Effects of Storage Conditions on Dissolution Rates of Indomethacin Capsules.

Abstract

Using indomethacin (IND) capsules (Caps) before the date of expiration, we conducted the dissolution tests that are prescribed in the 17th Revision Japanese Pharmacopoeia (JP 17) and found a preparation within a serial number (Lot) that failed to satisfy the specified dissolution rate. Thus, we investigated factors that decrease dissolution rates of IND Caps during storage at room temperature (r.t.). In elution profiles of IND Caps samples, dissolution rates decreased as the expiration date approached. Moreover, after extended elution of formulations with unacceptable 20 min dissolution rates, dissolution rates remained in less of those specified in JP 17. Moreover, changes in dissolution profiles of preparations with pending expiry did not reflect changes in Caps shells, suggesting changes in the active contents. However, IND contents of the offending preparations decreased very little, even under accelerated conditions. Thus, in further experiments, we investigated preservation conditions of IND Caps, and found that humidity greatly decreases dissolution rates, and preservation of press-through package (PTP) sheets were also suggested to affect IND Caps. Finally, we found that the use of aluminum bag packaging prevents decreases in dissolution rates of IND Caps.