Research Article Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid Dispersion of Darunavir Saleha Rehman, 1 Bushra Nabi, 1 Mohammad Fazil, 1 Saba Khan, 1 Naimat Kalim Bari, 2 Romi Singh, 3 Shavej Ahmad, 3 Varinder Kumar, 3 Sanjula Baboota, 1 and Javed Ali 1 1 Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi 110062, India 2 Institute of Nanoscience and Technology, Phase X, Mohali, Chandigarh, Punjab, India 3 Research and Development Centre, Sun Pharmaceuticals Industries Ltd., Gurgaon, Haryana, India Correspondence should be addressed to Javed Ali; javedaali@yahoo.com Received 7 July 2017; Revised 15 September 2017; Accepted 2 October 2017; Published 31 October 2017 Academic Editor: Kamla Pathak Copyright © 2017 Saleha Rehman et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Te aim of the present study was to improve bioavailability of an important antiretroviral drug, Darunavir (DRV), which has low water solubility and poor intestinal absorption through solid dispersion (SD) approach incorporating polymer with P- glycoprotein inhibitory potential. Methods. A statistical approach where design of experiment (DoE) was used to prepare SD of DRV with incorporation of P-glycoprotein inhibitors. Using DoE, diferent methods of preparation, like melt, solvent evaporation, and spray drying method, utilizing carriers like Kolliphor TPGS and Soluplus were evaluated. Te optimized SD was characterized by DSC, FTIR, XRD, and SEM and further evaluated for enhancement in absorption using everted gut sac model, efect of food on absorption of DRV, and in vivo prospect. Results and Discussion. DSC, FTIR, XRD, and SEM confrmed the amorphicity of drug in SD. Oral bioavailability studies revealed better absorption of DRV when given with food. Absorption studies and in vivo study fndings demonstrated great potential of Kolliphor TPGS as P-glycoprotein inhibitor for increasing intestinal absorption and thus bioavailability of DRV. Conclusion. It is concluded that SD of DRV with the incorporation of Kolliphor TPGS was potential and promising approach in increasing bioavailability of DRV as well as minimizing its extrusion via P-glycoprotein efux transporters. 1. Introduction Acquired Immunodefciency Syndrome (AIDS) has been one of the most devastating pandemic diseases over the last few decades caused by its etiologic agent Human Immunodef- ciency Virus (HIV). Latest reports reveal that globally 40 million people are infected with HIV including 2.1 million from India in 2013 [1]. HIV is responsible for killing helper T-lymphocytes (CD4 + T-cells) which play a key role in the process of gaining immunity to specifc pathogens, including HIV itself. No complete cure is possible for people with AIDS and life-long treatment with a combination of antiretroviral drugs; that is, Highly Active Antiretroviral Terapy (HAART) is the only therapeutic intervention with proven efcacy against HIV infection [2, 3]. HIV protease inhibitors (PIs) currently are the key com- ponents of frst-line therapy in both treatment-resistant and treatment-experienced patients. Te introduction of novel second-generation PIs such as Darunavir Ethanolate (DRV) with activity against wild type HIV-1 virus and multidrug resistant strains requires at least four concomitant mutations in the viral genome for resistance development, thus provid- ing clinicians with superior drugs to counter the development of resistance [4]. DRV is coadministered with food and low dose Ritonavir (RTV), a potent CYP3A4 inhibitor as a phar- macokinetic booster to result in clinically relevant increase in the systemic exposure (bioavailability increase by up to 40%) of DRV [5, 6]. However, DRV sufer from disadvantages such as low solubility in water (0.15 mg/ml) and poor intestinal uptake due to drug efux through active efux transporter P- glycoprotein (P-gp) and by drug metabolism via Cytochrome P450 (CYP) 3A [7, 8]. Te current clinical antiretroviral therapies have subop- timal therapeutic efect attributed to poor bioavailability of anti-HIV drugs which is due to either their poor solubility, extreme frst pass metabolism, extrusion into intestine lumen Hindawi BioMed Research International Volume 2017, Article ID 8274927, 17 pages https://doi.org/10.1155/2017/8274927