Quality Control Tests for Capsules PDF

Quality control tests for Capsules Capsules    Types of capsules Sizes and capacity of capsules Sizes of pharmaceutical capsules Hard gelatin capsules: Gelatin is a natural, safe, non-allergenic, clean, and economical ingredient. HPMC capsules.  stable at low humidity levels, hav...

Quality control tests for Capsules Capsules    Types of capsules Sizes and capacity of capsules Sizes of pharmaceutical capsules Hard gelatin capsules: Gelatin is a natural, safe, non-allergenic, clean, and economical ingredient. HPMC capsules.  stable at low humidity levels, have low moisture content (3–8%), and low static charge.  HPMC is more suitable for moisture-sensitive products, hygroscopic products, and for low relative humidity applications.  HPMC is not of animal origin and, therefore, does not pose a risk of contamination with organisms that cause bovine spongiform encephalopathy (BSE) or transmissible spongiform encephalopathy (TSE)  HPMC capsules are used in a wide range of OSD pharmaceuticals as well as nutraceuticals, dietary supplements, and herbal products, due to the vegetarian nature of HPMC. Starch capsules.  made from potato starch.  dissolution is pH independent  Suitable for enteric coating.  The moisture content of starch capsules ranges between 12–14% w/w, with more than 30% being tightly bound. Polyvinyl acetate (PVA) capsules.  Capsules made from PVA  can be used for filling insoluble drugs dissolved in polyethylene glycol (PEG) 400.  The oxygen permeability of PVA is low, resulting in a high barrier to oxygen. Liquid-filled hard capsules (LFHC).  Two-piece hard capsules made of either gelatin or HPMC  can be used for filling and band sealing non-aqueous liquid, paste, suspension, hot melts, and other vehicles that melt up to 70 °C and for moisture-sensitive drugs  Liquid encapsulation technology helps overcome many problems associated with the use of softgel capsules including: high cost, waste, cross-contamination, migration of the drug into the capsule shell, and issues with low bioavailability. The gelatin used for liquid-filled capsules has a bloom strength of approximately 220–280 for hard capsules and 150–200 for softgels. Soft gelatin capsules (SGC).  SGC have soft, globular, gelatin shells somewhat thicker than hard gelatin capsules.  The gelation is plasticized by the addition of glycerin, sorbitol, or a similar polyol.  It may contain preservatives to prevent the fungal growth. General MCQs Chemically “Gelatine” is, A. Protein B. Fat C. Carbohydrate D. Semisynthetic protein derivative 2. Smallest size of the Capsule is denoted by which number? A. 0 B. 1 C. 2 D. 5 Type A gelatin is normally derived from: A. Pork skin B. Beef Skin C. Bones D. Fish skin Gelatin is the hydrolyzed product of: A. Pectin B. Collagen C. Gelatin itslef is a natural substance directly obtained from skin and bones D. Tannins Type A gelatin has its isoelectric point in the region of: A. pH 7.0 B. pH 9.0 C. pH 4.7 D. pH 3.0 Green bones are used for the preparation of gelatin of type: A. Type A B. Type B C. Type C D. Both Type A and B  Type of Gelatin obtained by acid hydrolysis is : A. Type A B. Type B C. Both A and B D. Gelatin doesn’t require acid treatment.   1. 2. 3. In-process quality control tests for Soft and hard gelatin capsule       Finished product quality control tests for capsules Quality control of capsules: Weight variation test     Limits for weight variation test The individual weights should be with in limit of 90110% of average weight. If not all of capsules fall with in the limits, Weigh 20 capsules individually Remove the net content of each capsule with the aid of a small brush and Weigh the empty shells individually NET WT OF CONTENTS INDIVIDUALLY = THE WT OF SHELL-GROSS WT Determine the average net content from the sum of individual net weight, Then determine the difference b/w each individual net content and average net content LIMITS- “Not more then 2 of the differences are greater then 10% of the avg net content • No case is the difference greater then 25% weight range Weight variation limits for Hard gelatin capsules If more than 2 ,but not more then 6 capsules deviate from the avg. b/w 10-25% Determine the net contents of an additional 40 capsules LIMITS- NMT 6 of 60 capsules should exceed from 10% of the avg. net content No capsule should exceed 25% differene Determine the avg content of entire 60 capsules Determine the 60 deviations from the new average Weight variation test for soft capsules 1. 2. 3. 4. Disintegration test  Disintegration of hard and soft gelatin capsules is evaluated to ensure that the drug substance is fully available for dissolution and absorption from the gastrointestinal tract.  If 6 capsules are tested, all 6 of the capsules should disintegrate within the specified time limit mentioned in the monograph.  If one or two capsules fail to disintegrate then repeat the test on an additional 12 capsules the requirement is met if not fewer than 16 of the total of 18 capsules are disintegrated Dissolution test        Capsule sinkers Sinkers FACTORS AFFECTING DRUG DISSOLUTION FROM HARD GELATIN CAPSULES       Silica Pouch CONTENT UNIFORMITY     Physical stability of capsules  Capsule fragility or rupture test:- Force required to rupture the capsule is determined. Physical stability capsule  Unprotected soft capsules (i.e., capsules that can breathe) rapidly reach equilibrium with the atmospheric conditions under which they are stored.  The variety of materials capsulated, which may have an effect on the gelatin shell, together with the many gelatin formulations that can be used, makes it imperative that physical standards are established for each product.  The physical stability of soft gelatin capsules is associated primarily with the pick-up or loss of water by the capsule shell. Capsule stability or shelf life test      “The tests are strictly relevant to the integrity of the gelatin shell and should not be confused as stability tests for the active ingredients in the capsule content.” Effect of storage condition on capsule shell  If moisture uptake is prevented by proper packaging, the above control capsule should have satisfactory physical stability at temperatures ranging from just above freezing to as high as 60 0C.  As the humidity increases the moisture content pickup of capsules increases.  For the unprotected control capsule, low humidities (less than 20 % RH), low temperature (less than 2 C) and high temperatures (greater than 38 C) or combinations of these conditions have only transient effects.  High humidity (>60%RH at 21-240c ) produces more lasting effects on the capsule shell Effect of storage condition on capsule shell  The effect of temperature and humidity on capsule shell has been shown in Table below Temperature Humidity Effects 21-24 C 60 % Capsules becomes softer, tackier and bloated Greater than 24 Greater than 45 % More rapid and pronounced effect, unprotected capsules melts and fused together Microbial content  The capsules are tested to ensure lack of growth of bacteria and mould by microbiological tests.  These tests are usually carried out by incubation of the capsule contents in a growth medium and counting the colonies formed after a predefined period of time. PACKAGING AND STORAGE OF CAPSULES  Capsules should be packed in a well-closed glass or plastic containers and stored in a cool place.  These type of containers have advantage over cardboard boxes that they are more convenient to handle and transport and protect the capsules from moisture and dust.  To prevent the capsules from rattling a tuft of cotton is placed over and under the capsules in the vials.  In vials containing very hygroscopic capsules a packet-containing desiccant like silica gel or anhydrous calcium chloride may be placed to prevent the absorption of excessive moisture by the capsules.  Now a days capsules are strip packaged which provide sanitary handling of medicines, ease in counting and identification Clamshell blister Plastic bottles Blister packaging Heat sealed blister on cardboard Plastic Ziplock pouch Raw material The gelatin of the capsule shells should be assayed for various physical properties like:  bloom strength, viscosity and its loss (by atomic force microscopy) Chemical tests like purity, microbial properties, and limits for heavy metals like arsenic, ash content should be determined.  • The colorants should also be checked for purity, limits for heavy metals, color properties, dye content, Bloom strength of gelatin  The gel strength of gelatin is a measure of the cohesive strength of the cross-linking that occurs between gelatin molecules.  The measure of cohesive strength of the cross-linking that occurs between gelatin molecules and its proportional to molecular weight is called BLOOM STRENGHT  Bloom is determined by measuring the weight in grams required to move a plastic plunger that is 0.5 inches in diameter 4mm into 6.66% gelatin gel that has been held at 100C for 17hrs.  Bloom may vary with the requirements, ranges from 150 to 250g. Number of grams called bloom value Types of gelatin based on Bloom value  The higher the bloom value, the higher the melting and gelling point of gel and the shorter is gelling time.  The higher the Bloom strength of gelatin used, the more physically stable is the resulting capsule shell.  Category Bloom number Avg. Molecular mass 1 Low bloom 50-125 20,000-25,000 2 Medium bloom 175-225 40,000 -50,000 3 Higher bloom 225-325 50,000-100,000 https://www.youtube.com/watch?v=svvC3aR6AXw Gelatin Bloom Tester https://www.youtube.com/watch?v=svvC3aR6AXw