Crisdesalazine Composition Balancing Dissolution Rate and Stability
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Solution Overview
Problem
Crisdesalazine, a poorly water-soluble drug, faces challenges in achieving both stability and dissolution rate due to its pH-dependent solubility, with alkaline ingredients enhancing solubility but compromising stability, and existing formulations fail to maintain long-term stability and effective absorption.
Innovation Solution
A pharmaceutical composition comprising crisdesalazine or a pharmaceutically acceptable salt with an anionic or nonionic surfactant having an HLB value of 8 or higher, along with mannitol and microcrystalline cellulose as diluents, and an acidifying agent to maintain pH below 7, ensuring stability and dissolution rate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If alkaline ingredients are included to enhance solubility, then dissolution rate is improved, but stability deteriorates
Solution Approach 1:
The patent changes the pH parameter of the formulation by incorporating alkaline substances (such as sodium bicarbonate, magnesium hydroxide, or calcium carbonate) to create a more favorable pH environment for crisdesalazine dissolution. This parameter change enables the poorly water-soluble drug to dissolve more effectively in the gastrointestinal tract, resolving the contradiction between dissolution rate and stability by optimizing the chemical environment for drug release.
Solution Approach 2:
The patent introduces alkaline substances as intermediary agents that mediate between the poorly soluble crisdesalazine and the gastrointestinal fluids. These intermediaries (alkaline ingredients) create a localized pH buffer that enhances drug solubility without requiring the entire formulation to be unstable, thus improving dissolution while maintaining overall formulation stability through controlled pH modulation.
2Ease of manufacture
If formulation is made without considering pH-dependent properties, then manufacturing is simpler, but absorption rate deteriorates
Solution Approach 1:
The patent applies pH parameter changes by incorporating alkaline substances into the formulation to match the pH-dependent solubility characteristics of crisdesalazine. This simple parameter adjustment (adding pH-modifying ingredients) significantly improves absorption rate without complicating the manufacturing process, as these ingredients can be easily incorporated into standard pharmaceutical formulations.
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 and bioavailability of crisdesalazine, maintaining stability and reducing impurities over time, suitable for treating neurodegenerative and inflammatory diseases.
Implementation Method 1
a surfactant having an HLB (Hydrophilic and Lipophilic Balance) value of 8 or greater
Implementation Method 2
crisdesalazine is a very poorly soluble drug, exhibiting low solubility under acidic pH conditions and high solubility under alkaline pH conditions
Data Source
Figure 1~2
AI summary
The present invention relates to a pharmaceutical composition comprising crisdesalazine or a salt thereof, which has improved stability by reducing the content of related substances of crisdesalazine, and has an increased dissolution rate by improving the intrinsic solubility thereof. The composition of the present invention secures stability and bioavailability, and thus is more effective in treating neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, epilepsy accompanied by free radical neurotoxicity, cerebral trauma, spinal injury, and the like), inflammatory diseases (gastritis, colitis, pancreatitis, arthritis, diabetic inflammation, inflammatory bowel disease, nephritis, hepatitis, arteriosclerosis inflammation, and the like), stress disorders (anxiety disorder, depression, and the like), and the like.