Quality Control Tests For Pharmaceutical Capsules
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 370C throughout the test. The capsule passes the test if it completely dissolves within 10
mins giving odorless, neutral (or slightly acidic).
Weight variation2
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.
Content uniformity2
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
Disintegration:
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 + 20C. 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.
Dissolution
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 +
0.50C. 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
Raw materials1
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
Machine output
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
Moisture content can be monitored with the aid of data the drying kilns (oven for drying) 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.
Printing inspection
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.
Final inspection
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
Bibliography:
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.
