Solid Pharmaceutical Composition Micronization
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Solution Overview
Problem
Current pharmaceutical compositions of PPARĪ³ modulators, specifically the besylate salt of compound 101, face challenges with low bioavailability and stability due to limited solubility and susceptibility to leakage or precipitation in liquid-filled capsules, which affects their efficacy and shelf-life.
Innovation Solution
A solid pharmaceutical composition is developed with a mean particle size of the besylate salt of compound 101 less than 150 microns, prepared through micronization and wet granulation with pharmaceutically acceptable excipients, enhancing bioavailability and stability while avoiding the issues associated with liquid-filled capsules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the besylate salt of compound 101 is used in liquid-filled capsules, then solubility and bioavailability are improved, but the formulation becomes prone to leakage and precipitation over time
Solution Approach 1:
The patent transforms the physical state of the formulation from liquid to solid by changing the particle size parameter of the besylate salt through micronization (reducing to less than 150 microns). This parameter change enables the formulation to achieve both good dissolution/bioavailability and capsule stability, resolving the contradiction between improved bioavailability and capsule reliability.
2Stability of the object's composition
If the besylate salt of compound 101 is used, then stability and hygroscopic properties are improved, but solubility in aqueous and organic solvents is severely limited
Solution Approach 1:
The patent applies segmentation by reducing the besylate salt into fine particles with mean size less than 150 microns. This segmentation increases the surface area to volume ratio, which significantly improves dissolution rate and apparent solubility while maintaining the chemical stability of the besylate salt form.
3Ease of operation
If liquid-filled capsules are used for the besylate salt, then dissolution and bioavailability are achieved, but leakage and contamination occur over time
Solution Approach 1:
The patent changes the physical state parameter from liquid to solid formulation. The solid micronized besylate salt formulation maintains excellent dissolution characteristics while eliminating the harmful effects of leakage and contamination associated with liquid-filled capsules, thereby resolving the contradiction between ease of dissolution and protection from harmful factors.
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 solid composition achieves excellent dissolution and bioavailability comparable to oil-based liquid-filled capsules, with improved stability and reduced risk of leakage or precipitation, ensuring effective and prolonged therapeutic action.
Implementation Method 1
micronizing the compound of formula (I)
Implementation Method 2
performing wet granulation of the compound of formula (I) in combination with one or more pharmaceutically acceptable excipients
Data Source
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AI summary
Provided are pharmaceutical compositions in solid form comprising a selective modulator of PPAR-? suitable for oral dosage to treat subjects having PPAR-? mediated conditions. Provided further are methods of manufacturing the compositions, and methods of treating a PPAR-? mediated condition.