Functionality Advancement of Poorly Soluble Drug by Comparative Study of Solubilizing Techniques with Molecular Simulation to in vivo evaluation

Abstract

:This study aimed at the functionality advancement of poorly soluble model drug i.e. Cefixime with HPBCD using comparative study of different solubility enhancement methods. CFX formulations with hydroxypropyl-β-cyclodextrin (HP-β-CD) prepared by different solubility enhancement methods viz.,physical mixture, kneading method, solvent evaporation, spray drying, lyophilization/freeze drying, microwave irradiation method and compared their solubility enhancement as well as dissolution. The optimized complexes characterized using ATR, 1H-NMR, ROSEY, XRD, SEM and DSC for confirming the complexation. In-vivo pharmacokinetic studies were performed using male wister rats (N=6) through oral route. Hydroxy propyl Beta cyclodextrin inclusion complexation prepared by spray drying method was found to be optimized for complexation with cefixime. Spray drying method was found to be better than other complexation techniques on basis of in-vitro dissolution studies. ATR, NMR, XRD, and DSC confirmed the formation of complex. The in silico anticipations for mode of incorporation were in agreeing with the experimental proton NMR measure. The bioavailability of cefixime was found to be enhanced more than3 times. In comparison to pure drug, statistically significant increase in the oral bioavailability was obtained with the HP-β-CD inclusion complex which was prepared by spray drying technique, with 347% increase in terms of Cmax. This comparative study gave idea about best suited method for solubility enhancement along with molecular docking and NMR studies for anticipating mode of inclusion & thus, ultimately, improving the oral bioavailability of CFX.

Effect of inclusion of citric acid and Lutrol® F-68 on ziprasidone and β-cyclodextrin complexation: Characterization, solubility and dissolution studies

“…X-ray powder diffraction (PXRD) study was carried out to confirm the formation of a new solid system. The diffraction pattern of ZPR showed several sharp high-intensity peaks at diffraction angles (2θ) of 10.6, 12.2, 16.3, 24.2, 25.2, and 27.1° indicating its crystalline nature [25]. The X-ray diffractograms of β-CD also showed several intense peaks due to its crystalline nature.…”

“…ZPR has a pKa value of 6.5 and it is poorly water-soluble (0.007 mg/mL at 37 °C) and highly lipophilic [23]. Many researchers have tried different methods to improve the solubility of ZPR by modifying the physicochemical characteristics like nanocrystal approach by the process of media milling [23,24], solid dispersion technique using carriers like soluplus, pluronic, hydroxypropyl β-CD, sulfobutyl ether β-CD, β-CD [24][25][26][27][28] and self-nano emulsifying pellets [29].…”

Cyclodextrin Inclusion Complexes with Antibiotics and Antibacterial Agents as Drug-Delivery Systems—A Pharmaceutical Perspective

“…The magnitude of the difference between the two approaches (Pluronic—solid dispersion and β-CD—IC) was not due to the ability of the Pluronic to enhance permeation, but only to its ability to improve solubility [ 80 ]. Another study found that the spray-drying method achieved the greatest solubility improvement of the cefixime complex with HP-β-CD compared to other methods, including solvent evaporation, co-grinding, microwave irradiation, and freeze-drying [ 81 ]. These studies showed that the binary system of cefixime showed greater antimicrobial activity against S. aureus and E. coli than cefixime alone.…”