In vitro controlled drug release from loaded microspheres - dose regulation through formulation

PURPOSE: Drug release profiles were established for ibuprofen encapsulated within several types of microspheres and a range of dissolution buffer media to study the effect these variables have in controlling the rate and extent of drug release. METHODS: Fatty acid microspheres containing ibuprofen were prepared by a process previously developed and refined to produce microspheres of a known size and composition, namely 80-125 ?m diameter and an excipient to ibuprofen ratio of 3:1. Drug release profiles from these encapsulated formulations were compared with those obtained for the dissolution of ibuprofen alone under the same conditions. RESULTS: Stearic acid microspheres were found to only partially retard the release of ibuprofen over a twenty minute period compared with the dissolution of ibuprofen alone. However, a significant retardation of ibuprofen release was observed with cetostearyl alcohol microspheres over the same period of time. Secondly, drug release profiles for encapsulated ibuprofen were determined using five distinct dissolution buffer media; sodium phosphate, potassium phosphate, citric acid and phosphate mix, MOPS and tris. Significant differences in the extent and rate of drug release were recorded between the different dissolution buffer solutions. These differences were also shown to be independent of variations in pH, temperature, buffer concentrations and the type of cations present. CONCLUSIONS: The presence and choice of microsphere formulation, and the choice of buffer present in the dissolution solution, can influence drug release in vitro, i.e. it is possible to achieve controlled drug release from microspheres. To explain the control achieved through the choice of buffer in solution it is proposed that the buffer anion exerts a stabilising influence on the ibuprofen-microsphere matrix