Amorphous Pitolisant Hydrochloride Composition for Stability and Solubility
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Solution Overview
Problem
Existing pharmaceutical formulations of pitolisant hydrochloride lack stability, solubility, and bioavailability, posing challenges in effectively treating excessive daytime sleepiness and cataplexy in narcolepsy patients, with potential side effects and complex, costly preparation processes.
Innovation Solution
A novel pharmaceutical composition comprising amorphous form of pitolisant hydrochloride is prepared using a granulation technique, specifically wet granulation, by converting pitolisant base into hydrochloride with hydrochloric acid in a solvent and mixing with pharmaceutically acceptable excipients, enhancing solubility and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If crystalline form of pitolisant hydrochloride is used, then manufacturing stability is improved, but solubility and bioavailability are reduced
Solution Approach 1:
The patent changes the physical state parameter of pitolisant hydrochloride from crystalline to amorphous form. This parameter change enables the drug to achieve both manufacturing stability and improved solubility/bioavailability simultaneously, as the amorphous form provides higher溶解性 while the controlled preparation process ensures manufacturing consistency.
Solution Approach 2:
The patent creates a composite pharmaceutical composition combining amorphous pitolisant hydrochloride with specific excipients and carriers. This composite formulation maintains the stability benefits of the amorphous form while enhancing solubility and bioavailability through the synergistic effects of the excipient system.
2Ease of manufacture
If conventional pharmaceutical formulations are used, then manufacturing simplicity is maintained, but stability and solubility are insufficient
Solution Approach 1:
The patent employs parameter changes in the preparation process, specifically controlling pH, temperature, and solvent composition during the formation of amorphous pitolisant hydrochloride. These controlled parameter changes enable the creation of a stable amorphous formulation while maintaining relatively simple manufacturing procedures.
Solution Approach 2:
The patent uses specific excipients and carriers as intermediaries in the formulation process. These intermediaries facilitate the creation of stable amorphous pitsolisant hydrochloride while maintaining manufacturing simplicity, as the excipients act as mediators that guide the drug through the formulation process without requiring complex equipment or procedures.
3Stability of the object's composition
If complex preparation processes are used to improve stability, then formulation stability is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent achieves formulation stability through controlled parameter changes in a straightforward preparation process. By optimizing pH, temperature, and solvent composition during a simple amorphization process, the patent achieves stable formulations without requiring complex multi-step procedures or specialized equipment.
Solution Approach 2:
The patent employs readily available excipients and carriers that can be easily obtained and integrated into the formulation. These inexpensive, readily available materials enable stable formulation without requiring costly or complex preparation processes, as the excipients are simple substances that can be incorporated through conventional mixing and processing techniques.
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 amorphous form of pitolisant hydrochloride provides comparable dissolution and bioavailability to known formulations like Wakix, with improved stability and reduced complexity in preparation, offering a cost-effective and safer treatment option for narcolepsy symptoms.
Implementation Method 1
converting pitolisant base into hydrochloride with hydrochloric acid in a solvent
Implementation Method 2
provides comparable dissolution and bioavailability to known formulations
Data Source
AI summary
The present invention relates to a pharmaceutical composition compositions, that comprise amorphous form of pitolisant or pharmaceutically acceptable salts thereof, which is efficacious, chemically stable and physiologically balanced for safety and efficacy. The said invention is used for treatment of excessive daytime sleepiness (EDS) and cataplexy in adult patients with narcolepsy. Further the invention relates to the process for preparation of said pharmaceutical composition.