Original Article PROTOTYPE SELF EMULSIFYING SYSTEM OF ETRAVIRINE: DESIGN, FORMULATION AND IN VITRO EVALUATION G. B. PREETHI 1* , H. N. SHIVAKUMAR 2 , M. RAVI KUMAR 4 , N. SWETA 4 1,2,4 Department of Pharmaceutics, KLEU College of Pharmacy, Bengaluru, 3 Geethanjali College of Pharmacy, Cheeryal (V), Keesara (M), RR District, Telangana Email: preethigb.mmm@gmail.com Received: 21 Sep 2017, Revised and Accepted: 09 Jan 2018 ABSTRACT Objective: Lipid-based formulations have gained much attention, particularly on self-emulsifying drug delivery systems (SEDDS), to improve the oral bioavailability of lipophilic drugs. In the present study, an attempt was made to develop and evaluate prototype SEDDS of poorly soluble antiviral BCS class IV drug etravirine. Methods: Various oils, surfactants and co-surfactants were screened for their suitability in the formulation of SEDDS. Based on the screening, gelucire 44/14, as the oil, labrasol as a surfactant and transcutol HP as the co-surfactant were selected. SEDDS with drug etravirine was formulated and evaluated for emulsifying ability, dilution potential and microscopic properties. The emulsion area for each of the combination of oil and surfactant co-surfactant mixture (Smix) was determined by the construction of pseudo-ternary phase diagrams. Results: The optimized formulation with oil (gelucire 44/14) and Smix (labrasol: transcutol HP, 6:1) in a ratio of 2:8 exhibited a rapid emulsification rate and a good polydispersibility index of 0.103±0.012 indicating uniformity of the formed droplets. The size of the droplets was determined by zetasizer and was found to be in 200 nm range. The drug release from the final formulation after 2hr was found to be 41.15%±0.5 compared to 19.3%±3.8 of pure drug indicating enhanced dissolution profile of the drug. Conclusion: In vitro study illustrated enhanced dissolution rate of formulated prototype SEDDS of BCS class IV drug etravirine for oral delivery. Keywords: Etravirine, SEDDS, Gelucire 44/1, BCS class IV, Labrasol, Transcutol © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijap.2018v10i2.22714 INTRODUCTION Though management of HIV infection has been done successfully with antiviral drug therapy it is coupled with several limitations and inconveniences. The reason being most of the anti-retroviral drugs display poor oral bioavailability and a short half-life owing to poor aqueous solubility, extensive first-pass effect and gastrointestinal degradation. This invariably results in localized HIV in the certain inaccessible region of the body such as the CNS, the lymphatic system and macrophages [1, 2]. FDA has approved etravirine a second generation Non-nucleoside reverse transcriptase inhibitors (NNRTI) for the treatment of HIV-1 infection as it displays sustained virologic efficacy in a patient with NNRTI resistant HIV-1 infection. The drug undergoes extensive first- pass metabolism as it is metabolized by hepatic cytochrome P450 (CYP) 3A4 and other members of the CYP2C family. Etravirine is categorized under BCS class IV drug by virtue of its low aqueous solubility and permeability. It is highly lipophilic drug with log P value greater than 5 as it is nearly insoluble in water over a wide range of physiological pH [3-7]. BCS class IV drugs are challenging molecule in product development as they exhibit low solubility and low permeability. However, formulation approaches similar to those for BCS class II drugs could be practically applied to BCS class IV drugs. Various approaches to overcome the poor aqueous solubility of drug candidates have been investigated and reported in the literature. In recent years, Lipid- based formulations have been utilized to enhance the oral bioavailability of BCS class IV drugs and Self emulsifying drug delivery systems (SEDDS) is one among them [8-12]. SEDDS are an isotropic mixture of oils, surfactants and co- surfactants, which forms fine o/w emulsion upon dilution with the aqueous gastrointestinal medium on gentle agitation [13-16]. For lipophilic drug compounds exhibiting dissolution rate limited absorption, these systems offer an advantage to deliver lipophilic drugs to the systemic circulation, by avoiding the dissolution step (25). SEDDS improve the mucus permeation, rate and extent of absorption by facilitated intestinal lymphatic transport of drugs, as they are known to protect against enzymatic hydrolysis and inhibit P-gp efflux [17-19]. Some of the commercially successful antiviral SEDDS formulations are norvir (ritonavir) and Fortovase (saquinavir) generates (amprenavir), sustivas (efavirenz), and kaletras (lopinavir and ritonavir) [8]. Based on extensive review of literature it is understood that there is not much work done on SEDDS of etravirine. Thus the current study was aimed to develop prototype SEDDS of etravirine and evaluate the emulsifying ability, microscopic property, stability and it's in vitro dissolution. MATERIALS AND METHODS Material Etravirine was obtained as a generous gift sample from Apotex Pharmachem INC (Bengaluru, India). Labrafil 2125 CS, peceol, gelucire 44/14, labrafac, lipophile WL 1349, lauroglycol-90, maisine- 35, labrasol and transcutol-HP are gift samples obtained from Gattefosse India (Mumbai, India). Captex 300 and captex 355 are gifted samples from Abitec Corporation (India). Tween 20, tween 60, span 20, span 80, PEG 200, PEG 400 were purchased from SD fine chemicals (Mumbai, India). Tri-Ester F-810 generous gift from India commercial company Private Ltd. Capmul MCM C8 L2p and captex 200 P are gifted samples from IMCD India private limited (Mumbai, India). All other chemicals and reagents were of analytical grade and procured from Merck (Mumbai, India) and SD Fine Chem. (Mumbai, India). Determination of solubility of etravirine in various vehicles The solubility of etravirine was determined in various oils, surfactants and co-surfactants by adding an excess amount of Etravirine in 1 ml of a pure vehicle taken in glass tubes and the mixture was heated at 60 °C in a water bath and vortexed intermittently to facilitate the solubilization. The drug suspension was equilibrated at 25 °C in a thermostatically controlled bath for 48 International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 10, Issue 2, 2018