Abstract
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.
Highlights
The value of microparticulate delivery systems as orally administered controlled-release dosage forms has been evident for years
The addition of a polar cosolvent to CH2Cl2 or replacement of CH2Cl2 may act in two different ways: increasing the polymer precipitation rate and at the same time decreasing the encapsulation efficiency (EE), due to the confluence of the aqueous phases of the multiple emulsion; there can be a sensitive balance between these opposite effects
The trends observed for all the cosolvents used were similar
Summary
The value of microparticulate delivery systems as orally administered controlled-release dosage forms has been evident for years. Appropriate preparation techniques should be designed and complex investigations of the effects of the emphasized physicochemical factors should be performed to overcome the drawbacks of the microparticles. Optimization of the preparation process is advantageous for efficient drug entrapment; the factors may alter the distribution of the microparticle parameters markedly, determining the drug release mechanism. The integrity of the forming microsphere wall is controlled by the rate of migration of the organic solvent to the outer aqueous phase and by the rate of evaporation from this phase. The rate of solvent extraction is limited by the water-solubility of the organic solvent used, while the evaporation rate depends on its boiling point. At the water-organic phase interface, cosolvents with low affinity for the polymer are the first to diffuse out from the W1/O emulsion droplet, depending on their physicochemical properties [1]. Removal of organic solvents during manufacturing is critical, and it is an industrial requirement to test the amount of residual organic solvents
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