: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.
Abstract:In modern times, people are suffering from many mental health disorders like schizophrenia, bipolar disorders and many psychoses. Hence, it is essential to treat these mental disorders using medications as well as with assistance from caregivers for the social well being of person. This study was focussed on improving solubility & dissolution of poorly soluble drug Ziprasidone using different formulation approaches like solid dispersion & inclusion complexation. Different solubility enhancing techniques like physical mixing, solvent evaporation, microwave irradiation, lyophilization & spray drying were used for the along with four different polymers i.e Kollidon, Soluplus, Pluronic and HPβCD. The prepared formulations were evaluated for saturated solubility, dissolution, ATR, SEM, XRD, pharmacodynamic and pharmacokinetic in vivo study. The prepare formulations showed increment in solubility as well as dissolution. The order of solubility enhancement for the studied polymers was found to be of following order: Soluplus>HPβCD>Kollidon>Pluronic. In the pharmacodynamic study, the optimized solid dispersion showed the calming effect on mice when compared to pure Ziprasidone. The pharmacokinetic study demonstrated the increase in oral absorption of Ziprasidone in all prepared formulations and it followed the same order as that solubility & dissolution enhancement. The Soluplus-solid dispersion prepared by spray drying technique was found to be suitable in enhancing oral absorption with significant (p < 0.05) enhancement in Cmax & AUC than pure Ziprasidone. Hence, comparative study was helpful in increasing oral bioavailability Of Ziprasidone in choosing the suitable polymer with decreasing the dose and increasing patient adherence to therapy.
Cefixime is BCS class 2/4 drug whose oral absorption is limited by its solubility and/or permeability. The use of HPBCD is proved to be better complexing agent for enhancing solubility as well as permeability of drugs. At the same time spray drying is the one step continuous drying process making it attractive technique for industrial application. Therefore, the current study was undertaken to unite the use of HPBCD and spray drying alongside with optimizing it through Design of Experiments (DOE) approach by means of Box-Behnken design for the benefit of drugs like Cefixime that needs to be redeveloped for better therapeutic efficacy. These formulations were evaluated by solubility studies, process yield and total drug content with help of independent variables like air inlet temperature, aspirator rate and pump feed rate. The optimized formulation was also characterized by SEM, FTIR analysis and in vitro dissolution study. Inlet air temperature was found to be the most important parameter for the spray dried material characteristics, followed by the aspirator flow rate whereas Feed flow rate was found less significant. The results indicate that formulation parameters are at least important than process parameters when designing a proper process for spray drying inclusion complex. The optimized formulation was also then compressed into tablet and was compared with marketed formulation where it showed comparable dissolution.
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