| 摘要: | 失眠的症狀包括難以入睡、夜間多次醒來、躺下後無法入睡、早上醒來後無法再入睡、即使感到疲倦也難以在白天小睡，感到疲倦和煩躁，並因疲勞而難以集中注意力。若失眠症狀持續時間少於3個月，則稱為短期失眠；若持續3個月或更長時間，則稱為慢性失眠。
GABA代表γ-氨基丁酸，是中樞神經系統中的一種神經遞質，可以抑制或減慢神經細胞的活動。它在調節大腦活動中扮演著關鍵角色，參與各種生理和心理過程，包括放鬆、睡眠和減少焦慮。GABA也可用作膳食補充劑，在臨床上也被研究用於促進放鬆和緩解壓力。
我們的研究旨在開發和評估一種多單元給藥系統，利用流動床包衣技術生產GABA緩釋圓粒，以在治療失眠症方面擁有更廣泛的應用。本研究選用了三種常見的緩釋膜衣材料(Eudragit? RS 30D、Eudragit? NE 30D、Kollicoat? SR 30D)，並結合兩種水溶性增塑劑(檸檬酸三乙酯、丙二醇)對緩釋膜衣的物理性質進行了分析。使用動態機械分析儀對聚合物薄膜進行了乾燥和潮濕狀態下的測試。最終，結果顯示在不與GABA相互作用的情況下，Kollicoat? SR 30D併用TEC作為增塑劑具有最佳的彈性和韌性。在溶離率研究中，GABA-SR圓粒在40%包衣增重且使用TEC 10%作為塑化劑的條件下，呈現出持續8小時並釋放出85%藥物的曲線。安定性研究也顯示藥物含量在3個月內保持在90%以上。體內試驗顯示，相較於GABA市售膠囊(THORNE?)，使用GABA-SR圓粒可以提高相對口服生體可用率10倍。
總而言之，我們成功製備了GABA-SR圓粒製劑，展現出極佳的安定性和理想的藥物釋放曲線。
Insomnia symptoms include difficulty falling asleep, frequent awakenings during the night, inability to fall back asleep when lying down at night, inability to nap during the day despite feeling tired, and experiencing fatigue, irritability, and difficulty concentrating due to lack of sleep. If insomnia symptoms persist for less than three months, it is referred to as short-term insomnia. If insomnia lasts for three months or longer, it is called chronic insomnia.
GABA, short for gamma-aminobutyric acid, is a neurotransmitter in the central nervous system that inhibits or slows down the activity of nerve cells. It plays a crucial role in regulating brain activity and is involved in various physiological and psychological processes, including relaxation, sleep, and anxiety reduction. GABA is also used as a dietary supplement and has been studied for its potential in promoting relaxation and relieve stress.
Our study aims to develop and evaluate a multi-unit drug delivery system using fluidized bed coating technology to produce GABA-releasing pellets, with greater applications in the treatment of insomnia. Three common sustained-release coating materials (Eudragit? RS 30D, Eudragit? NE 30D, and Kollicoat? SR 30D) were analyzed in combination with two water-soluble plasticizers (triethyl citraand te, propylene glycol) for the physical properties of the sustained-release coatings. Polymer films were characterized using a dynamic mechanical analyzer under dry and humid conditions. Finally, Kollicoat? SR 30D combined with TEC as a plasticizer demonstrated optimal flexibility and toughness without interacting with GABA. In the dissolution rate study, GABA-SR pellets with 40% coating weight gain using TEC 10% as a plasticizer exhibited a release profile, releasing 85% of the drug over 8 hours. Stability studies also indicated that the drug content remained above 90% within three months., In vivo testing showed a tenfold increase in relative oral bioavailability using GABA-SR pellets compared to a GABA commercial capsule (THORNE?).
In conclusion, GABA-SR pellets have been successfully prepared, demonstrating excellent stability and ideal drug release profiles. |
