Ondansetron

The study aimed to formulate and evaluate sustained release ondansetron tablet. Conventional ondansetron tablets not only produce rapid and relatively high peak blood levels resulting in adverse effects but also should be administered three to four times daily. These drawn backs can be overcome by designing a suitable sustained release formulation. Sustained release tablets of ondansetron to be taken once daily were formulated with ondansetron hydrochloride equivalent to 8 mg of ondansetron base. Matrix system based on swellable as well as non-swellable polymers was selected for sustaining the drug release. Different polymers such as hydroxypropylmethylcellulose (HPMC), Carbopol were studied. Combinations of non-swellable polymers with HPMC were also tried in order to get the desired sustained release profile over a period of 24 h. The effect of drug to polymer ratio on in vitro release was studied. The marketed formulation was evaluated for different parameters such as appearance, weight variation, drug content and in vitro drug release. The optimized formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. In vivo studies were carried out for the optimized formulation in six healthy human volunteers and the pharmacokinetic parameters.

For evaluation of the antiemetic effects of the drugs animal models (Ferret,cat dog etc) are used. Although good guidelines may be established through the animal experiments, they may not give accurate indication of the antiemetic effect of the antiemetic drugs in patients due to species differences in pharmacokinetic and pharmacodynamic responses. Therefore, Ipecacuanha-induced emesis and flare models are used to predict more accurately the antiemetic effect of the antiemetic drugs. In ipecacuanha-induced emesis model in 10 healthy human volunteers slow intravenous injection of ondanserton -2 ml. (4 mg) was given over 5 minutes.Thirty minutes after inj. ondanserton, 30 ml. oral syrup of tincture ipecac was given with glassful of water. Then the parameters like time, number and duration of emesis were noted over 6 hour’s period. In flare model in 6 healthy human volunteers Injection Serotonin 0.05 ml of 12.98 µM was given intradermally on the flexor aspect of forearm. Resulting flare response was measured over 5 minutes. At the end of half an hour, injection ondansetron and same dose of injection serotonin was given intradermally. Resulting flare response was measured in the similar way. Out of these two models, ipecac model is technically easy and clinically relevant but its tolerability is less. Flare model has excellent tolerability but it is technically not very easy. Thus one can choose the effective model accordingly. Key words: Antiemetic, Ipecacuanha, Ondansetron, Serotonin