Rucaparib Salt Solid-State Forms for Stability and Dissolution
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Solution Overview
Problem
There is a need for additional solid state forms of Rucaparib and its salts to improve processing properties, handling characteristics, stability, and dissolution profiles, which are crucial for effective formulation and administration in cancer treatment.
Innovation Solution
The development of new solid state forms of Rucaparib and its salts, such as crystalline forms VII and VIII, characterized by specific X-ray powder diffraction patterns, which offer improved chemical stability, solubility, and mechanical stability, facilitating the preparation of pharmaceutical compositions for cancer treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If new solid state forms of Rucaparib and its salts are developed, then stability, solubility, and processing properties are improved, but the complexity of the formulation development process increases
Solution Approach 1:
The patent applies parameter changes by developing multiple solid state forms (polymorphs, salts, solvates) of Rucaparib with different physical and chemical parameters. Each solid state form exhibits distinct properties such as solubility, stability, and processing characteristics, allowing optimization of formulation parameters to achieve desired therapeutic outcomes while managing development complexity through systematic exploration of parameter space
2Quantity of substance
If high drug loading is required for effective cancer treatment, then therapeutic efficacy is improved, but manufacturability and compressibility become more difficult to achieve
Solution Approach 1:
The patent utilizes parameter changes by selecting specific solid state forms of Rucaparib with optimized physical properties that enable high drug loading (45% w/w or more) while maintaining manufacturability. The choice of particular polymorphs and salts allows adjustment of compressibility and flow properties to achieve both high potency and ease of manufacturing in tablet formulations
3Ease of operation
If different salts and solid state forms are used, then dissolution profile and bioavailability can be optimized, but the number of materials to be evaluated increases
Solution Approach 1:
The patent applies parameter changes by systematically evaluating different salts and solid state forms of Rucaparib to optimize dissolution profiles and bioavailability. By changing the chemical and physical parameters of the API (selecting specific salts like tosylate, camsylate, and different polymorphs), the patent enables fine-tuning of dissolution characteristics while providing a structured approach to managing the evaluation of multiple material forms
Data Source
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AI summary
The present disclosure encompasses solid state forms of Rucaparib and of Rucaparib salts, and pharmaceutical compositions thereof.