Microballoons of Famotidine: A non-effervescent gastroretentive controlled drug delivery system using Eudragit L-100

By Narayana Charyulu.R, Basavaraj B.V, Madhavan V 


A non-effervescent multiparticulate floating microballoons of famotidine using Eudragit - L100 polymer in ethyl alcohol and dichloromethane organic solvent system was prepared by emulsion solvent diffusion method for improving the bioavailability. 32 response surface central composite design was chosen to study the influence of rate of stirring, polymer concentration and temperature on the drug entrapment and drug release parameters. Better entrapment and drug release was achieved at a lower possible polymer concentration and stirring rate and especially at 40°C. The drug encapsulation was found to be 80 % against the predicted 76 %. The formation of a discrete sphere with a hollow was confirmed by SEM photographs. The micromeritic properties revealed better flowability and packability of the microballoons. The in vitro percentage buoyancy was around 86 ± 0.42 with good floatability upto 12 h. In vitro dissolution profile showed prolonged release of drug upto 92 % over 12 h demonstrating non-Fickian diffusion mechanism of drug release. Acute oral toxicity studies performed as per OECD guidelines on wistar rats showed no mortality with normal haematological and biochemical values. Histopathogical studies also supported the possibility of any toxicity on lower animal models. The mean gastric volume for control, famotidine and FAL-D1 was found to be 6.51 ± 0.199, 4.01 ± 0.130 and 3.93 ± 0.098 ml. Free acidity and total acidity for the optimized formulation by pylorus ligation method was found to be 48.16 ± 1.16 mEq/l/100g and 151.50 ± 1.505 mEq/l/100g respectively compared to 57.66 ± 2.27 and 180.33 ± 1.14 of control group, 44.83 ± 1.66 and 134.83 ± 1.424 mEq/l/100g of pure drug. Appreciable rise in the pH towards alkalinity 5.133 ± 0.202 of FAL-D1 substantiated the ulcer protection activity of the formulation. Residual solvent analysis for ethanol and dichloromethane by gas chromatography was found to be within the limits of ICH guidelines for impurities. Long term and accelerated stability studies showed the integrity of the drug without any significant changes in the physical properties. Thus microballoons of famotidine with acrylic polymer Eudragit L-100 could to be an ideal novel floating dosage form for regulating the drug delivery into the upper part of the intestine with assured enhancement in oral bioavailability.  

Key words: Microballoons, central composite design, In vitro buoyancy, antiulcer activity, residual solvents 

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