Floating-pulsatile Release Multiparticulate System for Chronopharmacotherapy: Effect of Some Hydrophobic Additives on the Buoyancy and Release Behavior of Particles

Abstract

A blend of floating and pulsatile principles of a drug delivery system would have the advantage that a drug can be released in the upper gastrointestinal (GI) tract after a lag period, which is anticipated for chronotherapy. In this study, microballoons were prepared by an emulsion solvent diffusion technique using Eudragit S100, and hydrophobic additive (magnesium stearate, stearic acid or talc) for time- and site-specific drug release of piroxicam. The effect of hydrophobic additives on the production yield of floating microparticles, buoyant ability for 8 h, release of drug in simulated GI fluids (simulated gastric fluid [SGF] and simulated intestinal fluid [SIF]), mean particle size, apparent particle density, encapsulation efficiency of drug and physical state of incorporated drug were studied. Both production yield and buoyancy of the microballoons were affected by additives in the following order: magnesium stearate, stearic acid>free-additive>talc. The observed difference in yield and the buoyancy of the microballoons could be attributed to the hydrophobic character of the additives and the shell rigidity of the obtained microballoons. Incorporation of hydrophobic additives in the microballoons was found to impart the desired release properties to the microballoons by providing a 2-phase release pattern with initial slow release (5-6%) through 8 h in SGF followed by rapid pulse release (>92%) in SIF through 15 min. The microballoons co-formulated with magnesium stearate or stearic acid, combining excellent buoyancy and suitable drug release pattern of piroxicam, could be useful in chronopharmacotherapy in arthritis.