Effect of dual surfactants and different processing parameters on the controlled release of a poorly water-soluble drug from ethyl cellulose microspheres
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The objective of this work was to study effects of different formulation (dual surfactants, surfactant structure), and processing factors on different formulation parameters of ethyl cellulose microspheres fabricated by a non-aqueous emulsion solvent evaporation method. Ethyl cellulose microspheres containing theophylline were prepared at different combined hydrophilic lipophilic balance (CHLB) by using different dual surfactants combinations of high HLB (Tween 40, Brij 58) and low HLB (Span 65) surfactants in an emulsion-solvent evaporation process. The external phase used was light mineral oil and the internal phase was acetone. Individual and combination effects of combined hydrophilic lipophilic balance (CHLBs) of dual surfactants; surfactant structures, different preparation temperature (220C and 350C) on microsphere properties like yield, particle size distribution, geometric mean diameters, initial drug release, and drug release characteristic of the microspheres were evaluated. With an increase in CHLB of the dual surfactant combination of span 65+Tween40, we noted decrease in the geometric mean diameter, and an increase in the dissolution rate and initial drug release. When surfactants with similar or closely matching HLB values but with different chemical-structure including polyoxyethelene sorbitan monopalmitate with HLB 15.6, and polyoxyethylene cetyl ether with HLB 15.7 were studied, we noted decrease in the geometric mean diameter, increase in the dissolution rate and initial drug release of microspheres. With increasing microsphere preparation temperature from 220C to 350C, geometric mean diameter of microspheres decreased, the particle size distribution widened, the sphericity of microspheres was improved, and the % drug loading, the initial drug release rate, the t50 release time increased. By changing the surfactant structure from polyoxyethelene sorbitan monopalmitate to polyoxyethylene cetyl ether in combination with microsphere preparation temperature, percent drug loading and drug release was altered, and drug release mechanism was affected with some microsphere batches showing near zero-order release.