Relacorilant Softgel Composition for Excipient Compatibility
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Solution Overview
Problem
Many heteroaryl-ketone fused azadecalin compounds are difficult to formulate into stable and bioavailable pharmaceutical compositions due to poor solubility, incompatibility with excipients, and instability, leading to unsuitable formulations for therapeutic use.
Innovation Solution
Development of formulations containing relacorilant (R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone with 18-22% relacorilant, 56-64% lauroyl polyoxyl glyceride, and 18-22% propylene glycol monocaprylate, optionally with antioxidants, encapsulated in softgel capsules for improved stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If heteroaryl-ketone fused azadecalin compounds are formulated for therapeutic administration, then therapeutic activity is achieved, but solubility and bioavailability are poor
Solution Approach 1:
The patent uses solubilizing agents and formulation excipients as intermediaries to bridge the hydrophobic relacorilant compound and the aqueous biological environment. These intermediaries enable the compound to be administered orally while maintaining its therapeutic GR antagonistic activity, resolving the contradiction between therapeutic efficacy and solubility.
2Reliability
If heteroaryl-ketone fused azadecalin compounds are formulated for therapeutic administration, then therapeutic activity is achieved, but stability is poor
Solution Approach 1:
The patent applies preliminary stabilization measures by formulating relacorilant with protective excipients and optimizing the formulation composition before administration. This preliminary action prevents degradation during storage and administration, ensuring the compound remains stable and maintains its therapeutic activity throughout the treatment process.
3Reliability
If heteroaryl-ketone fused azadecalin compounds are formulated for therapeutic administration, then therapeutic activity is achieved, but compatibility with excipients is poor
Solution Approach 1:
The patent systematically evaluates and optimizes formulation parameters including excipient selection, concentration ratios, and formulation composition to achieve compatibility between relacorilant and formulation ingredients. By adjusting these parameters, the formulation achieves both therapeutic efficacy and compatibility with necessary excipients for stable formulation.
Data Source
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AI summary
Disclosed herein are novel formulations containing relacorilant ((R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone) that are suitable for administration, including oral administration, to patients suffering from disorders amenable to treatment by glucocorticoid receptor modulators (GRMs). Single unit dosage forms comprise softgel capsules containing these formulations. Such softgel capsules may contain, e.g., relacorilant formulations containing 25 milligrams (mg), 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, or other amounts of relacorilant. These novel formulations and single unit dosage forms may be used to treat diseases and disorders including Cushing's syndrome, Cushing's Disease, and other disorders.