儲藏型緩釋微粒控釋劑型，常用於口服製劑以控制藥物在胃腸道釋出速率，減少藥物血中濃度的波動，維持藥物的血中濃度，還可以改善傳統立即釋放劑型重複投藥的不便。
羅匹尼羅(ropinirole)是一種非麥角類多巴胺作用劑，在體內的半衰期為6小時，目前廣泛地用於治療帕金森氏症。ropinirole為一種易溶性的藥物，如果給予傳統之立即釋放劑型，病人必須一天服用三次。因此若將ropinirole製成緩釋劑型，使藥物持續釋放，可以增加病人的服藥便利性，以及維持穩定的血中濃度。
本篇研究目的是將ropinirole利用儲藏型之處方設計來製備控制釋放的製劑。並探討控釋處方內聚合物比例，聚合物包覆量，塑化劑種類，聚合物媒液性質及各項製備變數對於藥物釋放之影響。此外，ropinirole在不同包衣材質之安定性也在本研究中探討。評估緩釋微粒釋放的溶離條件是參照美國藥典所記載之籃式法（Basket），溫度為攝氏37±0.5度，每分鐘100轉。藥物先在pH1.2鹽酸溶液2小時後，加入磷酸鈉溶液，調整為pH6.8持續至24小時。以250 nm波長的紫外光偵測器來偵測藥物的溶離百分比。
由實驗結果得知：當包覆層中乙基纖維素(EC)在聚合物中比例越高時，藥物釋放的速率越慢。而緩釋微粒所包覆聚合物的比例越多，亦會導致藥物的釋放速率變慢。此外，當使用水溶性塑化劑時藥物釋放速率會比使用非水溶性塑化劑為快。若使用EC做為控制釋放材質，當溶於有機相包而覆於藥蕊表面，其相較於使用水相EC懸浮液而言其最後藥物釋放較不完整。而以polyvinyl acetate – polyvinyl pyrrolidone為主之懸浮液作為控制釋放材質其藥物釋放速率較以EC水相懸浮液作為控制釋放質之藥物釋放速率為快。在處方安定性測試中，發現ropinirole會受到鹼性材質之影響，而有降解的情況發生。
本篇研究將易溶性模式藥物ropinirole藉由不同的處方設計及製程來探究藥物釋放的效果。此研究顯示在適當選擇配方及材質下，ropinirole控制釋放劑型之製備是可行的。 Pellet system is often used in dosage form design to achieve controlled drug delivery. The major advantages of this system are the reduction of dosing frequency, reduction of side effects because effective concentration is maintained, and increase of patient compliance.
Ropinirole, a nonergoline dopamine agonist for Parkinson’s disease, is used as a model drug in this study. Due to the relatively short half life of ropinirole. Patients have to take the drug three times per day. In order to reduce dosing frequency and improve patient compliance, it is imperative to develop controlled-release formulation for ropinirole.
The aims of this study are to prepare the controlled-release pellet formulations for ropinirole and to evaluate various formulation factors on drug release. The formulation factors include different ratios of ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) in the coating polymers, coating thickness, plasticizers, spraying vehicle of polymers and polymer types. The pellet-coating system was prepared by using fluidized-bed apparatus. Chemical stability of ropinirole in various pellet formulation was also assessed using HPLC.
Dissolution tests were performed according to the USP basket method under 37±0.5℃ and 100 rpm. A pH change medium was used: pellets were in 750ml of 0.1N HCl in the first 2 hours, and then change the medium to pH 6.8 by adding 250 ml of 0.2 M tribasic sodium phosphate. The drug dissolution rates were obtained by UV detection at 250 nm.
The results indicate that drug release rates can be decreased by increasing ratio of ethyl cellulose in the polymer blend and increasing the weight of polymer coating. Drug release rates using soluble plasticizer were faster than those of insoluble plasticizer. The drug releases for polymer suspended in aqueous solution were more complete than those of polymer dissolved in organic solvent. The stability results show that ropinirole was degraded by alkaline excipient. This study demonstrated the feasibility of extending the release of ropinirole using pellet system.
