Improved bioavailability of timolol maleate via transdermal transfersomal gel: Statistical optimization, characterization, and pharmacokinetic assessment

AbstractTimolol maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from extensive first pass effect, resulting in a reduction of oral bioavailability (F%) to 50% and a short elimination half-life of 4h; parameters necessitating its frequent administration. The current study was therefore, designed to formulate and optimize the transfersomal TiM gel for transdermal delivery. TiM loaded transfersomal gel was optimized using two 23 full factorial designs; where the effects of egg phosphatidyl choline (PC): surfactant (SAA) molar ratio, solvent volumetric ratio, and the drug amount were evaluated. The formulation variables; including particle size, drug entrapment efficiency (%EE), and release rate were characterized. The optimized transfersomal gel was prepared with 4.65:1 PC:SAA molar ratio, 3:1 solvent volumetric ratio, and 13mg drug amount with particle size of 2.722μm, %EE of 39.96%, and a release rate of 134.49μg/cm2/h. The permeation rate of the optimized formulation through the rat skin was excellent (151.53μg/cm2/h) and showed four times increase in relative bioavailability with prolonged plasma profile up to 72h compared with oral aqueous solution. In conclusion, a potential transfersomal transdermal system was successfully developed and the factorial design was found to be a smart tool, when optimized

Bacterial Exopolysaccharides as New Natural Coagulants for Surface Water Treatment

Abstract: Coagulation-flocculation step is one of the most important steps during surface w ate r tre atm e n t. Che m ic al co ag ul an ts are o rdin ary use d such as al um . Howe ve r, the se chemical coagulants are dangerous to environment and human health. Natural coagulants derived from natural sources receive much attention during last years. This study aimed to isolate new bacterial exopolysaccharides from Bacillus licheniformis, B. insolitus and B. alvei to be used as natural coagulants during coagulation-flocculation process. Efficiency of extracted bacterial exopolysaccharides was examined through removal ability of bacterial indicators and some physicochemical parameters of River Nile water samples. Bacterial exopolysaccharides showed great removal percent when used as sole coagulant materials. Addition of alum to bacterial exopolysaccharides enhance removal efficiency

Effect of orientation on in-isolation and in-soil geosynthetic properties

Geosynthetics have been extensively used in pavement systems, either by placing the geosynthetic at the interface between the base and subbase layers or at the interface between the subbase and subgrade layers or within the unbound base course layer to enhance the performance of roadways under repeated traffic and environmental loads. Gaining a better understanding on the geosynthetic and soil-geosynthetic interaction properties along various directions is important for geosynthetics that are subjected to multi-directional loads. Previous studies have investigated the effect of geosynthetic orientation on the unconfined tensile properties of biaxial and triangualr geogrids, whether by using numerical software or by using analytical analysis. However, the effect of geosynthetic orientation on the soil-geosynthetic interaction properties has not extensively been studied. Furthremore, properties of geotextiles have also not extensively been studied along various directions. The objective of this research is to gain a better understanding of the impact of the geosynthetic orientation on the geosynthetic and soil-geosynthetic interaction properties. Two types of test were used to achieve the objective of this research: (1) Wide-width tensile tests, which were used to investigate the impact of geosynthetic orientation on the geosynthetic properties, and (2) Soil-geosynthetic interaction tests, which were used to study the impact of geosynthetic orientation on the soil-geosynthetic interaction properties. Three types of geosynthetics that have similar mass per unit area were used in this study. This included: a triangular geogrid, a biaxial geogrid, and a woven geotextile. Geosynthetic and soil-geosynthetic interaction properties were evaluated for each geosynthetic along various directions. Variation of these properties were also compared between the three products tested. Effect of various components of the experimental setup and the test design on the findings were also evaluated. Evaluation of the results obtained from the wide-width tensile tests indicated that the ultimate tensile strength and tensile stiffness of the geogrid with triangular aperture shapes, were comparatively uniform along all tested directions. However, the ultimate tensile strength and tensile stiffness of the woven geotextile and the geogrid with rectangular aperture shapes, were highly dependent on the direction of tensile load. When the tensile load was applied along the machine or the cross-machine directions, the ultimate tensile strength and tensile stiffness of the woven geotextile and the biaxial geogrid were noticeably high. However, when the tensile load was applied along other directions (i.e., 30˚, 45˚, and 60˚), the ultimate tensile strength and tensile stiffness were comparatively low. Evaluation of the results obtained from the soil-geosynthetic interaction tests indicated that the ultimate pullout resistance and the stiffness of the soil-geosynthetic composite (KSGC) of the triangular geogrid were relatively uniform along all tested directions. However, the ultimate pullout resistance and the stiffness of the soil-geosynthetic composite (KSGC) of the woven geotextile and the biaxial geogrid were highly dependent on the direction of tensile load. When the pullout load was applied along the machine or the cross-machine directions, the ultimate pullout resistance and the stiffness of the soil-geosynthetic composite (KSGC) were found to be comparatively high. However, when the pullout load was applied along other directions (i.e., 30˚, 45˚, and 60˚), the ultimate pullout resistance and the stiffness of the soil-geosynthetic composite (KSGC) were found to be comparatively low. Overall, findings from this study indicate that the triangular geogrid tested in this study provided an isotropic in-plane behavior both in-isolation and under confinement of soil. However, the in-isolation and under confinement responses of the biaxial geogrid and the woven geotextile evaluated in this study were found to be highly anisotropic. Specifically, although the biaxial geogrid and the woven geotextile were found to have high mechanical properties in the machine and cross-machine directions, their properties along other directions were found to be comparatively low.Civil, Architectural, and Environmental Engineerin

Gastroretentive raft liquid delivery system as a new approach to release extension for carrier-mediated drug

Gabapentin (GBP), an antiepileptic and anti-neuropathic agent, suffers from short half-life (5–7 h), has narrow absorption window, and is absorbed via carrier-mediated mechanism resulting in frequent dosing, poor compliance, and poor bioavailability (<60%). Moreover, GBP is a freely water-soluble drug, thus it is considered a challenging candidate to be formulated as extended release dosage form. In this study, raft forming systems were investigated as a potential drug delivery system for prolonging gastric residence time of GBP. A 23 full factorial design was adopted to study the effect of formulation variables (% gellan gum, % GMO, and % LM-pectin 101), on the percent of GBP released at different time intervals (1, 5, and 8 h) as well as the gel strength, and thus was achieved an optimized formula with zero-order release profile suitable for once-daily administration. In vivo assessment was performed in rats to evaluate gastric residence of the gel formed. In addition, the oral bioavailability of GBP relative to commercially available Neurontin® immediate release oral solution was also investigated. Significant increase was observed for Cmax, AUC(0–t), and AUC(0–∞). The increase in relative bioavailability of GBP from the optimized formula was 1.7 folds