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Prof. R. Shanthini 22 Oct 2012 Content of Lecture 18: - -Compression & Compaction in Tablets Formation PM3125: Lectures 18 to 21.

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Presentation on theme: "Prof. R. Shanthini 22 Oct 2012 Content of Lecture 18: - -Compression & Compaction in Tablets Formation PM3125: Lectures 18 to 21."— Presentation transcript:

1 Prof. R. Shanthini 22 Oct 2012 Content of Lecture 18: - -Compression & Compaction in Tablets Formation PM3125: Lectures 18 to 21

2 Prof. R. Shanthini 22 Oct 2012 Principle of tablet production Active substance synthesis Blending and Granulation Compression Coating Package

3 Prof. R. Shanthini 22 Oct 2012 Advantages and disadvantages of compressed tablets Advantages and disadvantages of compressed tablets Types of tablets Types of tablets Tablet compression machine Tablet compression machine Tableting methods Tableting methods Compressed tablets Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University

4 Prof. R. Shanthini 22 Oct 2012 Production aspect Production aspect  Large scale production at lowest cost  Easiest and cheapest to package and ship  High stability User aspect (doctor, pharmacist, patient) User aspect (doctor, pharmacist, patient)  Easy to handling  Lightest and most compact  Greatest dose precision & least content variability  Coating can mark unpleasant tastes & improve acceptability Advantages Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University

5 Prof. R. Shanthini 22 Oct 2012 Some drugs resist compression into dense compacts Some drugs resist compression into dense compacts Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating Disadvantages Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University

6 Prof. R. Shanthini 22 Oct 2012 Types of tablets – Production process Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University  Compressed tablets  Multiple compressed tablets Tablet within a tablets: core and shell Tablet within a tablets: core and shell Multilayer tablet Multilayer tablet  Sugar coated tablets Protect tablets from moisture Protect tablets from moisture Mask odor and flavor Mask odor and flavor Elegance Elegance

7 Prof. R. Shanthini 22 Oct 2012 Types of tablets – Production process Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University  Film coated tablets Thin film coat Thin film coat Soluble or insoluble polymer film Soluble or insoluble polymer film  Chewable tablets Rapid disintegrate Rapid disintegrate Antacid, flatulance: rapid action Antacid, flatulance: rapid action Children drug Children drug  Effervescent tablets Dissolve in the water before drink Dissolve in the water before drink

8 Prof. R. Shanthini 22 Oct 2012 Drugs Drugs Fillers, diluent, bulking agent Fillers, diluent, bulking agent  To make a reasonably sized tablet Binders Binders  To bind powders together in the wet granulation process  To bind granule together during compression Disintegrants Disintegrants  To promote breakup of the tablets  To promote rapid release of the drug Ingredients used in tablet formulations Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University

9 Prof. R. Shanthini 22 Oct 2012 Lubricants Lubricants  To reduce the friction during tablet ejection between the walls of the tablet and the walls of the die cavity Glidants Glidants  Reducing friction between the particles  To improve the flow properties of the granulations Antiadherants Antiadherants  To prevent adherence of the granules to the punch faces and dies Ingredients used in tablet formulations (contd.) Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University

10 Prof. R. Shanthini 22 Oct 2012 Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University Dissolution (enhancers and retardants) Dissolution (enhancers and retardants) Wetting agents Wetting agents Antioxidants Antioxidants Preservatives Preservatives Coloring agents Coloring agents Flavoring agents Flavoring agents Ingredients used in tablet formulations (contd.)

11 Prof. R. Shanthini 22 Oct 2012 Essential properties of tablets Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University Accurate dosage of medicament, uniform in weight, appearance and diameter Accurate dosage of medicament, uniform in weight, appearance and diameter Have the strength to withstand the rigors of mechanical shocks encountered in its production, packaging, shipping and dispensing Have the strength to withstand the rigors of mechanical shocks encountered in its production, packaging, shipping and dispensing Release the medicinal agents in the body in a predictable and reproducible manner Release the medicinal agents in the body in a predictable and reproducible manner Elegant product, acceptable size and shape Elegant product, acceptable size and shape Chemical and physical stabilities Chemical and physical stabilities

12 Prof. R. Shanthini 22 Oct 2012 Tablet production Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University Powders intended for compression into tablets must possess two essential properties Powders intended for compression into tablets must possess two essential properties  Powder fluidity The material can be transported through the hopper into the die The material can be transported through the hopper into the die To produce tablets of a consistent weight To produce tablets of a consistent weight Powder flow can be improved mechanically by the use of vibrators, incorporate the glidant Powder flow can be improved mechanically by the use of vibrators, incorporate the glidant  Powder compressibility The property of forming a stable, intact compact mass when pressure is applied The property of forming a stable, intact compact mass when pressure is applied

13 Prof. R. Shanthini 22 Oct 2012 Tableting procedure Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University Filling Filling Compression Compression Ejection Ejection

14 Prof. R. Shanthini 22 Oct 2012

15 Schematic diagram showing the manufacture of single and bilayer tablets utilising uniaxial compaction. A — Die filling B — Compression C — Decompression D — Lower punch removal and reapplication of load to the upper punch E — Tablet fully ejected 1 refers to the final compaction conditions

16 Prof. R. Shanthini 22 Oct 2012 WET GRANULATIONDRY GRANULATIONDIRECT COMPRESSION 1. Milling and mixing of drugs and excipients 2. Preparation of binder solution 2. Compression into slugs or roll compaction 2. Compression of tablet 3. Wet massing by addition of binder solution or granulating solvent 3. Milling and screening of slugs and compacted powder 4. Screening of wet mass4. Mixing with lubricant and disintegrant 5. Drying of the wet granules5. Compression of tablet 6. Screening of dry granules 7. Blending with lubricant and disintegrant to produce “running powder” 8. Compression of tablet

17 Prof. R. Shanthini 22 Oct 2012 It is a process in which primary powder particles are made to adhere to form larger, multiparticle entities called granules. It is the process of collecting particles together by creating bonds between them. Bonds are formed by compression or by using a binding agent. Granulation

18 Prof. R. Shanthini 22 Oct 2012 Granulation (contd.) The most common reasons given to justify granulating are:  To impart good flow properties to the material,  To increase the apparent density of the powders,  To change the particle size distribution,  Uniform dispersion of active ingredient.

19 Prof. R. Shanthini 22 Oct 2012 Binders Used in tablet formulations to make powders more compressible and to produce tablets that are more resistant to breakage during handling. In some instances the binding agent imparts viscosity to the granulating solution so that transfer of fluid becomes difficult. This problem can be overcome by adding some or all binding agents in the dry powder prior to granulation.

20 Prof. R. Shanthini 22 Oct 2012 Some granulation, when prepared in production sized equipment, take on a dough-like consistency and may have to be subdivided to a more granular and porous mass to facilitate drying. This can be accomplished by passing the wet mass through an oscillating type granulator with a suitably large screen or a hammer mill with either a suitably large screen or no screen at all.

21 Prof. R. Shanthini 22 Oct 2012 Oscillating type granulator Hammer mill

22 Prof. R. Shanthini 22 Oct 2012 Drying The most common conventional method of drying a granulation continues to be the circulating hot air oven, which is heated by either steam or electricity. The important factor to consider as part of scale-up of an oven drying operation are airflow, air temperature, and the depth of the granulation on the trays. If the granulation bed is too deep or too dense, the drying process will be inefficient, and if soluble dyes are involved, migration of the dye to the surface of the granules. Drying times at specified temperatures and airflow rates must be established for each product, and for each particular oven load.

23 Prof. R. Shanthini 22 Oct 2012 Fluidized bed dryers are an attractive alternative to the circulating hot air ovens. The important factor considered as part of scale up fluidized bed dryer are optimum loads, rate of airflow, inlet air temperature and humidity.

24 Prof. R. Shanthini 22 Oct 2012 Reduction of Particle size Compression factors that may be affected by the particle size distribution are flowability, compressibility, uniformity of tablet weight, content uniformity, tablet hardness, and tablet color uniformity. First step in this process is to determine the particle size distribution of granulation using a series of “stacked” sieves of decreasing mesh openings. Particle size reduction of the dried granulation of production size batches can be carried out by passing all the material through an oscillating granulator, a hammer mill, a mechanical sieving device, or in some cases, a screening device.

25 Prof. R. Shanthini 22 Oct 2012 Oscillating type granulator Hammer mill

26 Prof. R. Shanthini 22 Oct 2012 Blending Type of blending equipment often differs from that using in laboratory. In any blending operation, both segregation and mixing occur simultaneously are a function of particle size, shape, hardness, and density, and of the dynamics of the mixing action. Particle abrasion is more likely to occur when high-shear mixers with spiral screws or blades are used. When a low dose active ingredient is to be blended it may be sandwiched between two portions of directly compressible excipients to avoid loss to the surface of the blender.

27 Prof. R. Shanthini 22 Oct 2012 Equipments used for mixing Sigma blade mixer. Planetary mixer. Twin shell blender. High shear mixer Planetary mixer

28 Prof. R. Shanthini 22 Oct 2012 Dry Granulation (slugging) A dry powder blend that cannot be directly compressed because of poor flow or compression properties. This is done on a tablet press designed for slugging, which operates at pressures of about 15 tons, compared with a normal tablet press, which operates at pressure of 4 tons or less. Slugs range in diameter from 1 inch, for the more easily slugged material, to ¾ inch in diameter for materials that are more difficult to compress and require more pressure per unit area to yield satisfactory compacts. If an excessive amount of fine powder is generated during the milling operation the material must be screened & fines recycled through the slugging operation.

29 Prof. R. Shanthini 22 Oct 2012 Dry Compaction Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch. Materials of very low density require roller compaction to achieve a bulk density sufficient to allow encapsulation or compression. One of the best examples of this process is the densification of aluminum hydroxide. Pilot plant personnel should determine whether the final drug blend or the active ingredient could be more efficiently processed in this manner than by conventional processing in order to produce a granulation with the required tabletting or encapsulation properties.

30 Prof. R. Shanthini 22 Oct 2012 Compression The ultimate test of a tablet formulation and granulation process is whether the granulation can be compressed on a high-speed tablet press. During compression, the tablet press performs the following functions: 1. Filling of empty die cavity with granulation. 2. Precompression of granulation (optional). 3. Compression of granules. 4. Ejection of the tablet from the die cavity and take-off of compressed tablet.

31 Prof. R. Shanthini 22 Oct 2012 Tablet compression machines Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University Hopper for holding and feeding granulation to be compressed Hopper for holding and feeding granulation to be compressed Dies that define the size and shape of the tablet Dies that define the size and shape of the tablet Punches for compressing the granulation within the dies Punches for compressing the granulation within the dies Cam tracks for guiding the movement of the punches Cam tracks for guiding the movement of the punches Feeding mechanisms for moving granulation from the hopper into the dies Feeding mechanisms for moving granulation from the hopper into the dies

32 Prof. R. Shanthini 22 Oct 2012 Singe punch machine Source: Assoc. Prof. Dr. Jomjai Peerapattana, Faculty of Pharmaceutical Sciences, Khon Kaen University The compression is applied by the upper punch The compression is applied by the upper punch Stamping press Stamping press

33 Prof. R. Shanthini 22 Oct 2012 Singe punch rotary machine

34 Upper and Lower Collar Collar locker Singe punch machine

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