Development of protocatechualdehyde proliposomes-based sustained-release pellets with improved bioavailability and desired pharmacokinetic behavior for angina chronotherapy

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• 作者：Shuangshuang Zhang ; Hongxiang Yan ; Panpan Yu ; Yulong Xia ; Wenli Zhang ; Jianping Liu ; ^{jianpingliu1293@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Protocatechualdehyde (PubChem CID ; 8768) ; Cholesterol (PubChem CID ; 5997) ; Mannitol (PubChem CID ; 6251) ; κ-Carrageenan (PubChem CID ; 11 ; 966 ; 249) ; Chloroform (PubChem CID ; 6212) ; Ethanol (PubChem CID ; 702) ; Tetrahydrofuran (PubChem CID ; 8028) ; Methanol (PubChem CID ; 887) ; Ethyl acetate (PubChem CID ; 8857) ; Acetic acid (PubChem CID ; 176)
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：10 October 2016
• 年：2016
• 卷：93
• 期：Complete
• 页码：341-350
• 全文大小：1954 K

文摘

The present study was aimed to develope a proliposomal formulation to decrease the hepatic first-pass metabolism of protocatechualdehyde (PD), followed by pellet coating to modify the drug release for angina chronotherapy. PD proliposomes were prepared by depositing PD-phospholipid complex on mannitol powders to improve the drug encapsulation. Afterwards, the PD proliposomes were prepared into pellet cores via extrusion-spheronization using 10% κ-carrageenan as pelletization aid prior to the development of PD sustained-release pellets (PD-SRPs). Eudragit® NE 30D was chosen as coating material and the desired drug release profile of PD-SRPs was calculated for formulation optimization by deconvolution based on the circadian rhythm of variant angina. A high similarity factor (f₂ = 85.72) was achieved when the coating weight was 30% and the sustained release behavior also prevented the destruction of liposomes by gastric fluids. Pharmacokinetic studies revealed a basically consistent trend between the actual and the predicted plasma concentration-time curve with absolute percent errors (%PE) of concentrations < 10% in 2–12 h. Meanwhile, a relative bioavailability of 200% was achieved compared with pure PD. Therefore, the development of proliposomes-based PD-SRPs was an effective strategy to provide both improved oral bioavailability and desired drug plasma concentration-time course for angina chronotherapy.