β-cyclodextrin modification by cross-linking polymerization as highly porous nanomatrices for olanzapine solubility improvement; synthesis, characterization and bio-compatibility evaluation

Abstract Herein, we report highly porous and amorphous nanomatrices developed by cross-linking polymerization with subsequent condensation technique for solubility, dissolution and ultimately bioavailability enhancement of poorly soluble drug olanzapine (OLN). β-cyclodextrin was chemically cross-linked with monomer 2-acrylamido 2-methylpropane sulfonic acid (AMPS) by using methylene bis acrylamide (MBA) as cross-linking agent. Developed nanomatrices were characterized by zetasizer, FTIR, XRD, SEM, DSC, swelling, sol-gel, drug loading, stability, porosity (%), solubility, and in-vitro dissolution analysis. The developed porous nanomatrices are intended for oral administration of poorly soluble drugs therefore, to determine the biocompatibility of the system to the biological environment, in-vivo cytotoxicity study was also conducted using rabbit model which endorsed the safety of the nanomatrices with biological system. The particle size of nanomatrices were found 152.30 ± 07.46 d.nm. XRD analysis depicted the highly amorphous nature of nanomatrices while. To evaluate the pharmacokinetic profile of olanzapine, in-vivo studies were also conducted. The in-vivo and dissolution experiments revealed that drug release characteristics were significantly improved by nanomatrices as compared with the reference product (OLANZIA®). The solubility of olanzapine by the developed nanomatrices was enhanced noticeably up to 40.11 times which is higher than previously reported β-cyclodextrin formulations. The efficient method of preparation, improved solubility, rapid and high dissolution and non-toxic βCD-co-poly (AMPS) nanomatrices may be a promising approach for oral delivery of poorly soluble drugs.