Micronized Indibulin Formulation for Oral Bioavailability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The poorly soluble tubulin inhibitor Indibulin has low bioavailability due to its poor solubility in hydrophilic solvents, leading to insufficient plasma levels and efficacy in existing pharmaceutical formulations, which are either complex to manufacture or cause adverse side effects when using organic solvents or high concentrations of lactic acid.
Innovation Solution
A pharmaceutical formulation of micronized Indibulin combined with a hydrophilic surfactant and common encapsulation excipients, resulting in a granulate with a particle size of less than 20 µm for improved bioavailability, which is then used to create tablets or capsules, enhancing plasma levels without the limitations of previous formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If Indibulin is formulated as pure powder or granules, then manufacturing is simple, but bioavailability is very low due to poor solubility
Solution Approach 1:
The active ingredient Indibulin is micronized to reduce particle size to less than 20 μm, which increases the surface area and improves dissolution rate and bioavailability while maintaining formulation simplicity
Solution Approach 2:
A hydrophilic surfactant is introduced as an intermediary substance to enhance the solubility and dissolution of the poorly water-soluble Indibulin, thereby improving bioavailability without requiring complex formulation processes
2Reliability
If organic solvents are used to improve solubility, then bioavailability increases, but toxicity increases making them unsuitable for human use
Solution Approach 1:
The solvent system is changed from toxic organic solvents to aqueous hydrophilic surfactant solutions, altering the chemical parameters to achieve both safety for human use and adequate solubility enhancement for improved bioavailability
3Reliability
If highly concentrated organic acids are used as solvents, then solubility improves, but the amount administrable is limited by taste and side effects
Solution Approach 1:
A hydrophilic surfactant is used as an intermediary to enhance solubility without the adverse taste and side effects associated with highly concentrated organic acids, allowing for more flexible dosing
Solution Approach 2:
The concentration of acidic excipients is reduced by using hydrophilic surfactants, changing the formulation parameters to eliminate taste issues and side effects while maintaining adequate solubility
4Reliability
If lactic acid solution is used for oral administration, then bioavailability is good, but dosage is limited by taste and side effects
Solution Approach 1:
Hydrophilic surfactants serve as intermediary substances that provide the solubility enhancement needed for good bioavailability without the taste and side effects that limit dosage flexibility in lactic acid solutions
Solution Approach 2:
The formulation parameters are changed by replacing or supplementing lactic acid with hydrophilic surfactants, maintaining adequate solubility for good bioavailability while removing the constraints on dosage flexibility
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 formulation achieves significant bioavailability and effective plasma levels comparable to a lactic acid solution, while avoiding its drawbacks, such as taste issues and dosage limitations, with improved tolerability and higher dosing possibilities.
Implementation Method 1
at least one hydrophilic surfactant
Data Source
AI summary
The present invention relates to a pharmaceutical formulation for oral administration of the poorly soluble and therefore hardly bioavailable tubulin inhibitor Indibulin and a process for its manufacture. In particular, there is provided a pharmaceutical formulation of lndibulin for oral administration comprising a granulate containing micronized lndibulin having a particle size of less than 20 µm for at least 99 vol.-% of the particles, at least one hydrophilic surfactant, and one or more capsulation excipients.