Development of Noveld-Cycloserine Tablet with Improvement of Drug Stability and Dissolution-Equivalence to thed-Cycloserine-Loaded Commercial Hard Capsule

Abstract

The purpose of this study was to develop a noveld-cycloserine tablet with improved stability and dissolution equivalent to thed-cycloserine-loaded commercial hard capsule. The effect of alkalizing agents on thed-cycloserine was investigated. Numerousd-cycloserine tablets were prepared with various calcium hydroxide contents, using direct or wet granulation compression, and their stability and dissolution were assessed compared to the commerciald-cycloserine-loaded hard capsule. Long-term stability of the selectedd-cycloserine tablet in aluminum polyvinylchloride blister were conducted at 25 degrees C/60% RH or 40 degrees C/75% RH for 6 months. Amongst the stabilizers tested, calcium hydroxide gave the best stability at 60 degrees C/75% RH for 2 days due to its alkaline and waterproofing properties. Calcium hydroxide hardly affected dissolution of drug from the tablets but considerably increased stability of drug in the tablets. Particularly, the tablet prepared withd-cycloserine, calcium hydroxide, polyvinylpyrrolidone, and talc in the weight ratio of 250/250/40/7.5 using direct compression gave similar dissolution but significantly improved stability compared to the commercial hard capsule. This tablet, packaged in aluminum polyvinylchloride blister, was stable in the above accelerated conditions for 6 months. Therefore, this noveld-cycloserine tablet with enhanced stability and dissolution equivalent to the commercial hard capsule would be recommended as an alternative.