Wet Granulation Lab 2 PDF

University of kirkuk College of pharmacy Department of pharmaceutical Practical Industrial Pharmacy II 5th Year 1st Semester 2nd Lab : wet granulation method for preparation of tablet...

University of kirkuk College of pharmacy Department of pharmaceutical Practical Industrial Pharmacy II 5th Year 1st Semester 2nd Lab : wet granulation method for preparation of tablet BY : Ph Hiba Najat Ph Maryam Gawdet Granulation Granules : Defined as a dosage form composed of dry aggregates of powder particles that may contain one or more APis, with or without other ingredients. They may be swallowed as such, dispersed in food, or dissolved in water. Granules are frequently compacted into tablets or filled into capsules, with or without additional ingredients. Granulation : is the process that the fine powders are converted to granules using either wet granulation or dry granulation that improve flowability of the powder to ensure a uniform fill of the die cavity and good compressibility. Wet granulation Powder Granules Flowability & Compressibility Dry granulation Reason Of Granulation 1. To enhance the flow properties of powder mix. 2. To prevent segregation of powder components during tableting or storage. 3. To reduce the incidence of dust production. 4. To reduce cross-contamination and hazard associated with the generation of toxic dust that may arise during manufacturing processes. 5. To improve the compression characteristics of drug substances. 6. To improve the appearance of the final product. Wet granulation Granulation Dry Granulation Wet Granulation Wet granulation : process of formation granules by binding the powder together by using an adhesive (binder). Granules are formed by the addition of a granulation liquid (usually water or alcohol ) onto a powder bed. The liquid contains binder or granulating agent ( adhesive substances ) that helps bind the powder particles together The binder can be added in different ways : 1-Dissolved or suspended in the granulation liquid (most common approach). 2-Added as a dry powder, followed by addition of the granulation liquid. The method of introducing the binder (as a liquid or dry) depends on: 1. Solubility of the binder: the prepared solution should be fluid enough to disperse readily in the mass. 2. Components of the mixture: the mixture should be moist, there is a limit to the amount of the solvent added (granulating liquid). Since, in general, the mass should merely be moist rather than wet or pasty When small amount of solvent is needed, the binder added as dry powder but when large quantity is required, the binder added as solution. In summary small quantity of solvent binder blended in with the dry powders initially large quantity of solvent binder usually dissolved in the liquid. Role of liquid in granulation Advantages of wet granulation method 1-Improve flowability and compressibility of the powder, so the powder is easily compressed (due to the stick of powder particles together that are surrounded by layer of a binder) in addition to the low pressure and low energy comparing to dry granulation (prolong machine age). 2-Can be used for high dose drug with weak compressibility that is not affected by heat and moisture. 3-Maintaining uniform distribution for low dose drug. 4-Improve the dissolution rate of hydrophobic drug because of the presence of moisture of the already used water. 5-Maintaining good content uniformity due to prevention of particle segregation. Limitation of wet granulation 1-The greatest disadvantage of wet granulation is its cost. It is an expensive process because of labor, time, equipment, energy and space requirements. 2-Loss of material during various stages of processing 3-Stability may be major concern for moisture sensitive or thermo labile drugs 4-Multiple processing steps add complexity and make validation and control difficult. 5-An inherent limitation of wet granulation is that any incompatibility between formulation components is aggravated. The steps required are : 1-weighing and blending the ingredients 2-preparing a dampened powder or a damp mass by addition of binder or adhesive or so-called granulating agent. 3-screening I the dampened powder or damp mass into granules (to achieve granules). 4-drying the granulation 5-Sieving II for homogenization (to ensure homogenized shape of the already formed granules to a regular spherical shape and uniformed size). 6-adding lubricant and blending 7-forming tablets by compression.  steps required in wet granulation Weighing Blending granulation sieving I Compression Lubrication sieving II Drying General notes regarding some steps in the process : In Mixing : Fillers include lactose, microcrystalline cellulose, starch, powdered sucrose, and calcium phosphate. The choice of filler usually based on : 1-The experience of the manufacturer with the material 2-its relative cost 3-its compatibility with the other formulation ingredients For example : calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between the two agents that results in reduced tetracycline absorption from the GI tract. In wetting :Care must be excercised not to over wet or underwet the powder overwetting causes: 1.formation of clumps of powder. ( When too much liquid is added, particles can stick together excessively, creating larger masses that are difficult to break down during granulation ). 2. Some of the material may block the sieve or screen(sticky). 3. Slow drying process. and underwetting can result in tablets that are too soft and tend to crumble. In drying : After drying step the granules should contain some degree of humidity to act as a binder (not be 100% free of humidity) as over drying may leads to weak force and friable granules. Experimental work : ⦿ Sulfadiazine was selected as a model drug to be prepared by wet granulation method. ⦿ Sulfadiazine is weak base, white powder, stable in dry air and not affected by moisture or heat but decomposed in presence of light. ⦿ According to these properties the preferable method for preparation is wet granulation method. ⦿Sulfa drug are not prepared by direct compression because: 1.They had bad flowability because they present as fine powder or fine crystals 2.They are used in large doses and direct compression is only used for intermediate doses Procedure : 1-weigh the ingredients except the lubricant and mix them (After preparation of binder liquid like acacia , gelatins or starch). 2-Add binder solution drop by drop to the mixture until a wet mass is obtained. 3-Sieve wet mass to obtain suitable granules size. 4-Dry the wet granules for 10 minutes. 5-Seive again to homogenize the dried granules. 6-Weigh the granules and calculate real number of tablets to know the exact amount of lubricant that should be added. 7-Compress after addition of lubricant.  substance function weight Calculate the weight of acacia in each Sulfadiazine API 500 mg tablet If we use for example (5ml of Calcium Diluent 250 mg 10%w/v) carbonate Explotab Disintegrant 50 mg 10 gm 100 ml Zinc stearate Lubricant 10 mg X gm 5 ml X= 0.5 gm (500mg) for 10 tablets Acacia mucilage Binder 50 mg 10% Calculate the Exact amount of lubricant (Zinc stearate) by calculation of real number of tablets Real number = weight of granules / weight of one tablets without lubricant 8500 / 850 tablets = 10 tablets Exact amount of lubricant = real number * amount of lubricant in one tablet 10 x 10 = 100mg so 100 mg should added THANK YOU