Quality control should be carried out during all stages of manufacturing operation which is the primary requirement of good manufacturing practices.
Empty hard capsules1
According to Japanese Pharmacopoeia, the test called 'purity' uses five capsules which are tested individually. Each is placed in a 100 ml conical flask and shaken vigorously after adding 50 ml of water 37C throughout the test. The capsule passes the test if it completely dissolves within 10 mins giving odorless, neutral (or slightly acidic).
For hard capsules: Accurately weigh 10 capsules. By suitable means the contents of each capsule should be removed. The weights of emptied shells should be recorded individually. The difference of both the weights will yield the net weight of the contents. Then calculate acceptance value.
For soft capsules: pre weigh 10 capsules. Cut the capsules by suitable means (either scissors or any open blade) remove the contents by washing with a suitable solvent and let the solvent evaporate by placing them at room temperature for about 30 mins. Weigh the individual shells. Calculate the acceptance value.
Hard capsules containing 25 mg or more of the drug contents should meet content uniformity requirements.
Assay 10 capsules individually and calculate the acceptance value.
The requirement is met if the acceptance value of 10 capsules is less than or equal to 15%. If acceptance value is greater than 15% or is about 25 % then, test the next 20 units and calculate the acceptance value. The 30 capsules if less than or equal to 15% and no individual unit is 1-25*0.01 nor more than 1+25*0.01.
Calculation of acceptance value:
(Reference value-mean of individual contents ) + acceptability constant * sample standard deviation
The disintegration of capsules is different from those of tablets because the determination of end point is difficult owing to the adhesive nature of shell. The shell pieces after disintegration may agglomerate forming large mass of gelatin taking more time to dissolve and may adhere to the mesh thus, blocking the holes.
According to USP, place one dosage unit in each of the tubes of the basket with water or any other specified medium (depends on individual monograph) maintained at 37 + 2C. Attach a removable wire cloth with a plain square weave of 1.8-2.2 mm of mesh aperture and a wire diameter of 0.60-0.655 mm to the surface of upper rack of the basket assembly. Observe the capsules for a time limit (specified in individual monograph), at the end of prescribed time, all of the capsules must have been disintegrated excluding the fragments from the capsule shell. If 1 or 2 capsules fail, the test should be repeated on additional of 12 capsules. Then, not fewer than 16 of the total 18 capsules tested should disintegrate completely.
Place each of the capsules in the apparatus 1, excluding air bubbles from the surface of the capsule. Operate immediately at specified rate within specified dissolution medium at 37 + 0.5C. Aliquots should be withdrawn at specified time points mentioned in individual monograph.
The requirements are met if the quantity of active ingredients dissolved conforms the following:
1) At stage 1 (S1): When 6 capsules are tested, amount of each of the dissolved content should not be less than +/- 5% of the mentioned in monograph.
2) At stage 2 (S2): when 6 capsules are tested, the average of 12 (both from step 1and 2) should be equal to or greater than 15% and no capsule should be than 15%.
3) At stage 3 (S3): when 12 capsules are tested, the average of 24 capsules (all 1,2 and 3 steps) should be equal to or greater than the amount mentioned in the monograph, not more than two units are less than 15% and no unit s less than 25%.
NOTE: 15%, 25% represent Q1 and Q2 unless and otherwise mentioned in the monograph.
"Quality is not the step that can be incorporated at last, it is mandatory and should be inbuilt into the products" to, make this happen, apart from all these mandatory tests certain other tests can be performed like
The gelatin of the capsule shells should be assayed for various physical properties like bloom strength3, viscosity and its loss (by atomic force microscopy).4 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, subsidiary dye content and color value.5
The manufacturing machine's output should be monitored continuously via the dimensional correctness during each lot production.
The color of the capsules should be checked against a standard strip; in case of any changes the gelatin solution should be adjusted by adding standardized dye solutions which can be ensured via thin layer chromatography.
Moisture content can be monitored with the aid of data the drying kilns can be adjusted.
Loss on drying
Determination of loss on drying via the oven method consumes more time. To prevent this advanced methods like infrared balances, humidity meter etc.
Sorting of defects
After electronic or manual inspection, they are sampled by quality control inspectors. The results should meet the inspection plan, if not the capsules should be resorted or rejected depending upon frequency of faults.
Quality inspectors sample the lot and are inspected for quality of print. The results will again be compared with the inspection plan and in case if it does not match then, either capsules should be resorted or rejected depending upon number of faults present.
After the capsules are placed in final containers, samples are checked for various parameters like dimensions, physical defects and color. These samples are also subjected to various microbial tests also.6
THIS BLOG DOESNOT CONTAIN PLAGIARIZED MATERIAL
1. Fridrun Podczeck, Brian E Jones. Pharmaceutical capsules. 2nd ed. Pharmaceutical press.UK.2004.p.89-90 and 239-58.
2. US Pharmacopoeia 30-NF25. May 1, 2007.
3. Gelatin Gels. Brookfield. Can be accessed from http://www.brookfieldengineering.com/education/applications/texture-gela...
Accessed on 1st Oct 2010.
4. Benmouna F, Johannsmann D. Viscoelasticity of gelatin surfaces probed by AFM noise analysis. Langmuir.2004;20(1):188-93.
5. Carmen Socaciu. Analysis of synthetic food colorants. Food colorants Chemical and Functional properties. Carmen Socaciu editor. CRC press 2008.
6. Satinder ahuja, Stephen Acypinski. Modern pharmaceutical analysis. Academic press. 2001.