FORMULATION AND OPTIMIZATION OF NATURAL GUM BASED EXTENDED RELEASE TABLETS OF LOSARTAN USING D-OPTIMAL MIXTURE DESIGN
Losartan potassium is one of the widely prescribed antihypertensive drug administered orally and for its long acting effect at reduced dosage frequency; the extended release tablet formulations are essentially required. The aim of the present research was to develop extended release tablet of losartan potassium, exploring natural gums, i.e., xanthan gum and guar gum as drug release modifiers. The tablets were prepared by wet granulation method and the formulation optimization for obtaining appropriate drug release profile using optimum contents of natural gums was done by D-optimal mixture design using Design Expert® software. The independent variables studied were the amount of xanthan gum (X1), guar gum (X2) and lactose (X3) taking various combinations of total amount of gum and ratio of xanthan gum to guar gum under given constraint range. The dependent (response) variables studied were % drug release in 1hr(Y1), 4hr(Y2), 7hr(Y3) and 10hr(Y4). The developed tablets were evaluated for physical properties, i.e., hardness, friability, weigh variation and in-vitro drug release profiles. For studying the effect of formulation components on in-vitro drug release profiles, the polynomial equations and response surface plots were generated and the optimized formulation was selected on the basis of maximum value of desirability. The in-vitro release and swelling study was performed and model fitting of the release data was done. The drug release data of developed formulation demonstrated best fit in zero-order model and Korsmeyer–Peppas plot suggested case II transport as the release mechanism of the drug from hydrophilic matrix. The findings suggested that natural gums based extended release tablets formulation could be successfully explored as platform technology for many other potential drugs.
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