Preparation, characterization, in-vitro and toxicological evaluation of carbopol based nanogels for solubility enhancement of Valsartan

Abstract

Solubility is an essential criterion for attaining desired concentration of the drug within the systemic circulation to ensure intended pharmacological action. The main setback for the formulation development of new chemical entities and generic drugs is their lower aqueous solubility. Therefore, a drug carrier system is needed which not only enhances the solubility of low aqueous soluble drugs but also maintains a constant pharmacological action of drugs within predetermined intervals of time. For this purpose, authors prepared carbopol 934-co-poly(itaconic acid) (CPcPIA) nanogels by the free radical polymerization technique for the solubility enhancement of Valsartan. The polymeric nanogels were characterized and studied for further evaluation. FTIR studies indicated no interactions between the drug and nanogel contents. SEM showed a porous and sponged structure of particles without any agglomeration. Similarly, higher thermal stability was detected for the fabricated nanogel compared to its constituents, while reduction in crystallinity of the drug and excipients was shown by XRD analysis, indicating the amorphous nature of the polymeric nanogels. Average particle size and zeta potential of prepared nanogels were found 290.32 nm and –8.32 mV, respectively. Furthermore, various studies such as sol-gel fraction, dynamic swelling, drug loading, in-vitro drug release studies, solubility, and toxicity study were conducted for the developed nanogels. A significant increase in the solubility of Valsartan (2.002, 2.976, and 3.543 mg/mL) was observed by polymeric nanogels in pH 1.2, deionized distilled water, and pH 7.4 as compared to reference product. Toxicity study indicated no toxic effect of prepared nanogels on rabbit's species. Thus, it can be demonstrated from the results that synthesized nanogels are not only limited to a specific class of drug but the solubility of all low aqueous soluble drugs can be enhanced by the prepared networks of nanogels.