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Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies.
Mol Pharm. 2017 04 03; 14(4):1231-1242.MP

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 through 1H 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+Show Affiliations

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.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.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences , Bangalore 560 064, India.Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University , Manipal 576 104, India.Schrodinger , Bengaluru 560 086, Karnataka India.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28248111

Citation

Sherje, Atul P., et al. "Inclusion Complexation of Etodolac With Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies." Molecular Pharmaceutics, vol. 14, no. 4, 2017, pp. 1231-1242.
Sherje AP, Kulkarni V, Murahari M, et al. Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies. Mol Pharm. 2017;14(4):1231-1242.
Sherje, A. P., Kulkarni, V., Murahari, M., Nayak, U. Y., Bhat, P., Suvarna, V., & Dravyakar, B. (2017). Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies. Molecular Pharmaceutics, 14(4), 1231-1242. https://doi.org/10.1021/acs.molpharmaceut.6b01115
Sherje AP, et al. Inclusion Complexation of Etodolac With Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies. Mol Pharm. 2017 04 3;14(4):1231-1242. PubMed PMID: 28248111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies. AU - Sherje,Atul P, AU - Kulkarni,Vaidehi, AU - Murahari,Manikanta, AU - Nayak,Usha Y, AU - Bhat,Pritesh, AU - Suvarna,Vasanti, AU - Dravyakar,Bhushan, Y1 - 2017/03/01/ PY - 2017/3/2/pubmed PY - 2017/10/27/medline PY - 2017/3/2/entrez KW - arginine KW - binary inclusion complex KW - computational modeling KW - dissolution improvement KW - etodolac KW - solubility enhancement KW - ternary inclusion complex SP - 1231 EP - 1242 JF - Molecular pharmaceutics JO - Mol. Pharm. VL - 14 IS - 4 N2 - 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 through 1H 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. SN - 1543-8392 UR - https://www.unboundmedicine.com/medline/citation/28248111/Inclusion_Complexation_of_Etodolac_with_Hydroxypropyl_beta_cyclodextrin_and_Auxiliary_Agents:_Formulation_Characterization_and_Molecular_Modeling_Studies_ L2 - https://dx.doi.org/10.1021/acs.molpharmaceut.6b01115 DB - PRIME DP - Unbound Medicine ER -