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Title: Synthesis and Characterization of Some Novel N-Vinyl Pyrrolidone Based Copolymers for Controlled Drug Delivery
Authors: Huma, Farhat
Keywords: Natural Sciences
Chemistry & allied sciences
Physical chemistry
Techniques, equipment & materials
Analytical chemistry
Inorganic chemistry
Organic Chemistry
Issue Date: 2013
Publisher: Quaid-i-Azam University Islamabad, Pakistan
Abstract: Six series of N-vinyl pyrrolidone based copolymers were synthesized by free radical solution polymerization of N-vinyl pyrrolidone and n-alkyl methacrylate monomers. The n-butyl methacrylate and n-hexyl methacrylate were selected as the hydrophobic counterpart. In the first part of the study properties of uncrosslinked poly(N-vinyl pyrrolidone-co-n-alkyl methacrylate) copolymers were modified by varying the weight % ratio of the two monomers. Elemental analyses, FTIR, 1H and 13C NMR spectroscopic analyses techniques were used for structure elucidation of the copolymers. Thermal stabilities and glass transition temperatures of the copolymers were directly related to the amount of n-alkyl methacrylate as well as the alkyl chain length of methacrylate comonomer. The water uptake characteristics of the copolymers were related to the amount of hydrophilic NVP incorporated into these copolymers. The hydrophobic drug dexamethasone was loaded into the copolymers with optimum water uptake and prolonged aqueous stability. The drug release studies were carried out at physiological temperature 37 °C and pH 7.4 for 35 days. Controlled drug release was observed from the selected copolymer films during the study time period. The cumulative drug release was found to be mainly controlled by the amount of hydrophilic monomer and molecular weight of the copolymers. In the second part of present study crosslinked poly(N-vinyl pyrrolidone-co-n-alkyl methacrylate) copolymers were synthesized at fixed weight % ratio of N-vinyl pyrrolidone and n-alkyl methacrylate monomers (i.e NVP : nAMA = 90:10) using various concentrations of polyfunctional monomers employed as crosslinking agents. The effect of crosslinker concentration and functionality on gel content, thermal stability, water uptake, internal morphology and drug release was investigated. Gel contents and thermal stability of the crosslinked copolymers increased with increasing crosslinker concentration as well as its functionality. The water uptake at 37 °C decreased with increasing crosslinker concentration and functionality however the increase in alkyl chain length of alkyl methacrylate resulted in increased water uptake. The crosslinked copolymers with optimized crosslinker concentrations exhibited controlled drug release patterns at 37 °C and pH 7.4. Higher amounts of cumulative drug release were observed for copolymers crosslinked with trifunctional crosslinkers leading to complete drug release in 20-22 days while the copolymers crosslinked with difunctional crosslinker exhibited controlled drug release upto 35 days. The kinetics and mechanism of the drug release was also analyzed.
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