Pulmonary Drug Delivery System Delivery Migraine Therapy Research

Migraine attack affects approximately 18% of female and 6% of male population inthe world. Most of patients with migraine take medicine for treatment and generallyconsider the rapid onset of action as a top priority. Of various strategies to reduce thetime required for the relief of symptoms, development of novel drug delivery systemssuch as delivering drugs via nasal tract and subcutaneous way has successfully lead toimprove pharmacokinetic parameters associated with rapid onset of action, such asbioavailability and tmax, relative to peroral administration. The primary objective ofthe present study was to investigate the feasibility of utilizing pulmonary drugdelivery system as an alternative means to achieve the rapid onset of action usingrizatriptan as a model drug.Toward this, a HPLC assay was developed and validated for the analysis ofrizatriptan in both rat plasma and rat brain tissue samples and results showed that theassay exhibited excellent specificity, repeatability and reproducibility, and consistentrecovery. In addition, the biodistribution profiles of rizatriptan in the blood and brainof Wistar rats after peroral, subcutaneous, intranasal and intratracheal administrationwas subsequently investigated. The results indicated that pulmonary delivery ofrizatriptan may achieve maximum plasma and brain concentrations significantly morerapidly compared with intranasal, subcutaneous and peroral administration. In order todeliver the drug to the lung efficiently, spray-drying was utilized for preparation ofcorrugated particles dispersible in HFA-134a in the absence of soluble surfactants andthe spray-dried particles were found to be in almost monodispersity with volumemedian diameters being about 3 m. In addition, when PVA 80 and hyaluronic acid (HA) was present as excipinets in particles, in vitro evaluation of releaseand mucociliary retention suggested that the particles could slightly reduce therelease rate but markedly increase the retention time, whereas particle dispersibilityand suspension stability in hydrofiuoroalkane-134a (HFA-134a) appeared to beenhanced with fine particle fraction being greatly increased as ejected from a metereddose inhaler. And finally, the spray-dried particles were also subjected to in vivoevaluation of pharmacokinetic profiles followed by intratracheal adminsration ofparticles to rats. The results demonstrated that intratracheal delivered rizatriptanparticles conferred excellent pharmacokinetic parameters associated with the rate ofabsorption and the onset of action in the plasma of rats with tmax being less than 2 minand bioavailability being over 90%, and in vivo absorption rate appeared to linearlycorrelate to in vitro release data. Therefore it was concluded that it could be suggestedthat pulmonary delivery is likely to lead to an accelerated therapeutic effect comparedwith other previous used routes of administration of triptans such as intranasal,subcutaneous and peroral administration, and inhalation delivery of triptans ispotentially promising to become an effective non-invasive route for the acutetreatment of migraine attack.