Polyvinylpyrrolidone K-30-Based Crosslinked Fast Swelling Nanogels: An Impeccable Approach for Drug's Solubility Improvement

Abstract

Poor solubility is a global issue of copious pharmaceutical industries as large number of drugs in development stage as well as already marketed products are poorly soluble which results in low dissolution and ultimately dosage increase. Current study is aimed at developing a polyvinylpyrrolidone- (PVP-K30-) based nanogel delivery system for solubility enhancement of poorly soluble drug olanzapine (OLP), as solubilization enhancement is the most noteworthy application of nanosystems. Crosslinking polymerization with subsequent condensation technique was used for the synthesis of nanogels, a highly responsive polymeric networks in drug's solubility. Developed nanogels were characterized by percent entrapment efficiency, sol-gel, percent swelling, percent drug loaded content (%DLC), percent porosity, stability, solubility, in vitro dissolution studies, FTIR, XRD, and SEM analysis. Furthermore, cytotoxicity study was conducted on rabbits to check the biocompatibility of the system. Particle size of nanogels was found with 178.99 ± 15.32 nm, and in vitro dissolution study exhibited that drug release properties were considerably enhanced as compared to the marketed formulation OLANZIA. The solubility studies indicated that solubility of OLP was noticeably improved up to 36.7-fold in phosphate buffer of pH 6.8. In vivo cytotoxicity study indicated that prepared PVP-K30-based formulation was biocompatible. On the basis of results obtained, the developed PVP-K30-co-poly (AMPS) nanogel delivery system is expected to be safe, effective, and cost-effective for solubility improvement of poorly soluble drugs.

Figure 1

Proposed scheme of prepared PVP-K30-based nanogels.

Figure 2

Particle size measurement of prepared PVP-K30-based nanogels.

Figure 3

FTIR spectra of (a) monomer AMPS, (b) PVP-K30, (c) pure OLP, and (d) OLP-loaded formulation (PNG-7).

Figure 4

SEM micrographs of developed PVP-K30-based formulation (PNG-7) at different resolutions.

Figure 5

PXRD analysis of (a) drug olanzapine (pure), (b) blank nanogels, and (c) OLP-loaded nanogels (PNG-7).

Figure 6

(a) Swelling index of developed nanogels (PNG1-PNG7) at phosphate buffer of pH 6.8. (b) Swelling index of developed nanogels (PNG1-PNG7) at HCL buffer of pH 1.2.

Figure 7

Sol-gel analysis of developed nanogel formulations (PNG-1 to PNG-7).

Figure 8

Solubility of OLP in prepared nanogels (PNG-1 to PNG-7) and in DW, HCl, and phosphate solutions of pH 6.8 and 1.2, respectively.

Figure 9

(a) Dissolution profile of prepared PVP-K30-based formulations and RP OLANZIA in phosphate buffer of pH 6.8. (b) Dissolution profile of prepared PVP-K30-based formulations (PNG1-PNG7) and RP OLANZIA in HCl solution (pH 1.2). (c) Mechanism illustrating the drug release from the prepared PVP-K30-based formulations.