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Improving oral bioavailability of metformin hydrochloride using water-in-oil microemulsions and analysis of phase behavior after dilution.
Int J Pharm. 2014 Oct 01; 473(1-2):316-25.IJ

Abstract

Microemulsions show significant promise for enhancing the oral bioavailability of biopharmaceutics classification system (BCS) class II drugs, but how about class III drugs remains unclear. Here we employed metformin hydrochloride (MET) as the model drug and prepared drug-loaded water-in-oil (W/O) microemulsions selecting different hydrophile-lipophile balance (HLB) surfactant systems, using HLB 8 as a cut-off. We examined the phase behaviors of microemulsions after dilution and attempted to correlate these behaviors to drug oral bioavailability. ME-A, including a lower content of surfactants (35%), underwent a transition of W/O emulsion and then became a stable O/W emulsion in a light milky appearance; ME-B, in contrast, introducing a higher content of surfactants (45%), still remained transparent or semitransparent upon dilution. Unexpectedly, ME-A showed significantly higher oral bioavailability, which can be reduced by blocking the lymphatic absorption pathway. Comparatively, the AUC of ME-B is lower, close to MET solution. Both microemulsions behaved similarly in intestinal perfusion test because of the dilution before perfusion, lacking of the important phase transition of W/O emulsion. These findings suggest that W/O microemulsions improve oral bioavailability of BCS class III drug by promoting lymphatic absorption. Analyzing the phase behavior of microemulsions after dilution may help predict the drug oral bioavailability and optimize formulations.

Authors+Show Affiliations

School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China. Electronic address: lsshhy@mail.sysu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25014370

Citation

Li, Yuan, et al. "Improving Oral Bioavailability of Metformin Hydrochloride Using Water-in-oil Microemulsions and Analysis of Phase Behavior After Dilution." International Journal of Pharmaceutics, vol. 473, no. 1-2, 2014, pp. 316-25.
Li Y, Song J, Tian N, et al. Improving oral bioavailability of metformin hydrochloride using water-in-oil microemulsions and analysis of phase behavior after dilution. Int J Pharm. 2014;473(1-2):316-25.
Li, Y., Song, J., Tian, N., Cai, J., Huang, M., Xing, Q., Wang, Y., Wu, C., & Hu, H. (2014). Improving oral bioavailability of metformin hydrochloride using water-in-oil microemulsions and analysis of phase behavior after dilution. International Journal of Pharmaceutics, 473(1-2), 316-25. https://doi.org/10.1016/j.ijpharm.2014.07.011
Li Y, et al. Improving Oral Bioavailability of Metformin Hydrochloride Using Water-in-oil Microemulsions and Analysis of Phase Behavior After Dilution. Int J Pharm. 2014 Oct 1;473(1-2):316-25. PubMed PMID: 25014370.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improving oral bioavailability of metformin hydrochloride using water-in-oil microemulsions and analysis of phase behavior after dilution. AU - Li,Yuan, AU - Song,Jiaqi, AU - Tian,Ning, AU - Cai,Jie, AU - Huang,Meihong, AU - Xing,Qiao, AU - Wang,Yalong, AU - Wu,Chuanbin, AU - Hu,Haiyan, Y1 - 2014/07/08/ PY - 2014/04/02/received PY - 2014/06/26/revised PY - 2014/07/07/accepted PY - 2014/7/12/entrez PY - 2014/7/12/pubmed PY - 2015/5/15/medline KW - Lymphatic transport KW - Metformin hydrochloride KW - Oral bioavailability KW - Phase behaviors KW - W/O microemulsions SP - 316 EP - 25 JF - International journal of pharmaceutics JO - Int J Pharm VL - 473 IS - 1-2 N2 - Microemulsions show significant promise for enhancing the oral bioavailability of biopharmaceutics classification system (BCS) class II drugs, but how about class III drugs remains unclear. Here we employed metformin hydrochloride (MET) as the model drug and prepared drug-loaded water-in-oil (W/O) microemulsions selecting different hydrophile-lipophile balance (HLB) surfactant systems, using HLB 8 as a cut-off. We examined the phase behaviors of microemulsions after dilution and attempted to correlate these behaviors to drug oral bioavailability. ME-A, including a lower content of surfactants (35%), underwent a transition of W/O emulsion and then became a stable O/W emulsion in a light milky appearance; ME-B, in contrast, introducing a higher content of surfactants (45%), still remained transparent or semitransparent upon dilution. Unexpectedly, ME-A showed significantly higher oral bioavailability, which can be reduced by blocking the lymphatic absorption pathway. Comparatively, the AUC of ME-B is lower, close to MET solution. Both microemulsions behaved similarly in intestinal perfusion test because of the dilution before perfusion, lacking of the important phase transition of W/O emulsion. These findings suggest that W/O microemulsions improve oral bioavailability of BCS class III drug by promoting lymphatic absorption. Analyzing the phase behavior of microemulsions after dilution may help predict the drug oral bioavailability and optimize formulations. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/25014370/Improving_oral_bioavailability_of_metformin_hydrochloride_using_water_in_oil_microemulsions_and_analysis_of_phase_behavior_after_dilution_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(14)00501-8 DB - PRIME DP - Unbound Medicine ER -