AN OVERVIEW OF THE AZOLES OF INTEREST

In the last years, the risk of human fungal infections has been extensively increased with the increasing immune suppressed patients. Fortunately, the therapy of fungal infections has been undergone an explosive period of development. It was found that the use of currently available azoles in combination with other antifungals is likely to provide enhanced efficacy. But, several factors lead to therapeutic failure or relapse after the antifungal therapy. These factors are concerned with the different characteristics of the antifungal (s) used. Thus, specialists should be carefully investigated the different characteristics of antifungals to avoid these factors and further to use the antifungals optimally. The present review discussed the different characteristics of the azoles of interest, to recognize the differences in pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and potential drug interactions of these antifungal agents. However, the present review explore that the azoles of interest are sufficiently diverse in pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and potential drug interactions allowing specialists to differentiate among these agents based upon their characteristics when tailoring therapy to meet the needs of a particular patient. Moreover, further advances in antifungal chemotherapy will be necessary to improve management of invasive mycoses in the future

FORMULATION AND EVALUATION OF FLURBIPROFEN SUSTAINED RELEASE MATRIX TABLETS USING AN ALTERNATIVE TECHNIQUE AS POTENTIAL ECONOMIC APPROACH

Objective: Development of sustained released tablets of flurbiprofen (FP) using an alternative technique to the traditional method of wet granulation process aiming to lower labor cost of the granulation process and formulating tablets with better characteristics. Methods: Eight matrix tablets formulae of FP were prepared by the alternative technique. The various characteristics of FP prepared tablets were investigated and comparatively evaluated by FP tablets prepared by the traditional method. The release data was analyzed according to various kinetic equations. The ulcerogenic effects of some FP tablets formulae were evaluated. Results: FP tablets prepared by the alternative technique displayed the best physical characteristics. All FP prepared tablets displayed good sustained-release patterns. FP tablets prepared by the traditional method showed a progress decrease in drug dissolution by increasing matrix concentration and hence, more matrix agent or multiple granulations was needed which makes granulation process to be difficult and cost. While, FP tablets prepared by the alternative technique displayed dissolution profiles with minimal differences in-between reflecting the low labor cost of granulation process where good sustained patterns could be obtained by a minor of the matrix agent. Histologically, the ulcerogenic effects of FP on the rats were highly reduced by FP tablets prepared by the alternative technique rather than others. The release kinetics of different prepared FP tablets displayed a coupled release pattern between diffusion and dissolution. Conclusion: This work proved the potential of the alternative technique as an effective economic approach for formulating FP sustained released tablets with better characteristics and low labor cost

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples

Enhancing Oral Bioavailability of Simvastatin Using Uncoated and Polymer-Coated Solid Lipid Nanoparticles

Simvastatin (SVA) is a well-prescribed drug for treating cardiovascular and hypercholesterolemia. Due to the extensive hepatic first-pass metabolism and poor solubility, its oral bioavailability is 5%. Solid lipid nanoparticles (SLNs) and hydrogel-coated SLNs were investigated to overcome the limited bioavailability of SVA. Four different lipids used alone or in combination with two stabilizers were employed to generate 13 SLNs. Two concentrations of chitosan (CS) and alginate (AL) were coating materials. SLNs were studied for particle size, zeta potential, in vitro release, rheology, and bioavailability. The viscosities of both the bare and coated SLNs exhibited shear-thinning behavior. The viscosity of F11 (Chitosan 1%) at 20 and 40 rpm were 424 and 168 cp, respectively. F11 had a particle size of 260.1 ± 3.72 nm with a higher release; the particle size of F11-CS at 1% was 524.3 ± 80.31 nm. In vivo studies illustrated that F11 had the highest plasma concentration when compared with the SVA suspension and coated chitosan (F11 (Chitosan 1%)). Greater bioavailability is measured as (AUC0→24), as compared to uncoated ones. The AUC for F11, F11-CS 1%, and the SVA suspension were 1880.4, 3562.18, and 272 ng·h/mL, respectively. Both bare and coated SLNs exhibited a significantly higher relative bioavailability when compared to that from the control SVA

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)