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

Histological evaluation of pulp response to Pulpine NE versus Biodentine as direct pulp capping materials in a dog model

Objective: The material used for pulp capping has a significant impact on the outcome of vital pulp therapy. This study compared the pulp tissue response to Pulpine NE versus Biodentine as direct pulp capping materials in a dog model. Methods: Twenty-four teeth in two mongrel dogs (1-2-year-old) were used. In each dog (n=12 teeth), the dental pulps were exposed in 8 teeth (2 experimental groups, 4 teeth each) and left unexposed in 4 teeth (control group, n=4 teeth). A class V cavity was performed on the buccal surface of the selected teeth in the experimental groups. The exposed pulps were capped either with Pulpine-NE (group I) or Biodentine (group II). Then, the cavities were restored with Riva resin modified glass ionomer filling material. One dog was euthanized at 14 days after pulp capping and the second dog was euthanized after 45 days. Histological analysis of the continuity of dentin bridge, tissue disorganization and inflammatory reaction were statistically analyzed. Results: The results revealed that Biodentine exhibited statistically significant higher dentin bridge formation than Pulpine NE after 14 and 45 days (PConclusion: Pulpine NE was capable of inducing reparative dentin when used as a direct pulp capping material. Nevertheless, Biodentine showed more efficient dentin bridge formation, tissue organization and anti-inflammatory potential than Pulpine NE

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

Transdermal agomelatine microemulsion gel: pyramidal screening, statistical optimization and in vivo bioavailability

Agomelatine is a new antidepressant having very low oral drug bioavailability less than 5% due to being liable to extensive hepatic 1st pass effect. This study aimed to deliver agomelatine by transdermal route through formulation and optimization of microemulsion gel. Pyramidal screening was performed to select the most suitable ingredients combinations and then, the design expert software was utilized to optimize the microemulsion formulations. The independent variables of the employed mixture design were the percentages of capryol 90 as an oily phase (X1), Cremophor RH40 and Transcutol HP in a ratio of (1:2) as surfactant/cosurfactant mixture ‘Smix’ (X2) and water (X3). The dependent variables were globule size, optical clarity, cumulative amount permeated after 1 and 24 h, respectively (Q1 and Q24) and enhancement ratio (ER). The optimized formula was composed of 5% oil, 45% Smix and 50% water. The optimized microemulsion formula was converted into carbopol-based gel to improve its retention on the skin. It enhanced the drug permeation through rat skin with an enhancement ratio of 37.30 when compared to the drug hydrogel. The optimum ME gel formula was found to have significantly higher Cmax, AUC 0–24 h and AUC0–∞ than that of the reference agomelatine hydrogel and oral solution. This could reveal the prosperity of the optimized microemulsion gel formula to augment the transdermal bioavailability of agomelatine

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