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Development of protocatechualdehyde proliposomes-based sustained-release pellets with improved bioavailability and desired pharmacokinetic behavior for angina chronotherapy.
- Source :
-
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2016 Oct 10; Vol. 93, pp. 341-50. Date of Electronic Publication: 2016 Aug 26. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Angina Pectoris blood
Animals
Anticoagulants blood
Benzaldehydes blood
Biological Availability
Catechols blood
Delayed-Action Preparations administration & dosage
Delayed-Action Preparations pharmacokinetics
Drug Compounding
Drug Liberation
Liposomes
Male
Mannitol chemistry
Phospholipids chemistry
Rabbits
Angina Pectoris metabolism
Anticoagulants administration & dosage
Anticoagulants pharmacokinetics
Benzaldehydes administration & dosage
Benzaldehydes pharmacokinetics
Catechols administration & dosage
Catechols pharmacokinetics
Chronotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0720
- Volume :
- 93
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 27568854
- Full Text :
- https://doi.org/10.1016/j.ejps.2016.08.040