Stability of a Parenteral Formulation of Betamethasone and Levobupivacaine

Abstract

Background: The therapeutic management of syndromes presenting simultaneously pain and inflammation often requires the administration of anesthetic and corticosteroid drugs by epidural administration. In this article, we studied a mixture that combines betamethasone and levobupivacaine, which demonstrates prolonged analgesic effects. To our knowledge, the stability of such a mixture in epidural solution has not been examined. Objective: To evaluate the chemical, physical, and microbiological stability of an extemporaneously prepared mixture. Methods: A solution of betamethasone acetate 1 mg/mL, betamethasone phosphate 1 mg/mL, and levobupivacaine hydrochloride 0.83 mg/mL was prepared in saline. The components were analyzed by high-performance liquid chromatography for up to 270 days of storage, protected and exposed to light, at room temperature, and stored in the refrigerator and at 45°C. In addition, sterility, organoleptic properties, and pH of the admixture were monitored. Results: There are no significant differences between drug concentrations obtained at room temperature and at refrigerated temperature. The accelerated conditions (45°C) demonstrated different results among the actives: betamethasone acetate and levobupivacaine hydrochloride are affected while betamethasone phosphate remains stable. The stability of the mixture does not depend on light exposure. The validity period of the different components in the mixture was estimated as 120 days for betamethasone phosphate and 163 days for levobupivacaine hydrochloride; betamethasone acetate remained unchanged during 155 days. Conclusion: Analgesic mixtures of betamethasone and levobupivacaine can be stored at ambient temperature in polypropylene vials for up to 120 days at the studied concentrations. These data enable the rationalization of the centralized preparation in the hospital pharmacy.