Enhancement of cyclosporin A solubility by d-alphatocopheryl-polyethylene-glycol-1000 succinate (TPGS)

The aqueous solubility of cyclosporin A (CyA) in the presence of various concentrations of TPGS ranging from 0.01 to 0.50 mM was studied at three temperatures (5, 20, and 37°C). Compared to previously reported solubility data in triple distilled water, solubility in the presence of TPGS was significantly increased at all temperatures. Surface tension and light scattering measurements showed that solubilization in TPGS multimers is the main mechanism responsible for the increased CyA solubility at 20°C and 37°C. In contrast, the increased CyA solubility at 5°C appears to be mediated by other mechanism(s), such as association of TPGS in patients CyA. These data substantiate the view that the enhanced bioavailability of CyA, when coadministered with TPGS in patients suffering from cholestasis, is due to the increased solubility of CyA in the presence of TPGS. © 1994

Unusual solubility behaviour of cyclosporin A in aqueous media

Abstract— The solubility of cyclosporin A was determined in water and in Sorensen buffers at pH 1.2 and 6.6 at temperatures ranging from 5 to 37°C. No differences in solubility behaviour were observed among the three aqueous media. Solubility was found to be inversely proportional to the temperature in each medium, indicating that the heat of solution was exothermic in each case. 1991 Royal Pharmaceutical Society of Great Britai

Correlation between acinetobacter baumannii resistance and hospital use of meropenem, cefepime, and ciprofloxacin: Time series analysis and dynamic regression models

Acinetobacter baumannii is one of the most difficult-to-treat pathogens worldwide, due to developed resistance. The aim of this study was to evaluate the use of widely prescribed antimi-crobials and the respective resistance rates of A. baumannii, and to explore the relationship between antimicrobial use and the emergence of A. baumannii resistance in a tertiary care hospital. Monthly data on A. baumannii susceptibility rates and antimicrobial use, between January 2014 and December 2017, were analyzed using time series analysis (Autoregressive Integrated Moving Average (ARIMA) models) and dynamic regression models. Temporal correlations between meropenem, cefepime, and ciprofloxacin use and the corresponding rates of A. baumannii resistance were documented. The results of ARIMA models showed statistically significant correlation between meropenem use and the detection rate of meropenem-resistant A. baumannii with a lag of two months (p = 0.024). A positive association, with one month lag, was identified between cefepime use and cefepime-resistant A. baumannii (p = 0.028), as well as between ciprofloxacin use and its resistance (p < 0.001). The dynamic regression models offered explanation of variance for the resistance rates (R2 > 0.60). The magnitude of the effect on resistance for each antimicrobial agent differed significantly. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Pharmacokinetics of oral cefatrizine in pregnant and non-pregnant women with reference to fetal distribution

Objective: To investigate the effect of gestation on the pharmacokinetics of orally administered beta-lactams, choosing cefatrizine as the model antibiotic. Setting: A tertiary teaching hospital. Design: Prospective study. Methods: In 20 women with affected fetuses, 17 by beta-thalassemia major and 3 with congenital malformations, termination of gestation between 19 and 24 weeks was induced by intra-amniotic administration of prostaglandin F-2 alpha. Pharmacokinetics of cefatrizine in maternal and fetal blood were studied after the administration of three 1 g doses of oral cefatrizine, every 12 h. Twenty female non-pregnant volunteers consisted the control group. Results: Gestation was found to decrease substantially both cefatrizine oral bioavailability and maximum serum plasma concentration (42.8 and 44.5%, respectively) but increased elimination half-life. This effect can be attributed to a substantial increase of the apparent volume of distribution of cefatrizine in relation to a moderate increase of clearance that occurs during pregnancy. Fetal serum cefatrizine levels were lower for the first few hours after administration and then exceeded the corresponding maternal ones. Conclusions: Our results indicate that gestation decreases the oral bioavailability of cefatrizine. A delay in the maternal drug elimination compared to non-pregnant controls was more pronounced in the fetus. Copyright (c) 2007 S. Karger AG, Basel

Formulation and Evaluation of a Protein-loaded Solid Dispersions by Non-destructive Methods

The purpose of this investigation was to develop solid dispersion (SD) formulation of cyclosporine (CyA) using polyethylene glycol (PEG-6000) to enhance its dissolution rate followed by nondestructive method for the prediction of both drug and carrier. SD formulations were prepared by varying the ratio of CyA and PEG-6000 by solvent evaporation technique and characterized by dissolution, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), powder X-ray diffraction (PXRD), near infrared (NIR) and near infrared chemical imaging (NIR-CI). Dissolution data revealed enhanced dissolution of CyA when compared with pure CyA. DSC results showed that the crystallinity of PEG-6000 has decreased as indicated by decrease in the enthalpy of fusion and melting peak in the formulations. FTIR data demonstrated no chemical interaction between drug and carrier. The surface morphology of SD formulations was similar to PEG-6000 particle. NIR-CI disclosed homogeneity of SD matrix as indicated by symmetrical histograms with smaller values of skewness. Similar to NIR, a multivariate peak evaluation with principal component analysis and partial least square (PLS) were carried out with PXRD spectral data. PLS models with both techniques showed good correlation coefficient and smaller value of root mean square of errors. The accuracy of model for predicting CyA and PEG-6000 in NIR and PXRD data were 5.22%, 5.35%, 5.27%, and 2.10%, respectively. In summary, chemometric applications of non-destructive method sensors provided a valuable means of characterization and estimation of drug and carrier in the novel formulations