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Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin.
Int J Pharm. 2014 Dec 30; 477(1-2):159-66.IJ

Abstract

The therapeutic efficacy of repaglinide (RPG) is limited by the low and variable oral bioavailability owing to its limited aqueous solubility. In our present study, the development and evaluation of inclusion complex applying hydroxypropyl-β-cyclodextrin (HP-β-CD) for the improvement of oral bioavailability of repaglinide was investigated systematically. The inclusion complex of repaglinide was prepared by lyophilization technique using drug: hydroxypropyl-β-cyclodextrin (1:15 mole). The prepared complexation was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), NMR spectroscopy and evaluated by dissolution studies. The (1)H NMR was used in the structure study of repaglinide-HP-β-CD (RPG-HP-β-CD) inclusion complex. The analysis proved the higher probability of the repaglinide A-ring into the narrow rim of the β-cyclodextrin molecule. All the characterization information confirmed the formation of RPG-HP-β-CD inclusion complex. The in vivo pharmacokinetics of RPG-HP-β-CD and their physical mixture were performed in beagle dogs. For the first time, a simple, rapid, and sensitive LC-MS/MS method for determination of RPG in beagle dog plasma was developed. The Cmax and AUC0-t of RPG-HP-β-CD were 2.5 and 2 times higher than that of the physical mixture. These results suggested that the interaction of repaglinide with HP-β-CD could notably improve the dissolution rate and bioavailability of repaglinide comparing with its physical mixture.

Authors+Show Affiliations

Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China. Electronic address: hezhonggui@vip.163.com.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

25455768

Citation

Liu, Meina, et al. "Preparation, Characterization and in Vivo Evaluation of Formulation of Repaglinide With Hydroxypropyl-β-cyclodextrin." International Journal of Pharmaceutics, vol. 477, no. 1-2, 2014, pp. 159-66.
Liu M, Cao W, Sun Y, et al. Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin. Int J Pharm. 2014;477(1-2):159-66.
Liu, M., Cao, W., Sun, Y., & He, Z. (2014). Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin. International Journal of Pharmaceutics, 477(1-2), 159-66. https://doi.org/10.1016/j.ijpharm.2014.10.038
Liu M, et al. Preparation, Characterization and in Vivo Evaluation of Formulation of Repaglinide With Hydroxypropyl-β-cyclodextrin. Int J Pharm. 2014 Dec 30;477(1-2):159-66. PubMed PMID: 25455768.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin. AU - Liu,Meina, AU - Cao,Wen, AU - Sun,Yinghua, AU - He,Zhonggui, Y1 - 2014/10/16/ PY - 2014/07/20/received PY - 2014/09/16/revised PY - 2014/10/12/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2016/3/22/medline KW - Hydroxypropyl- KW - Inclusion complex KW - NMR spectroscopy KW - Pharmacokinetics KW - Phase solubility studies KW - Repaglinide KW - β-cyclodextrin SP - 159 EP - 66 JF - International journal of pharmaceutics JO - Int J Pharm VL - 477 IS - 1-2 N2 - The therapeutic efficacy of repaglinide (RPG) is limited by the low and variable oral bioavailability owing to its limited aqueous solubility. In our present study, the development and evaluation of inclusion complex applying hydroxypropyl-β-cyclodextrin (HP-β-CD) for the improvement of oral bioavailability of repaglinide was investigated systematically. The inclusion complex of repaglinide was prepared by lyophilization technique using drug: hydroxypropyl-β-cyclodextrin (1:15 mole). The prepared complexation was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), NMR spectroscopy and evaluated by dissolution studies. The (1)H NMR was used in the structure study of repaglinide-HP-β-CD (RPG-HP-β-CD) inclusion complex. The analysis proved the higher probability of the repaglinide A-ring into the narrow rim of the β-cyclodextrin molecule. All the characterization information confirmed the formation of RPG-HP-β-CD inclusion complex. The in vivo pharmacokinetics of RPG-HP-β-CD and their physical mixture were performed in beagle dogs. For the first time, a simple, rapid, and sensitive LC-MS/MS method for determination of RPG in beagle dog plasma was developed. The Cmax and AUC0-t of RPG-HP-β-CD were 2.5 and 2 times higher than that of the physical mixture. These results suggested that the interaction of repaglinide with HP-β-CD could notably improve the dissolution rate and bioavailability of repaglinide comparing with its physical mixture. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/25455768/Preparation_characterization_and_in_vivo_evaluation_of_formulation_of_repaglinide_with_hydroxypropyl_β_cyclodextrin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(14)00761-3 DB - PRIME DP - Unbound Medicine ER -