Enhancement of Docetaxel Absorption Using Ritonavir in an Oral Milk-Based Formulation.

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Oncology

Background:

• Docetaxel is a sparingly soluble antineoplastic agent typically administered intravenously.
• Limited oral bioavailability hinders the development of oral docetaxel formulations.
• Novel drug delivery systems are needed to improve oral docetaxel administration.

Purpose of the Study:

• To develop a novel milk-based formulation of docetaxel for oral administration.
• To evaluate the oral bioavailability and pharmacokinetic performance of the developed formulation.
• To investigate the role of ritonavir as an absorption enhancer for oral docetaxel.

Main Methods:

• Pre-formulation studies including solubility and content uniformity.
• In vivo pharmacokinetic evaluation in mice using oral docetaxel formulations.
• Comparison with marketed intravenous docetaxel (Taxotere®) and co-administration with ritonavir.

Main Results:

• Oral docetaxel formulations showed limited absorption without ritonavir.
• Ritonavir significantly enhanced oral bioavailability of both marketed and milk-based formulations.
• Incorporating ritonavir into the milk-based formulation resulted in greater drug exposure and prolonged absorption.

Conclusions:

• A novel milk-based docetaxel formulation demonstrates potential for oral chemotherapy.
• Ritonavir acts as an effective absorption enhancer for oral docetaxel.
• This formulation offers a potentially non-toxic and patient-friendly alternative to intravenous docetaxel.