Fospropofol Oral Bioavailability via pH Modification
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Solution Overview
Problem
Current oral administration methods for fospropofol face challenges in achieving adequate bioavailability with minimal subject-to-subject variability, as existing dosage forms struggle to provide consistent and effective delivery of propofol.
Innovation Solution
The development of pharmaceutical dosage forms comprising fospropofol or its pharmaceutically acceptable salts, co-administered with a pharmaceutically acceptable acid, specifically designed to enhance oral bioavailability and reduce inter-subject variability through controlled pH and release mechanisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If fospropofol is administered orally using conventional dosage forms, then the administration route is improved (from intravenous to oral), but bioavailability and consistency are worsened (inadequate bioavailability with high subject-to-subject variability)
Solution Approach 1:
The patent changes the pH parameter of the gastrointestinal environment by co-administering fospropofol with pharmaceutically acceptable acids. This pH modification optimizes the dissolution and absorption characteristics of fospropofol, thereby improving oral bioavailability and reducing inter-subject variability in a manner that maintains reliability while enabling easier oral administration
2Device complexity
If fospropofol is administered orally without acid co-administration, then the formulation complexity is reduced, but bioavailability is worsened (inadequate and variable)
Solution Approach 1:
The patent introduces pharmaceutically acceptable acids as intermediary substances that mediate between fospropofol and the gastrointestinal environment. These acids temporarily modify the local pH to enhance fospropofol dissolution and absorption, thereby improving bioavailability without requiring complex formulation technologies or multiple components in the fospropofol dosage form itself
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The proposed solution significantly increases propofol plasma concentrations and area under the curve (AUC) while reducing variability, demonstrating improved bioavailability and therapeutic efficacy compared to traditional administration methods.
Implementation Method 1
co-administered with a pharmaceutically acceptable acid, specifically designed to enhance oral bioavailability and reduce inter-subject variability through controlled pH and release mechanisms
Implementation Method 2
Fospropofol disodium, a water-soluble, phosphono-O-methyl prodrug of propofol
Data Source
AI summary
The present disclosure provides pharmaceutical compositions for oral administration of fospropofol, or pharmaceutically acceptable salts of fospropofol, as well as methods of oral administration of fospropofol.