Improved solubility, dissolution, and oral bioavailability for atorvastatin-Pluronic® solid dispersions

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Cardiovascular Pharmacology

Background:

• Atorvastatin (AT) is a widely prescribed statin for cardiovascular disease prophylaxis.
• Limited oral absorption of AT restricts its therapeutic efficacy.
• Amphiphilic carriers offer potential to improve drug solubility and bioavailability.

Purpose of the Study:

• To develop and characterize atorvastatin formulations using Pluronic F127® and Pluronic F68®.
• To evaluate the in vitro dissolution and in vivo oral absorption of the developed formulations.
• To assess the potential of Pluronic® carriers in enhancing AT's therapeutic benefits.

Main Methods:

• Formulation of AT with Pluronic F127® and F68® in hard capsules.
• In vitro characterization including solubility, FTIR, DSC, and X-RPD.
• In vitro dissolution rate studies.
• In vivo pharmacokinetic studies in New Zealand rabbits.

Main Results:

• Pluronic® incorporation significantly improved AT solubility.
• No chemical interactions were observed between AT and Pluronic® carriers.
• Dissolution studies showed up to 93% AT dissolution within 30 minutes.
• In vivo studies demonstrated markedly increased AT absorption (Cmax and AUC0-12) compared to controls and Lipitor®.

Conclusions:

• Formulation with Pluronics® profoundly enhances AT dissolution and absorption.
• This approach offers a viable strategy to improve AT's therapeutic and clinical efficacy.
• Pluronic®-based formulations hold promise for optimizing cardiovascular disease treatment.