Formulation and optimization of dimenhydrinate emulgels for topical delivery using response surface methodology.

Development of dimenhydrinate (DMN) emulgel formulation has been described in this work with enhanced permeation for transdermal delivery of DMN for effective management of motion sickness. Various DMN emulgel formulations were prepared using central composite design in response surface methodology. Propylene glycol and olive oil were used in varying ratios as permeation enhancers along-with carbopol-934 as gelling agent. Prepared formulations were evaluated by physico-chemical properties, stability and Fourier transform infrared spectroscopy (FTIR) studies. In-vitro drug release was studied using cellophane membrane. Formulation F2 showed maximum drug permeation following diffusion-based release mechanism and was used in further studies. Rat skin was used in Franz cell for ex-vivo studies to determine various permeation kinetic parameters. FTIR studies provided no evidence of chemical interaction between DMN and polymers used, whereas molecular docking revealed formation of a stable complex in the presence of aqueous environment with stable intermolecular binding and the complex was well hydrated. No evidence of skin irritation was observed in human volunteers following application of the optimized formulation. Histopathology data of the rat skin showed a decreased proliferation of the lymphocytes whereas monocytes were induced. In conclusion, combination of propylene glycol and olive oil was successfully employed for delivery of DMN through transdermal route with good permeability and prolonged release time that can be highly beneficial in treating motion sickness in unusual circumstances.

How many adults with temporal epilepsy have a mild course and do not require epilepsy surgery?

Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults and commonly requires surgical treatment. While an overwhelming preponderance of literature supports the notion that a large percentage of patients with TLE benefit from surgery, there is a paucity of outcome data on patients who demonstrate a sustained response to pharmacological treatment. In this study, we present an adult cohort of patients with TLE, with the purpose of identifying the proportion of patients with a mild course of the disease, as well as potential risk factors. A prospective cohort study of all patients with TLE assessed and followed by the Saskatchewan Epilepsy Program, from 1 March 2007 to Jan 29(th) 2014. Patients were dichotomized as having a mild (seizure freedom without surgical intervention) or severe (surgical intervention required and/or failure to achieve seizure remission) course. Descriptive statistics, odds ratios and confidence intervals were calculated to identify predictors of seizure freedom. The cohort consisted of 159 patients. Mean patient age at last follow-up visit was 46±14.4 (range: 19-88) years. Mean follow-up period was 43.4±22.6 (6 to 84) months. Forty-six patients (29%) demonstrated mild-course TLE while 113 (71%) had a severe course of TLE. Patients with a mild course of TLE were more likely to be older (p = 0.002), have late-onset epilepsy (p < 0.001) with shorter evolution (p < 0.001). A good response to the first antiepileptic drug (OR: 6.8; 95% CI: 2.5-19; p < 0.001) was associated with a mild course of TLE. Although a majority of patients with TLE eventually require surgery, operative treatment is not necessary for all patients. This study identifies prognostic factors that may help patients and clinicians characterize long-term outcome.