Pitolisant Formulation With Alkalinizing Agents for Faster Absorption
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Solution Overview
Problem
Existing pharmaceutical formulations of pitolisant and doxepin hydrochloride exhibit slow absorption rates, necessitating a need for faster onset of action for treating sleep disorders and insomnia.
Innovation Solution
Combining pitolisant or doxepin hydrochloride with an alkalinizing agent, such as magnesium carbonate or potassium bicarbonate, to accelerate the absorption of these drugs through the intestinal barrier.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If pitolisant hydrochloride is administered in conventional formulation, then the drug is stable and safe for administration, but the absorption time is prolonged (peak plasma concentration reached approximately three hours after administration)
Solution Approach 1:
The patent changes the pH parameter of the gastrointestinal environment by co-administering alkalinizing agents (such as sodium bicarbonate, magnesium carbonate, or aluminum hydroxide) with pitolisant hydrochloride. This pH modification accelerates the dissolution and absorption of the drug, reducing the time to reach peak plasma concentration from approximately 3 hours to a shorter duration, while maintaining drug stability and safety
Solution Approach 2:
The patent introduces alkalinizing agents as intermediary substances that facilitate the absorption process. These agents temporarily modify the gastrointestinal pH environment to enhance drug dissolution and intestinal barrier crossing, acting as a mediator between the drug formulation and the absorption process without permanently altering the system
2Speed
If doxepin hydrochloride is administered in conventional formulation, then the drug provides therapeutic effect for insomnia, but the onset of action is delayed (peak plasma concentration reached 3.5 hours after administration)
Solution Approach 1:
The patent applies pH modification using alkalinizing agents to accelerate the dissolution and absorption of doxepin hydrochloride. By changing the gastrointestinal pH environment, the drug achieves faster onset of action, allowing patients to fall asleep more quickly while maintaining the therapeutic effect for insomnia treatment
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 combination results in a more rapid plasmatic absorption peak, with increased peak plasma concentration and bioavailability, reducing the time to reach Tmax by up to 50% and enhancing AUC by up to 50% compared to formulations without alkalinizing agents.
Implementation Method 1
active pharmaceutical ingredients that are typically administered in the form of a chloride salt may be more rapidly absorbed if they are administered in combination with an alkalinizing agent
Data Source
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AI summary
The present disclosure relates to new formulations comprising an alkalinizing agent for improving absorption of active pharmaceutical ingredients, such as pitolisant.