Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Development and In vitro and In vivo Evaluations of a Microemulsion Formulation for the Oral Delivery of Oxaprozin

Author(s): Fangming Yin, Shu Meng, Xin Zhao, Huining Wang, Yingkai Ning, Yangdulin Li and Zaixing Chen*

Volume 19, Issue 3, 2022

Published on: 05 January, 2022

Page: [347 - 356] Pages: 10

DOI: 10.2174/1567201818666210914092745

Price: $65

Abstract

Background: Oxaprozin is labeled as a Class II drug in the biopharmaceutical classification system, and its poor solubility in the entire gastrointestinal tract may be the main reason for its insufficient oral absorption capacity.

Objective: The purpose of this study was to develop an oxaprozin formulation to enhance its oral absorption.

Methods: Oxaprozin-loaded microemulsions were prepared using the titration method and pseudoternary phase diagram. Characterization experiments were performed on microemulsion preparations, including pH, particle size, shape, zeta potential, and stability (thermodynamic, dilution, and differential scanning calorimetry). Then, the in vitro release of the microemulsion and in vivo pharmacokinetics in rats were evaluated.

Results: Several microemulsion formulations were prepared. The optimal formulation was 15% oleoyl macrogolglycerides, 35% Tween 20/isopropanol (Km=2), and 50% distilled water. Its particle size met the requirements, and it had a spherical shape with a negatively charged surface. This microemulsion-loaded drug was applied to in vitro release and in vivo pharmacokinetic experiments at 7.47 mg/mL. In vitro release of the oxaprozin-loaded microemulsion best fit the firstorder model, while the microemulsion preparation had a certain sustained-release effect. In vivo pharmacokinetic experiments indicated that the microemulsion formulation significantly delayed the peak time of the blood concentration and simultaneously prolonged the half-life of drug elimination.

Conclusion: The obtained data revealed satisfactory results for this novel microemulsion of oxaprozin, which is very meaningful for clinical trials.

Keywords: Oxaprozin, microemulsion, transmission electron microscopy, differential scanning calorimetry, in vitro release, pharmacokinetic parameters.

« Previous Next »
Graphical Abstract

[1]
Li, H.; Pan, T.; Cui, Y.; Li, X.; Gao, J.; Yang, W.; Shen, S. Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique. Int. J. Nanomedicine, 2016, 11, 3777-3788.
[http://dx.doi.org/10.2147/IJN.S105419] [PMID: 27540291]
[2]
Liu, W.; Zhai, Y.; Heng, X.; Che, F.Y.; Chen, W.; Sun, D.; Zhai, G. Oral bioavailability of curcumin: Problems and advancements. J. Drug Target., 2016, 24(8), 694-702.
[http://dx.doi.org/10.3109/1061186X.2016.1157883] [PMID: 26942997]
[3]
Xu, M.; Yu, Q.; Zhao, Q.; Chen, W.; Lin, Y.; Jin, Y. Development and In vitro-In Vivo evaluation of a water-in-oil microemulsion formulation for the oral delivery of troxerutin. Drug Dev. Ind. Pharm., 2016, 42(2), 280-287.
[http://dx.doi.org/10.3109/03639045.2015.1047849] [PMID: 26165244]
[4]
Gupta, S.; Kesarla, R.; Omri, A. Formulation strategies to improve the bioavailability of poorly absorbed drugs with special emphasis on self-emulsifying systems. ISRN Pharm., 2013, 2013, 848043.
[http://dx.doi.org/10.1155/2013/848043] [PMID: 24459591]
[5]
Callender, S.P.; Mathews, J.A.; Kobernyk, K.; Wettig, S.D. Microemulsion utility in pharmaceuticals: Implications for multi- drug delivery. Int. J. Pharm., 2017, 526(1-2), 425-442.
[http://dx.doi.org/10.1016/j.ijpharm.2017.05.005] [PMID: 28495500]
[6]
Maestrelli, F.; Mura, P.; Cirri, M.; Mennini, N.; Ghelardini, C.; Di Cesare, M.L. Development and characterization of fast dissolving tablets of oxaprozin based on hybrid systems of the drug with cyclodextrins and nanoclays. Int. J. Pharm., 2017, 531(2), 640-649.
[http://dx.doi.org/10.1016/j.ijpharm.2017.05.033] [PMID: 28522425]
[7]
Shah, N.; Seth, A.; Balaraman, R.; Sailor, G.; Javia, A.; Gohil, D. Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: Optimization and in-vivo pharmacokinetic study. Drug Dev. Ind. Pharm., 2018, 44(4), 687-696.
[http://dx.doi.org/10.1080/03639045.2017.1408643] [PMID: 29168671]
[8]
Lopes-de-Araújo, J.; Neves, A.R.; Gouveia, V.M.; Moura, C.C.; Nunes, C.; Reis, S. Oxaprozin-loaded lipid nanoparticles towards overcoming nsaids side-effects. Pharm. Res., 2016, 33(2), 301-314.
[http://dx.doi.org/10.1007/s11095-015-1788-x] [PMID: 26350105]
[9]
Mennini, N.; Cirri, M.; Maestrelli, F.; Mura, P. Comparison of liposomal and NLC (nanostructured lipid carrier) formulations for improving the transdermal delivery of oxaprozin: Effect of cyclodextrin complexation. Int. J. Pharm., 2016, 515(1-2), 684-691.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.013] [PMID: 27825863]
[10]
Cao, M.; Ren, L.; Chen, G. Formulation optimization and ex vivo and in vivo evaluation of celecoxib microemulsion-based gel for transdermal delivery. AAPS PharmSciTech, 2017, 18(6), 1960-1971.
[http://dx.doi.org/10.1208/s12249-016-0667-z] [PMID: 27914040]
[11]
Yin, Y.M.; Cui, F.D.; Mu, C.F.; Choi, M.K.; Kim, J.S.; Chung, S.J.; Shim, C.K.; Kim, D.D. Docetaxel microemulsion for enhanced oral bioavailability: preparation and in vitro and in vivo evaluation. J. Control. Release, 2009, 140(2), 86-94.
[http://dx.doi.org/10.1016/j.jconrel.2009.08.015] [PMID: 19709639]
[12]
Chaudhari, K.S.; Akamanchi, K.G. Novel bicephalous heterolipid based self-microemulsifying drug delivery system for solubility and bioavailability enhancement of efavirenz. Int. J. Pharm., 2019, 560, 205-218.
[http://dx.doi.org/10.1016/j.ijpharm.2019.01.065] [PMID: 30742985]
[13]
Huo, T.; Tao, C.; Zhang, M.; Liu, Q.; Lin, B.; Liu, Z.; Zhang, J.; Zhang, M.; Yang, H.; Wu, J.; Sun, X.; Zhang, Q.; Song, H. Preparation and comparison of tacrolimus-loaded solid dispersion and self-microemulsifying drug delivery system by in vitro/in vivo evaluation. Eur. J. Pharm. Sci., 2018, 114, 74-83.
[http://dx.doi.org/10.1016/j.ejps.2017.12.002] [PMID: 29222025]
[14]
Moghimipour, E.; Salimi, A.; Changizi, S. Preparation and microstructural characterization of griseofulvin microemulsions using different experimental methods: saxs and dsc. Adv. Pharm. Bull., 2017, 7(2), 281-289.
[http://dx.doi.org/10.15171/apb.2017.034] [PMID: 28761831]
[15]
Chintalapudi, R.; Murthy, T.E.; Lakshmi, K.R.; Manohar, G.G. Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine. Int. J. Pharm. Investig., 2015, 5(4), 205-213.
[http://dx.doi.org/10.4103/2230-973X.167676] [PMID: 26682191]
[16]
Nemoto, T.; Lee, X.P.; Kumazawa, T.; Hasegawa, C.; Fujishiro, M.; Marumo, A.; Shouji, Y.; Inagaki, K.; Sato, K. High-throughput determination of nonsteroidal anti-inflammatory drugs in human plasma by HILIC-MS/MS. J. Pharm. Biomed. Anal., 2014, 88, 71-80.
[http://dx.doi.org/10.1016/j.jpba.2013.08.023] [PMID: 24036363]
[17]
Sangsen, Y.; Wiwattanawongsa, K.; Likhitwitayawuid, K.; Sritularak, B.; Graidist, P.; Wiwattanapatapee, R. Influence of surfactants in self-microemulsifying formulations on enhancing oral bioavailability of oxyresveratrol: Studies in Caco-2 cells and In Vivo. Int. J. Pharm., 2016, 498(1-2), 294-303.
[http://dx.doi.org/10.1016/j.ijpharm.2015.12.002] [PMID: 26680318]
[18]
Sunazuka, Y.; Ueda, K.; Higashi, K.; Tanaka, Y.; Moribe, K. Combined effects of the drug distribution and mucus diffusion properties of self-microemulsifying drug delivery systems on the oral absorption of fenofibrate. Int. J. Pharm., 2018, 546(1-2), 263-271.
[http://dx.doi.org/10.1016/j.ijpharm.2018.05.031] [PMID: 29763688]
[19]
Ghosh, P.K.; Majithiya, R.J.; Umrethia, M.L.; Murthy, R.S. Design and development of microemulsion drug delivery system of acyclovir for improvement of oral bioavailability. AAPS PharmSciTech, 2006, 7(3), 77.
[http://dx.doi.org/10.1208/pt070377] [PMID: 17025257]
[20]
Cavalcanti, A.L.; Reis, M.Y.; Silva, G.C.; Ramalho, I.M.; Guimarães, G.P.; Silva, J.A.; Saraiva, K.L.; Damasceno, B.P. Microemulsion for topical application of pentoxifylline: in vitro release and In Vivo evaluation. Int. J. Pharm., 2016, 506(1-2), 351-360.
[http://dx.doi.org/10.1016/j.ijpharm.2016.04.065] [PMID: 27130362]
[21]
Kumar, R.; Sinha, V.R. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surf. B Biointerfaces, 2014, 117, 82-88.
[http://dx.doi.org/10.1016/j.colsurfb.2014.02.007] [PMID: 24632034]
[22]
Masiiwa, W.L.; Gadaga, L.L. Intestinal permeability of artesunate-loaded solid lipid nanoparticles using the everted gut method. J. Drug Deliv., 2018, 2018, 3021738.
[http://dx.doi.org/10.1155/2018/3021738] [PMID: 29854465]
[23]
Shinde, U.A.; Modani, S.H.; Singh, K.H. Design and development of repaglinide microemulsion gel for transdermal delivery. AAPS PharmSciTech, 2018, 19(1), 315-325.
[http://dx.doi.org/10.1208/s12249-017-0811-4] [PMID: 28717973]
[24]
Moghimipour, E.; Salimi, A.; Eftekhari, S. Design and characterization of microemulsion systems for naproxen. Adv. Pharm. Bull., 2013, 3(1), 63-71.
[PMID: 24312814]
[25]
Yang, M.; Gu, Y.; Yang, D.; Tang, X.; Liu, J. Development of triptolide-nanoemulsion gels for percutaneous administration: Physicochemical, transport, pharmacokinetic and pharmacodynamic characteristics. J. Nanobiotechnol., 2017, 15(1), 88.
[http://dx.doi.org/10.1186/s12951-017-0323-0] [PMID: 29202753]
[26]
Subongkot, T. Development and mechanistic study of a microemulsion containing vitamin E TPGS for the enhancement of oral absorption of celecoxib. Int. J. Nanomed., 2019, 14, 3087-3102.
[http://dx.doi.org/10.2147/IJN.S201449] [PMID: 31118624]

Rights & Permissions Print Cite
Article Metrics
46
2
© 2024 Bentham Science Publishers | Privacy Policy