Melt Extrusion Solid Ambroxol Preparations
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Solution Overview
Problem
Existing solid ambroxol preparations face challenges in reproducibility and low active ingredient content due to dependence on particle size distribution and manufacturing issues, such as those encountered in spray solidification processes, which complicates the adjustment of active ingredient release.
Innovation Solution
The development of solid ambroxol-containing preparations produced by melt extrusion using a mixture of ambroxol hydrochloride, hydrogenated vegetable oil, fatty acid esters or hydroxy fatty acid esters, and pharmaceutical excipients, allowing for adjustable release profiles and high active ingredient content.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If spray solidification process is used to produce ambroxol pellets, then active ingredient release can be controlled, but manufacturing complexity increases and active ingredient content is limited to less than 35%
Solution Approach 1:
The patent changes the fundamental manufacturing parameter from spray solidification to melt extrusion, enabling continuous production with simplified equipment while achieving reproducible active ingredient release profiles and higher active ingredient content (30-80%) in the preparation
Solution Approach 2:
The patent replaces the complex spray solidification mechanical system with a simpler melt extrusion system, where the active ingredient is mixed with a low-melting-point lipid carrier and extruded through a die, eliminating the need for complex spray equipment while maintaining release control
2Ease of manufacture
If spray solidification process is used, then pellets can be produced, but active ingredient content is limited to less than 35% due to spraying problems
Solution Approach 1:
The patent fundamentally changes the manufacturing approach from spray-based to melt extrusion-based processing, allowing active ingredient contents of 30-80% by weight to be achieved without the spraying limitations that capped previous formulations at less than 35%
Solution Approach 2:
The patent creates a composite material system where ambroxol hydrochloride is combined with a low-melting-point lipid carrier (melting range 40-90°C), enabling high active ingredient content while maintaining manufacturability through melt extrusion of the composite mixture
3Quantity of substance
If high active ingredient content is achieved in solid preparations, then dosage efficiency improves, but release control becomes more difficult
Solution Approach 1:
The patent introduces a low-melting-point lipid carrier as an intermediary substance that facilitates both high active ingredient loading (30-80%) and controlled release, acting as a matrix that holds the active ingredient and regulates its dissolution profile through the lipid's melting characteristics
Solution Approach 2:
The patent utilizes the melting point parameter of the lipid carrier (40-90°C) as a control mechanism, where the phase transition temperature of the lipid matrix directly influences the release profile, enabling reproducible release characteristics even at high active ingredient concentrations
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
This method enables reproducible production of ambroxol preparations with adjustable release characteristics, achieving high active ingredient content and bioequivalence to commercial forms, while simplifying the manufacturing process and reducing dependence on particle size.
Implementation Method 1
the active ingredient being embedded in a low-melting lipid with a melting range of 40-90 °C
Implementation Method 2
obtainable by melt extrusion of a mixture consisting of ambroxol hydrochloride, hydrogenated vegetable oil, fatty acid esters or hydroxy fatty acid esters
Data Source
Figure 1~2
Figure 3~4
Figure 5
AI summary
The present invention relates to solid ambroxol-containing preparations, obtainable by melt extrusion of a mixture consisting of a) 30 to 80% by weight ambroxol hydrochloride, b) 2 to 68% by weight of at least one hydrogenated vegetable oil, c) 2 to 68% by weight of at least one mixture containing esters of fatty acids and/or esters of hydroxyl fatty acids and d) 0 to 66% by weight of one or more pharmaceutical auxiliaries, in each case based on the total amount of the preparation and also to the use thereof for secretolytic treatment in acute and chronic bronchopulmonary diseases.