Stomach Specific Drug Delivery System of Ketoconazole Floating Alginate Beads

In the present research work, a multiple unit-type oral floating dosage form of Ketoconazole capable of floating in the gastric condition were developed using an ionotropic gelation method to prolong gastric residence time. Ketoconazole is an antifungal drug which is used in the treatment of fungal infections. In this study, an attempt was made to increase the gastric residence time of Ketoconazole in acidic pH. Preformulation study was carried out by performing an identification test, a solubility test, and compatibility study. Central composite design model was used to study different formulations. The formulations of stomach-specific floating alginate beads were formulated by using polymers sodium alginate and HPMC K15M, Olive oil was used as a floating agent and they were evaluated by using micrometric and physical parameters which include measurement of bulk density, tapped density, Carr's index, angle of repose, practical yield, particle size, entrapment efficiency, swelling index, floating time and Surface morphology. Drug content was estimated by using UVSpectrophotometric method and results were found to be within the acceptance limit. The release profile of the drug was determined by in vitro dissolution study. Short term stability studies also performed and results revealed that formulation was found to be stable and effective. Jyoti V. Pattanshetti*, U. B. Bolmal, A. P. Gadad Department of Pharmaceutics, KLE’s College Of Pharmacy, KLE University, Belagavi, Karnataka. Submission: 19 July 2018 Accepted: 27 July 2018 Published: 30 August 2018 www.ijppr. humanjournals.com Citation: Jyoti V. Pattanshetti et al. Ijppr.Human, 2018; Vol. 13 (1): 72-88. 73 INTRODUCTION Ketoconazole is a synthetic, broad-spectrum antifungal agent containing imidazole as a basic heterocyclic nucleus. The oral absorption of Ketoconazole is facilitated by gastric acidity, being a weak acid the drug is well absorbed from the upper portion of the duodenum. Ketoconazole is a weak dibasic compound that has pKa values of 6.5 and 2.9. It shows a pHdependent solubility profile. Ketoconazole has an excellent solubility at acidic pH below 3, but its solubility drops dramatically to <1 mg/ml at pH 4. The solubility of Ketoconazole decreases to only 0.002 mg/ml with an increase in pH. Ketoconazole shows high solubility at acidic pH results in its complete dissolution in normal stomach. However, as it moves into the higher pH (pH 6–7) environment of a small intestine, precipitation of Ketoconazole is a concern. In addition, at the higher pH conditions of a hypochlorhydric stomach, Ketoconazole incompletely dissolves, resulting in diminished bioavailability. As oral absorption of Ketoconazole is facilitated by gastric acidity, it was thought to formulate floating alginate beads of Ketoconazole to increase its solubility in the gastric pH [1,2]. Gastroretentive drug delivery systems are the systems which are retained in the stomach for a longer period of time and thereby, improve the bioavailability of drugs. Gastric retention can be achieved by the mechanism of mucoadhesion, floatation, swelling, high density, sedimentation. Floating microbeads improve patient compliance by decreasing dosing frequency, the better therapeutic effect of short half-life drugs can be achieved [3]. In the present study, an attempt has been made to prepare floating alginate beads of ketoconazole by ionotropic gelation method to increase gastric residence time in acidic pH. Figure no 1: Chemical structure of Ketoconazole www.ijppr. humanjournals.com Citation: Jyoti V. Pattanshetti et al. Ijppr.Human, 2018; Vol. 13 (1): 72-88. 74 MATERIALS AND METHODS