title: Solubility and dissolution enhancement of efavirenz hot melt extruded amorphous solid dispersions using combination of polymeric blends: A QbD approach.
abstract: Efavirenz is a non-nucleoside reverse transcriptase inhibitor and categorized in to BCS class II drug. The aim of the present investigation was to apply quality by design approach to enhance the solubility, dissolution and stability of amorphous solid dispersions (ASDs) of efavirenz using a combination of Soluplus® and HPMCAS-HF polymers. In design of experiments, the user defined quadratic model was used to study the effect of variable concentrations of Soluplus® and HPMCAS-HF for the formation of ASDs of efavirenz. Similarly, a prototype ASD was made using Soluplus® as a carrier with efavirenz loading of 30%. The efavirenz ASDs granular extrudates were evaluated for saturation solubility as well as dissolution rate studies. X-ray powder diffraction, Differential scanning calorimetry, Fourier transform infrared, Atomic force microscopy and FTIR imaging to determine the solid state of efavirenz in the ASDs. DSC and XRD data confirmed that bulk crystalline efavirenz transformed to the amorphous form during the hot melt extrusion processing. Prototype ASD batch showed instability upon storage as per ICH guidelines over a period of 6months, observations inferred from DSC, XRD and in vitro dissolution studies. The maximum dissolution rate was observed when Soluplus® and HPMCAS-HF was in ratio of (60:20) as optimized by design of experiments study. Moreover, the optimized ASDs batch were stable at 40°C, 75% RH for a period of 6months without any dissolution rate changes, and remained into amorphous state.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, University under Section-3 of UGC Act-1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, N. P. Marg, Matunga, Mumbai 400019, India. Electronic address: jaywantpawar.ict@gmail.com.
authors.forename: Jaywant
authors.initials: J
authors.lastname: Pawar
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, University under Section-3 of UGC Act-1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, N. P. Marg, Matunga, Mumbai 400019, India.
authors.forename: Apurva
authors.initials: A
authors.lastname: Tayade
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, University under Section-3 of UGC Act-1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, N. P. Marg, Matunga, Mumbai 400019, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Gangurde
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, University under Section-3 of UGC Act-1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, N. P. Marg, Matunga, Mumbai 400019, India.
authors.forename: Kailas
authors.initials: K
authors.lastname: Moravkar
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, University under Section-3 of UGC Act-1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, N. P. Marg, Matunga, Mumbai 400019, India.
authors.forename: Purnima
authors.initials: P
authors.lastname: Amin
mesh_terms: D000480:Alkynes; D048588:Benzoxazines / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003521:Cyclopropanes; D004304:Dosage Forms; D065546:Drug Liberation; D006358:Hot Temperature; D018625:Microscopy, Atomic Force; D011108:Polymers / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D004304:Dosage Forms; D011108:Polymers; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz
keywords: Efavirenz; FTIR imaging; HPMCAS-HF; Hot melt extrusion; Solubility; Soluplus®