Polymer Synthesis, Characterization and Exploring their Pharmaceutical Applications

Abstract

Background: Polymers represent a class of ubiquitous materials which can provide the possibility for a myriad of applications. The keen interest of pharmaceutical industries in macromolecules for the fabrication of various drug delivery systems promoted synthesis of numerous polymers to use successfully in drug delivery devices & systems [1]. Polysaccharides are well-accepted class of polymers in pharmaceutical applications. Among a large number of varieties, natural polysaccharides are widely explored in research and proven for their effectiveness. The use of natural polymers for pharmaceutical applications is attractive because they are potentially biodegradable and with few exceptions, also biocompatible, capable of chemical modifications, economical, non-toxic, and readily available [2]. Among various natural polysaccharides, chitosan and starch are widely used in many pharmaceutical applications either directly or using their derivatives. Chitosan possesses excellent biodegradable properties and helps in controlling drug release, but its solubility is complex. Starch is having versatile applications however processing is difficult if used alone in drug delivery. Physical blends of starch- chitosan is used in some applications. But blends had not shown promising results in terms of physical properties & drug release. Thus, the present study was focused on synthesis a copolymer using a chemical crosslinking technique. Moreover, chemical crosslinking of starch and chitosan for drug delivery using glyoxal is not reported in research till date. The study was extended by exploring developed copolymer in drug delivery system. Method of Approach: The work was divided into two parts: 1. Synthesis of copolymer Based on the exhaustive literature survey, various methods were adopted to develop copolymers of starch and chitosan. After series of experiments, copolymers were developed by chemical crosslinking of starch and chitosan with glyoxal. Various combinations were prepared and characterized for rapid viscosity analysis (RVA), differential scanning calorimetry (DSC),infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray microanalysis (EDXA). The optimized copolymer was also evaluated with transmission electron microscopy (TEM). 2. Exploring optimized copolymer ratio in drug delivery. The polymer was used as an excipient in model formulation with a model drug, to explore the suitability of the developed copolymer in drug delivery application. From the exhaustive study of synthesized copolymer properties like film forming, solubility, dissolution properties, etc. it was decided to explore its performance for oral drug delivery. The optimized copolymer was utilized for the development of immediate release formulation. Carvedilol was selected as a model drug. It belongs to BCS class II and widely used as an antihypertensive agent. Trials were carried out for the development of tablet formulation. For optimization of the blend of excipients, SeDeM expert system was used. Tablets were evaluated for weight variation test, crushing strength (hardness), friability, wetting time, drug content, disintegration time, in- vitro dissolution studies. The optimized formulation was also evaluated for stability studies as per ICH guidelines. Results: Starch – chitosan copolymers prepared in different compositions, from 0% starch (crosslinked chitosan) to 100% starch (crosslinked starch) at every 10% increment. The crosslinking reaction was carried out between starch and chitosan. Glyoxal was selected as a crosslinking agent. As it is more powerful crosslinker, less toxic and more soluble in water, so easy to remove unreacted glyoxal from the product compared to glutaraldehyde. Developed copolymer was characterized by various parameters. DSC of the copolymer confirms that all raw polymers were completely reacted. Viscosity behavior of the copolymer was found quite different from parent polymers or parent crosslinked polymers. DSC studies confirmed the functional and structural changes in a new copolymer. Measurement of the degree of swelling confirmed the high degree of crosslinking. The same has been confirmed by the solubility study results. Infrared Spectroscopy (FTIR) confirmed crosslinking reaction between amines of the chitosan with hydroxyl groups of starch and chitosan. XRD study of optimized polymer indicated the decrease in the crystallinity compared to parent polymers. SEM and EDXA of all the composition indicated the cluster form of surface morphology of the developed polymer, which is quite different from parent molecules, i.e. starch and chitosan. The physical properties of the copolymer were studied to explore pharmaceutical applications. The copolymers showed a poor swelling property. The developed copolymer found insoluble in water and conventional solvents. However, the flow and compression properties [Bulk (Db) and powder was compressed to tablet, and all the parameters were found within the acceptable limits. The disintegration study shown promising results as these copolymers disintegrate within few seconds. Thus, it was selected for further development of fast disintegrating tablet using carvedilol as a model drug. Based on precompression properties, formulations were also optimized for drug delivery applications using SeDeM expert system. Similarly, these tablets were characterized for all pharmacopoeial parameters. Its performance was compared with commercially available superdisintegrants like Ac-Di-Sol, Sodium starch glycolate, L-HPC etc. The developed copolymer shows comparable disintegration time. The time of disintegration was found in the following order: Ac-Di-Sol, < Developed (starch- chitosan) copolymer < Sodium starch glycolate < L-HPC. The optimized tablet formulation has shown 98.74% drug release in 15 sec and disintegration time was 8 sec. Thus, the study proves that synthesized copolymer has wide application in drug delivery and can be used to improve the solubility of other similar BCS class II drug.