Development and Characterization of Gastro-Retentive Blend Microparticles of Sumatriptan: Design, Optimization, ex vivo, and in vitro Evaluation for Oral Drug Delivery

Migraine is a complex neurological disorder of the brain which is often accompanied with headache, gastrointestinal, neurologic, and sometime aural symptoms [1, 2]. Sumatriptan (ST) is a serotonin receptor agonist (5-hydroxytryptamine or 5-HT receptor) used to treat migraine and cluster headaches [3]. However, ST is rapidly but incompletely absorbed following oral administration (15%) because of the high first-pass metabolism [4]. On the other hand, a large number of patients suffer from nausea and vomiting during multiple migraine attacks, which may result in inadequate absorption of ST in oral therapy. The sustained release drug delivery systems for ST can be useful to reduce dosing frequency, enhance drug oral bioavailability, minimize gastrointestinal adverse effects, and improve the effectiveness of drug in the management of migraine. However, a major problem commonly associated with the conventional sustained release drug delivery systems is a shorter mean retention time in the stomach. Moreover, traditional oral preparations lead to large fluctuations in the plasma drug level [5]. Thus, increasing the retention time of dosage form in the stomach while improving their stability in the gastric medium is an excellent strategy to bypass this problem. Various gastroretentive drug delivery systems including expanding and swelling systems, floating drug delivery systems, mucoadhesive systems, and modified-shape systems have been proposed to improve the gastric retention time of drugs [6]. Among gastro-retentive systems, microparticles with floating and mucoadhesive capabilities have attracted large interest owing to their capacity to interact with the mucosal site, improving the retention time of drug in the stomach for a long period of time. Afterwards, the payload is slowly released at the specific time and rate from the carrier. This leads to a large concentration gradient which C o r re s p o n d e n c e