A PROCESS FOR PREPARING PARENTERAL COMPOSITION OF ONDANSETRON HYDROCHLORIDE

Abstract

The present disclosure relates to a process for preparing parenteral composition of ondansetron hydrochloride. The composition is useful for the treatment of nausea and vomiting associated with cancer chemotherapy and that occurring postoperatively.

Oral administration in the form of a conventional tablet, pill or capsule constitutes the preferred route of administration of pharmaceuticals since this route is generally convenient and acceptable to patients.  However, one of the major concerns associated with oral administration, is patient compliance.  This is particularly evident in the case of pediatric or geriatric patients who are unwilling or face difficulty in swallowing such conventional dosage forms.  Further, it is highly desirable, particularly in the treatment of acute conditions, that pharmaceutical compositions have a rapid and consistent onset of action combined with suitable bioavailability.

Parenteral administration, apart from providing quicker onset of action, results in more predictable blood serum concentrations of the drug.  Further, losses in the gastrointestinal tract due to metabolism, binding to food and other causes are eliminated.  For similar reasons, parenteral administration permits dose reduction.  It is also the preferred method of drug delivery in emergency situations and is useful in non-cooperative patients.

Ondansetron, chemically described as, 1,2,3,9-tetrahydro-9-methyl-3- [(2-methyl-lH-imidazol-l-yl) methyl]-4H-carbazol-4-one, is an antiemetic agent due to its selective action on the 5-HT3 receptors.

Ondansetron is available commercially as tablets, orally disintegrating tablets, solutions and parenterals.  In marketed compositions (sold under brand name ZOFRAN® by Glaxo), ondansetron is used as a free base in rapidly disintegrating tablets and as a hydrochloride salt in injections, tablets for oral administration and oral solutions.  Currently available parenteral dosage form of ondansetron is Zofran and Zofran Preservative Free.

U.S. Patent No. 4,695,578 discloses ondansetron and physiologically acceptable salt or solvate thereof.

Chinese Patent Application No. 1555795 discloses ondansetron hydrochloride injection in the form of freeze dried powder prepared from ondansetron hydrochloride, pharmacologically acceptable excipient and water for injection.  The process involves dissolving ondansetron hydrochloride in the water, adding excipient, stirring, regulating pH value, filtering, and freeze drying.

PCT Application WO 98/00159 discloses compositions for administering acid addition salts of compounds, including ondansetron hydrochloride, by intramuscular injection. In the method disclosed, a sterile parenteral composition of a liquid vehicle containing the acid addition salt in solution is adjusted in pH for reducing the development of undesirable side e...