DESIGN, DEVELOPMENT AND IN VITRO EVALUATION OF COMBINED FLOATING- BIOADHESIVE DRUG DELIVERY SYSTEMS OF ATENOLOL Original Article RABI NARAYAN PANIGRAHY*, SINDHURA GUDIPATI, KRISHNA MOHAN CHINNALA Department of Pharmaceutics, School of Pharmacy, Nalla Narasimha Reddy Education Society’s Group of Institutions, Chowdariguda, Ghatkesar, Hyderabad 500088 Email: rabi.papu@gmail.com Received: 10 Nov 2015 Revised and Accepted: 12 Dec 2015 ABSTRACT Objective: A combination of the Floating-Bioadhesive system will overcome the drawbacks of floating & bioadhesive systems if used alone and will have a significant effect on improving the therapeutic effect of the drug involved. The present study involves the formulation and in vitro evaluation of atenolol floating-Bioadhesive tablet for prolonged residence in the stomach for the treatment of hypertension. Methods: The tablets were prepared by direct compression method using directly compressible polymers such as, Hydroxy Propyl Methyl Cellulose (HPMC) K15M, Guar gum, Carbopol, and sodium alginate. The tablets were evaluated for buoyancy test, mucoadhesion force, swelling study, drug content, ex-vivo mucoadhesion strength and in-vitro release profile. Sodium bicarbonate was used for producing the effervescent base for the buoyancy of tablets. Results: Formulation batch contains sodium alginate which has shown highest percentage cumulative drug release up to 99.12%. No significant change was observed in physical appearance, drug content, float ability or in vitro dissolution pattern after storage at 45 °C/75% RH for three months. Conclusion: In this present research work it was concluded that the cumulative drug release increased when the viscosity and concentration of the polymer was increased. Keywords: Hypertension, Ex vivo mucoadhesion strength, Carbopol, Atenolol. The swelling properties were increased with increasing polymer concentration and contributed to the drug release from the tablet matrix. © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION Many orally-administered drugs display poor bioavailability when administered as conventional dosage form, i.e. the rate and extent to which the drugs are absorbed is less than desirable. With several drugs, absorption may be as little as 30% or less of the orally administered dose. To compensate for this effect, a very large dose is often administered so that absorption of the therapeutically required quantity of the drug can occur. This technique may prove costly with expensive drugs, and the unabsorbed drug may also have undesirable side effect within the gastrointestinal tract. In addition, poorly absorbed drug often display large inter and intra-subject variability in bioavailability. This problem may be overcome by modified release drug delivery system with a prolonged residence time in the stomach [1]. Atenolol is a cardioselective β-blocker widely prescribed for an asymptomatic condition such as hypertension. It is poorly absorbed from the lower gastrointestinal tract. The oral bioavailability of atenolol was reported to be 50% [2]. The human jejunal permeability and extent of absorption is low [3]. Thus, it seems that an in gastric residence time may increase the extent of absorption and bioavailability of the drug. The recommended adult oral dosage of atenolol is 50 mg twice daily for the effective treatment of hypertension. However, fluctuations of drug concentration in plasma may occur, resulting in side effects or a reduction in drug concentration at receptor side. As the drug is effective when the plasma fluctuations are minimized, therefore sustained release dosage form of atenolol is desirable. The short biological half-life of drug (6 to 8 h) also favors the development of sustained release formulations. In this study, an effervescent floating system and bioadhesive system were used in combination. Floating dosage forms are meant to remain floating on the gastric fluid when the stomach is full after a meal. However, as the stomach empties and the tablet reaches the pylorus, the buoyancy of the dosage form may be reduced. It may be that the dosage form will then pass through the pylorus into the small intestine. Thus, the buoyancy of an FDDS in the stomach may be limited to only 3–4 h. Furthermore, floating systems do not always release the drug at the intended site. In a bioadhesive drug delivery system, it is quite likely that the system becomes dislodged from the stomach mucosa wall when the system is full and the semi-liquid contents are churning around due to the effect of peristalsis [4]. A floating-Bioadhesive system would overcome these drawbacks of floating and Bioadhesive systems and would have a significant effect on improving the therapeutic effect of the drug involved [5] . MATERIALS AND METHODS The present study involves the formulation and in vitro evaluation of atenolol floating-Bioadhesive tablet for prolonged residence in the stomach for the treatment of Hypertension. Atenolol was supplied as a gift sample from GVK Pharma, Hyderabad. Micro Crystalline Cellulose (MCC), HPMC K15M and Sodium alginate were brought from Signet chemical corporation, Mumbai. Sodium bicarbonate and Carbopol obtained from Loba Chem. Pvt. Ltd., Mumbai. Guar gum was supplied from Noveon chemicals, Mumbai. Pre-formulation studies Drug-excipient compatibility studies The drug and excipients must be compatible with one another to produce a product that is stable, efficacious, attractive, easy to administer and safe. The compatibility studies provide the framework for the drugs combination with excipients in the fabrication of the dosage form. The study was carried out to establish that the therapeutically active drug has not undergone any changes after it has been subjected to processing steps during formulation of tablets. Compatibility studies were carried out by mixing definite proportions of drug and excipient and kept in glass vials, which are stored at 55 °C (2 w) and 40±2 °C/75±5 % RH (4 w)[6]. Differential scanning calorimetry (DSC) The DSC analysis was carried out using Differential Scanning Calorimeter (SDT 2960 TA Instrument, USA). Samples were placed in a platinum crucible, and the DSC thermograms were recorded at a heating rate of 10 °C/min in the rage 20 °C to 350 °C, at a nitrogen flow of 20 ml/min. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 2, 2016