FORMULATION AND EVALUATION OF ORAL DELIVERY SYSTEMS FOR POORLY ABSORBED DRUGS USED IN OSTEOPOROSIS

Abstract

Bisphosphonates (BPs) are drugs found useful in physiological regulation of calcification, bone resorption and currently have become drug of choice for the management of osteoporosis. The major drawback of the clinically utilized BPs is their poor oral absorption from the GI tract, typically less than 1% is absorbed which is due to their poor permeability. In addition, the BPs have been associated with undesirable gastrointestinal effects. Risedronate sodium (RIS) is a bisphosphonates popularly indicated for osteoporosis that belongs to BCS Class III and has poor oral bioavailability due to less permeability. The present work attempted to improve poor permeability of RIS through dual approaches, multiple emulsion and sublingual spray formulations which were found promising. In first approach Initially RIS w/o/w multiple emulsion formulations were prepared and evaluated for determining significant causative factors and their effect on formulation properties. Consequently determined causative factors were included in central composite design and total 18 formulations were prepared and evaluated for appearance, pH, globule size, viscosity, % creaming, pourability, drug entrapment efficiency, in vitro drug release, ex-vivo permeation study. Numerically optimized F19 formulation was additionally subjected for zeta potential and stability test. Stability of F19 was improved by including surfactant blend, phase volume ratio and hydrophilic polymer in outer water phase and stabilized F19B was evaluated for in vivo absorption study. The second approach involved formulation of propellant free RIS sublingual spray using face centered central composite design in which independent variables considered were concentration of drug, co-solvent and spreading agent while responses as spray pattern, spray angle and drug permeation and optimized by numerical method to get optimized sublingual spray FO. Total 16 formulations of RIS sublingual spray were prepared. All formulations were evaluated for spray pattern, spray angle, leak