Enhancement of Solubility, Transport Across Madin-Darby Canine Kidney Monolayers and Oral Absorption of Pranlukast Through Preparation of a Pranlukast-Phospholipid Complex

Abstract

This study aimed to enhance the solubility of a poorly water-soluble drug, pranlukast, as well as its transport across MadinDarby canine kidney (MDCK) monolayers, thus increasing its oral bioavailability. To accomplish this aim, we prepared a pranlukast-phospholipid complex (PPC). The PPC was prepared by solvent-evaporation and characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), infrared (IR) spectroscopy, and solubilization studies. The solubility of pranlukast in the PPC was increased from 1.03 ± 0.32 g/ml to 160.63 ± 2.72 g/ml with a yield of 96.39 ± 1.20% when the PPC was prepared under optimal conditions. TEM images showed that the PPC particles had a spherical shape. XRD data indicated that pranlukast in the PPC was either in an amorphous form or in a dispersed molecular distribution. IR analysis confirmed the interaction between pranlukast and the phospholipids. The transport mechanism of the PPC and non-complexed pranlukast across MDCK cells was measured and was observed to be significantly greater for the former than for the latter. The in vivo bioavailability of the PPC in rats hastened the onset of pranlukast-induced therapeutic effects, with C max and AUC increases of 21.88-and 28.64-fold, respectively, compared with raw crystals. In addition, an in vivo imaging method was used to corroborate that the PPC exhibited rapid circulatory distribution and gastrointestinal tract accumulation. These results indicate that PPC appears to be a promising drug delivery system for pranlukast, improving drug absorption and decreasing side effects by reducing the required oral dose.

Isolation, Characterization, and Toxicity Study of Stress Degradation Products of Pranlukast Hydrate

“…Pranlukast hydrate (PRN) {4-oxo-8-[4-(4-phenylbutoxy)­benzoylamino]-2-(tetrazole-5-yl)-4 H -1-benzopyran hemihydrate} is the first orally active, novel, potent, and selective cysteinyl leukotriene receptor antagonist (CysLT 1 ). , It is used in the treatment of asthma where it reduces the bronchospasm caused by the development of allergen-induced mega choline airway hyperresponsiveness and hence results in an excellent recovery of normal lung function within a short time. − …”