Development and characterization of buoyant theophylline microspheres with near zero order release kinetics

Abstract

The objective of this study was to prepare floating theophylline microspheres with zero order release profiles for use as buoyant reservoirs with increased retention time in the stomach. The microspheres were prepared by a modified emulsion-solvent evaporation method using a polymer mixture of cellulose acetate butyrate and Eudragit RL 100 (1:1). The drug-polymer dispersions were pressurized under carbon dioxide gas which dissolved in the drug-polymer dispersions and formed bubbles upon the release of the pressure. Some of the bubbles were entrapped in the dispersed drug-polymer droplets and eventually formed internal cavities in the microspheres. The resulting microspheres were characterized for size distribution, morphology, density, drug-polymer content, buoyant capacity and drug release behaviour. The microspheres were spherical with relatively smooth surfaces with round hollow cavities. The microspheres and low densities (less than 1 g/cm3) and remained floating for more than 24 h in pH 1.2 and 7.5 buffers. The dissolution profiles of the floating theophylline microspheres showed near zero order kinetics and sustained release in both pH 1.2 and 7.5 buffers. Modified microspheres processed with the addition of 2% w/v polysorbate 80 to the internal phase had smaller sizes, lower densities and faster drug release compared with those without the addition of the surfactant.

Gastroretentive dosage forms: A review with special emphasis on floating drug delivery systems

“…Numbers of investigations have been done employing this particular method, and floating microspheres (Stithit et al, 1998;Soppimath et al, 2001a) were primarily dosage form of choice. The effect of formulation and process variables such as: polymer type, drug and polymer ratio, type of solvent, organic solvents ration, concentration of plasticizer in aqueous phase, temperature of aqueous phase, stirring rate, time of stirring were evaluated on the yield, particle size, loading, release, and floating behavior of microspheres (Leet et al, 1999;Streubel et al, 2002;Sato et al, 2004).…”

Cellulose esters in drug delivery

“…Price and co-workers (Stithit et al 1998) reported formation of microparticles of theophylline in a 1:1 blend of CAB-171-15 and Eudragit RL 100 (an acrylate/methacrylate copolymer that contains acid, ester, and quaternary amino groups). The polymers were dissolved and the drug ''dispersed'' in acetone, then the solution was saturated with CO 2 .…”

In vitro and in vivo evaluation of ranitidine hydrochloride loaded hollow microspheres in rabbits

“…To overcome such drawbacks, multiple-unit drug delivery systems have been developed, because the multiple-unit particulate systems (such as microspheres) could pass through the gastrointestinal tract (GIT) to avoid the variety of gastric emptying, and thus reduce interindividual difference in the absorption of the drug. Moreover, release the active ingredients at a sustained release rate in a larger area in the stomach is to reduce high regional concentration and risk of drug burst release compared to the single unit dosage forms (Stithit et al, 1998). At present, approaches to increase the gastric residence time include: floating system (Murata et al, 2000), swellable and expandable system (Hou et al, 2003), high density system (Rednick et al, 1970), bioadhesive system (Vasir et al, 2003), and altered shape system (Kedzierewicz et al, 1999).…”