title: Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies.
abstract: The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and to study the effect of l-arginine (l-Arg) as an auxiliary agent on the complexation efficiency of HP-β-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies. The mechanism of inclusion interaction of guest and host was established through1H NMR, molecular docking, and molecular dynamics studies. On the basis of preliminary screening studies, l-Arg was found to be the most efficient auxiliary agent for the present research problem. The change in crystallinity of ETD was evident from DSC and PXRD studies which indicated the formation of new solid forms. A remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HP-β-CD was observed in the presence of l-Arg in ternary complexes with improvement in solubility and dissolution of ETD than binary complexes. However, inclusion complexes of ETD obtained by computational studies is in good correlation with the results obtained through experimental methods. More stable complex formation with l-Arg was confirmed by molecular simulation studies too. Thus, the present study led to the conclusion that the ternary complex of ETD-HP-β-CD-l-Arg could be an innovative approach to augment the solubility and dissolution behavior of ETD.
authors.affiliation: Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy , Gate No. 1, SVKM Campus, V. M. Road, Vile Parle (W), Mumbai 400 056, India.
authors.forename: Atul P
authors.identifier: 0000-0001-7306-1646
authors.initials: AP
authors.lastname: Sherje
authors.affiliation: Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy , Gate No. 1, SVKM Campus, V. M. Road, Vile Parle (W), Mumbai 400 056, India.
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences , Bangalore 560 064, India.
authors.forename: Manikanta
authors.initials: M
authors.lastname: Murahari
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University , Manipal 576 104, India.
authors.forename: Usha Y
authors.initials: UY
authors.lastname: Nayak
authors.affiliation: Schrodinger , Bengaluru 560 086, Karnataka India.
authors.forename: Pritesh
authors.initials: P
authors.lastname: Bhat
authors.affiliation: Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy , Gate No. 1, SVKM Campus, V. M. Road, Vile Parle (W), Mumbai 400 056, India.
authors.forename: Vasanti
authors.initials: V
authors.lastname: Suvarna
authors.affiliation: Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy , Gate No. 1, SVKM Campus, V. M. Road, Vile Parle (W), Mumbai 400 056, India.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Dravyakar
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001120:Arginine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D017308:Etodolac / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods; D008958:Models, Molecular; D062105:Molecular Docking Simulation / Q000379:methods; D011208:Powders / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D011208:Powders; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017308:Etodolac; D001120:Arginine
keywords: arginine; binary inclusion complex; computational modeling; dissolution improvement; etodolac; solubility enhancement; ternary inclusion complex