Oxprenolol-loaded bioadhesive microspheres: preparation and in vitro / in vivo characterization

Abstract

Biologically adhesive delivery systems offer important advantages over conventional drug-delivery systems. In this paper, microspheres intended as a sustained release carrier for oral or nasal administration have been prepared by associating a known bioadhesive polymer, poly(acrylic acid), in gelatin microspheres. A model drug oxprenolol hydrochloride was chosen. It was found that some of the formulation variables can influence the characteristics of the beads in a controlled manner. The internal structure of the microspheres studied by X-ray diffraction, thermal analysis and optical microscopy showed the absence of drug crystals in microspheres and a lowering in the glass transition temperature. The dynamic swelling of the beads obeyed the square root of time and a shift from the diffusional to the relaxational process dependent on the content of poly(acrylic acid) in gelatin microspheres was observed. As expected, drug release from gelatin/poly(acrylic acid) microspheres was influenced by the poly(acrylic acid) content in beads, by the particle size of microspheres and by the pH of the medium. The mechanism of release was analysed by applying the empirical exponential equation and by calculation of the approximate contribution of the diffusional and relaxational mechanisms to the anomalous release process by fitting the data to the coupled Fickian/Case II equation. In vitro and in vivo experiments in rats showed good adhesive characteristics of the gelatin/poly(acrylic acid) microspheres, which were greater if the poly(acrylic acid) content was greater. A significant retardation in gastric and intestinal emptying time of the beads was observed. This was also suggested by the bioavailability of the model drug after intragastric and intranasal administration of the microspheres. The pharmacokinetic parameters after microsphere administration were more appropriate to a slow release drug-delivery system. The work suggests the potential of this pharmaceutical delivery system as an alternative controlled-release dosage form, either for oral or nasal administration.

Novel Gastroretentive Floating Pulsatile Drug Delivery System Produced via Hot-Melt Extrusion and Fused Deposition Modeling 3D Printing

“…A strategy to increase the residence time of the drugs to overcome the above-mentioned drawbacks is necessary for optimal therapeutic outcomes. Numerous strategies have been used to increase the residence time of the dosage forms in the stomach, including mucoadhesive systems [8,9], high-density systems that sink to the bottom of the stomach [10], swelling systems [11] and floating systems [12][13][14]. Among these strategies, floating systems are considered superior as they do not interfere with the physiological activity of the gastrointestinal tract [15].…”

Chitosan microspheres as a delivery system for nasal insufflation

“…The microparticulate delivery systems are considered as a reliable means to deliver the drug to the target site with specificity, if modified, and to maintain the desired concentration at the site of interest without untoward effects. Microspheres constitute an important part of these particulate drug delivery systems by virtue of their small size and efficient carrier characteristics [1][2][3][4].…”

Preparation and evaluation of cefquinome‐loaded gelatin microspheres and the pharmacokinetics in pigs

“…Furthermore, the particle size of microspheres was reported to be largely affected by the stirring rate in the emulsification process (Govender et al., ; Preda & Leucuta, ). Similar results were observed in this study, the mean diameter of GMS decreased as the stirring rate increased from 500 to 1,100 rpm.…”