RESULTS: The cumulative voting-based aggregation algorithm (CVAA), cluster-based similarity partitioning algorithm (CSPA) and hyper-graph partitioning algorithm (HGPA) were examined. The F-measure and Quality Partition Index method (QPI) were used to evaluate the clusterings and the results were compared to the Ward's clustering method. The MDL Drug Data Report (MDDR) dataset was used for experiments and was represented by two 2D fingerprints, ALOGP and ECFP_4. The performance of voting-based consensus clustering method outperformed the Ward's method using F-measure and QPI method for both ALOGP and ECFP_4 fingerprints, while the graph-based consensus clustering methods outperformed the Ward's method only for ALOGP using QPI. The Jaccard and Euclidean distance measures were the methods of choice to generate the ensembles, which give the highest values for both criteria.
CONCLUSIONS: The results of the experiments show that consensus clustering methods can improve the effectiveness of chemical structures clusterings. The cumulative voting-based aggregation algorithm (CVAA) was the method of choice among consensus clustering methods.
Methods: The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response.
Results: The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and -37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).
PURPOSE: A Central Composite Rotatable Design (CCRD) of Response Surface Methodology (RSM) was used purposely to optimize process parameters conditions for formulating nanoemulsion containing aripiprazole using high emulsification methods.
METHODS: This design is used to investigate the influences of four independent variables (overhead stirring time (A), shear rate (B), shear time (C), and the cycle of high-pressure homogenizer (D)) on the response variable namely, a droplet size (Y) of nanoemulsion containing aripiprazole.
RESULTS: The optimum conditions suggested by the predicted model were: 120 min of overhead stirring time, 15 min of high shear homogenizer time, 4400 rpm of high shear homogenizer rate and 11 cycles of high-pressure homogenizer, giving a desirable droplet size of nanoemulsion containing aripiprazole of 64.52 nm for experimental value and 62.59 nm for predicted value. The analysis of variance (ANOVA) showed the quadratic polynomial fitted the experimental values with F-value (9.53), a low p-value (0.0003) and a non-significant lack of-fit. It proved that the models were adequate to predict the relevance response. The optimized formulation with a viscosity value of 3.72 mPa.s and pH value of 7.4 showed good osmolality value (297 mOsm/kg) and remained stable for three months in three different temperatures (4°C, 25°C, and 45°C).
CONCLUSION: This proven that response surface methodology is an efficient tool to produce desirable droplet size of nanoemulsion containing aripiprazole for parenteral delivery application.
MATERIALS AND METHODS: Eighty patients who fulfilled the UK Working Party's Diagnostic Criteria for Atopic Dermatitis were included in the cross-sectional study. A standardized case report form was formulated to collect the demographic data and disease profile of the participants. AD severity was evaluated using the EASI and SCORAD score. All patients underwent a complete ophthalmological evaluation.
RESULTS: The prevalence of ocular manifestations among the patients with AD was 48.8%. Fifty-four (67.5%) patients had facial dermatitis and 37 (46.2%) showed periorbital signs. The mean AD disease duration was 10.99 ± 11.20 years. Majority of the patients had mild to moderate AD. The most frequent ocular manifestation was allergic conjunctivitis (18.75%) followed by cataract (8.75%) and ocular hypertension (8.75%). Among the patients with ocular manifestations, 27 (69.2%) patients regularly applied topical corticosteroids on the face. The use of systemic corticosteroids was seen in 19 (42.2%) patients. Prolonged AD duration was significantly associated with the development of ocular manifestations.
CONCLUSIONS: Nearly half of the patients with AD were complicated with ocular disease regardless of the AD severity, facial dermatitis and presence of periorbital signs. Long disease duration is associated with ocular manifestations, especially steroid related complications.