PPARδ Agonist Formulation with Croscarmellose Sodium
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Solution Overview
Problem
Current treatments for primary mitochondrial myopathies (PMM) are lacking, with no approved therapies available, and existing PPARδ agonist compounds face stability and delivery issues that hinder their effectiveness in clinical use.
Innovation Solution
Development of stable pharmaceutical compositions comprising a PPARδ agonist compound, such as Compound (I), in combination with croscarmellose sodium, which ensures excellent dissolution stability and bioavailability for effective medical application, including specific dosing regimens for long-term treatment of PMM.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PPARδ agonist compounds are used for treating primary mitochondrial myopathies, then therapeutic efficacy is improved, but stability and delivery issues worsen
Solution Approach 1:
The patent applies composite materials by formulating the PPARδ agonist compound with croscarmellose sodium, a disintegrant excipient, to create a stable pharmaceutical composition. This composite formulation resolves the stability issue while maintaining therapeutic efficacy, as croscarmellose sodium enhances the structural stability and dissolution characteristics of the compound.
Solution Approach 2:
The patent employs parameter changes by optimizing the formulation parameters of the pharmaceutical composition, including the ratio of PPARδ agonist to croscarmellose sodium, granulation parameters, and compression parameters. These parameter optimizations improve both the stability and bioavailability of the compound while maintaining its therapeutic effect.
2Reliability
If PPARδ agonist compounds are administered to patients, then treatment effectiveness is improved, but dissolution stability deteriorates
Solution Approach 1:
The pharmaceutical composition combines PPARδ agonist with croscarmellose sodium to create a composite that exhibits improved dissolution stability. The disintegrant properties of croscarmellose sodium enhance the dissolution rate and stability of the compound in physiological conditions, thereby maintaining treatment effectiveness.
Solution Approach 2:
The patent optimizes formulation parameters such as the concentration of croscarmellose sodium, granulation moisture content, and tablet compression force to achieve optimal dissolution stability. These parameter changes ensure that the compound maintains its therapeutic effectiveness while improving dissolution characteristics.
3Reliability
If PPARδ agonist compounds are used for clinical application, then therapeutic benefit is improved, but bioavailability decreases
Solution Approach 1:
The composite pharmaceutical formulation with croscarmellose sodium improves the bioavailability of the PPARδ agonist by enhancing its dissolution rate and stability in the gastrointestinal tract. This allows a greater quantity of the active compound to be absorbed systemically, thereby improving therapeutic benefit.
Solution Approach 2:
The patent optimizes pharmacokinetic parameters through formulation adjustments, including the use of croscarmellose sodium to improve dissolution rate and stability. These parameter changes enhance the oral bioavailability of the compound, ensuring adequate systemic exposure for therapeutic effect.
Data Source
AI summary
The present disclosure relates to methods of use of an agonist of peroxisome proliferator-activated receptors delta (PPARδ) (e.g., Compound (I) or a pharmaceutically acceptable salt thereof disclosed herein), for example, for treating patients having primary mitochondrial myopathies (PMM). The present disclosure also relates to a pharmaceutical composition comprising an agonist of peroxisome proliferator-activated receptors delta (PPARδ) and croscarmellose sodium.