Starch Nanoparticles for the Controlled Release of the Antidiabetic Drug-Tolbutamide

Abstract

In the era of development of novel and more powerful drugs, a major part of attention is being diverted towards method of administration of these pharmaceutically active substances. One of these approaches is the controlled delivery of drug so as to achieve the desirable administration patterns. Recently, nanoparticles are being investigated to ensure site-targeted and efficient delivery of the therapeutic agents. Moreover, efforts are being made towards preparing nanoparticles using natural polymers like PLGA, chitosan, alginates, starch, etc. The aim of the current study, was to prepare nanoparticles for controlled delivery of tolbutamide by nanoprecipitation technique using starch as a polymer and sodium tripolyphosphate as a crosslinking agent. Starch is a natural, biodegradable and inexpensive biopolymer that has the ability to form intra and intermolecular crosslinked structures, on interaction with polyanions, like sodium tripolyphosphate (TPP). Tolbutamide loaded starch-TPP crosslinked nanoparticles were prepared using nanoprecipitation technique in which aqueous alkaline medium and ethanol were used as a solvent and an organic non-solvent respectively. An experimental design was prepared using response surface methodology (RSM), and the given formulations were prepared and evaluated for drug entrapment efficiency and in-vitro drug release behavior. Various characterization studies like were performed using facilities such as FT-IR, SEM, DLS and X-RD for the RSMoptimized formulation in order to study the interaction between tolbutamide and starch-TPP crosslinked nanoparticles. Tolbutamide loaded starch-TPP crosslinked nanoparticle formulation optimized using RSM, containing 5% maize starch, 88.2 mg tolbutamide and 2 g TPP, showed around 85% of in-vitro drug release in a controlled manner and had around 54.97% of drug encapsulation efficiency, poly dispersity index value of about 0.27 and a diameter around 111.2 nm. The resultant amorphous structure, suggested by X-RD graphs of starch crosslinked nanoparticles containing tolbutamide, might result in better dissolution rate which might lead to increased drug efficacy. Moreover, the preparation method that was used, turned out to have extremely low complexity, consumed lesser energy, decreased amount of solvent and did not require any addition of toxic chemicals. Hence, this method can be employed for the preparation of drug loaded starchcrosslinked nanocomposites having desirable properties. Also, RSM turns out to be a promising technique not just in order to prepare an experimental design to minimize the number of experimental runs but also to predict the optimized formulation.