In Process Quality Control Tests For Capsules [Autosaved].pptx

In Process Quality Control Tests For Capsules

1. In Process Quality Control Tests For Capsules Submitted to: Dr. R. S. Chandan Associate Professor Pharmaceutical Chemistry JSS College of Pharmacy , Mysuru Submitted by: N. Surendra chowdary M. Pharm, 1 st Year Pharmaceutical Analysis. JSS College Of Pharmacy, Mysuru

2. Contents : 1.Introduction to Capsules : 2. In-process quality control (IPQC) tests for capsules

3. Introduction to Capsules : Definition: Capsules are dosage forms in which API and excipients are enclosed in the hard/soft water soluble container made of gelatin . Where Hard gelatin capsule - Consist of cap and body – filled with powders, pellets, granules. While the soft gelatine capsule is filled with liquid (oil)/semisolid (paste)

4. In-process quality control (IPQC) tests for capsules: The primary objective of an IPQC system is to monitor all features of a product that may affect its quality and to prevent errors during processing. IPQC tests for capsules are: 1)Stability tests. i . Shell integrity test. ii. Determination of shelf life. 2) Test for purity of shell 3) Invariability tests. i . Weight variation test. ii. Content uniformity test. 4) Disintegration test. 5) Dissolution test. 6) Moisture permeation test. 7) Batch-Release tests.

5. 1. Stability Studies: Stability tests for capsules are performed to know the integrity of gelatin capsule shell (but not to know the stability of therapeutically active agent) and for determining the shelf life of capsules. Before actually performing the tests, the following facts have to be remembered: The capsule shells are to be stabilized to known atmospheric conditions with relative humidity about 20-30% & temperature about 21-24 degree centigrade. The capsules are to be proceeded for further tests only after they re-establish the equilibrium at room temperature. Stability test includes: a) Shell integrity tests: b) Determination of shelf life: Shelf life or the expiry date of packed capsules is determined under normal storage conditions.

6. a) Shell integrity test: This test is performed to find out the integrity of capsule shell . Method: The capsules which are to be tested and the standard capsules are placed in one of the above conditions for two weeks with periodic examination. The gross and the net changes occurring in them are as follows: The standard capsule shells kept at room temperature and 80% RH becomes more soft, sticky and swollen. ii. The test capsules kept under the same conditions undergo the following changes: Gross changes include color fading, discoloration, disintegration, leaking and turning brittle or soft. Net changes include loss of volatile ingredients, grooves growing darker and wider and a little change in color of the shell. Many times due to slower drying, soft spots appear over the test capsules which touch container or the other capsules. These types of spots are not developed in the standard capsules. Later on these spots turn harder and are not considered as defects of the capsule shells. In case they do not turn harder (due to capsule ingredients) physical stability problems may arise. So such flaws must be corrected as soon as possible by altering the ingredients of the shell are the fill materials.

7. 2. Test for purity of shell: Procedure: In this five capsules are used. The capsules are tested individually, each one is taken a part, placed in a 100 ml conical flask, 50 ml of water is added and the flask is shaken repeatedly. During the test the water is maintained at 37 ± 2 degree centigrade All the capsules must completely dissolve in 10 minutes. The resulting solution must be odor less and neutral or slightly acidic. Capsule specifications:

8. 3. Invariability tests: 3.1) Weight variation test: 3.1.1)Weight variation test for Hard gelatin capsules: 1. Individually weigh twenty filled capsules and determine their average weight. 2. Calculate the weight variation of every capsule against the average weight 3. If the variation exceeds ± 10%, then determine the actual weight of the medicament separately and compare it with the overall average weight. 4. According to the specifications in some pharmacopoeias, the overall weight of two capsules can differ by ±10% from the overall average weight. But no capsules can differ by more than ±25%. 5. If the overall average weight of 2-6 capsules differ by ± 10 -25%, then repeat the same procedure with 40 more capsules. 6. When 60 capsules are taken for test, only six capsules can differ from the overall average weight by more than 10%. In no case they should differ more than ± 25%. Uniformity of weight:

9. 3.1.2) Weight variation test for soft gelatin capsules: Individually weigh 10 filled capsules. Empty the contents of capsules by washing with suitable solvents. Allow the solvents to evaporate from the contents at room temperature for about half-an-hour. Take necessary steps to prevent the uptake or/and loss of moisture. Net contents are calculated by weighing the empty capsule shells separately. Finally, the contents of therapeutically active ingredient are determined from the out come of the assay directed in the individual monographs in pharmacopoeia. 3.2) Content uniformity test: Invariable distribution of drug substance persists as a problem in case of solid dosage forms This problem remains at a higher level in case of potent drugs. For this reason, 30 capsules, are used for assaying the drug content. Method: At first, 10 capsules are assayed individually to determine the percentage purity of the active ingredient out of these 10 capsules should be within the range of 85-115%. In case 1-3 capsules are outside the stated range (75-125%), then additional tests are performed on the remaining 20 capsules. The net result of the 30 capsules assayed should prove that at least 27 capsules are within the desired extremes. i.e., between 85-115% and no capsule is beyond the stated range i.e., between 75-125%.

10. 4) Disintegration test: Disintegration test is a method to evaluate the rate of disintegration of solid dosage forms (capsules or tablets). Disintegration is defined as the breakdown of solid dosage form into small particles after it is ingested. IP specifications: • Length of glass tubes - 77.5 ± 2.5 mm. • Internal diameter of glass tubes – 2.15mm. • Thickness of walls of glass tubes – 2 mm. • Diameter of plastic plates – 90 mm. • Thickness of plastic plates – 6 mm. • Diameter of wire screen – 2 mm. • Diameter of stainless steel disk – 22 mm. Method: A capsule is placed in every glass tube and basket containing these glass tubes is positioned in the basket containing the required fluid such that all capsules dip properly. The apparatus is then operated for specified time. The capsule passes the disintegration test when none of the drug particles remain on the mesh/wire screen i.e., the capsule must disintegrate and all particles must pass through the mesh with in the time specified in monograph. However the insoluble coating particles or the soft mass without palpable core are exempted.

11. 4.1. Disintegration test for hard gelatin capsules: Place 6 capsules in each of 6 tubes of the basket. Instead of adding a disk attaches to removable mesh wire cloth. Operate the apparatus using simulated gastric fluid maintained at 37±2 c. Observe the capsules within time specified in the individual monograph (30 min for hard or 60 min for soft gelatin capsules). Result: All the capsules have disintegrated except for fragments from the capsule shell. If 1 or 2 capsules fail to disintegrate completely, repeat the test on 12 additional capsules. Not less than 16 out of 18 capsules tested disintegrate completely

12. 5) Dissolution Test: Dissolution test is an official method to determine the dissolution rate of solid dosage form. Dissolution rate is defined as “ the rate at which drug is released into the systemic circulation from the dosage form”. Dissolution test for oral dosage forms like capsules and tablets is a prerequisite for evaluation of the product quality. The bioavailability of a drug depends upon dissolution rate of its dosage form. Dissolution test is performed in two ways: The In vivo dissolution test is performed on healthy living objectives (animals). This is very expensive and time consuming process. 2. Whereas, the In vitro dissolution test is performed in dissolution apparatus under simulated biological conditions. This is an inexpensive and less time consuming process. In vitro – In vivo correlations of Dissolution

13. Method of Dissolution: When one capsule is tested, the amount of dissolved drug in the solution is calculated as a percentage of the amount of dissolved active ingredient (P) specified in the individual monograph. When more than one capsule is being tested, the dissolution test is carried out through three stages. • Stage-1 (T1): six capsules are tested and accepted if each of them is not less than the monograph specified limit + 5 % i.e., p + 5 %. • Stage-2(T2): If the dosage form fails T1 then additional six capsules are tested. The result is acceptable if the average of the 12 capsules is greater than or equal to P, and none of them is less than P – 15%. • Stage-3(T3): If the capsules still fail the test, then additional 12 capsules are tested and are accepted if the average of all the 24 is greater than or equal to P, if not more than two or less than P – 15 % and none4 of them is less than P – 25 %. Dissolution apparatus

14. 6) Moisture permeation test: To assure the suitability of containers for packaging capsules, USP has stated some rules and regulations. According to these rules and regulations, the moisture permeating feature of capsules packaged in single unit containers (blister pack or strip pack) and unit dosage containers (glass or plastic bottles) are to be determined Procedure To perform this test, one capsule in the single-unit container or the unit dose container is packed along with the dehydrate pellets, which have the property of changing the colour in the presence of moisture. The packaged capsule is then placed for a certain period of time in the atmosphere of known humidity. Any change in the colour of dehydrated pellets reveals the absorption of moisture. The weight of test capsule is then compared with the weighs of capsules under test. The differences in weights give the amount of moisture absorbed. 7) Batch-Release tests: The quality control testing of the batch can be divided in to Physical and chemical tests . 7.1 Physical tests: 7.1.1 Appearance: A description of appearance that may be an indication of batch to batch variability will also provide any indication of change during stability studies. Example: Dull vs shiny Polished vs unpolished

15. 7.1.2. Vacuum leakage test: It determines the seal strength and it is generally a predictive stress test. Method: In this test, the intact soft gelatin capsules are placed under vacuum for 4 hrs at room temperature and the number of leakages determined. Depending up on % of leakers, the batch will be accepted or rejected.

16. References: 1. The theory and practice of Industrial Pharmacy by Lachman, Lieberman, Kanig , Third edition 2. Text book of Physical Pharmaceutics by C.V.S. Subrahmanyam. 3. www.google.com. 4. Remington’s The Practice of Pharmaceutical Sciences; Volume II. 5. Indian pharmacopoeia 2007, Volume I.

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