Preparation Of Ultrafine Sumatriptan Succinate For Dry Powder Inhalation

Migraine is a common, chronic, incapacitating neurovascular disorder which is characterized by attacks of severe headaches, autonomic nervous system dysfunction. Recently, selective serotonin (5-HT) receptor agonists that constrict dilated vessels have been used to dramatically attenuate migraine headaches. Sumatriptan succinate (SS) is an agonist of a vascular5-hydroxytryptamine receptor subtype (a member of the5-H1B/1G family), which is present in the human basilar artery and in the vasculature of human dura mater, and which causes vasoconstriction. This action in humans correlates with the relief of migraine headaches. It is available in several dosage forms including products for oral, intranasal, subcutaneous and rectally. However, they are unacceptable to some individuals for their inconvenience. The pulmonary delivery for SS may be a viable alternative for self-administration, whereby these limitations could be overcome. Particle size and its distribution are the most important design variables of a dry powder inhalation (DPI) formulation. Drug particles with smaller diameter are easier to enter the respiratory tract and reach the alveoli, which ensure accurate dosing of the drugs for good lung deposition. Therefore, the particle size reduction of SS is an effective method to improve the efficiency of pulmonary drug delivery. In this study, ultrafine SS particles were successfully prepared via reactive precipitation method using sumatriptan base (ST) and succinic acid. Furthermore, the aerosol performance of the as-prepared SS was evaluated using an Aeroliser connected to a multi stage liquid impinger operating at60L/min.The results in beaker demonstrated that, of these systems, tetrahydrofuran (THF) was the best to obtain fine particles, and the optimal condition was:the mol ratio of ST to succinic acid less than1:1, temperature at0-7℃, stirring time longer than6min, stirring speed more than10000rpm. The resulting dispersion was then filtrated (or centrifugated) and the filtered paste could be re-dispersed in a suitable solvent such as ethyl acetate for spray drying. The as-prepared SS particles had a mean length of1μm and a narrow particle size distribution. The structure of the as-prepared product was the same as the commercial one as confirmed by FT-IR and XRD analysis.Subsequently, the preparation of ultra-fine SS without addition of surfactants was carried out by combing rotating packed bed (RPB) with precipitation method. Under the optimal condition, the average size of particles prepared from internal circulating RPB was about1μm.The aerosol performance of the as-prepared SS showed that the fine partial fraction (FPFtotal) of drug powder obtained in a beaker and an inside circulation RPB was20%than that of commercial material. The powder via vacuum drying showed bad aerosol performance for its bad dispersibility. Whereas, the powder re-dispersed in ethyl acetate via spray drying show a high FPFemitted up to63.51%. Therefore, ultrafine SS powder can be obtained by reactive precipitation for inhalation.