ALBUMIN MICROSPHERES AS A MEANS OF DRUG-DELIVERY TO THE LUNG - ANALYSIS OF THE EFFECTS OF PROCESS VARIABLES ON PARTICLE SIZES USING FACTORIAL DESIGN METHODOLOGY

Albumin microspheres (MS) in the size range of 7-11 mu m in diameter w ere prepared using high-speed homogenisation and subsequent heat denat uration. The effects of several process variables on the particle size were evaluated by both empirical optimisation and factorial design. U sing analysis of variance, the pH of the protein solution and the stir ring rate during heat denaturation were shown to have significant effe cts on the particle size of the resultant MS (p < 0.01). MS prepared a t low pH values and/or slow stirring rates had larger particle sizes. A small amount of butan-1-ol (< 10% v/v) in the oil phase improved the appearance of MS but had no significant effect upon size. An inter-re lationship was shown to exist between pH, stirring rate and butan-1-ol content (p < 0.01). Albumin concentration and phase volume ratio had slight but insignificant effects (p > 0.1) on the particle size.