Nilkumhang, Suchada; (2008) Preparation and evaluation of microparticles to target drugs to different regions of the gastrointestinal tract. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

A novel method based on the emulsification solvent evaporation (ESE) technique has been used to prepare modified release microparticles. The aims of this study were to investigate whether the ESE method was suitable for the production of delayed release (pH sensitive and a combined pH sensitive and microflora responsive) microparticles and extended release (pH independent) microparticles. Further objectives included the characterisation of the microspheres and to identify the key parameters influencing the particle formation process and the distribution of drugs within the systems. The ESE method used was shown to be a universal technique in the preparation of various types of modified release systems from a range of polymers (polymethacrylate (Eudragit L and S), hydroxypropylmethylcellulose phthalate, polyvinyl acetate phthalate, ethylcellulose and polyvinyl acetate) not only for targeting the upper and lower gastrointestinal tract but also for slow release applications. It was evident that the stability of the emulsion system could be used as a tool to screen for microparticle formulation since a stable emulsion provided particles of small size and with a spherical shape whereas an unstable emulsion led to the formation of irregular shaped structures. The physicochemical properties of the drug could also be used to predict the characteristics of the microparticles. Confocal laser scanning microscopy revealed that the pattern of drug distribution within the microparticles was greatly affected by the partition coefficient and the solubility of the drug in the internal phase. Furthermore, it was found that the process parameters had great impact on the properties of the microparticles. The encapsulation efficiency and microparticle size were influenced by the concentration of the emulsifier, while the drug release characteristics were most affected by drug loading. Finally, the knowledge gained from the findings in this thesis can contribute to decision making in formulation design and development of microparticulate systems.

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