Probing physiological media composition and polymer- plasticizer interactions on dissolution of pH-responsive systems

This study explored the in vitro dissolution of pH-responsive methacrylic acid methylmethacrylate copolymer 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 buffers (Hanks and Krebs) were explored as potential dissolution media as they are more representative of the ionic and buffer composition of small intestinal fluids. In comparison to compendia! phosphate buffers, they were found to provide a better reflection of the in vivo disintegration times of these ileo-colonic tablets as reported in the literature. Jejunal fluids were obtained from human volunteers and Hanks buffer provided a very good reflection of buffer capacity and solubility of 5-ASA in these fluids. The dissolution of acrylic film coatings was found to be influenced by the plasticizer component of the formulation. A small library of plasticizers was screened with the objective of determining parameters that correlate to dissolution of polymer free films. Free film dissolution was measured using two-compartment permeation cells. Dielectric properties of the films were studied by TSDC (thermally stimulated depolarisation currents). Secondary relaxations were deconvoluted and identified. Glass transition temperature (Tg) (indicator of segmental mobility) was measured using TSDC, differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). Plasticizer structure and solubility were identified as determining factors in dissoiution of acrylic free films. Low temperature TSDC spectra showed a relationship of the total secondary relaxation area and relaxation area of the carboxylic acid functional group of the polymer with dissolution time. No correlation was found amongst the glass transition temperatures obtained by TSDC, DSC and DMA with dissolution time of the films. Although the Tg trend was similar for the films, Tg values obtained by TSDC were lower than those observed by DMA and DSC. Immediate release 5-ASA and prednisolone tablets were coated with the different Eudragit SI plasticizer formulations. The formulations with the extreme dissolution profiles gave rise to similar trends for the coated tablets and free films however the formulations with intermediate dissolution onset times displayed different trends in the two states. These differences were reasoned to be due to drug and excipients in the core interacting with the coat. These findings will contribute to a mechanistic approach in formulation development.EThOS - Electronic Theses Online ServiceGBUnited Kingdo