title: Development of protocatechualdehyde proliposomes-based sustained-release pellets with improved bioavailability and desired pharmacokinetic behavior for angina chronotherapy.
abstract: 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 2-12h. 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.
authors: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Shuangshuang
authors: S
authors: Zhang
authors: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Hongxiang
authors: H
authors: Yan
authors: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Panpan
authors: P
authors: Yu
authors: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Yulong
authors: Y
authors: Xia
authors: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Wenli
authors: W
authors: Zhang
authors: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: jianpingliu1293@163.com.
authors: Jianping
authors: J
authors: Liu
mesh_terms: D000787:Angina Pectoris / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001547:Benzaldehydes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002396:Catechols / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019454:Chronotherapy; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004339:Drug Compounding; D065546:Drug Liberation; D008081:Liposomes; D008297:Male; D008353:Mannitol / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011817:Rabbits
chemical_list: D000925:Anticoagulants; D001547:Benzaldehydes; D002396:Catechols; D003692:Delayed-Action Preparations; D008081:Liposomes; D010743:Phospholipids; D008353:Mannitol; C005581:protocatechualdehyde
keywords: Acetic acid (PubChem CID: 176); Angina chronotherapy; Chloroform (PubChem CID: 6212); Cholesterol (PubChem CID: 5997); Deconvolution; Ethanol (PubChem CID: 702); Ethyl acetate (PubChem CID: 8857); Mannitol (PubChem CID: 6251); Methanol (PubChem CID: 887); Pellets; Proliposomes; Protocatechualdehyde; Protocatechualdehyde (PubChem CID: 8768); Tetrahydrofuran (PubChem CID: 8028); κ-Carrageenan (PubChem CID: 11,966,249)