Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen

Abstract

Polyelectrolyte complexes (PECs) are attractive carriers with recognized potential to enhance oral delivery of poorly soluble high-dosed low-molecular-weight drugs. The formulation of solid oral dosage forms requires the drying of PECs, which may affect their physicochemical and biopharmaceutical properties. The aim of this study was to investigate the effect of spraydrying on the properties of ibuprofen-loaded chitosan/xanthan gum PECs and to assess the drug release kinetics from such PECs filled into hard capsules in comparison with corresponding PECs which are dried under ambient conditions. The yield, ibuprofen content, entrapment efficiency, and residual moisture content of spray-dried PECs were lower than those of ambient-dried PECs. Better flowability of spray-dried PECs was attributed to the almost spherical particle shape, shown by scanning electron microscopy. DSC and PXRD analysis confirmed the amorphization of ibuprofen during spray-drying. All the investigated PECs, obtained by drying under ambient conditions as well as by spray-drying, had high rehydration capacity both in 0.1 M hydrochloric acid (pH 1.2) and phosphate buffer pH 7.4. In vitro ibuprofen release from dried PECs was controlled during 12 h with the release of approximately 30% of entrapped ibuprofen. Spray-dried PECs provided better control of ibuprofen diffusion from the carrier compared to the ambientdried ones.

Modeling of in vitro drug release from polymeric microparticle carriers

“…On the other hand, for the ambient-dried PEC, ibuprofen release during the first 3 h (in pH 1.2) followed the Korsmeyer-Peppas kinetics (typical for drug carriers with swelling ability), and during the next 9 h in phosphate buffer pH 7.4 the first-order kinetics (Table II) (drug release rate dependent on its concentration). The suggested mechanism of ibuprofen release was a combination of diffusion after the swelling of PECs, relaxation of polymer chains, and erosion (11). Other hydrophobic anti-inflammatory drugs were also incorporated into microspheres in order to achieve their controlled release.…”

“…However, a common drawback of biopolymer based microparticles is an initial burst release phase causing a lack in the optimal control of drug loading and release, and a poor correlation between in vitro release profiles and in vivo therapeutical outcomes (5)(6)(7)(8). In order to establish better control over drug release from such biocompatible polymer microparticles, various technological strategies are proposed, including the formation of polyelectrolyte complexes (9)(10)(11), layer-by-layer (LBL) self-assembly of nanofilms (12,13), chemical cross-linking or introduction of molecules sensitive to environmental stimuli (14)(15)(16)(17)(18)(19)(20)(21). In this way, complex carriers are created which, according to the internal morphology, can be classified as microspheres (i.e., monolithic polymer matrix-based microparticles) or microcapsules (i.e., core-shell microparticles comprising a reservoir surrounded by a polymer wall).…”