Formulation Optimization of Sustained-Release Ammonio Methacrylate Copolymer Microspheres. Effects of Log P and Concentration of Polar Cosolvents, and Role of the Drug/Copolymer Ratio

Pharmaceutics

Péter Sipos¹  Rrt Rajkó²  Klára Pintye-H༽i¹  István Erős¹ 

[1]Department of Pharmaceutical Technology, University of Szeged, Eotvos str. 6, 6720 Szeged, Hungary

[2]Department of Mechanical and Process Engineering, University of Szeged, Dugonics squ. 13, 6720 Szeged, Hungary

关键词: microspheres;    formulation optimization;    cosolvents;    drug/copolymer ratio;    spray drying;    factorial design study;   

DOI  :  10.3390/pharmaceutics3040830

来源: mdpi

【 摘 要 】

The objectives of this work were the formulation optimization of the preparation process parameters and to evaluate spray-dried sustained-release microspheres using ammonio methacrylate copolymer (AMC) as a polymer matrix. The effects of log P and the concentrations of the cosolvents (acetone, methyl ethyl ketone and n-butyl acetate) and different drug/copolymer ratios as independent variables on the physicochemical parameters (the W₁/O emulsion viscosity, the microsphere production yield, the average particle size, the encapsulation efficiency) and the cumulative in vitro drug release as dependent variables were studied. The optimization was carried out on the basis of the 3³ factorial design study. The optimization process results showed that addition of polar cosolvents proved effective, linear relationships were observed between the independent and the dependent variables. The best conditions were achieved by microspheres prepared by using a low/medium cosolvent log P, cosolvent concentration of 25–50% v/v and a drug/copolymer ratio of 1:16. The microspheres ensured sustained release with Nernst and Baker-Lonsdale release profiles.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.