product is to be manufactured. 3. Their cost must be acceptably low. 4. They must not be contradicted by themselves (eg sucrose) or because of a component (eg sodium) in any segment of the population. 5. They must be physiologically inert.
Pg 325 LAchman
Friday, April 28, 2017

22. 6. They must be physically and chemically stable by themselves and in combination with the drug(s) and other tablet components. 7. They must be free of any unacceptable microbiological ‘load’. 8. They must be color-compatible (not produce any off-color appearance). 9. If the drug product is also classified as a food, (certain vitamin products), the diluent and other excipients must be approved direct food additives. 10. They must have no deleterious effect on the bioavailability of the drug (s) in the product.
Friday, April 28, 2017

23. Granulation
Granulation is the process in which powder particles are made to adhere to form larger particles called granules. Pharmaceutical granules typically have a size range between 0.2 and 4.0 mm, depending on their subsequent use.
Reasons for granulations:
To prevent segregation of the constituents in the powder mix
To improve the flow properties of the mix
To improve the compression characteristics of the mix
Friday, April 28, 2017

24. Other reasons…
The granulation of toxic materials will reduce the hazard of the generation of toxic dust which may arise when handling powders.
Materials which are slightly hygroscopic may adhere and form a cake if stored as a powder. Granulation may reduce this hazard as the granules will be able to absorb some moisture and yet retain their flow ability because of their size.
Granules being denser than the parent powder mix occupy less volume per unit weight.
Friday, April 28, 2017

25. Methods of granulation
Two types: 1. Dry granulation and 2. wet granulation
Dry granulation: In the dry granulation methods the primary powder particles are aggregated at high pressure. It is done by two processes i.e. i. slugging and ii. roller compaction.
Wet granulation: It involves the massing of a mix of dry primary powder particles using a granulating fluid. The granulating fluid contains a solvent that must be volatile so that it can be removed by drying, and non-toxic.
Friday, April 28, 2017

26. Granulation mechanisms
A. Particle bonding mechanisms B. Granule formation mechanisms
Friday, April 28, 2017

27. A. Particle bonding mechanisms
To form granules bonds must be formed between powder particles so that they adhere and these bonds must be sufficiently strong to prevent breakdown of the granules to powder in subsequent handling operations.
The five primary bonding mechanisms between particles are:
Adhesion and cohesion forces in the immobile liquid films between individual primary powder particles.
Interfacial forces in mobile liquid films within the granules
The formation of solid bridges after solvent evaporation
Attractive forces between solid particles
Mechanical interlocking
Friday, April 28, 2017

28. B. Mechanisms of granule formation
Nucleation Transition Ball growth
Friday, April 28, 2017

29. Pharmaceutical granulation equipment
Wet granulator:
There are three main types of granulator used in the pharmaceutical industry for wet granulation
Shear granulator
High-speed mixer/granulator
Fluidized-bed granulator
Friday, April 28, 2017

30. Pharmaceutical granulation equipment
Fluidized-bed granulator
The fluid bed granulator performs the following steps:
The powder particles are fluidized in a stream of air
Granulating fluid is sprayed from a nozzle onto the powder bed
The wet granulates are then dried in the heated fluidizing air system
Friday, April 28, 2017

31. Pharmaceutical granulation equipment
Fluidized-bed granulator
Friday, April 28, 2017

32. Pharmaceutical granulation equipment
Dry granulator: Slugging: The dry powders can be compacted using a large heavy duty rotary tablet machine. This process is known as slugging. The compacts made in the process is known as slugs. A hammer mill is then used to break down the compacts or slugs.
Friday, April 28, 2017

33. Pharmaceutical granulation equipment
Dry granulator:
Roller compaction:
In this process powder mix are squeezed between two counter rotating rollers to form a compressed sheet.
This formed sheet is normally weak and brittle and breaks immediately into flakes.
These flakes are later broken into granules.
Friday, April 28, 2017

34. Pharmaceutical granulation equipment
Roller compactor
Friday, April 28, 2017

35. Roller compaction: (a) Alexanderwerk and (b) Hutt types.
Friday, April 28, 2017

36. Tablet Granulations: Basic Characteristics
There are many formulation and process variables involved in the granulation step, and all of these can affect the characteristics of the granulations produced.
Therefore, methods to measure certain granulation characteristics have been developed to monitor granulation suitability for tableting.
Friday, April 28, 2017

37. Particle Size & Shape Surface Area Density Strength & Friability
Flow Properties
Repose Angle
Hopper Flow Rates
Compaction
Friday, April 28, 2017

38. Difference between compression and compaction
Powder compression is defined as the reduction in volume of a powder owing to the application of a force.
Because of the increased proximity of particle surfaces accomplished during the compression, bonds are formed between particles which provide coherence to the powder, i.e. a compact is formed.
Compaction is defined as the formation of a solid specimen of defined geometry by powder compression.
Friday, April 28, 2017

39. Tablet Manufacturing Stages in tablet formation
Tablets are prepared by forcing particles into close proximity to each other by powder compression, which enables the particles to cohere into a porous, solid specimen of defined geometry.
The compression takes place in a die by the action of two punches, the lower and the upper, by which the compressive force is applied
Friday, April 28, 2017

40. The process of tableting can be divided into three stages (sometimes known as the compaction cycle).
Friday, April 28, 2017

41. 1. Die filling
This is normally accomplished by gravitational flow of the powder from a hopper via the die table into the die (although presses based on centrifugal die filling are also used).
The die is closed at its lower punch.
Friday, April 28, 2017

42. 2. Tablet formation
The upper punch descends and enters the die and the powder is compressed until a tablet is formed.
During the compression phase, the lower punch can be stationary or can move upwards in the die.
After maximum applied force is reached, the upper punch leaves the powder, i.e. the decompression phase.
Friday, April 28, 2017

43. 3. Tablet ejection
During this phase the lower punch rises until its tip reaches the level of the top of the die.
The tablet is subsequently removed from the die and die table by a punching device.
Friday, April 28, 2017

44. Tablet compression machines
Tablets are made by compressing a formulation containing a drug or drugs with excipients on stamping machines called presses. Tablet compression machines or tablet presses are designed with the following basic component:
Hopper for holding and feeding granulation to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granulation within the dies
Cam tracks for guiding the movement of the punches
Feeding mechanisms for moving granulation from the hopper into the dies
Friday, April 28, 2017

45. Tablet compression machines
Various types of machines are used.
Tablet presses are classified as either single-punch or multi-station rotary presses. They are as follows:
Single punch machine
Multi punch machine
Rotary tablet machine
High speed rotary tablet machine
Multi layer rotary tablet machine
Multi-station presses are termed rotary because the head of the tablet machine that holds the upper punches, dies, and lower punches in place rotates. As the head rotates, the punches are guided up and down by fixed cam tracks, which control the sequence of filling, compression, and ejection.
Friday, April 28, 2017

46. Single punch tablet press
Friday, April 28, 2017

47. A tablet machine’s output is regulated by 3 basic characteristics of its design:
Number of tooling sets
Number of compression stations
Rotational speed of the press
There are many modifications and options that can be obtained from various manufacturers.
One modification, found on most modern high-speed tablet presses, is the use of hydraulic or pneumatic pressure to control the pressure rolls in place of the older spring type pressure…..gives a smoother pressure or compressive load force over a longer period of time.
Friday, April 28, 2017

48. Methods of Tablet Manufacture
There are 3 basic methods of preparation of compressed tablets.
Each method has its own advantages, disadvantages and limitations.
Friday, April 28, 2017

49. The manufacture of granulations for tablets compression may follow one or a combination of three established methods:
Wet granulation
Dry granulation or compression granulation &
Direct compression

50. Steps for Tablet Production

51. Friday, April 28, 2017

52. In-Process Quality Control
During the compression of tablets, in-process tests are routinely run to monitor the process, including tests for tablet weight, weight variation, hardness, thickness, disintegration, and various evaluations of elegance.
The in-process tests are performed by production and/or quality control (QC) personnel.
Friday, April 28, 2017

53. The following standards or quality control tests are carried out on compressed tablets:
General appearance
Size and shape
Unique identification of marking
Organoleptic properties
Hardness
6. Friability
7. Weight variation test
8. Content uniformity test
9. Disintegration test
10. Dissolution test

54. Coated Tablets
Friday, April 28, 2017

55. Tablet Coating
Tablet coating is a process by which an essentially dry, outer layer of coating material is applied to the surface of a dosage form in order to confer specific benefits that broadly range from facilitating product identification to modifying drug release from the dosage forms.
28 April 2017

56. Tablet Coating Principle
Tablet coating is an additional step in the manufacturing process… increases the cost of the product.
Therefore, the decision to coat a tablet is usually based on one or more of the following objectives:
28 April 2017

57. Reasons for Coating To mask the taste, odor, or color of the drug
To provide physical and chemical protection for the drug
To control the release of the drug from the tablet
To protect the drug from the gastric environment of the stomach with an acid-resistant enteric coating
To incorporate another drug or formula adjuvant in the coating to avoid chemical incompatibilities or to provide sequential drug release
To improve the pharmaceutical elegance by use of special colors and contrasting printing.
NOTE: see Aulton for more reasons
28 April 2017

58. There are 3 primary components involved in tablet coating:
Tablet properties
Coating process: coating equipment, parameters of the coating process, facility & ancillary equipment, automation in coating process
Coating components
28 April 2017

59. Tablets to be coated must possess following properties:
1. Tablets must be resistant to abrasion and chipping.
2. Tablets should have smooth surface for proper coating.
3. The tablets must be in constant motion during the early drying phase to prevent tablet agglomeration.
4. The spherical shape of tablet is preferable for coating process. This will allow the tablets to roll freely in the coating pan with minimal tablet-to-tablet contact.
28 April 2017

60. Equipments for Tablet Coating
Standard (conventional) coating pan
Perforated coating pan
Fluidized bed (air suspension) coater
Pellegrini Pan System
Accela-Cota System
Air Suspension System
Immersion Sword System
Hi-Coater Systems
Immersion Tube System
Driacoater System
Glatt Coater System
28 April 2017

61. Spray Application Systems Low pressure, air atomized
Coating Process
Spray Application Systems
High pressure, airless
Low pressure, air atomized
28 April 2017

62. Types of Coatings Sugar Coating Film Coating Compression Coating
28 April 2017

63. Materials Used in Film-Coating
The coating materials may be a physical deposition of the material on the tablet substrate, or they may form a continuous film with a wide variety of properties depending upon the composition of the coating formulations.
Examples of physical deposition of the coating materials are the techniques of sugar, shellac, and wax coatings.
A wide variety of polymers are used commercially for tablet coating.
Mon, Sept 01, 2014

64. An ideal film coating material should have the following attributes:
Solubility in solvent of choice for coating preparation.
Solubility required for the intended use eg, pH-dependent solubility (enteric coating)
Capacity to produce an elegant looking product
Stability in the presence of heat, light, moisture, air, and the substrate being coated. The film properties should not change with aging.
Essentially no color, taste, or odor.
Compatibility with common coating solution additives.
Mon, Sept 01, 2014

65. 7. Nontoxicity with no pharmacological activity, and ease of application to the particles or tablets. 8. Resistance to cracking, and provision of adequate moisture, light, odor, or drug sublimation barrier when desired. 9. No bridging or filling of the debossed tablet surfaces by the film former. 10. Ease of printing procedure on high-speed equipment.
Mon, Sept 01, 2014

66. No commercially available material fulfils all requirements of an ideal coating material.
A pharmaceutical scientist usually formulates a coating solution to achieve certain desired properties for the film-coated product.
The available film formers can be classified into nonenteric and enteric materials.
Mon, Sept 01, 2014

67. Film-coating formulations
Currently, the majority of film-coating processes involves the application of a coating liquid where a significant proportion of a major component (the solvent/vehicle) is removed by means of a drying process that is concurrent with the application of that coating liquid.
Film-coating formulations typically compromise:
1. Polymer
2. Plasticizer
3. Colourants
4. Solvent/vehicle
Wed, Aug 27, 2014

68. Friday, April 28, 2017

69. 1. It should either dissolve or disperse the polymer system.
Some important considerations for an ideal solvent system are as follows:
1. It should either dissolve or disperse the polymer system.
2. It should easily disperse other coating solution components into the solvent system.
3. Small concentrations of polymers (2 to 10%) should not result in an extremely viscous solution system (>300cps), creating processing problems.
4. It should be colourless, tasteless, odorless, inexpensive, nontoxic, inert, and nonflammable.
5. It should have a rapid drying rate (the ability to coat a 300 kg load in 3 to 5 hours).
6. It should have no environmental impact.
Wed, Aug 27, 2014

70. Differences between sugar & film coating
Fri, Feb