Mixed micelles formulation for carvedilol delivery: In-vitro characterization and in-vivo evaluation

ÖZTÜRK K., ARSLAN F. N., ÖZTÜRK S. C., ÇALIŞ S.

INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol.611, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 611
  • Publication Date: 2022
  • Doi Number: 10.1016/j.ijpharm.2021.121294
  • Journal Name: INTERNATIONAL JOURNAL OF PHARMACEUTICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Carvedilol, Polymeric micelle, Mixed micelle, Pluronic (R) F127, Triblock copolymer, D-alpha-tocopheryl polyethylene glycol 1000 succinate, Cysteine HCl, DRUG-DELIVERY, POLYMERIC MICELLES, ORAL BIOAVAILABILITY, SOLID DISPERSION, AMINO-ACIDS, SOLUBILITY, DESIGN, CYTOTOXICITY, IMPROVEMENT, STABILITY
  • Hacettepe University Affiliated: Yes

Abstract

Carvedilol (CAR) is a widely studied, beta and alpha-1 blocker, antihypertensive drug due to its poor water solubility and low oral bioavailability (25-35%). The aim of this work is to improve poor water solubility and the pharmacokinetic parameters of carvedilol by using an optimized and self-assembly prepared micelle formulation. Optimized micelle formulation composed of Pluronic (R) F127, D-alpha-tocopheryl polyethylene glycol 1000 succinate, L-cysteine HCl in a ratio of 4:3:3. Micellar size, polydispersity index, zeta potential, morphology, critical micelle concentration, thermal behaviors, in-vitro dissolution of micelles and pharmacokinetic parameters in rats were characterized in this study. Carvedilol aqueous solubility increased (up to 271-fold) as a result of its encapsulation within a mixed micelle formulation. The measured micellar sizes of blank and carvedilol loaded mixed micelles are lower than 30 nm with size distributions of 26.69 +/- 2.93 nm and 24.16 +/- 4.89 nm, respectively. Transmission electron microscopy revealed that the micelles were spherically shaped. There is a significant enhancement of carvedilol dissolution compared to commercially available tablet formulation (f2 < 50). The invivo test demonstrated that the t(1/2) and AUC(0-infinity )values of micelles were approximately 10.89- and 2.65-fold greater than that of the commercial tablets, respectively. Based on our study, bring such applications into being may provide effective new drugs for treatment armamentarium of cardiovascular diseases and hypertension in near future.