| || || Raj, Kushaal Kirtesh|
| || || Development of novel biocompatible blend membranes of .ðCarrageenan/Chitosan for drug delivery applications |
Author:Raj, Kushaal Kirtesh
Institution: University of the South Pacific.
Subject: Chitosan -- Biotechnology, Chitosan -- Therapeutic use
Call No.: Pac TP 248 .65 .C55 R35 2015
Copyright:Under 10% of this thesis may be copied without the authors written permission
Abstract: In this research, kappa()-carrageenan was extracted using different strengths of potassium hydroxide (KOH) from the sea-weed Kappaphycus alvarezii from farms in Fiji. The extracted -carrageenan based on their physicochemical properties was blended with chitosan, another natural marine polysaccharide, and crosslinked with a natural terrestrial product, genipin, to prepare hydrogels that could be used as drug delivery systems. Chapter one provides an overview of the importance and the applications of the biocompatible polymers namely, chitosan and carrageenan. The second chapter deals with the extraction of -carrageenan from the seaweed using various concentrations of the alkali (KOH) solution and precipitating it in alcohol. Infrared spectra of the extracted -carrageenan was similar to the reference material. With an increasing alkali concentration for the extraction, the yield of - carrageenan increased while the sulfate content, determined by gravimetric method, and the viscosity average molar mass decreased. The mechanical property of the - carrageenan gels determined by the texture analyser, showed an improvement for gels extracted with increasing alkali concentration up to 0.3 M. Higher alkali treatment ( > 0.3 M) showed a sharp decline in strength. The melting temperature, determined from differential scanning calorimetry, also showed an increase for gels extracted using up to 0.3 M KOH. The Young’s modulus increased up to 0. 3 M only, making it the most elastic gel of all the alkali extracts. The activation energy of viscous flow was found to decrease for the -carrageenan solutions extracted with increasing alkali concentration and provided evidence for the behaviour of the gels in terms of chain length and its transformation to helical form. The -carrageenan solutions followed the Non-Newtonian fluid behaviour. The third and the fourth chapters deal with hydrogels made by blending - carrageenan extracted using KOH of concentration 0.1 and 0.3 M in different ratios v with chitosan and crosslinking it with genipin. Drug loading technique was done in two ways; matrix method (chapter 3) and the encapsulation method (chapter 4). In chapter three, the membranes for drug release were prepared by blending varying amounts (20, 30 & 40 vol %) of -carrageenan with chitosan and cross-linked with genipin. FTIR analysis showed that -carrageenan did not crosslink with chitosan, thus a semi-interpenetrating network was formed. Swelling and drug release from the membranes were investigated in four different release media (gastric juice, acetate buffer, intestinal fluid and distilled/deionized water) which had a pH of 1.20, 4.50, 6.80, 6.89 respectively. The drug content in the swelling media was measured by UV/Vis spectrophotometer at 291 nm. Swelling and drug release was found to be dependent on the ionic composition, pH of the media and the concentration gradient. Membranes containing -carrageenan treated with 0.3M KOH showed faster release than 0.1 M. In both cases, increasing amounts of -carrageenan showed more and faster release of the drug. In chapter four, the preparation of the membranes was similar to that done in chapter three with the exception that the drug was capsulated within the membrane and the whole sample was used for drug release investigation. This study was carried out in a pharmaceutical lab following the sink conditions and the pharmacopoeial method to study the release kinetics. Four equations; the Zero order, First order, the Higuchi plot and the Korsmeyer Peppas equations were used to explain the release kinetics and mechanism. The release was found to be pH dependent. Highly acidic pH media lead to the erosion of the membrane and hence the immediate release of the drug was achieved within the first 15 and 30 min respectively. In a more neutral pH, release was slow and was due to diffusion. The fifth chapter is the general conclusion reached from this investigation and also provides recommendations for further investigations especially in the use of - carrageenan for the development of membranes for pharmaceutical research.