Pharmacokinetic evaluation of quetiapine fumarate controlled release hybrid hydrogel: a healthier treatment of schizophrenia

Drug Delivery

Shehla Iftikhar¹  Muhammad Zeeshan Danish²  Nighat Aziz³  Obaid Ullah⁴  Faiza Maryam⁵  Hashmat Ullah⁵  Muhammad Akhlaq⁵  Abid Hussain⁵  Muhammad Ramzan⁵  Muhammad Adeel⁶  Abdelhamid Elaissari⁷ 

[1] Department of Oncology, SEENAR Hospital, Quetta, Pakistan;Department of Pharmaceutics, University College of Pharmacy, University of Punjab, Lahore, Pakistan;Department of Pharmacology, Gomal Medical College, Dera Ismail Khan, Pakistan;Drug Regulatory Authority of Pakistan, Islamabad, Pakistan;Faculty of Pharmacy, Gomal University, Dera Ismail Khan, Pakistan;Institute of Chemical Sciences, Gomal University, Dera Ismail Khan, Pakistan;Univ Lyon, University Claude Bernard Lyon-1, CNRS, Lyon, France;

关键词: Quetiapine fumarate;    cross-linking;    hydrogels;    pH-sensitive;    pharmacokinetics;   

DOI  :  10.1080/10717544.2018.1458922

来源: publisher

【 摘 要 】

The current study aimed to rationally develop and characterize pH-sensitive controlled release hydrogels by graft polymerization of gelatin (Gel) and hydroxypropyl methyl cellulose (HPMC) in the presence of glutaraldehyde (GA) using quetiapine fumarate for the treatment of schizophrenia. The prepared hydrogels discs were subjected to various physicochemical studies including: swelling, diffusion, porosity, sol-gel analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Three different pH values (1.2, 6.8 and 7.4) were used to determine shape, transition, and controlled release behavior of prepared hydrogels. Various kinetic models including zero order, first order, Higuchi model and Power Law equation were applied on drug release data. The optimized hydrogels were subjected to in vivo studies using albino rabbits. Swelling and release results were found to be insignificant (p < .05) evidencing that there was no significant difference in swelling and drug release rate of hydrogels in different pH mediums. Swelling, porosity, gel-fraction, and drug released (%) were found to be dependent on concentrations of Gel, HPMC, and GA. Kinetic models revealed that QTP-F release followed non-Fickian diffusion. In-vivo studies contributed significantly higher plasma QTP-F concentration (Cmax), time for maximum plasma concentration (Tmax), area under the curve (AUC0–inf) and half-life (t1/2) as 18.32 ± 0.50 µg/ml, 8.00 ± 0.01 hrs, 6021.2 ± 5.09 µg.hrs/ml and 10.06 ± 0.43 hrs, respectively, for test-hydrogels when compared to reference market brand (Qusel® 200 mg, Hilton Pharma, Karachi, Pakistan) QTP-F tablets. It might be concluded that QTP-F loaded pH-sensitive hydrogels were developed successfully with reduced dosing frequency for schizophrenia.

【 授权许可】

CC BY