Formulation development and evaluation of regio-selective bilayer floating tablets of propranolol for sustained release and rosuvastatin calcium for immediate release

The present study was aimed to develop regio-selective bilayer floating tablets containing propranolol hydrochloride as SR layer and Rosuvastatin calcium as IR layer for hypertensive patients. Combination therapy of beta-blocker and HMGCo-A Reductase inhibitors is recommended for treatment of hypertensive patients. The drug excipient interaction was investigated with FTIR spectroscopy. The study indicated that there was no interaction between the drug and the excipients used in the formulations. The floating matrix layer was formulated with hydrophobic polymer (ethyl cellulose) and hydrophilic polymers (HPMC K4M, HPMC K100 and Xanthan gum) to retard the drug release upto 12 hours. The rosuvastatin calcium solid dispersion of different ratios (1:1, 1:2, 1:3, and 1:4) was prepared by taking starch phosphate as a novel carrier for the drug. From the dissolution results of rosuvastatin solid dispersion, two ratios which exhibit enhanced dissolution of rosuvastatin calcium were selected. The immediate release rosuvastatin calcium layer was formulated with sodium starch glycolate (4%). All the formulations were evaluated for physical characteristics, drug content, dissolution, release kinetics and stability studies. The tablets were formulated by wet granulation method because the flow property of the drugs and the blends were poor. The formulated granules were evaluated and showed good flow property. The tablets were found to be within the limits with respect to uniformity of weight, hardness, thickness, diameter and friability. The disintegration time of the IR tablets containing solid dispersion in ratio of 1:4 and SSG 4 % was found to be optimum. The drug content of the formulated IR tablets was found to be within the limits. The invitro dissolution studies were performed for all the IR-SD formulations. The formulations RC-1, RC-2 and RC-3 released 46.05, 77.79 and 101.29 at the end of 15 minutes. Thus the formulation RC-3 has enhanced solubility of rosuvastatin calcium and it was optimized formulation and selected for compression with bilayer floating tablets. The drug content of the formulated Propranolol hydrochloride SR floating tablets was found to be within Pharmacopoeial limits. The drug content of the bilayer floating tablets was estimated by simultaneous estimation method and it was found to be within Pharmacopoeial limits. In vitro dissolution studies were performed for all the bilayer floating tablet formulations. The formulation RBFT-7 containing HPMC K4M 20% Released the drug upto 12 hours. Floating lag time of bilayer floating tablets was within 3 minutes and floating duration was more than 12 hours. In vitro dissolution study was performed for bilayer floating tablets. At the end of 15 minutes the release was found to be 101.29% for immediate release layer of Rosuvastatin calcium and at the end of 12th hour the release was found to be 101.01 % for sustained release layer of Propranolol hydrochloride. Release kinetics of sustained release layer of bilayer floating tablets followed zero order release kinetics. The release of the drug was dependent on diffusion, swelling and erosion of the polymer. The stability studies showed that the formulated bilayer floating tablets were stable and did not show any significant changes in the physical characteristics, drug content and dissolution. The results obtained were found to be within acceptable limits. Thus the formulated bilayer floating tablets of propranolol hydrochloride and rosuvastatin calcium was found to be stable. Regio- selective bilayer floating tablets of rosuvastatin calcium for immediate release and propranolol hydrochloride for sustained release was formulated to reduce the frequency of administration and to reduce hypertension.