Evaluation of hydrophilic,hydrophobic and waxy matrix excipients for sustained release tablets of Venlafaxine hydrochloride

Objective: Venlafaxine is freely soluble In water and administered orally as hydrochloride salt In two to three divided doses. In the present investigation different release retarding matrices have been evaluated for sustained release of venlafaxine hydrochloride (VH) from the formulated tablets.

Materials and methods: Sustained release matrix tablets were formulated using different hydrophilic, hydrophobic and waxy materials as matrix formers. Tableting was done by pre-compression, direct compression and hot melt granulation depending on the type of matrix material used and evaluated for different tests. The formulated tablets were compared with commercial venlafaxine products. In vitro drug dissolution profiles were fitted In different mathematical models to elucidate the release mechanism.

Results: Dissolution data showed that commercial formulations Venlor XR^® and Venfax PR^® released the entire drug withIn 8?h where as the formulated tablets with hydroxypropylmethylcellulose (HPMC) and cetyl alcohol as matrix formers provided sustained release of drug for 14–15?h. The release was found to follow Hixson Crowel and Higuchi kinetics for HPMC and cetyl alcohol tablets, respectively.

Conclusion: The developed matrix tablet formulations with HPMC and cetyl alcohol provided sustained release profiles for prolonged periods than commercial formulations.     

Adsorptive stripping differential pulse voltammetric determination of venlafaxine and desvenlafaxine employing Nafion–carbon nanotube composite glassy carbon electrode

A Nafion-carbon nanotube-modified glassy carbon electrode (NAF-CNT-GCE) was developed for the determination of venlafaxine (VF) and desvenlafaxine (DVF). The electrochemical behavior of both these molecules was investigated employing cyclic voltammetry (CV), chronocoulometry (CC), electrochemical impedance spectroscopy (EIS) and adsorptive stripping differential pulse voltammetry (AdSDPV). The surface morphology of the electrodes has been studied by means of scanning electron microscopy (SEM). These studies revealed that the oxidation of VF and DVF is facilitated at NAF-CNT-GCE. After optimization of analytical conditions employing this electrode at pH 7.0 in Britton–Robinson buffer (0.05 M) for VF and pH 5.0 in acetate buffer (0.1 M) for DVF, the peak currents for both the molecules were found to vary linearly with their concentrations in the range of 3.81 × 10⁻⁸–6.22 × 10⁻⁵ M for VF and 5.33 × 10⁻⁸–3.58 × 10⁻⁵ M for DVF. The detection limits (S/N = 3) of 1.24 × 10⁻⁸ and 2.11 × 10⁻⁸ M were obtained for VF and DVF, respectively, using AdSDPV. The prepared modified electrode showed several advantages, such as simple preparation method, high sensitivity, very low detection limits and excellent reproducibility. The proposed method was employed for the determination of VF and DVF in pharmaceutical formulations, urine and blood serum samples.     

Spray-Dried Buccal Mucoadhesive Microparticles of Venlafaxine Based on Cress Seed Mucilage: In Vitro,in Vivo Evaluation in Rabbits

Lepidium sativum Linn. (Cruciferea) is known as garden cress or cress. Venlafaxine is prescribed in schizophrenia and anxiety. It shows a tendency of hepatic first-pass metabolism, which affects its bioavailability. The objective of this study is the extraction of cress seed mucilage and development of buccal mucoadhesive microparticles of venlafaxine based on the mucilage using a spray-drying technique. The optimized formulation was evaluated in vitro and the bioavailability of the same formulation in rabbits was assessed. Cress seed mucilage was extracted and used to prepare microparticles with varying concentrations in formulations F1–F5 (1–5% w/w) using a spray-drying technique. The microparticles were evaluated for yield, particle size, incorporation efficiency, swelling property, in vitro mucoadhesion, and in vitro drug release. Microparticles were characterized by differential scanning colorimetry, scanning electron microscopy, and X-ray diffraction studies. In vivo evaluation was carried out in rabbits. Formulation F5 showed maximum mucoadhesion (88.38 ± 1.46%), greater incorporation efficiency (89.42 ± 2.52%), and the highest swelling index (0.93 ± 0.01) compared to the other formulations. F5 showed a marked increase in bioavailability after buccal administration (52.55%) compared to an oral route (39.40%). Time to reach C _max of 23.49 ± 0.33 ng/mL was 120 min for buccal microparticles in comparison to oral solution, which took 180 min to reach C _max of 17.98 ± 1.14 ng/mL. Cress seed mucilage is suitable for production of the mucoadhesive microparticles using a spray-drying method because significant improvement in bioavailability by buccal mucoadhesive microparticles was observed.     

艾司西酞普兰与文拉法辛缓释剂治疗广泛性焦虑障碍的对照研究

目的: 观察艾司西酞普兰与文拉法辛缓释剂治疗广泛性焦虑障碍的疗效和安全性。方法: 将74例符合《国际疾病与相关健康问题统计分类(ICD)第10版》(ICD-10)广泛性焦虑障碍的患者随机分成艾司西酞普兰组(n=38)和文拉法辛缓释剂组(n=36),治疗持续8周,用汉密尔顿焦虑量表(HAMA)评定患者焦虑症状及疗效,用汉密尔顿抑郁量表(HAMD)评定患者的抑郁症状,同时用不良反应量表(TESS)和实验室检查评估治疗安全性。结果: 治疗1周末两组HAMA评分开始明显下降(P<0.01),第1、2、4周末艾司西酞普兰组HAMA减分率明显高于文拉法辛缓释剂组(P<0.05),但是第8周末两组的减分率无统计学差异(P>0.05)。8周末两组的治愈率分别为 60.5%和 66.7%,有效率分别为78.9%和 86.1%,文拉法辛缓释剂组显著高于艾司西酞普兰组(P<0.01)。8周末两组HAMD评分较治疗前也均有明显下降(P<0.01)。两组不良反应差异无统计学意义(P>0.05)。结论: 文拉法辛缓释剂治疗广泛性焦虑总体疗效优于艾司西酞普兰,但是艾司西酞普兰起效快于文拉法辛缓释剂,两者安全性无明显差异。     

盐酸万拉法新的合成

以4－甲氧基苯乙腈为原料,经四步反应合成了盐酸万拉法新,含量99．5％,总收率77．1％。该方法具有操作简单、原料价格低廉、还原收率高、对环境污染小的特点．是一条适合工业化生产的合成路线。     

Voltammetric determination of venlafaxine as an antidepressant drug employing Gd2O3 nanoparticles graphite screen printed electrode

Graphite screen printed electrode modified with Gd_2 O_3 nanoparticles(Gd_2 O_3/SPE) was developed for the determination of venlafaxine(VF). The Gd_2 O_3 nanoparticles were thoroughly characterized by scanning electron microscopy(SEM), transmission electron microscopy(TEM) and X-ray diffraction(XRD) analyses. To study the electrochemical behaviour of venlafaxine cyclic voltammetry(CV), chronoamperometry(CHA)and differential pulse voltammetry(DPV) were employed. These studies reveal that the oxidation of venlafaxine is facilitated at Gd_2 O_3/SPE. After optimization of analytical conditions, analysis of venlafaxine using the modified electrode in 0.1 mol/L PBS(pH 7.0) demonstrates that the peak currents corresponding to venlafaxine vary linearly with its concentration in the range of 5.0 ×10~(-6)-9.0 × 10~(-4) mol/L. The detection limit(S/N = 3) of 2.1 × 10~(-7) mol/L is obtained for venlafaxine using DPV. The prepared modified electrode benefits from advantages such as simple preparation method, high sensitivity and low detection limit.Moreover, the evaluation of practical applicability of this proposed method is successful in the identification of venlafaxine in pharmaceutical formulations, urine and water samples.     

Treating wastewater from a pharmaceutical formulation facility by biological process and ozone

Wastewater from a pharmaceutical formulation facility (TevaKS, Israel) was treated with a biological activated-sludge system followed by ozonation. The goal was to reduce the concentrations of the drugs carbamazepine (CBZ) and venlafaxine (VLX) before discharging the wastewater to the municipal wastewater treatment plant (WWTP). Both drugs were detected at extremely high concentrations in TevaKS raw wastewater ([VLX] = 11.72 ± 2.2 mg/L, [CBZ] = 0.84 ± 0.19 mg/L), and resisted the biological treatment. Ozone efficiently degraded CBZ: at an O₃ dose-to-dissolved organic carbon ratio of 0.55 (O₃/DOC), the concentration of CBZ was reduced by >99%. A lower removal rate was observed for VLX, which was decreased by ～98% at the higher O₃/DOC ratio of 0.87. Decreasing the pH of the biologically treated effluent from 7 to 5 significantly increased the ozone degradation rate of CBZ, while decreasing the degradation rate of VLX. Ozone treatment did not alter the concentration of the effluent's DOC and filtered chemical oxygen demand (COD_f). However, a significant increase was recorded (following ozonation) in the effluent's biological oxygen demand (BOD₅) and the BOD₅/COD_f ratio. This implies an increase in the effluent's biodegradability, which is highly desirable if ozonation is followed by a domestic biological treatment. Different organic byproducts were formed following ozone reaction with the target pharmaceuticals and with the effluent organic matter; however, these byproducts are expected to be removed during biological treatment in the municipal WWTP.     

1-[2-氨基-1-（对甲氧基）乙基]环己醇的合成工艺改进

改进了抗抑郁药文拉法新的中间体1-[2-氨基-1-（对甲氧基）乙基]环己醇的合成工艺，以对甲氧基苯乙腈和环已酮为原料，硼氢化钾和三氯化铝作为还原催化剂，经缩合和加氢还原反应，总收率78．2％。反应条件温和，成本较低，适合工业化生产。     

相转移催化法合成文拉法新盐酸盐

通过对多条文拉法新盐酸盐合成路线的分析最终确定了通过缩合、加氢还原、甲基化的三步反应以对甲氧基苯乙腈为起始原料的合成方法。首先是缩合反应以对甲氧基苯乙腈和环己酮以及四丁基溴化氨为相转移催化剂合成α-(1-羟基环己基)-对甲氧基苯乙腈;第二步是以NiCl2/NaBH4作为还原剂,催化加氢合成1-[2-氨基-1-(4-甲氧基苯基)乙基]环己醇;最后一步以甲醛作为甲基化试剂进行甲基化反应合成盐酸盐文拉法新。其中相转移催化剂的使用,提高了反应收率,缩短了反应时间。