Augmentation of Permeability of Drugs having P-Glycoprotein Inhibition for Efficiency in Nocturnal Acid Breakthrough
Purpose : Ranitidine is a BCS class III drug having low oral, lipophilicity and is susceptible to the Pglycoprotein (P-gp) efflux mechanism. Permeation enhancers enhance the bioavailability of ranitidine by increasing the partition coefficient (Koct/buffer there by increasing the lipophilicity and permeability. The main) aim of the present work is to overcome the problems of ranitidine bioavailability by expending permeation enhancers and P-gp inhibitors.
Methodology : The existence of synergistic activity in permeation enhancement effect was studied using EDTA, citric acid, oleic acid, caprylic acid, sodium glycocholate and sodium deoxycholate. The P-gp inhibitor used here was felodipine, a first generation inhibitor showed P-gp inhibition activity at a concentration where it shows it pharmacological action. Three formulations were formulated and subjected to various physiochemical evaluations like weight variation, friability, hardness, drug content, in vitro drug release and kinetic studies.A continuous dissolution-absorption system was designed using everted intestine segment.
Results : Synergistic effect in enhancing the permeability of ranitidine was found to exist between chelating agents in combination with fatty acids and its derivatives. From the precompression parameters data of the lubricated blend, it was found that the flow ability was good and can be compressed into tablets by direct compression method. The formulated ranitidine immediate release tablets exhibited first order release kinetics, resulting in rapid and complete release for two h.
Conclusion : The effective drug permeability (Peff) after three h or formulations TAB, TAB37, TAB37-PGP and TAB-MARK is 2.60, 3.17, 3.66 and 2.68, respectively. This shows that the permeability through chick intestine is more from TAB37-PGP by increased P-gp inhibition.
- Kararli TT. Gastrointestinal absorption of drugs. Crit Rev Ther Drug Carrier Syst. 1989;6(1): 39-86.
- Devane J and Butler J. The impact of in vitro-in vivo relationships on product development. Pharm Technol. 1997; 21(9):146-59.
- Fass R. Nocturnal acid breakthrough: A critical assessment. HospPhysician. 2004; 40: 47–52.
- Farup C, Kleinman L, Sloan S, Ganoczy D, Chee E and Lee C. The impact of nocturnal symptoms associated with gastroesophageal reflux disease on healthrelated quality of life. Arch Intern Med. 2001; 161(1): 45.
- Abdul WB and Larry FL. Colonic metabolism of ranitidine: Implications for its delivery and absorption. Int J Pharm. 2001; 227(1): 157-65.
- Hollander D, Ricketts D, Boyd CAR and Phil D. Importance of probemolecular geometry in determining intestinal permeability. Can J Gastroenterol. 1988; 2:35A– 38A.
- Larhed W, Artursson P, Grasjo J and Bjork E. Diffusion of drugs in native and purified gastrointestinal mucus. JPharm Sci. 1997;86: 660-65.
- Valizadeh H, Mehatari M and Parvin ZM. Evidence for Enhanced Intestinal Absorption of Digoxin by PGlycoprotein Inhibitors. Trop J Pharm Res. 2012; 11 (6): 939-45.
- Devendra S, Pankaj KS and Udai VSS. Enhancement of intestinal absorption of poorly absorbed drugs by using various permeation Enhancers: an overview.World J Pharma Pharm Sci. 2013; 2(1): 17998.
- Anilkumar P, Badarinath AV, Naveen N, Prasad K,Ravi SRB, Hyndhavi M, Nirosha M.A rationalized description on study of intestinal barrier, drug permeability and permeation enhancers. JGlobal Trend Pharm Sci. 2011, 2(4): 431-49.
- Ravindra BM, Sampath KM. Formulation and absorption enhancement of metformin oral tablets. Indo Am JPharm Res. 2013; 3(10): 8273-79.
- DevendraS, Pankaj KS and Udai VSS. Development, optimization and evaluation of solid dosage form of Thiocolchicoside by using absorption enhancers. Scholar Res Lib Der Pharmacia Lettre. 2013; 5(3):40514.
- 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 PharmSci. 1990; 79: 476–82.
- HadjiioannouTP, Christian GD, Koupparis MA and Macheras PE. Quantitative calculations in Pharmaceutical practice and research. New York: VCH Publishers INC; 1993, p 345-8.
- Bourne DWA. Pharmacokinetics. In: Banker GS, Rhodes CT. Modern Pharmaceutics. 4rth ed., New York: Marcel Dekker Inc; 2002, p 67-92.