Self-emulsifying drug delivery system for enhanced solubility of asenapine maleate: design, characterization, in vitro, ex vivo and in vivo appraisal.

Autor: Avasarala H; a Department of Pharmaceutical Technology , AU College of Pharmaceutical Sciences, Andhra University , Visakhapatnam , India.; b Aditya Pharmacy College , Surampalem , India., Dinakaran SK; b Aditya Pharmacy College , Surampalem , India., Kakaraparthy R; c Department of Pharmacology , Aditya College of Pharmacy , Surampalem , India., Jayanti VR; a Department of Pharmaceutical Technology , AU College of Pharmaceutical Sciences, Andhra University , Visakhapatnam , India.
Jazyk: angličtina
Zdroj: Drug development and industrial pharmacy [Drug Dev Ind Pharm] 2019 Apr; Vol. 45 (4), pp. 548-559. Date of Electronic Publication: 2019 Feb 03.
DOI: 10.1080/03639045.2019.1567758
Abstrakt: Self-emulsifying drug delivery systems (SES) were developed to improve oral bioavailability of asenapine maleate (ASM), an antipsychotic drug with challenging amphiphobic nature and extensive pre-systemic metabolism. ASM-SES was prepared by choosing the proportion of oil, surfactant, co-surfactant from constructed phase diagram. The in vitro and ex vivo evaluation was done. In vivo evaluation was done through pharmacokinetic and pharmacodynamic studies. Role of lymphatic absorption was studied by lymphatic absorption inhibition study. A formulation consisting of 9.9%, 59.4%, 29.7% and 1% of oil, surfactant, co-surfactant, and drug respectively was considered as optimized formulation. After various evaluation test, the globule size and zeta potential for optimized formulation (SES 4 ) were found to be 137.9 nm and -28.8 mV respectively. A maximum of 99.64 ± 0.16% of ASM was released from SES 4 in 60 minutes of time. The flux (ex vivo study) increased by 2.33 folds, which prove the enhanced release and permeation of ASM when loaded into SES. The animals administered with SES 4 showed higher activity and good pharmacodynamic response than the control and ASM-Suspension, which may be due to the greater availability of the drug. The maximum pharmacodynamic response was observed at the t max determined by Pharmacokinetic studies. The bioavailability increased by 1.64 folds with 16.55 ± 3.11% as extend of lymphatic absorption (r = 0.9732). Good in vitro in vivo correlation was observed. ASM-SES is a novel approach to effectively deliver ASM and improve the oral bioavailability.
Databáze: MEDLINE
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