Amorphous Abiraterone Acetate Solid Dispersion for Food-Effect Reduction
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Solution Overview
Problem
Abiraterone acetate exhibits low aqueous solubility and bioavailability, leading to significant pharmacokinetic variability and a positive food effect, necessitating the development of formulations with improved solubility, stability, and reduced food effect.
Innovation Solution
A pharmaceutical composition comprising a solid dispersion of amorphous abiraterone acetate with pharmaceutically acceptable excipients, including polymers, surfactants, plasticizers, pH modifiers, disintegrating agents, and preservatives, to enhance solubility, stability, and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If abiraterone acetate is formulated as a conventional solid dosage form, then manufacturing is simple, but solubility and bioavailability are poor
Solution Approach 1:
The patent changes the physical state of abiraterone acetate from crystalline to amorphous form, which fundamentally alters its dissolution properties and bioavailability without requiring complex manufacturing processes
Solution Approach 2:
The patent creates a solid dispersion system combining amorphous abiraterone acetate with excipients (such as HPMC, PEG, or other polymers) to achieve both improved solubility and manufacturing feasibility
2Reliability
If abiraterone acetate is administered in conventional formulations, then dosing is straightforward, but pharmacokinetic variability is high
Solution Approach 1:
The patent transforms the drug from crystalline to amorphous state, which provides more consistent dissolution behavior and reduces inter-individual pharmacokinetic variability while maintaining a relatively simple tablet or capsule formulation
3Reliability
If abiraterone acetate is formulated to improve solubility, then bioavailability increases, but stability decreases due to amorphous-to-crystalline transition
Solution Approach 1:
The patent formulates amorphous abiraterone acetate in a matrix of excipients (such as hydrophilic polymers like HPMC, PEG, or other stabilizing materials) that physically stabilize the amorphous state and prevent crystallization during storage
Solution Approach 2:
The patent creates a local environment around the amorphous drug molecules using excipients that provide molecular spacing and prevent reorganization into crystalline structures, thereby maintaining solubility enhancement over time
4Reliability
If Zytiga tablets are taken to achieve therapeutic effect, then cancer treatment is effective, but food effect significantly alters absorption
Solution Approach 1:
The patent changes the dissolution characteristics of abiraterone acetate through amorphization, which reduces the impact of food on absorption by providing more consistent dissolution behavior regardless of gastric conditions, thereby increasing administration 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 composition achieves improved solubility, stability, and bioavailability, reducing the food effect and variability in drug absorption, allowing for effective cancer treatment at lower doses.
Implementation Method 1
amorphous dispersions of drugs in various types of excipients tend to convert to crystalline forms over time
Implementation Method 2
solid dispersion of amorphous abiraterone acetate and one or more pharmaceutically acceptable excipients
Data Source
AI summary
The present invention relates to a pharmaceutical composition comprising solid dispersion of amorphous abiraterone acetate and one or more pharmaceutically acceptable excipients, having improved solubility, stability, bioavailability, and no positive food effect. The present invention also relates to a method for its preparation, a dosage form comprising such compositions, and the use of the said composition or dosage form as a medicament for the treatment of prostate cancer.