Studies on dissolution mechanism of drugs from ethylcellulose microcapsules.

Abstract

The dissolution behavior of 4 drugs from ethylcellulose (EC) microcapsules (MC) was examined at various temperatures. From the early dissolution curves, the apparent dissolution rate constants and permeability constants (Pm) were estimated. The permeation across a Millipore filter and an EC cast membrane were also examined for comparison. The value of activation energy of Pm of MC ranged from 4.0 to 7.6 kcal/mol, independently of the drug solubility, and were close to those obtained for permeation through the Millipore filter and EC cast membrane. Pm values in the thickness. These results suggested that the drugs were not transported through the polymer phase but through the water channels existing in the MC membrane. Superposition analysis was applied to the dissolution curves measured at various temperatures and it was found that the extent of the superposition was better for less water-soluble drugs. The dependency of drug permeation through MC on wall thickness (from 5 to 20 .mu.m) was examined using isoniazid. Pm values decreased linearly up to about 12 .mu.m and were constant for a thicker wall at all dissolution temperatures. The activation energy of the dissolution rate constants increased with increasing wall thickness. The water, channels were classified into two types, one with fairly large pores or cracks and which was was predominant in thicker films.