de Sousa, Joao Jose Martins Simoes; (1997) The influence of formulation on the formation of and drug release from film coated pellets. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

An attempt has been made to establish relationships between drug solubility, drug level, filler solubility, filler level and film coat level and the formation of and drug release from film coated pellets. The experimental design was based on the study of the different groups of influencing factors. The formulation design was centred on a preparation based on propranolol hydrochloride: lactose; cellulose microcrystalline (2:3:5). The drug and filler were successively replaced by more soluble and insoluble materials. The uncoated pellets were produced by an extrusion/spheronization process. Water at different levels was used as a binding agent to obtain the wet mass. It was found that it behaved as an active excipient due to its influence on pellet performances. The uncoated pellets were analysed for their physical characteristics of median particle size, geometric shape, density, porosity, mechanical strength, specific surface area and surface appearance. The coat system analysed was based on a plasticized ethylcellulose derivative (Surelease E-7-7050) at a 5% level (weight gain). The experimental design comprised a comparison of the same polymer in a higher and lower level, other polymer materials and a study of the plasticization effect. The analysis of the dissolution data was based on the determination of statistical moments, the mean dissolution time (MDT) and its variance (VDT) and their relationship applied in the calculation of the release rate constant. The relative dispersion coefficient (RDC) was used as a discriminatory factor between common mathematical kinetic models (zero-order, first order, square root of time and cube root law). Preparations showing a non-Fickian release were analysed according to the general exponential equation. Simulated release profiles based on the determination of model independent variables were used for the prediction of the release behaviour. The ANOVA and canonical analysis performed allows respectively the qualification and quantification of single and cross effects. Based on these results predictions were drawn relating the uncoated pellet formulation and coat level to the drug release profile.

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