title: Design of a novel crosslinked HEC-PAA porous hydrogel composite for dissolution rate and solubility enhancement of efavirenz.
abstract: The purpose of this research was to synthesize, characterize and evaluate a Crosslinked Hydrogel Composite (CHC) as a new carrier for improving the solubility of the anti-HIV drug, efavirenz. The CHC was prepared by physical blending of hydroxyethylcellulose (HEC) with poly(acrylic acid) (PAA) (1:1) in the presence of poly(vinyl alcohol) (PVA) (as a crosslinker) (1:5) under lyophilization. Efavirenz was loaded in situ into the CHC in varying proportions (200-600 mg). The CHC demonstrated impressive rheological properties (dynamic viscosity=6053 mPa; 500 s(-1)) and tensile strength (2.5 mPa) compared with the native polymers (HEC and PAA). The physicochemical and thermal behavior also confirmed that the CHC was compatible with efavirenz. The incorporation of efavirenz in the CHC increased the surface area (4.4489-8.4948 m(2)/g) and pore volume (469.547-776.916Å) of the hydrogel system which was confirmed by SEM imagery and BET surface area measurements. The solubility of efavirenz was significantly enhanced (150 times) in a sustained release manner over 24h as affirmed by the in vitro drug release studies. The hydration medium provided by the CHC network played a pivotal role in improving the efavirenz solubility via increasing hydrogen bonding as proved by the zeta potential measurements (-18.0 to +0.10). The CHC may be a promising alternative as an oral formulation for the delivery of efavirenz with enhanced solubility.
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa; Biomaterials Department, National Research Centre, 33El Bohouth St.(former EL Tahrir St.), Dokki, Giza P.O. 12622, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Mabrouk
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
authors.forename: D R
authors.initials: DR
authors.lastname: Chejara
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa; Department of Pharmaceutics, M.M.U. College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India.
authors.forename: J A S
authors.initials: JA
authors.lastname: Mulla
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
authors.forename: R V
authors.initials: RV
authors.lastname: Badhe
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
authors.forename: Y E
authors.initials: YE
authors.lastname: Choonara
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
authors.forename: L C
authors.initials: LC
authors.lastname: du Toit
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa. Electronic address: viness.pillay@wits.ac.za.
authors.forename: V
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000737:chemistry; D048588:Benzoxazines / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003521:Cyclopropanes; D020100:Hydrogels / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D012212:Rheology / Q000379:methods; D012995:Solubility; D013718:Tensile Strength; D014783:Viscosity
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D001672:Biocompatible Materials; D003521:Cyclopropanes; D020100:Hydrogels; D011108:Polymers; D011142:Polyvinyl Alcohol; D002482:Cellulose; C002283:hydroxyethylcellulose; C098320:efavirenz
keywords: Dissolution rate; Efavirenz; Hydrogel composite; Oral solubility; Physical crosslinking; Rheology