Controlled-Release Neuroactive Steroid Composition for Steady Plasma Levels
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Solution Overview
Problem
Current treatments for mood disorders, such as obsessive-compulsive disorder, post-traumatic stress disorder, and social anxiety disorder, face challenges in maintaining sustained therapeutic plasma levels of 3α-hydroxy-3β-methoxymethyl-21-(1'-imidazolyl)-5α-pregnan-20-one, leading to variable efficacy and side effects due to rapid absorption and short half-life.
Innovation Solution
A pharmaceutical composition comprising 3α-hydroxy-3β-methoxymethyl-21-(1'-imidazolyl)-5α-pregnan-20-one or its pharmaceutically acceptable salt/solvate, combined with controlled-release formulations, providing sustained therapeutic plasma levels through appropriate pharmacokinetic parameters like T max, C max, and AUC, achieved via technologies like controlled-release coatings and multiparticulate delivery systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional immediate-release formulations are used, then rapid absorption and quick onset of action are achieved, but therapeutic plasma levels cannot be maintained due to short half-life, leading to variable efficacy and side effects
Solution Approach 1:
The pharmaceutical composition is divided into multiple functional components: immediate-release portions for rapid absorption and controlled-release portions for sustained delivery. This segmentation allows different parts of the formulation to perform different functions - one portion provides quick onset while another maintains therapeutic levels over extended periods
Solution Approach 2:
The invention changes the release rate parameter of the active compound by using different formulation technologies. Controlled-release coatings and multiparticulate systems modify the dissolution and absorption kinetics, transforming the pharmacokinetic profile from rapid-short to sustained-prolonged while maintaining therapeutic efficacy
2Reliability
If higher doses are administered to maintain therapeutic levels, then efficacy is improved, but side effects increase due to exceeding safe plasma concentration thresholds
Solution Approach 1:
The controlled-release formulation provides a feedback-controlled delivery system where the release rate is regulated to maintain plasma concentrations within the therapeutic window. The formulation automatically adjusts release based on dissolution kinetics and absorption rates, preventing both sub-therapeutic and toxic levels
Solution Approach 2:
The invention ensures continuous delivery of the active compound at optimized rates, maintaining steady-state plasma concentrations within the therapeutic range (5-500 ng/mL). This continuous controlled action eliminates the peaks and valleys associated with immediate-release formulations, ensuring reliable efficacy without toxic accumulation
3Duration of action of moving object
If multiple daily doses are given to maintain plasma levels, then therapeutic coverage is improved, but dosing complexity and patient compliance deteriorate
Solution Approach 1:
The controlled-release formulation is pre-engineered with built-in release mechanisms that automatically maintain therapeutic levels throughout the dosing interval. The formulation contains pre-formulated matrix systems, coated particles, or osmotic devices that control release kinetics without requiring patient intervention or dose adjustments during the dosing period
Data Source
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AI summary
The present invention relates to a pharmaceutical composition, comprising 3α-hydroxy-3β-methoxymethyl-21-(1'-imidazolyl)-5a-pregnan-20-one or a pharmaceutically-acceptable salt or solvate thereof, and one or more pharmaceutically-acceptable excipients, wherein the composition provides steady state plasma levels of 3α-hydroxy-3β-methoxymethyl-21-(1'-imidazolyl)-5α-pregnan-20-one in a range of from 5 ng/mL to 500 ng/mL for a duration of from 6 h to 24 h following administration.