Abiraterone Acetate Complex for Reduced Food Effect
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Solution Overview
Problem
Abiraterone acetate has poor bioavailability and requires administration on an empty stomach due to a significant positive food effect, leading to variable pharmacokinetics and high doses, which complicates treatment for prostate and breast cancers.
Innovation Solution
A stable complex of Abiraterone acetate is formed with specific complexing agents like polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymers and excipients such as sodium deoxycholate, enhancing solubility, dissolution rate, and bioavailability, while eliminating the need for fasting and reducing dose variability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Abiraterone acetate is administered as a conventional formulation, then the drug can be delivered to patients, but it exhibits poor bioavailability and significant positive food effect requiring administration on an empty stomach
Solution Approach 1:
The patent applies composite materials by formulating Abiraterone acetate with multiple excipients including hydroxypropyl cellulose, sodium lauryl sulfate, and colloidal silicon dioxide to create a composite formulation that improves bioavailability and eliminates food effect requirements
Solution Approach 2:
The patent changes physical parameters of the drug formulation by controlling particle size distribution (D10: 1-5 μm, D50: 5-10 μm, D90: 10-20 μm) and using specific concentrations of excipients to optimize dissolution rate and bioavailability while eliminating fasting requirements
2Reliability
If Abiraterone acetate is administered at high doses to ensure therapeutic effect, then treatment efficacy is maintained, but dose variability increases due to food effect
Solution Approach 1:
The patent implements feedback control by optimizing the formulation to achieve consistent pharmacokinetic parameters (AUC and Cmax) regardless of food intake, thereby reducing dose variability and ensuring reliable treatment efficacy at standardized doses
Solution Approach 2:
The patent changes formulation parameters including using 50-150 mg of hydroxypropyl cellulose and 10-50 mg of sodium lauryl sulfate per 100 mg of Abiraterone acetate to control dissolution rate and eliminate food-effect variability
3Reliability
If Abiraterone acetate is formulated to improve solubility, then bioavailability increases, but the drug requires complex formulation with multiple excipients
Solution Approach 1:
The patent optimizes formulation parameters by using specific ratios of excipients (0.5-2 times weight of API for hydroxypropyl cellulose, 0.1-0.5 times weight of API for sodium lauryl sulfate) to achieve improved bioavailability while maintaining manageable formulation complexity
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 complex exhibits increased bioavailability, reduced food effect, and allows for significant dose reduction, ensuring consistent exposure and improved treatment efficacy for prostate and breast cancers without the need for fasting.
Implementation Method 1
A stable complex of Abiraterone acetate is formed with specific complexing agents like polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymers
Implementation Method 2
enhancing solubility, dissolution rate, and bioavailability
Implementation Method 3
excipients such as sodium deoxycholate, enhancing solubility, dissolution rate, and bioavailability
Data Source
AI summary
The present disclosure relates to pharmaceutically acceptable complex formulae comprising complexes of Abiraterone acetate and pharmaceutically acceptable excipients, process for the preparation thereof and pharmaceutical compositions containing them. The complex formulae of the present disclosure have improved physicochemical properties which results in reduced food effect which allows significant dose reduction and the abandoning of the requirement of taking the drug on an empty stomach.