In vitro and in vivo evaluation of clarithromycin solid dispersion prepared by spray-drying

Abstract

The aim of this study was to develop solid dispersions (SDs) of clarithromycin (CLA) using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and xanthan gum (XNG) as drug carriers. An in vitro dissolution study was performed in dissolution media of pH 6.8, and the results were compared with those of standard drugs. In vivo pharmacokinetic studies were carried out on an animal model (rabbits). The thermal behavior of each SD formulation was studied using differential scanning calorimetry analysis. It was concluded from the results that the crystalline nature of CLA had been transformed into an amorphous form in SDs. Pharmacokinetic parameters were observed to improve in HPMC- as well as XNG-based SDs compared with those of the standard drug. Additionally, powder X-ray diffraction analysis also confirmed the phase transition (crystalline to amorphous) of the drug present in SDs. Higher values of C max were found in the case of HPMC-based SDs, whereas t max values were prolonged in SDs based on XNG. Additionally, the enhanced half-life values indicated that SDs would have the potential to achieve a once-daily dose and improved patient compliance of drugs. Hence, the formulated SDs of a poorly soluble drug, based on HPMC and XNG as carriers, exhibited a more hydrophilic nature with enhanced aqueous solubility and therefore improved bioavailability compared with that of a standard drug.