Biodegradable Polymers: Drug Release Characteristics

Abstract

Four polymers namely: i) maleic acid-butane-1,4-diol polyester (MBP), ii) maleic acid-adipic acid-propane-1,2-diol co-polyester (MAPC), iii) malic acid-adipic acid-butane-1,4-diol co-polyester (MABP) and iv) maleic acid-citric acid-propane-1,2-diol co-polyester (MCPC) from different composition and ratios of their corresponding monomers were synthesized and characterized. Their biodegradation and in-vitro drug release behavior in simulated physiological environments were also investigated. All of these four polymers were synthesized using xylene as the reaction medium in Dean-Stark apparatus. The polycondensation temperature was varied from 130 to 1450C for different polymers. The reaction time was about 5 hours followed by 1 hour post curing and anhydrous FeCl3 (approximately 0.4% of the total weight) was used as catalyst. The synthesized co-polyesters were collected from the reaction vessel by dissolving them in acetone and re-precipitated using water as non-solvent. The purified co-polyesters were characterized by their solubility tests in common organic solvents, molecular weights, IR-spectra, elemental analyses, hydrolytic and soil degradation tests. Probable structures of the co-polyesters were also assigned. Molecular weight determination was carried out by end group analysis and viscosity method. Soil burial tests revealed that, all of these polyesters degraded biologically and normally mixed with soil imparting no natural imbalance. At room temperature, hydrolytic degradation study in solutions of different pH values showed that co-polyesters i), ii) and iii) remained almost intact in solutions of pH 0-3.0, slight degradation was observed in pH range 3.0-6.0 but they gradually degraded in solutions of pH >6.0. Such pH responsive degradation nature of these polyesters led us to investigate their possible application as enteric coating material. Diclofenac sodium and naproxen core (uncoated) tablets were used as model drugs for this purpose. Simulated physiological environments and procedures according to British pharmacopoeia (BP) were followed to monitor the drug release pattern of polymer coated tablets and satisfactory results were obtained. However, hydrolytic degradation study of the co-polyester (iv) reveals that in acid medium the polymer sample swells insignificantly. But in alkaline medium it swells well and the ester linkage is hydrolyzed with respect to time. Because of such time dependent pH responsive nature, this polyester was tried as a drug carrier for extended release drug-polymer matrix tablets and pure dichlofenac sodium was used as the model drug. The drug was incorporated in the polymer matrix by melt granulation process keeping the drug polymer ratio as 1:2. The prepared granules were compressed in a single punch tablet machine to get them in tablet forms. In-vitro drug release from these matrix tablets were studied spectrophotometrically under physiological condition (phosphate buffer of pH 7.4 at 370C). The release pattern has shown a bit higher release in the first hour, then a nearly zero order release for 10-11 hours followed by declining release for the subsequent few hours.