Tablet Granulation

Tablet Granulation

Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

Introduction • Granulation is the process in which primary powder particles are made to adhere to form larger, multi particle entities called granules. • Pharmaceutical granules typically have a size range between 0.2 and 4.0 mm. • Granules are used in the production of tablets or capsules. • Granules in such cases are made as an intermediate product and have a typical size range between 0.2 and 0.5 mm. Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

Reasons for Granulation • To prevent segregation of the constituents of the powder mix. – Segregation (or demixing) is due primarily to differences in the size or density of the components of the mix. – The smaller and/or denser particles concentrating at the base of a container – The larger and/or less dense ones above them. – An ideal granulation will contain all the constituents of the mix in the correct proportion in each granule and segregation of the ingredients will not occur Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

Granulation prevent segregation

Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

Reasons for Granulation • To improve the flow properties of the mix – Many powders, because of their small size, irregular shape or surface characteristics, are cohesive and do not flow well. – Poor flow will often result in a wide weight variation within the final product owing to variable fill of tablet dies etc.

Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

Reasons for Granulation • To improve the compaction characteristics of the mix – Some powders are difficult to compact even if a readily compactable adhesive is included in the mix and some are compacted easily. – This is associated with the distribution of the adhesive within the granule and is a function of the method employed to produce the granule. – Solute migration occurring during the postgranulation drying stage results in a binder-rich outer layer to the granules. – This in turn leads to direct binder–binder bonding, which assists the consolidation of weakly bonding materials. Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

Other Reasons • The granulation of toxic materials will reduce the hazard associated with the generation of toxic dust that 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 retain their flow ability because of their size. • Granules, being denser than the parent powder mix, occupy less volume per unit weight. They are therefore more convenient for storage or shipment. Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

Methods of Preparation Wet Granulation Method

Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

Wet Granulation • Wet granulation is widely employed method for the production of compressed tablets. • The steps required for the wet granulation can be divided into following stages: – Weighing and blending the ingredients. – Preparing the wet granulation. – Screening the dam mass in to pellets or granules. – Drying the granules. – Dry screening. – Lubricating and blending. – Tablet by compression. Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

WEIGHING AND BLENDING • The active ingredients and any diluents and disintegrating agent required in the tablet formulation are weighed in the amount required for the number of the tablet to be produced. • This mixture is mixed thoroughly . • The diluents used for this purpose are Lactose, kaolin, mannitol. • Disintegrating agent used include corn and potato starch, cellulose derivatives. Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

PREPARING THE WET GRANULATION

• Granulation is accomplished by adding liquid binder or adhesive to the powder. • The wet mass is then passed through the screen of desired mesh size. • The granules so obtained are dried. • Then again they are passed though a second screen of smaller mesh size to further reduce the size of the granules. • The binding agent used are – – – –

10-20% aqueous preparations of corn starch. 25-50% solution of glucose. Natural gums (acacia) Cellulose derivatives ( methylcellulose, methylcellulose) Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

carboxy

SCREEING THE DAMP MASS INTO PELLETS OR GANULES • The wet granulation is pressed through a No. 6 or 8 mesh size. • This may be done with hand or special machines.

Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

DRYING THE GRANULATION • The granules are dried in spl drying cabinets the have circulating air systems and are thermostatically controlled. • Among the newer methods employed for the drying is fluidization conducted in fluid bed drier.

Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

DRY SCREEING • The degree to which the granules are reduced depends upon the size of the punch and tablet to be produced. • The smaller tablet size, smaller the granules used. • Sizing of the granules is important so that die cavity of die is fully filled with granules. • The voids are air spaces could result in tablet of varying evenness. Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

LUBRICATION • After dry screening, dry lubricant Is generally added. • The more commonly used lubricants are talc, magnesium stearate and calcium stearate. • Range at which it is added is from as low as 0.1% to 5%.

Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

UTILITY OF LUBRICANTS • The improve the flow property of the granules from hopper to the die. • Prevent the adhesion of the tablet formulation to the punches and die during compression. • They reduce the friction between the die and the punch. • They provide a sheen to the finished product. Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal

FLOW CHART FOR THE WET GRANULATION

Anup Bajracharya, QA Officer, [email protected],Quest Pharmaceuticals (P) Ltd Nepal