Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.631347
Title: Spray dried drug delivery systems for ileo-colonic targeting
Author: Muttha, Dharmendra Kumar
ISNI:       0000 0004 5355 8884
Awarding Body: Kingston University
Current Institution: Kingston University
Date of Award: 2014
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Abstract:
Purpose: There is interest in targeting the ileo-colonic region of the gastro-intestinal tract either to treat colonic disorders, or take advantage of the low enzymatic activity and relatively high residence time. Four main approaches have been proposed for ileo-colonic delivery; pH triggered, time-dependent and bacterial degradable release systems, and prodrug formation. pH triggered systems are commonly used although there are inherent problems with such systems. Researchers have ascribed failures of disintegration with enteric coated tablets in the colon to the low volume of fluid content and high viscosity in the local environment. The aim of this work is to target the ileo-colonic region with a solid dispersion technique using polyvinylpyrrolidone (PVP) to maximise dissolution, and a methacrylic acid-methacrylate copolymer (Eudragit S/L 100) to trigger release. Methods: Solid dispersions were produced using two model drugs; indomethacin (a poorly-soluble weak acid) and atenolol (a soluble weak base). The optimisation of drug polymer ratio and effect of order of mixing the constituents to the feed solution for spray drying were investigated with indomethacin and subsequently performed with atenolol. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to examine the polymorphic form of the drug in the dispersion. The molecular interactions in the dispersion were studied by using infrared (IR) spectroscopy. Dissolution studies were performed across a range of pH. Results: DSC and XRD confirmed the formation of amorphous solid dispersions when drug (atenolol or indomethacin) was spray dried with the polymers. IR spectra showed peak-shifts indicative of molecular interactions between drug and polymer. Carrier controlled release was achieved with solid dispersions containing 10 % drug loading with 80:20 PVP- Eudragit S/L 100 contents. The alteration in dissolution rate of solid dispersions was ascribed to a mixture of particle size reduction, conversion to the amorphous form of the drug, the polymer characteristics, drug-polymer molecular interactions and particle surface morphological properties. Conclusion: pH-triggered drug release was successfully demonstrated in vitro with solid dispersions. The presence of strong molecular interactions and the high glass transition temperature of the resultant dispersions ensured they remained amorphous at least for six months under accelerated conditions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.631347  DOI: Not available
Keywords: Chemistry ; Pharmacy
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