Difference in the Dissolution Behaviors of Tablets Containing Polyvinylpolypyrrolidone (PVPP) Depending on Pharmaceutical Formulation After Storage Under High Temperature and Humid Conditions.

Abstract

Storage under high temperature and humid conditions has been reported to decrease the dissolution rate for some kinds of tablets containing polyvinylpolypyrrolidone (PVPP) as a disintegrant. The aim of this study was to elucidate the properties of pharmaceutical formulations with PVPP that cause a decrease in the dissolution rate after storage under high temperature and humid conditions by using model tablets with a simple composition. Model tablets, which consisted of rosuvastatin calcium or 5 simple structure compounds, salicylic acid, 2-aminodiphenylmethane, 2-aminobiphenyl, 2-(p-tolyl)benzoic acid or 4.4'-biphenol as principal agents, cellulose, lactose hydrate, PVPP and magnesium stearate as additives, were made by direct compression. The model tables were wrapped in paraffin papers and stored for 2 weeks at 40°C/75% relative humidity (RH). Dissolution tests were carried out by the paddle method in the Japanese Pharmacopoeia 16th edition. Model tablets with a simple composition were able to reproduce a decreased dissolution rate after storage at 40°C/75% RH. These tablets showed significantly decreased water absorption activities after storage. In the case of tablets without lactose hydrate by replacing with cellulose, a decreased dissolution rate was not observed. Carboxyl and amino groups in the structure of the principal agent were not directly involved in the decreased dissolution. 2-Benzylaniline tablets showed a remarkably decreased dissolution rate and 2-aminobiphenyl and 2-(p-tolyl)benzoic acid tablets showed slightly decreased dissolution rates, though 4,4'-biphenol tablets did not show a decrease dissolution rate. We demonstrated that additives and structure of the principal agent were involved in the decreased in dissolution rate for tablets with PVPP. The results suggested that one of the reasons for a decreased dissolution rate was the inclusion of lactose hydrate in tablets. The results also indicated that compounds as principal agents with low affinity for PVPP may be easily affected by airborne water under high temperature and humid conditions.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.