Abstract
The present study was undertaken to develop sustained release (SR) matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg) for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R²) values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (P<0.05) differences were found among the drug release profile from different level of polymeric matrices. The release mechanism changed from non-fickian (n=0.489 for F-1) to fickian (n=0.439 and 0.429 for F-2, and F-3 respectively) as a function of decreasing the polymer concentration. The Mean Dissolution Time (MDT) values were increased with the increase in polymer concentration.
Highlights
The objective of an ideal drug delivery system is to deliver adequate amount of drug for an extended period for its optimum therapeutic activity
Administration of losartan potassium in a sustained release dosage form with dual characteristics, that is, burst release, followed by an extended release over 8 hours would be more desirable; as these characteristics would allow a rapid onset followed by protracted anti-hypertensive effect by maintaining the plasma concentration of the drug
Several studies were conducted on losartan potassium by using various hydrophilic and hydrophobic polymers for their in-vitro evaluation (Chithaluru et al, 2011; Shanmugam et al, 2011)
Summary
The objective of an ideal drug delivery system is to deliver adequate amount of drug for an extended period for its optimum therapeutic activity. Most drugs are inherently not long-lasting in the body, and require multiple daily dosing to achieve the desired blood concentration to produce therapeutic activity. To overcome such problems greater attention has been focused on sustained release drug delivery system (Chien, 1992). Losartan potassium is an orally active angiotensin-II receptor antagonist used in the treatment of hypertension due to mainly blockade of AT1 receptor. It is freely soluble in water, slightly soluble in acetonitrile, and soluble in isopropyl alcohol. Kollidon SR contains no ionic groups and is, inert to the drug substance (Reza, Quadir, Haider, 2003)
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