Amorphous Solid Solutions for Poorly Soluble Drugs
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Solution Overview
Problem
Existing methods for incorporating poorly water-soluble substances into formulations fail to achieve stable and high active ingredient loading, particularly in achieving an amorphous state, and often result in sticky, viscous polymers that are not suitable for processing.
Innovation Solution
A process involving the radical polymerization of a mixture comprising 30-80% N-vinyl lactam, 10-50% vinyl acetate, and 10-50% polyether, with embedding at temperatures above the melting point of the substances, using preferred compositions of 30-70% N-vinyl lactam, 15-35% vinyl acetate, and 10-35% polyether, to form copolymers that are then extruded with active ingredients, resulting in stable, amorphous solid solutions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If known polymeric solubilizers are used to solubilize poorly water-soluble substances, then solubilization capability is provided, but stable solid solutions are not formed and the active ingredient crystallizes during storage
Solution Approach 1:
The patent changes the chemical composition parameters of the polymer by incorporating specific ratios of N-vinyl lactam (30-80%), vinyl acetate (10-50%), and polyether (10-50%) units. This compositional parameter change creates a polymer matrix with optimized glass transition temperature and molecular mobility, preventing crystallization of the active ingredient while maintaining solubilization capability.
Solution Approach 2:
The patent creates a composite solid solution system where the active ingredient is molecularly dispersed within the copolymer matrix. The composite structure combines the solubilization properties of polyether units with the structural stability provided by N-vinyl lactam and vinyl acetate units, achieving both solubilization and crystallization prevention.
2Reliability
If graft polymers containing polyalkylene oxide are used as solubilizers, then solubilization is achieved, but the polymers are viscous and sticky liquids that are not suitable for processing
Solution Approach 1:
The patent modifies the physical state parameter by adjusting the polymer composition to achieve a glass transition temperature above ambient temperature. The specific ratio of rigid N-vinyl lactam and vinyl acetate units to flexible polyether units creates a solid, free-flowing powder with reduced viscosity and improved processability while retaining solubilization functionality.
Solution Approach 2:
The patent creates a composite polymer structure combining rigid structural units (N-vinyl lactam, vinyl acetate) with flexible solubilizing units (polyether). This composite architecture provides both the solubilization capability of polyether-containing polymers and the processability of solid materials, eliminating the viscous liquid problem.
3Ease of manufacture
If embedding is carried out at temperatures below the melting point of the active ingredient, then the polymer can be processed, but stable amorphous solid solutions with high active ingredient loading cannot be achieved
Solution Approach 1:
The patent utilizes the phase transition of the polymer matrix by heating above the melting point of the active ingredient during extrusion, then rapidly cooling to trap the active ingredient in an amorphous state within the polymer matrix. This phase transition approach enables high active ingredient loading while maintaining stability and preventing crystallization during storage.
Solution Approach 2:
The patent changes the temperature parameter during processing to exceed the active ingredient melting point, enabling complete mixing and molecular dispersion. The subsequent rapid cooling rate parameter change prevents crystallization, achieving stable amorphous solid solutions with 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 process enables the production of stable, amorphous solid solutions with high active ingredient loading, preventing crystallization and providing free-flowing, water-soluble powders suitable for pharmaceutical and cosmetic applications.
Implementation Method 1
the substances being amorphous in the extruded preparation
Implementation Method 2
An important requirement for such solid solutions is that they are stable even when stored over a long period of time, i.e. that the active ingredient does not crystallize
Implementation Method 3
which are obtained by radically initiated polymerization of a mixture of i) 30 to 80% by weight of N-vinyl lactam, ii) 10 to 50% by weight of vinyl acetate and iii) 10 to 50% by weight of a polyether
Implementation Method 4
the embedding takes place at temperatures above the melting point of the biologically active substances
Implementation Method 5
Embedding is carried out by extrusion
Data Source
AI summary
The invention relates to a method for producing preparations of substances poorly soluble in water, wherein the poorly soluble substances are present amorphously embedded in a copolymer, and the copolymer is obtained by radically initiated polymerization of a mixture of i) 30 to 80 wt% N-vinyl lactam, ii) 10 to 50 wt% vinyl acetate, and iii) 10 to 50 wt% of a polyether, with the stipulation that the sum of the components i), ii), and iii) is equal to 100 wt%, wherein the embedding of the poorly soluble substance into the copolymer occurs at temperatures above the melting point of the poorly soluble substances.