Abiraterone Acetate Formulation with Absorption Enhancer
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Solution Overview
Problem
Current pharmaceutical formulations of abiraterone acetate, such as Zytiga®, exhibit poor bioavailability and significant inter-individual variability, with food intake greatly affecting oral bioavailability, leading to inconsistent drug absorption.
Innovation Solution
A pharmaceutical composition comprising 300 mg of abiraterone acetate with an absorption enhancer like sodium 8-(salicylamido)caprylate, combined with lactose and a disintegrant, which provides bioequivalence to a 1000 mg dose of Zytiga® in a fasting state and reduces the impact of food on absorption, achieving consistent blood plasma levels and reduced intra-individual variation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional tablets (Zytiga®) are used, then the drug is approved for treatment, but bioavailability is poor and inter-individual differences are large
Solution Approach 1:
The patent changes the physical parameters of abiraterone acetate by reducing particle size to nano-scale (D90 < 500 nm) and incorporating absorption enhancers (SNAC/SNAD at 1-10% w/w), which fundamentally alters the drug's absorption characteristics to achieve consistent bioavailability across individuals
Solution Approach 2:
The patent introduces absorption enhancers (sodium N-(8-(2-hydroxybenzoyl)amino)caprylate or sodium N-(8-(2-hydroxybenzoyl)amino)decanoate) as intermediary substances that facilitate drug absorption through the intestinal mucosal barrier, acting as carriers that improve membrane permeability and reduce efflux pump activity
2Quantity of substance
If food is consumed, then caloric intake is provided, but oral bioavailability increases 17-10 fold
Solution Approach 1:
The patent converts the harmful effect of food on absorption variability into a benefit by incorporating absorption enhancers that actively promote drug absorption independent of food intake, thereby eliminating the harmful variability while maintaining adequate absorption even in fasting states
Solution Approach 2:
The patent uses a low dose (300 mg) of abiraterone acetate in combination with absorption enhancers to achieve the same pharmacokinetic effect as a high dose (1000 mg) of conventional tablets, reducing the overall quantity of drug needed while eliminating food effect variability
3Reliability
If 300 mg dose is used with absorption enhancer, then bioequivalence to 1000 mg Zytiga® is achieved, but formulation complexity increases
Solution Approach 1:
The patent creates a composite pharmaceutical formulation combining abiraterone acetate nanoparticles with absorption enhancers (SNAC/SNAD) and excipients in specific ratios, which achieves superior bioavailability and bioequivalence to high-dose Zytiga® while managing formulation complexity through defined composition ranges
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 composition achieves bioequivalence to a 1000 mg dose of Zytiga® with improved bioavailability and reduced food effect, resulting in consistent pharmacokinetic parameters and lower inter-individual variability, enhancing treatment efficacy for castration-resistant prostate cancer.
Implementation Method 1
improve the membrane permeability of the drug, or to inhibit the efflux pump to prevent the body from efflux of the absorbed drug, that is, the use of oral absorption enhancers
Data Source
AI summary
The present disclosure relates to a pharmaceutical composition. Specifically, a pharmaceutical composition of abiraterone acetate is provided, wherein a 300 mg dose of abiraterone acetate is bioequivalent to a 1000 mg dose of Zytiga® in healthy male subjects in a fasting state.