Orexin Receptor Antagonist Tablets With Fine Particle Dissolution Control
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Solution Overview
Problem
Existing solid pharmaceutical compositions of orexin receptor antagonists exhibit low dissolution rates, low bioavailability, and prolonged half-life, leading to adverse effects and inadequate clinical administration.
Innovation Solution
A solid pharmaceutical formulation with a compound represented by formula (I) or its pharmaceutically acceptable salts, featuring a particle size of D90 ≤ 50 µm, combined with specific excipients like microcrystalline cellulose, lactose, and disintegrants, to enhance dissolution and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If existing solid pharmaceutical compositions of orexin receptor antagonists are used, then the compound can be administered orally, but the dissolution rate is low and bioavailability is inadequate
Solution Approach 1:
The patent changes the particle size parameter of the active ingredient from conventional larger sizes to fine particles with D90 ≤ 50 µm. This parameter change significantly improves dissolution rate and bioavailability by increasing the surface area available for dissolution and enhancing wetting by dissolution media, directly resolving the technical contradiction between dissolution rate and bioavailability
Solution Approach 2:
The patent creates a composite pharmaceutical formulation combining the fine particle active ingredient with specific excipients including microcrystalline cellulose, lactose, and disintegrants. This composite structure optimizes both dissolution characteristics and bioavailability through synergistic effects of the formulation components, addressing the contradiction between dissolution rate and bioavailability
2Duration of action of moving object
If existing solid pharmaceutical compositions are used, then the compound can be administered, but the half-life is prolonged leading to adverse effects
Solution Approach 1:
The patent changes the particle size parameter to fine particles (D90 ≤ 50 µm), which alters the pharmacokinetic profile by reducing the half-life. This parameter change enables faster dissolution and metabolism, thereby reducing the duration of action to eliminate prolonged adverse effects while maintaining therapeutic efficacy
3Productivity
If the particle size of the active ingredient is reduced to D90 ≤ 50 µm, then dissolution rate and bioavailability are improved, but manufacturing precision requirements increase
Solution Approach 1:
The patent establishes a specific particle size parameter range (D90 ≤ 50 µm) that balances improved dissolution performance with achievable manufacturing precision. This parameter setting provides clear manufacturing guidelines while obtaining the desired pharmacokinetic benefits, resolving the contradiction between dissolution rate and manufacturing precision
Solution Approach 2:
The patent incorporates particle size reduction as a preliminary step in the manufacturing process, performing size classification before formulation. This preliminary action ensures consistent fine particle input to the formulation process, achieving both improved dissolution and controlled manufacturing precision through proactive process design
Data Source
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AI summary
The present invention relates to a solid pharmaceutical preparation and a preparation method therefor. Specifically, disclosed are a solid pharmaceutical preparation that comprises an orexin receptor antagonist compound and a preparation method therefor, the solid pharmaceutical preparation comprising an active ingredient of a compound represented by formula I, a filler, a binder, a disintegrant, and a lubricant. The solid pharmaceutical preparation has good dissolution, stability and in vivo bioavailability.