ABSTRACT
PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.
Subject(s)
Humans , Breast Neoplasms , Breast , Disease-Free Survival , Follow-Up Studies , Incidence , Neutropenia , Paclitaxel , Peripheral Nervous System Diseases , Polymers , Treatment OutcomeABSTRACT
For this experiment, Oleic Acid and Cremophor EL based Loratadine SEDDS were prepared. Different amount of solvent and surfactant were used to prepare SEDDS. After preparation of different formulations their dissolution studies were performed at 50-rpm, paddle method in which dissolution medium was maintained at 37°C (0.5°C) temperature by using Dissolution Tester USP II. Three capsules from each formulation were used in each dissolution study and the release profile of Loratadine was monitored up to one hour. For the formulation development with fixed dose Loratadine (10 mg) and varying amounts of oleic Acid and Cremophor EL were used. In the experiment major determinant is found to be surfactant concentration. In all cases it is found that higher surfactant concentration increased the drug release. Other two determinant factors are amount of Oleic acid and percent drug loading. It was observed that without Cremophor EL, drug release from the formulation was slow. The rate and extent of drug release increased from the matrices with increasing the amount of Cremophor EL in the formulation.
ABSTRACT
In this study, a solubility enhancing technique, Self-emulsifying drug delivery system (SEDDS), was considered to be developed for Ibuprofen, a poorly soluble drug. Capmul PG 8 was used as a co-solvent. As surfactant, hydrophilic surfactant Cremophor EL was considered. A fixed amount of Ibuprofen was added with fixed amount of excipients. Capmul PG8 showed a good solubilizing capacity which dissolved 300 mg/ml of Ibuprofen. Cremophor EL also showed a good solubilizing capacity which dissolved 300 mg/ml of Ibuprofen. Ibuprofen is a poorly soluble drug which was used as experimental drug and pH 7.2 phosphate buffer was used as dissolution medium. The amount of drug was measured form the absorbance of UV spectrophotometer at 221 nm. A 3-level factorial design was carried out to optimize the formulation using design expert software trial version 8.0.3.1. Capmul PG8 and Cremophor EL were used as independent variables where percent drug release at 5, 15 and 45 minutes. The optimized formula contains 24.10 mg Capmul PG8 and 71.02 mg Cremophor EL which releases 27.78%, 44.6% and 74.24% ibuprofen at the mentioned time interval. The present study shows that the Capmul PG8 and Cremophor EL have effect the release profile of capsule Ibuprofen. It is found that it is possible to increase the release of Ibuprofen by using Capmul PG8 and Cremophor EL.
ABSTRACT
In this study, a solubility enhancing technique, Self-emulsifying drug delivery system (SEDDS), was considered to be developed for Ibuprofen, a poorly soluble drug. Capmul PG 8 was used as a co-solvent. As surfactant, hydrophilic surfactant Cremophor EL was considered. A fixed amount of Ibuprofen was added with fixed amount of excipients. Capmul PG8 showed a good solubilizing capacity which dissolved 300 mg/ml of Ibuprofen. Cremophor EL also showed a good solubilizing capacity which dissolved 300 mg/ml of Ibuprofen. Ibuprofen is a poorly soluble drug which was used as experimental drug and pH 7.2 phosphate buffer was used as dissolution medium. The amount of drug was measured form the absorbance of UV spectrophotometer at 221 nm. A 3-level factorial design was carried out to optimize the formulation using design expert software trial version 8.0.3.1. Capmul PG8 and Cremophor EL were used as independent variables where percent drug release at 5, 15 and 45 minutes. The optimized formula contains 24.10 mg Capmul PG8 and 71.02 mg Cremophor EL which releases 27.78%, 44.6% and 74.24% ibuprofen at the mentioned time interval. The present study shows that the Capmul PG8 and Cremophor EL have effect the release profile of capsule Ibuprofen. It is found that it is possible to increase the release of Ibuprofen by using Capmul PG8 and Cremophor EL
ABSTRACT
(-)-∆9-Tetrahydrocannabinol (∆9-THC), a psychoactive component of marijuana, has been reported to induce oxidative damage in vivo and in vitro. In this study, we administered (∆9-THC to healthy C57BL/6J mice aged 15 weeks in order to determine its effect on hepatic redox state. Mice were divided into 3 groups: (∆9-THC (N = 10), treated with 10 mg/kg body weight (∆9-THC daily; VCtrl (N = 10), treated with vehicle [1:1:18, cremophor EL® (polyoxyl 35 castor oil)/ethanol/saline]; Ctrl (N = 10), treated with saline. Animals were injected ip twice a day with 5 mg/kg body weight for 10 days. Lipid peroxidation, protein carbonylation and DNA oxidation were used as biomarkers of oxidative stress. The endogenous antioxidant defenses analyzed were glutathione (GSH) levels as well as enzyme activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione reductase, and glutathione peroxidase (GPx) in liver homogenates. The levels of mRNA of the cannabinoid receptors CB1 and CB2 were also monitored. Treatment with ∆9-THC did not produce significant changes in oxidative stress markers or in mRNA levels of CB1 and CB2 receptors in the liver of mice, but attenuated the increase in the selenium-dependent GPx activity (∆9-THC: 8 percent; VCtrl: 23 percent increase) and the GSH/oxidized GSH ratio (∆9-THC: 61 percent; VCtrl: 96 percent increase), caused by treatment with the vehicle. ∆9-THC administration did not show any harmful effects on lipid peroxidation, protein carboxylation or DNA oxidation in the healthy liver of mice but attenuated unexpected effects produced by the vehicle containing ethanol/cremophor EL®.