Fadda, Hala Muhammad; (2007) Probing physiological media composition and polymer- plasticizer interactions on dissolution of pH-responsive systems. Doctoral thesis (Ph.D), University of London.

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Abstract

This study explored the in vitro dissolution of pH-responsive methacrylic acid methylmethacrylate polymer coated dosage forms, in particular Eudragit S coated 5-aminosalicylic acid (5-ASA) tablets for ileo-colonic delivery. Ionic parameters that influence the in vitro dissolution were identified as ionic strength, pKa of the buffer and its concentration. Physiological bicarbonate offers (Hanks and Krebs) were explored as potential dissolution media as they are more presentative of the ionic and buffer composition of small intestinal fluids. In comparison to impendial phosphate buffers, they were found to provide a better reflection of the in vivo integration times of these ileo-colonic tablets as reported in the literature. Jejunal fluids were ned from human volunteers and Hanks buffer provided a very good reflection of buffer ipacity and solubility of 5-ASA in these fluids. le dissolution of acrylic film coatings was found to be influenced by the plasticizer component of e formulation. A small library of plasticizers was screened with the objective of determining rameters that correlate to dissolution of polymer free films. Free film dissolution was measured ing two-compartment permeation cells. Dielectric properties of the films were studied by TSDC lermally stimulated depolarisation currents). Secondary relaxations were deconvoluted and jentified. Glass transition temperature (Tg) (indicator of segmental mobility) was measured using SDC, differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). asticizer structure and solubility were identified as determining factors in dissolution of acrylic e films. Low temperature TSDC spectra showed a relationship of the total secondary relaxation ea and relaxation area of the carboxylic acid functional group of the polymer with dissolution ne. No correlation was found amongst the glass transition temperatures obtained by TSDC, DSC id DMA with dissolution time of the films. Although the Tg trend was similar for the films, Tg dues obtained by TSDC were lower than those observed by DMA and DSC. imediate release 5-ASA and prednisolone tablets were coated with the different Eudragit S/asticizer formulations. The formulations with the extreme dissolution profiles gave rise to similar snds for the coated tablets and free films however the formulations with intermediate dissolution iset times displayed different trends in the two states. These differences were reasoned to be due drug and excipients in the core interacting with the coat. These findings will contribute to a mechanistic approach in formulation development.

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