Oral Bendamustine Formulation Stability and Bioavailability
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Solution Overview
Problem
Bendamustine's intravenous formulation is unstable after reconstitution, leading to reduced potency and impurity formation, and its oral administration results in poor bioavailability and high inter-individual variability due to solubility issues and incomplete gastrointestinal absorption.
Innovation Solution
Development of stable oral pharmaceutical compositions comprising bendamustine or its pharmaceutically acceptable ester, salt, or solvate, combined with non-ionic surfactants like polyethoxylated castor oil or ethylene oxide/propylene oxide block copolymers, which enhance dissolution and bioavailability by forming liquid-filled hard gelatin capsules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If bendamustine is formulated for intravenous administration as a lyophilized powder, then stability is improved, but ease of operation deteriorates due to requiring reconstitution and hospital supervision
Solution Approach 1:
The patent changes the physical and chemical parameters of bendamustine by converting it from a lyophilized powder requiring reconstitution to an orally disintegrating tablet formulation. This involves modifying the dosage form parameters (from injectable to oral), solubility characteristics, and release profile to achieve both stability and ease of administration without hospital supervision
2Ease of operation
If bendamustine is administered orally in capsule form, then ease of operation is improved, but bioavailability deteriorates due to poor dissolution and high inter-individual variability
Solution Approach 1:
The patent modifies the dissolution parameters of bendamustine by formulating it in an orally disintegrating tablet format with specific disintegration and dissolution characteristics. The formulation achieves rapid disintegration and complete dissolution within specified timeframes, ensuring reliable and consistent bioavailability while maintaining ease of oral administration
Solution Approach 2:
The patent uses composite formulation approaches combining bendamustine with excipients that enhance dissolution and disintegration properties. The orally disintegrating tablet employs a matrix of pharmaceutically acceptable materials that work together to achieve rapid breakdown and complete dissolution, ensuring reliable drug release and absorption
3Ease of operation
If bendamustine is formulated for oral administration, then ease of operation is improved, but stability deteriorates due to hydrolysis in aqueous environments
Solution Approach 1:
The patent changes the stability parameters by formulating bendamustine in an anhydrous or low-moisture matrix suitable for oral disintegrating tablets. The formulation controls water activity and protects the drug from hydrolysis while maintaining the ability to rapidly disintegrate and dissolve upon contact with gastrointestinal fluids, achieving both stability and ease of operation
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 compositions achieve a stable and rapid dissolution profile, reducing variability and improving bioavailability, allowing for effective oral administration without the need for immediate reconstitution and hospital supervision, while maintaining stability and safety.
Implementation Method 1
non-ionic surfactants like polyethoxylated castor oil or ethylene oxide/propylene oxide block copolymers, which enhance dissolution and bioavailability
Data Source
AI summary
In the present invention there is provided an oral pharmaceutical composition, comprising bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient, which is a pharmaceutically acceptable non-ionic surfactant, selected from the group consisting of polyethoxylated castor oil or derivative thereof and a block copolymer of ethylene oxide and propylene oxide.