Capsules physical stability

1.  Unprotected soft gelatin capsules rapidly reach equilibrium with the atmospheric conditions under which they are stored.

2.  This inherent characteristic warrants a brief discussion of the effects of temp and humidity on the products.

3.  General statements relative to the effects of temp and humidity on soft gelatin capsules must be confined to a control capsule that contains mineral oil with a gelatin shell having a dry glycerin to dry gelatin ratio of 0.5-1 and water to dry gelatin ratio of 1-1 and that is dried to equilibrium with 20-30% RH and 21-24^oC. 

The physical stability of soft gelatin capsules is associated primarily with the pick up or loss of water by the capsule shell .

If these are prevented by proper packaging ,the above controlled capsule should have satisfactory physical stability at S temp ranging from just above freezing to as high as 60⁰C.

As the humidity increases the moisture content  pickup of capsules increases.

 ex- 

At 30%RH at room temp shows that gelatin retain about 12% (48 mg) of water and glycerin 7% (14 mg)of water. At 60%RH the moisture content should be 17.4%. High humidity (>60%RH at 21-24⁰C) produce more lasting effects on the capsule shell.

Since as moisture is absorbed, the capsules become softer, tackier , and bloated.

The capsule manufacturer routinely conducts accelerated stability tests on new product as an integral part of the production development program.

The successful results are obtained by conducing at test conditions like

    80%RH at room temp in an open container

    40⁰C in open container

     40⁰C in closed container (glass bottle with tight screw cap)

Chemists conducting the physical stability test in their own lab should keep two important points in mind

1.  Prior to testing, the capsule should be equilibrated to known atmospheric conditions, preferably 20-30%RH at 21-24⁰C.

2.  Evaluation of the results of the previously described heat test should be made only after the capsules have returned to equilibrium to room temp.

Packaging and storage of capsules

Capsules should be packed in a well-closed glass or plastic containers and stored in a cool place.

1.  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.

2.  To prevent the capsules from rattling a tuft of cotton is placed over and under the capsules in the vials.

3.  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.

4.  Now a days capsules are strip packaged which provide sanitary handling of medicines, ease in counting and identification.

Pharmaceutical aspects of capsules

Essentially capsules are solid dosage form containing liquid medication and therefore offer certain advantages. They permit liquid medications to become easily portable.

These capsules easily pass the appropriate compendial tests and surpass other solid dosage form because liquid formulations can be more accurately and precisely compounded, blended, homogenized and measured or dispensed then can dry solid formulations.

Dissolution and disintegration-

The majority of drugs were more rapidly and completely available for dissolution from the soft gelatin capsule then from the commercial tablets and capsules in accordance to dissolution and disintegration time. The dissolution on capsules of chloramphenicol, using the modified USP apparatus (rotating bottle method), showed that

soft gelatin capsules brand to releases Hard shell capsule   brands B2 and D releases

22.3 to 24.8% in 30 min 100.7% and 87.2%

The physiologic availability of drugs is often improved by liquid drug substance i.e., it contains the drug in liquid form or in suspension. Nelson,in his review, points out that the availability of a drug for absorption of solid dosage forms decreases as below:

SOLUTION>SUSPENSION>POWDER FILLED CAPSULE>COMPRESSED TABLET >COATED TABLET

Problems & remedies for tablet coating

Quality control (Q. C.) tests for tablets

Uniformity of content of active ingredient (Uniformity of weight & Content uniformity)

1)  Disintegration test

2)  Dissolution test

3)  Friability test

Disintegration test for Tablets:

All tablets must pass a test for disintegration except Chewable tablets and some extended release tablets

Tablets must disintegrate in the time set in the individual monograph, usually 30 min., but varying from 2 min for nitroglycerin sublingual tablets to up to 4 hrs for buccal tablets.

The end point of the test (i.e. complete disintegration) is achieved when no tablet fragments remain on the screen (fragments of coating may remain).

Disintegration test for Enteric coated tablets: Enteric coated tablets are similarly tested except that the tablets are tested first in the simulated gastric fluid (0.1N HCl) for specific time (2hr in B.P.) for a positive test, after which no signs of disintegration, cracking or softening must be seen, followed by immersion in simulated intestinal fluid (Phosphate buffer pH 6.8) for the time stated in the individual monograph, during which time the tablets disintegrate completely.

Disintegration test for effervescent tablet-Place one tablet in a beaker containing 200 ml of water (15-25 °C) when the evolution of gas around the tablet stops, the tablet has disintegrated. The same procedures are performed for other 5 tablets. The tablets comply with the test if each of the six tablets used disintegrated within 5 min or as justified.

Dissolution test performed for

1)  To differentiate between formulations and to evaluate the potential effect of the formulation and other processes variables on drug bioavailability.

2)  To ensure bioequivalence from batch to batch.

3)  To ensure that the preparation comply with product specification, as it is a requirement for regulatory approval of marketing for the registered product.

4)  To indicate the performance of the preparation under the in vivo conditions. (It is possible to correlate dissolution rate of a drug with its bioavailability)

Friability test

During manufacturing and handling, tablets are subjected to stresses from collision and tablet sliding towards one another and other solid surfaces, which can result in the removal of small fragments and particles from the tablet surface. The result will be progressive reduction in weight and change in appearance.

Another application of the friability test capping or laminate when stressed by attrition inside the rotating cylinder present in the friability tester.

To examine this, tablets are subjected to uniform tumbling motion for specified time and weight loss not more than 1% generally is considered acceptable for most products.

Capping & Lamination

Capping is the partial or complete separation of the top or the bottom crown from the main body of the tablet.

Lamination is separation of the tablet into two or more distinct layers.

Causes of Capping & lamination problems in Tablets-

- Air entrapment during compression, the resulting tablet expand when the pressure of the tableting is released, resulting in splits or layers in the tablet

- Excess amount of lubricant which may decrease the tablet strength due to their interference with the bonding between the particles during compression.

Picking & Sticking in Tablets

Picking is the removal of the surface material of the tablet by the punch Sticking is the adhesion of the tablet material to the die wall this may be due to  excessive moisture or the inclusion of materials with low melting point (PEG & stearic acid) in the formulation. This problem could be managed by addition of suitable antiadherent.

Tablet mottling

Tablet mottling or dark areas. This problem occurs when a drug has different color than the tablet excipients or when a drug has colored degradation products. This problem also caused by intragranular migration of the soluble dye during the drying stage which may give rise to dry granules with a highly colored outer zone and interior. During compaction granules are fractured and the colorless interior is exposed resulting in mottled tablets.