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. 2021 Jan 5;22(1):24.
doi: 10.1208/s12249-020-01882-y.

pH-Independent Dissolution and Enhanced Oral Bioavailability of Aripiprazole-Loaded Solid Self-microemulsifying Drug Delivery System

Sundar Mahajan  1 , Dilpreet Singh  1 , Rashi Sharma  1 , Gurdeep Singh  1 , Neena Bedi  2
Affiliations

pH-Independent Dissolution and Enhanced Oral Bioavailability of Aripiprazole-Loaded Solid Self-microemulsifying Drug Delivery System

Sundar Mahajan et al. AAPS PharmSciTech. .

Abstract

The present study pursued the systematic development of a stable solid self-emulsifying drug delivery system (SMEDDS) of an atypical antipsychotic drug, aripiprazole (APZ), which exhibits poor aqueous solubility and undergoes extensive p-glycoprotein efflux and hepatic metabolism. Liquid SMEDDS excipients were selected on the basis of solubility studies, and the optimum ratio of surfactant/co-surfactant was determined using pseudo-ternary phase diagrams. The prepared formulations were subjected to in vitro characterization studies to facilitate the selection of optimum liquid SMEDD formulation containing 30% Labrafil® M 1944 CS, 46.7% Cremophor® EL and 23.3% PEG 400 which were further subjected to solidification using maltodextrin as a hydrophilic carrier. The optimized solid SMEDDS was extensively evaluated for stability under accelerated conditions, dissolution at various pH and pharmacokinetic profile. Solid-state attributes of the optimized solid SMEDDS indicated a marked reduction in crystallinity of APZ and uniform adsorption of liquid SMEDDS. Stability study of the solid SMEDDS demonstrated that the developed formulation retained its stability during the accelerated storage conditions. Both the optimized liquid and solid SMEDDS exhibited enhanced dissolution rate which was furthermore independent of the pH of the dissolution medium. Oral bioavailability studies in Sprague-Dawley rats confirmed quicker and greater extent of absorption with solid SMEDDS as evident from the significant reduction in Tmax in case of solid SMEDDS (0.83 ± 0.12 h) as compared with commercial tablet (3.33 ± 0.94 h). The results of the present investigation indicated the development of a stable solid SMEDDS formulation of APZ with enhanced dissolution and absorption attributes.

Keywords: SMEDDS; aripiprazole; microemulsion; self-emulsifying drug delivery system; solubility enhancement.

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References

    1. Whiteford HA, Ferrari AJ, Degenhardt L, Feigin V, Vos T. The global burden of mental, neurological and substance use disorders: an analysis from the Global Burden of Disease Study. PLoS One. 2015;10(2):e0116820. - PubMed - PMC
    1. Mossaheb N, Kaufmann RM. Role of aripiprazole in treatment-resistant schizophrenia. Neuropsychiatr Dis Treat. 2012;8:235–44. - PubMed - PMC
    1. Xu Y, Liu X, Lian R, Zheng S, Yin Z, Lu Y, et al. Enhanced dissolution and oral bioavailability of aripiprazole nanosuspensions prepared by nanoprecipitation/homogenization based on acid–base neutralization. Int J Pharm. 2012;438(1–2):287–95. - PubMed
    1. Mihajlovic T, Kachrimanis K, Graovac A, Djuric Z, Ibric S. Improvement of aripiprazole solubility by complexation with (2-hydroxy) propyl-β-cyclodextrin using spray drying technique. AAPS PharmSciTech. 2012;13(2):623–31. - PubMed - PMC
    1. Borbás E, Balogh A, Bocz K, Müller J, Kiserdei É, Vigh T, et al. In vitro dissolution-permeation evaluation of an electrospun cyclodextrin-based formulation of aripiprazole using μFlux™. Int J Pharm. 2015;491(1–2):180–9. - PubMed

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