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Current Drug Delivery

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

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Research Article

Enhancing Oral Bioavailability of Domperidone Maleate: Formulation, In vitro Permeability Evaluation In-caco-2 Cell Monolayers and In situ Rat Intestinal Permeability Studies

Author(s): Neslihan Üstündağ Okur*, Emre Şefik Çağlar, Mustafa Sinan Kaynak*, Mine Diril, Saniye Özcan and Hatice Yeşim Karasulu

Volume 21, Issue 7, 2024

Published on: 04 September, 2023

Page: [1010 - 1023] Pages: 14

DOI: 10.2174/1567201820666230214091509

open access plus

Abstract

Background: The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ultimately bioavailability of drugs.

Objective: This study aimed to develop and characterize new domperidone-loaded self-emulsifying drug delivery systems as an alternative formulation and to evaluate the permeability of domperidone-loaded self-emulsifying drug delivery systems by using Caco-2 cells and via single-pass intestinal perfusion method.

Methods: Three self-emulsifying drug delivery systems were prepared and characterized in terms of pH, viscosity, droplet size, zeta potential, polydispersity index, conductivity, etc. Each formulation underwent 10, 100, 200, and 500 times dilution in intestinal buffer pH 6.8 and stomach buffer pH 1.2, respectively. Female Sprague Dawley rats were employed for in situ single-pass intestinal perfusion investigations.

Results: Results of the study revealed that the ideal self-emulsifying drug delivery systems formulation showed narrow droplet size, ideal zeta potential, and no conductivity. Additionally, as compared to the control groups, the optimum formulation had better apparent permeability (12.74 ± 0.02×10-4) from Caco-2 cell monolayer permeability experiments. The study also revealed greater Peff values (2.122 ± 0.892×10-4 cm/s) for the optimal formulation from in situ intestinal perfusion analyses in comparison to control groups (Domperidone; 0.802 ± 0.418×10-4 cm/s).

Conclusion: To conclude, prepared formulations can be a promising way of oral administration of Biopharmaceutical Classification System Class II drugs.

Keywords: Domperidone, SEDDS, oral drug delivery, in situ intestinal permeability, Caco-2 cell, microbial colonization.

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[1]
Wang, X.; Meng, M.; Gao, L.; Liu, T.; Xu, Q.; Zeng, S. Permeation of astilbin and taxifolin in Caco-2 cell and their effects on the P-gp. Int. J. Pharm., 2009, 378(1-2), 1-8.
[http://dx.doi.org/10.1016/j.ijpharm.2009.05.022] [PMID: 19465099]
[2]
Desrosiers, M.R.; Weathers, P.J. Artemisinin permeability via Caco-2 cells increases after simulated digestion of Artemisia annua leaves. J. Ethnopharmacol., 2018, 210, 254-259.
[http://dx.doi.org/10.1016/j.jep.2017.08.038] [PMID: 28864166]
[3]
Kaynak, M.S.; Buyuktuncel, E.; Caglar, H.; Sahin, S. Determination of regional intestinal permeability of diclofenac and metoprolol using a newly-developed and validated high performance liquid chromatographic method. Trop. J. Pharm. Res., 2015, 14(1), 163-170.
[http://dx.doi.org/10.4314/tjpr.v14i1.23]
[4]
Mancia, G.; Fagard, R.; Narkiewicz, K.; Redon, J.; Zanchetti, A.; Bohm, M. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. Hypertens., 2013, 31(7), 1281-1357.
[http://dx.doi.org/10.1097/01.hjh.0000431740.32696.cc] [PMID: 23817082]
[5]
Das, S.; Chaudhury, A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech, 2011, 12(1), 62-76.
[http://dx.doi.org/10.1208/s12249-010-9563-0]
[6]
Nagare, N.; Damre, A.; Singh, K.S.; Mallurwar, S.R.; Iyer, S.; Naik, A. Determination of site of absorption of propranolol in rat gut using in situ single-pass intestinal perfusion. Indian J. Pharm. Sci., 2010, 72(5), 625-629.
[http://dx.doi.org/10.4103/0250-474X.78533] [PMID: 21694996]
[7]
Idkaidek, N.M.; Jilani, J.A.; Mansi, I.A. Evaluation of hydroxyethyldiclofenac intestinal absorption in rats. Pharmacology, 2005, 13, 158-163.
[8]
Zhang, Z.; Gao, F.; Bu, H.; Xiao, J.; Li, Y. Solid lipid nanoparticles loading candesartan cilexetil enhance oral bioavailability: In vitro characteristics and absorption mechanism in rats. Nanomed.: Nanotechnol. Biol. Med., 2012, 8(5), 740-747.
[http://dx.doi.org/10.1016/j.nano.2011.08.016]
[9]
Li, H.L.; Zhao, X.; Ma, Y.; Zhai, G.X.; Li, L.B.; Lou, H.X. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J. Control. Release, 2009, 133(3), 238-244.
[http://dx.doi.org/10.1016/j.jconrel.2008.10.002] [PMID: 18951932]
[10]
Kheradmandnia, S.; Vasheghani-Farahani, E.; Nosrati, M.; Atyabi, F. Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax. Nanomedicine., 2010, 6(6), 753-759.
[http://dx.doi.org/10.1016/j.nano.2010.06.003]
[11]
Fagerholm, U.; Johansson, M.; Lennernäs, H. Comparison between permeability coefficients in rat and human jejunum. Pharm. Res., 1996, 13(9), 1336-1342.
[http://dx.doi.org/10.1023/a:1016065715308] [PMID: 8893271]
[12]
Kanuganti, S.; Jukanti, R.; Veerareddy, P.R.; Bandari, S. Paliperidone-loaded self-emulsifying drug delivery systems (SEDDS) for improved oral delivery. J. Dispers. Sci. Technol., 2012, 33(4), 506-515.
[http://dx.doi.org/10.1080/01932691.2011.574920]
[13]
Kumar, G.P.; Rajeshwarrao, P. Nonionic surfactant vesicular systems for effective drug delivery-An overview. APSB, 2011, 1(4), 208-219.
[http://dx.doi.org/10.1016/j.apsb.2011.09.002]
[14]
Khan, F.; Islam, M.S.; Roni, M.A.; Jalil, R-U. Systematic development of self-emulsifying drug delivery systems of atorvastatin with improved bioavailability potential. Sci. Pharm., 80(4), 1027-1043.
[http://dx.doi.org/10.3797/scipharm.1201-06]
[15]
Shen, H.; Zhong, M. Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin. J. Pharm. Pharmacol., 2006, 58(9), 1183-1191.
[http://dx.doi.org/10.1211/jpp.58.9.0004] [PMID: 16945176]
[16]
Karpf, D.M.; Holm, R.; Kristensen, H.G.; Müllertz, A. Influence of the type of surfactant and the degree of dispersion on the lymphatic transport of halofantrine in conscious rats. Pharm. Res., 2004, 21(8), 1413-1418.
[http://dx.doi.org/10.1023/b:pham.0000036915.03725.19] [PMID: 15359576]
[17]
Chintalapudi, R.; Murthy, T.E.G.K.; 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]
[18]
Singh, A.K.; Chaurasiya, A.; Singh, M.; Upadhyay, S.C.; Mukherjee, R.; Khar, R.K. Exemestane loaded self-microemulsifying drug delivery system (SMEDDS): Development and optimization. AAPS PharmSciTech, 2008, 9(2), 628-634.
[http://dx.doi.org/10.1208/s12249-008-9080-6] [PMID: 18473177]
[19]
Buya, A.B.; Beloqui, A.; Memvanga, P.B.; Préat, V. Self-nano-emulsifying drug-delivery systems: From the development to the current applications and challenges in oral drug delivery. Pharmaceutics, 2020, 12(12), 1194.
[http://dx.doi.org/10.3390/pharmaceutics12121194] [PMID: 33317067]
[20]
Chatterjee, B.; Hamed Almurisi, S.; Ahmed Mahdi Dukhan, A.; Mandal, U.K.; Sengupta, P. Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view. Drug Deliv., 2016, 23(9), 3639-3652.
[http://dx.doi.org/10.1080/10717544.2016.1214990]
[21]
Mountfield, R.J.; Senepin, S.; Schleimer, M.; Walter, I.; Bittner, B. Potential inhibitory effects of formulation ingredients on intestinal cytochrome P450. Int. J. Pharm., 2000, 211(1-2), 89-92.
[http://dx.doi.org/10.1016/S0378-5173(00)00586-X]
[22]
Rege, B.D.; Kao, J.P.Y.; Polli, J.E. Effects of nonionic surfactants on membrane transporters in Caco-2 cell monolayers. Eur. J. Pharm. Sci., 2002, 16(4-5), 237-246.
[http://dx.doi.org/10.1016/S0928-0987(02)00055-6]
[23]
Lin, Y.; Shen, Q.; Katsumi, H.; Okada, N.; Fujita, T.; Jiang, X.; Yamamoto, A. Effects of labrasol and other pharmaceutical excipients on the intestinal transport and absorption of rhodamine123, a P-glycoprotein substrate, in rats. Biol. Pharm. Bull., 2007, 30(7), 1301-1307.
[http://dx.doi.org/10.1248/bpb.30.1301] [PMID: 17603171]
[24]
Cornaire, G.; Woodley, J.; Hermann, P.; Cloarec, A.; Arellano, C.; Houin, G. Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo. Int. J. Pharm., 2004, 278(1), 119-131.
[http://dx.doi.org/10.1016/j.ijpharm.2004.03.001] [PMID: 15158955]
[25]
Johnson, B.M.; Charman, W.N.; Porter, C.J.H. An in vitro examination of the impact of polyethylene glycol 400, Pluronic P85, and vitamin E d-alpha-tocopheryl polyethylene glycol 1000 succinate on P-glycoprotein efflux and enterocyte-based metabolism in excised rat intestine. AAPS PharmSci., 2002, 4(4), E40.
[http://dx.doi.org/10.1208/ps040440] [PMID: 12646011]
[26]
Patel, M.H.; Mundada, V.P.; Sawant, K.K. Novel drug delivery approach via self-microemulsifying drug delivery system for enhancing oral bioavailability of asenapine maleate: optimization, characterization, cell uptake, and in vivo pharmacokinetic studies. AAPS PharmSciTech, 2019, 20(2), 44.
[http://dx.doi.org/10.1208/s12249-018-1212-z] [PMID: 30617712]
[27]
Leichner, C.; Baus, R.A.; Jelkmann, M.; Plautz, M.; Barthelmes, J.; Dünnhaupt, S.; Bernkop-Schnürch, A. In vitro evaluation of a self-emulsifying drug delivery system (SEDDS) for nasal administration of dimenhydrinate. Drug Deliv. Transl. Res., 2019, 9(5), 945-955.
[http://dx.doi.org/10.1007/s13346-019-00634-1] [PMID: 30877627]
[28]
Constantinides, P.P. Lipid microemulsions for improving drug dissolution and oral absorption: Physical and biopharmaceutical aspects. Pharm. Res., 1995, 12(11), 1561-1572.
[http://dx.doi.org/10.1023/A:1016268311867] [PMID: 8592652]
[29]
Singh, A.K.; Chaurasiya, A.; Awasthi, A.; Mishra, G.; Asati, D.; Khar, R.K.; Mukherjee, R. Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system (SMEDDS). AAPS PharmSciTech, 2009, 10(3), 906-916.
[http://dx.doi.org/10.1208/s12249-009-9281-7] [PMID: 19609837]
[30]
Zhang, H.; Zhang, F-M.; Yan, S-J. Preparation, in vitro release, and pharmacokinetics in rabbits of lyophilized injection of sorafenib solid lipid nanoparticles. Int. J. Nanomed., 2012, 7, 2901-2910.
[http://dx.doi.org/10.2147/IJN.S32415] [PMID: 22787390]
[31]
Taha, E.I.; Al-Saidan, S.; Samy, A.M.; Khan, M.A. Preparation and in vitro characterization of self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate. Int. J. Pharm., 2004, 285(1-2), 109-119.
[http://dx.doi.org/10.1016/j.ijpharm.2004.03.034] [PMID: 15488684]
[32]
Wang, L.; Dong, J.; Chen, J.; Eastoe, J.; Li, X. Design and optimization of a new self-nanoemulsifying drug delivery system. J. Colloid Interface Sci., 2009, 330(2), 443-448.
[http://dx.doi.org/10.1016/j.jcis.2008.10.077] [PMID: 19038395]
[33]
Hellinger, É; Bakk, ML; Pócza, P; Tihanyi, K; Vastag, M Drug penetration model of vinblastine-treated Caco-2 cultures. Eur. J. Pharm. Sci., 2010, 41(1), 96-106.
[http://dx.doi.org/10.1016/j.ejps.2010.05.015]
[34]
Caliph, S.M.; Charman, W.N.; Porter, C.J. Effect of short-, medium-, and long-chain fatty acid-based vehicles on the absolute oral bioavailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph-cannulated and non-cannulated rats. J. Pharm. Sci., 2000, 89(8), 1073-1084.
[http://dx.doi.org/10.1002/1520-6017(200008)89:81073:aid-jps12>3.0.co;2-v] [PMID: 10906731]
[35]
Gundogdu, E.; Karasulu, H.Y.; Koksal, C.; Karasulu, E. The novel oral imatinib microemulsions: Physical properties, cytotoxicity activities and improved Caco-2 cell permeability. J. Microencapsul., 2013, 30(2), 132-142.
[http://dx.doi.org/10.3109/02652048.2012.704952] [PMID: 22789009]
[36]
Kogan, A.; Kesselman, E.; Danino, D.; Aserin, A.; Garti, N. Viability and permeability across Caco-2 cells of CBZ solubilized in fully dilutable microemulsions. Colloids Surf B Biointerfaces., 2008, 66(1), 1-12.
[http://dx.doi.org/10.1016/j.colsurfb.2008.05.006]
[37]
Artursson, P. Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. J. Pharm. Sci., 1990, 79(6), 476-482.
[http://dx.doi.org/10.1002/jps.2600790604] [PMID: 1975619]
[38]
Gershanik, T.; Haltner, E.; Lehr, C-M.; Benita, S. Charge-dependent interaction of self-emulsifying oil formulations with Caco-2 cells monolayers: binding, effects on barrier function and cytotoxicity. Int. J. Pharm., 2000, 211(1-2), 29-26.
[http://dx.doi.org/10.1016/S0378-5173(00)00591-3] [PMID: 11137336]
[39]
Wang, J.-J.; Sung, K.C.; Hu, O.Y.-P.; Yeh, C.-H.; Fang, J.-Y. Submicron lipid emulsion as a drug delivery system for nalbuphine and its prodrugs. J Control Release., 2006, 115(2), 140-149.
[http://dx.doi.org/10.1016/j.jconrel.2006.07.023]
[40]
Konsoula, R.; Barile, F.A. Correlation of in vitro cytotoxicity with paracellular permeability in Caco-2 cells. Toxicol In vitro., 2005, 19(5), 675-684.
[http://dx.doi.org/10.1016/j.tiv.2005.03.006]
[41]
Rathore, R.; Jain, J.P.; Srivastava, A.; Jachak, S.M.; Kumar, N. Simultaneous determination of hydrazinocurcumin and phenol red in samples from rat intestinal permeability studies: HPLC method development and validation. J. Pharm. Biomed. Anal., 2008, 46(2), 374-380.
[http://dx.doi.org/10.1016/j.jpba.2007.09.019] [PMID: 17988818]
[42]
Yang, Z.; Gan, G.; Sawchuk, R.J. Correlation between net water flux and absorptive clearance determined from in situ intestinal perfusion studies does not necessarily indicate a solvent drag effect. J. Pharm. Sci., 2007, 96(3), 517-521.
[http://dx.doi.org/10.1002/jps.20763]
[43]
Valicherla, G.R.; Dave, K.M.; Syed, A.A.; Riyazuddin, M.; Gupta, A.P.; Singh, A.; Mitra, K. Formulation optimization of Docetaxel loaded self-emulsifying drug delivery system to enhance bioavailability and anti-tumor activity. Sci. Rep., 2016, 6, 26895.
[http://dx.doi.org/10.1038/srep26895] [PMID: 27241877]
[44]
Shao, B.; Cui, C.; Ji, H.; Tang, J.; Wang, Z.; Liu, H.; Qin, M.; Li, X.; Wu, L. Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems: In vitro, in vivo and in situ intestinal permeability studies. Drug Deliv., 2015, 22(6), 740-777.
[http://dx.doi.org/10.3109/10717544.2014.898109] [PMID: 24670090]
[45]
Sangsen, Y.; Wiwattanawongsa, K.; Likhitwitayawuid, K.; Sritularak, B.; Wiwattanapatapee, R. Modification of oral absorption of oxyresveratrol using lipid based nanoparticles. Colloids Surf. B Biointerfaces, 2015, 131, 182-190.
[http://dx.doi.org/10.1016/j.colsurfb.2015.04.055]
[46]
Aboulfotouh, K.; Allam, A.A.; El-Badry, M.; El-Sayed, A.M. Self-emulsifying drug-delivery systems modulate P-glycoprotein activity: Role of excipients and formulation aspects. Nanomedicine (Lond.), 2018, 13(14), 1813-1834.
[http://dx.doi.org/10.2217/nnm-2017-0354] [PMID: 30074420]

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