ENHANCEMENT OF DISSOLUTION RATE OF HYDROCHLOROTHIAZIDE

Objective: The aim of this study was to enhance the dissolution rate of hydrochlorothiazide (HCTZ).Methods: Binary solid dispersions (SDs) of HCTZ with increasing weight ratios of poloxamer 407, polyethylene glycol 6000 (PEG 6000) or gelucire 50/13 were prepared by solvent evaporation technique. The solid dispersions were deposited on the surface of aerosil 200 to produce a dry product with large surface area. The SDs were characterized with respect to drug dissolution. The mechanism of dissolution enhancement was researched using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC).Results: The unprocessed drug showed erratic, slow dissolution which can be explained on the basis of its hydrophobic nature. Preparation of SDs with hydrophilic carriers resulted in a significant increase in the dissolution rate with most of the drug being liberated in the first 5 min. The dissolution pattern of the drug from the prepared SDs depends mainly on the type of polymer used, and the best dissolution pattern was observed in the SD prepared using 1:1 ratio of the drug to gelucire 50/13 in the presence of aerosil 200 as a carrier. FTIR studies revealed no interaction between the drug and polymers. DSC showed a change in the crystalline structure of the drug after SDs formation. This change can explain the recorded dissolution enhancement.Conclusion: The study presented a system capable of increasing the dissolution rate of HCTZ using polymers which can increase the intestinal permeability as well.Keywords: Hydrochlorothiazide, Poloxamer 407, PEG 6000, Gelucire 50/13, Solid dispersion, Dissolutio

Systematic review and meta-analysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer

Background: Febrile neutropenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer. Many biomarkers have been proposed as predictors of adverse events. We aimed to undertake a systematic review and meta-analysis to summarize evidence on the discriminatory ability of initial serum biomarkers of febrile neutropenic episodes in children and young people. Methods: This review was conducted in accordance with the Center for Reviews and Dissemination Methods, using three random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100485. Results: We found that 25 studies exploring 14 different biomarkers were assessed in 3,585 episodes of febrile neutropenia. C-reactive protein (CRP), pro-calcitonin (PCT), and interleukin-6 (IL6) were subject to quantitative meta-analysis, and revealed huge inconsistencies and heterogeneity in the studies included in this review. Only CRP has been evaluated in assessing its value over the predictive value of simple clinical decision rules. Conclusions: The limited data available describing the predictive value of biomarkers in the setting of pediatric febrile neutropenia mean firm conclusions cannot yet be reached, although the use of IL6, IL8 and procalcitonin warrant further study

Evaluation of skin absorption of drugs from topical and transdermal formulations

ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed

Measurement of Supercritical Carbon Dioxide Capillary Trapping in Core Analysis

Capillary trapping has been identified as a fast and effective method to render injected carbon dioxide (CO2) immobile as disconnected pore-scale droplets surrounded by brine. We measure trapped CO2 saturations in sandstones at conditions representative of storage locations. We compare the unsteady state and porous plate methods of achieving initial CO2 saturations before waterflooding to reach residual saturation. Brine and CO2 are equilibrated prior to injection to ensure immiscible displacements occur on the pore scale. The problems faced with un-equilibrated phases are discussed.The unsteady state and porous plate methods are shown to give different results in terms of maximum initial and residual saturations for Berea sandstone samples. With the unsteady state method maximum residual CO2 saturations of 25-28% are measured for corresponding maximum initial saturations of 35-40%. With the porous plate method a maximum residual saturation of 37% is measured for a maximum initial saturation of 90%. The implications for coreflood method selection during data gathering are discussed. The porous plate results are compared with oil-brine porous plate saturations measured on the same samples. CO2-brine residual saturations are shown to be slightly lower than the corresponding oil-brine measurements. We suggest that considerable carbon dioxide capillary trapping is possible in clean sandstones and discuss the implications for carbon storage in aquifers