Antidepressant Acid Addition Salts for Solubility and Stability
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Solution Overview
Problem
Existing antidepressants have low solubility, leading to limitations in pharmaceutical applications and high gastrointestinal side effects, along with a high discontinuation rate due to slow onset of efficacy and neglect of cognitive symptoms.
Innovation Solution
Development of acid addition salts of 2-methyl-5-(naphthalen-2-yl)octahydropyrrolo[3,4-c]pyrrole, specifically hydrochloride, maleate, and hydrobromide forms, with improved solubility and stability, using solvents like acetone and ethanol for preparation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the compound 2-methyl-5-(naphthalen-2-yl)octahydropyrrolo[3,4-c]pyrrole is used as an antidepressant, then it shows strong serotonin reuptake inhibition activity and low toxic side effects, but its solubility is low which limits its application in pharmaceutical process
Solution Approach 1:
The patent changes the physical chemical parameters of the compound by forming salt compounds with different acids (hydrochloric acid, maleic acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, citric acid, fumaric acid, succinic acid, ascorbic acid, and camphorsulfonic acid). This transformation modifies the solubility parameter while preserving the antidepressant activity, directly resolving the contradiction between high reliability and low solubility.
Solution Approach 2:
The patent creates composite salt compounds by combining the base compound with various acids to form new chemical entities (e.g., hydrochloride salt, maleate salt, hydrobromide salt). These composite materials exhibit improved solubility properties while maintaining the pharmacological activity of the parent compound, effectively addressing the solubility limitation.
2Reliability
If existing antidepressants are administered continuously for 2-4 weeks to be effective, then therapeutic effect is achieved, but discontinuation rate is high due to gastrointestinal side effects and slow onset
Solution Approach 1:
The patent modifies the pharmacokinetic parameters of the antidepressant by changing its salt form, which affects absorption rate and bioavailability. The salt compounds formed with different acids exhibit improved solubility and potentially faster absorption, reducing the time to onset of efficacy and allowing lower dosing frequencies, thereby reducing gastrointestinal side effects while maintaining therapeutic efficacy.
3Object-affected harmful factors
If the compound is administered at low dose due to strong activity, then toxic side effects are reduced, but solubility remains low limiting pharmaceutical application
Solution Approach 1:
The patent changes the solubility parameter of the compound by forming salt compounds with various acids. This allows the use of low doses (maintaining low toxic side effects) while simultaneously improving solubility to enable effective pharmaceutical formulation and administration, resolving the contradiction between reduced harm and limited application.
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 salts exhibit enhanced solubility and stability, reducing gastrointestinal side effects and increasing medication compliance, effectively addressing cognitive symptoms and depression recurrence.
Implementation Method 1
acid addition salt of an antidepressant compound 2-methyl-5-(naphthalen-2-yl)octahydropyrrolo[3,4-c]pyrrole
Implementation Method 2
the solubility of the compound is low, which limits its application in the pharmaceutical process to some extent
Data Source
Figure 1~2
Figure 3
AI summary
The present invention relates to a salt of a compound of formula (I), and a method for preparing the salt, a pharmaceutical composition containing the salt and the use thereof. The salt-forming acid of the salt of the compound of formula (I) is selected from a plurality of acids such as hydrochloric acid, maleic acid, hydrogen bromide, phosphoric acid and sulfuric acid. The salt of the compound of formula (I) has the advantages of a good stability, high solubility, low hygroscopicity, etc, and can be used for preparing a drug for treating and/or relieving depression.