تاريخ مجلس الدراسات العليا

2018-08-28

اسم الطالب

روند محمد صلاح دغمش

ملخص الرسالة

Valproic acid (VA) is a known Antiepileptic medication, is given orally in a form of solutions or tablets and intravenously. Due to, oscillations of its plasma levels from these dosage forms, the serious adverse side effects on various systems especially liver toxicity and liver damage, and the unpleasant bitter taste of the oral solutions, there is a need to formulate VA in a way to minimize plasma oscillation and the unwanted toxic side effects this can be achieved by controlling the release of the drug, VA was prepared as an intramuscular oil injectable solution, where VA is physically entrapped in castor oil vehicle. This injectable solution was prepared by using an ordinary mixing method, according to the US patent 9833459. By mixing ethyl alcohol, benzyl benzoate, valproic acid, ?-tocopherol, polysorbate 80 (tween® 80) and castor oil. A homogenous, pale yellow clear oily injectable solution was obtained. Three formulas with different concentrations of VA were prepared using this method (4 g, 5 g, and 6 g). These injectable solutions were analyzed for clarity, stability at different temperatures at 5?C ± 3?C, 25?C ± 2°C/60% RH ± 5% RH, and 40?C ± 2°C/75% RH ± 5% RH for the three formulas, quantify the drug content, viscosity determination, injectability testing and characterization of the in vitro release profile for the finished products. The three formulas had shown a great clarity against white back gowned and under a strong light, stability at different temperatures 5?C ± 3?C, 25?C ± 2°C/60% RH ± 5% RH, and 40?C ± 2°C/75% RH ± 5% RH were checked visually and using HPLC method, they show a great stability under these conditions, drug content for F1 was 107.7%, F2 was 98.4% and F3 was 93%, even the viscosity of the three formulas doesn't change by using different speed rates 25, 50 and 100 rpm, the viscosity for F1 was 20mPa?s, for F2 was 35.5mPa?s and for F3 was 52mPa?s, and the manual injectability testing for F1 performed by 20 different individuals gave a good timing profile approximately 15.73 sec. In addition the in vitro release for the three formulas in buffer solution PH 7.4, showed that the release started after 24hrs and lasts for 16 days and the % release reaches to 99.8% in F1, 99.40% in F2 and 97.8% in F3.