Ranitidine microemulsion was investigated for its pharmacodynamic and pharmacokinetic evaluation to find out the suitability of microemulsion as a potential drug delivery system in the treatment of ulcer. The bioavailability of ranitidine after oral administration is about 50% and is absorbed via the small intestine; this may be due to low intestinal permeability. Hence the aim of present investigation was to maximize the therapeutic efficacy of ranitidine by developing microemulsion to increase the intestinal permeability as well as bioavailability. A ground nut oil based microemulsion formulation with Tween-80 as surfactant and PEG-400 as cosurfactant was developed for oral delivery of ranitidine and characterized for physicochemical parameters. In pharmacodynamic studies, significant () variation in parameters estimated was found between the treated and control groups. Ranitidine microemulsion exhibited higher absorption and Cmax (863.20？ng·h/mL) than the standard (442.20？ng/mL). It was found that AUC0–24？hr obtained from the optimized ranitidine test formulation (5426.5？ng·h/mL) was significantly higher than the standard ranitidine (3920.4？ng·h/mL). The bioavailability of optimized formulation was about 1.4-fold higher than that of standard drug. This enhanced bioavailability of ranitidine microemulsion may be used as an effective and alternative drug delivery system for the antiulcer therapy. 1. Introduction Gastric ulcer is said to occur due to an imbalance between luminal acid synthesis and mucosal defense. Acid and pepsin components constitute the aggressive factors, and the mucous layer of mucin-bicarbonate secretion, prostaglandins, and other healing factors constitute the defensive factors [1]. The mucosal defense against these aggressive factors includes the function of the mucus-bicarbonate barrier, surface active phospholipids, prostaglandin, mucosal blood flow, cell renewal and migration, antioxidative enzymes, and some growth factors. Even though wide range of drugs available for the treatment of ulcer may do not fulfill the requirements and have many side effects such as arrhythmias, impotence and hemopoietic changes are noted. H2 antagonists, unlike anticholinergics, do not delay gastric emptying time which may reflexly stimulate gastric secretion because of food remaining in the stomach for long time. Also it does not cause abdominal colic and diarrhoea caused by proton pump inhibitors. In recent years large advance in chemical and pharmacological studies has contributed to the knowledge about new therapeutically active compounds and
References
[1]
S. Karthikeyan and K. Gobianand, “Antiulcer activity of ethanol leaf extract of Cassia fistula,” Pharmaceutical Biology, vol. 48, no. 8, pp. 869–877, 2010.
[2]
S. Ramchandran, G. Poovi, and M. D. Dhanaraju, “Evaluation of gastric and duodenal antiulcer activity of famotidine formulation in experimental animals,” Journal of Pharmacological and Toxicological, vol. 6, no. 2, pp. 189–195, 2011.
[3]
C. Zhang, L. Wang, X. Guan, et al., “Rapid determination of ranitidine in human plasma by liquid chromatography-tandem mass spectrometry and its application to a clinical pharmacokinetic study,” Chemical Research in Chinese Universities, vol. 26, no. 6, pp. 910–914, 2010.
[4]
D. Hollander, A. Tarnawski, W. J. Krause, and H. Gergely, “Protective effect of sucralfate against alcohol-induced gastric mucosal injury in the rat: macroscopic, histologic, ultrastructural , and functional time sequence analysis,” Gastroenterology, vol. 88, no. 1, pp. 366–374, 1985.
[5]
S. G. Patel, S. J. Rajput, A. Groshev, and V. B. Sutariya, “Preparation and characterization of microemulsion of cilostazol for enhancement of oral bioavailability,” Current Drug Delivery, vol. 11, no. 3, pp. 531–540, 2014.
[6]
Q. Cai, H. Sun, Y. Pen, et al., “A potent and orally active antagonist of multiple inhibitor of apoptosis proteins (IAPs) (SM-406/AT-406) in clinical development for cancer treatment,” Journal of Medicinal Chemistry, vol. 54, no. 8, pp. 2714–2726, 2011.
[7]
R. ParveenShaika, S. B. Puttagunta, C. B. Kothapalli, B. Z. S. Awen, and B. R. Challa, “A validated LC-MS/MS method for the determination of tolterodine and its metabolite in rat plasma and application to pharmacokinetic study,” Journal of Pharmaceutical Analysis, vol. 3, no. 6, pp. 489–499, 2013.
[8]
R. G. Thorne and W. H. Frey II, “Delivery of neurotrophic factors to the central nervous system: pharmacokinetic considerations,” Clinical Pharmacokinetics, vol. 40, no. 12, pp. 907–946, 2001.
[9]
J. Born, T. Lange, and W. Kern, “Sniffing neuropeptides: a transnasal approach to the human brain,” Nature Neuroscience, vol. 5, pp. 514–516, 2002.
[10]
L. Illum, “Nasal drug delivery: new developments and strategies,” Drug Discovery Today, vol. 7, no. 23, pp. 1184–1189, 2002.
[11]
M. R. Patel, R. B. Patel, J. R. Parikh, A. B. Solanki, and B. G. Patel, “Effect of formulation components on the in vitro permeation of microemulsion drug delivery system of fluconazole,” AAPS PharmSciTech, vol. 10, no. 3, pp. 917–923, 2009.
[12]
M. R. Patel, R. B. Patel, and J. R. Parikh, “Investigation of efficiency of isopropyl myristate-based oil in water microemulsions for topical delivery of fluconazole,” International Journal of Biomedical and Pharmaceutical Sciences, vol. 3, pp. 60–68, 2009.
[13]
M. R. Patel, R. B. Patel, J. R. Parikh, A. B. Solanki, and B. G. Patel, “Investigating effect of microemulsion components: In vitro permeation of ketoconazole,” Pharmaceutical Development and Technology, vol. 16, no. 3, pp. 250–258, 2011.
[14]
G. Sener, K. Paskaloglu, and G. Ayanoglu-Dülger, “Protective effect of increasing doses of famotidine, omeprazole, lansoprazole, and melatonin against ethanol-induced gastric damage in rats,” Indian Journal of Pharmacology, vol. 36, no. 3, pp. 171–174, 2004.
[15]
Y.-M. Yin, F.-D. Cui, C.-F. Mu, et al., “Docetaxel microemulsion for enhanced oral bioavailability: preparation and in vitro and in vivo evaluation,” Journal of Controlled Release, vol. 140, no. 2, pp. 86–94, 2009.
[16]
G. Sharma, K. Wilson, C. F. van der Walle, N. Sattar, J. R. Petrie, and M. N. V. Ravi Kumar, “Microemulsions for oral delivery of insulin: design, development and evaluation in streptozotocin induced diabetic rats,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 76, no. 2, pp. 159–169, 2010.
[17]
L. Hu, H. Wu, F. Niu, C. Yan, X. Yang, and Y. Jia, “Design of fenofibrate microemulsion for improved bioavailability,” International Journal of Pharmaceutics, vol. 420, no. 2, pp. 251–255, 2011.
[18]
H. Araya, M. Tomita, and M. Hayashi, “The novel formulation design of O/W microemulsion for improving the gastrointestinal absorption of poorly water soluble compounds,” International Journal of Pharmaceutics, vol. 305, no. 1-2, pp. 61–74, 2005.
