International Journal of Nanomedicine (Jan 2020)
Electrosprayed Polymeric Nanospheres for Enhanced Solubility, Dissolution Rate, Oral Bioavailability and Antihyperlipidemic Activity of Bezafibrate
Abstract
Ru Sun, 1 Chengwu Shen, 1 Shumaila Shafique, 2 Omer Mustapha, 2 Talib Hussain, 3 Ikram Ullah Khan, 4 Yasir Mehmood, 4 Khaleeq Anwer, 5 Yasser Shahzad, 3 Abid Mehmood Yousaf 3 1Department of Pharmacy, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250000, People’s Republic of China; 2Faculty of Pharmaceutical Sciences, Dow College of Pharmacy, Dow University of Health Sciences, Karachi 74200, Pakistan; 3Department of Pharmacy, COMSATS University Islamabad, Lahore 54000, Pakistan; 4Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan; 5Office of Chief Executive Officer, District Health Authority, Pakpattan 57400, PakistanCorrespondence: Abid Mehmood Yousaf; Talib HussainDepartment of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54000, PakistanTel +92-300-4774147; +92-345-7220536Email [email protected]; [email protected]: Bezafibrate is a BCS class II drug as it presents very low solubility in water; therefore, its bioavailability after oral administration is very poor. The aim of this work was to enhance solubility and dissolution rate of bezafibrate in water in order to enhance its oral bioavailability.Methods: Several formulations were prepared using PVP K30 and Cremophor ELP employing the solvent-evaporation method and the electrospraying technique. Solubility, release rate, bioavailability in male Sprague Dawley rats, and lipid profile attributes in Wistar rats were assessed in comparison with bezafibrate plain powder. Solid-state characterization was carried out using X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM).Results: All the formulations exerted positive effect towards the desired goal. In particular, the optimized formulation furnished about 14-fold enhanced solubility and 85.48 ± 10.16% drug was released in 10 min as compared with bezafibrate alone (4.06 ± 2.59%). The drug existed in the amorphous state in the prepared sample as confirmed by XRD and DSC, whilst no drug-excipient interactions were observed through FTIR analysis. Moreover, SEM revealed smooth-surfaced spherical particles of the optimized formulation. A 5.5-fold higher oral bioavailability was achieved with the optimized formulation in comparison with bezafibrate plain powder. Also, TG, LDL and TC were decreased, and HDL was increased considerably in HFD-treated rats.Conclusion: The optimized formulation consisting of bezafibrate, PVP K30 and cremophor ELP (1/12/1.5, w/w/w) might be a capable drug delivery system for orally administering poorly water-soluble bezafibrate with improved bioavailability and antihyperlipidemic effects.Keywords: aqueous solubility, bezafibrate, electrospraying, lipid profile, oral bioavailability, solid dispersion
