Pharmaceutical Quality Management
(i) Formulation studies :
When freshly prepared, all the capsules ruptured within 10 mins and disintegrated/ dissolved completely within 30 mins. However, storage of the above capsules for 2 months (at 40 and 50 degrees centigrade) showed significant changes in their rupture dissolution times.
The capsules containing copper sulphate, manganese sulphate and potassium iodide (both alone and in presence of RO), refrigerated (control) sample of capsules containing manganese sulphate + RO, KI and KI+ RO indicated a rupture time of more than 15 mins and a DT of more than 60 mins after storage for one
month. The refrigerated capsules of copper sulphate and copper sulphate + RO however, complied with the tests for rupture and DT when stored for a period of one month.
Hence, to further investigate the reason for such protracted disintegration, the capsules shell was analyzed for evidence of possible migration of metal ions from the capsules contents to the shell. The shells of both freshly prepared and stored capsules were analyzed quantitatively for copper, potassium and manganese ions using an atomic absorption spectrophotometer.
It was observed that copper ions migrated into the shells after storage at 40 degC for 7 days. The rate of migration of copper ions increased on increasing the temperature to 50 degC. Also, a 3- fold increase in concentration of the copper salt brought about a 16- fold rise in the rate of migration. But, the
rate of migration under accelerated temperature and increased storage period was independent of the presence of RO. At the refrigeration temperature, the rate of migration decreased 4- fold in case of capsules containing RO thereby indicating that RO had a protective action on the migration of copper ions from the content
into the shell.
Similar behavior was exhibited by potassium ions. However, unlike capsules containing copper sulphate, these containing KI stored in a refrigerated did not show any decrease in the rate of migration. Capsules containing manganese sulphate (alone and with RO) did not show any migration even under accelerated conditions of temperature. This could be because the ions with larger diameter may not fit into the void in the gelatin molecules.