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Simultaneous improvement in dissolution profile and content uniformity of lafutidine through co-inclusion in urea

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Abstract

In the present study, simultaneous improvement in dissolution profile and content uniformity of Lafutidine (LAF) has been achieved through co-inclusion in urea. LAF, a recently reported histamine H2 receptor antagonist used in the treatment of peptic ulcer, exhibits low aqueous solubility and dissolution rate limited absorption leading to its poor bioavailability. LAF is a potent and normally non-complexing substituted cyclic organic compound. Urea, a well known host for forming inclusion complexes with linear organic compounds was successfully employed for co-inclusion of LAF in the presence of readily complexing guest (RCG). The modified Zimmerschied calorimetric method was employed for the estimation of the minimum amount of RCG required for co-inclusion of lafutidine in urea. The formation of lafutidine urea co-inclusion complexes (LUCIC) was confirmed by DSC, FTIR, XRD and 1H-NMR studies. LUCIC complexes containing varying proportions of guests were prepared and subjected to thermal analysis using DSC. The thermal data was subjected to the regression analysis to study the influence of the relative molar proportion of RCG on the heat of decomposition of LUCIC. Study revealed good content uniformity of lafutidine in LUCIC. In vitro dissolution rate studies demonstrated steep improvement in dissolution profile of LAF—a BCS class II drug. The resulting dissolution data was subjected to various release kinetic models. Studies reveal that urea co-inclusion complex formation may be a promising technique for the formulation of potent poorly soluble drugs into immediate release products with improved content uniformity.

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Acknowledgments

The authors are thankful to Akums Drugs and Pharmaceuticals Ltd, New Delhi, India, for providing gift sample of Lafutidine. Thanks are due to SAIF, Panjab University, Chandigarh, India for providing XRD and NMR facilities. Thanks are also due to JCDM College of Pharmacy, Sirsa, India for allowing them to conduct DSC studies. Thanks are due to Indian Agricultural Research Institute, Pusa, New Delhi, India for providing facilities to conduct XRD studies.

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  1. Faculty of Pharmaceutical Sciences, Pt. B. D. Sharma University of Health Sciences, Rohtak, 124001, India

    Manish Dhall & A. K. Madan

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Dhall, M., Madan, A.K. Simultaneous improvement in dissolution profile and content uniformity of lafutidine through co-inclusion in urea. J Incl Phenom Macrocycl Chem 82, 335–350 (2015). https://doi.org/10.1007/s10847-015-0493-z

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