Tylonolide Polymorphs for Stable Pharmaceutical Compositions
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for cost-effective, high-yield processes to produce macrolides with stable crystalline forms that exhibit advantageous physical and chemical stability, as well as improved packing, thermodynamic, kinetic, surface, mechanical, and filtration properties, to enhance their use in treating diseases such as pasteurellosis and respiratory diseases in livestock and poultry.
Innovation Solution
The development of multiple crystalline forms of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide, including Form I, Form II, Form III, and Form IV polymorphs, and solvated crystalline forms like ethyl acetate and tert-butyl methyl ether solvates, which are characterized by specific spectral and thermal properties, and can be used to create stable pharmaceutical compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional macrolide production processes are used, then production cost is reduced, but physical and chemical stability of the crystalline form deteriorates
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing different crystalline forms (polymorphs I, II, III, IV) and solvates with distinct physical and chemical properties. Each crystalline form exhibits different stability characteristics, dissolution rates, and packing properties, allowing selection of the optimal form for specific pharmaceutical applications while maintaining cost-effectiveness through established production methods.
2Productivity
If high-yield production processes are implemented, then productivity increases, but crystalline stability and packing properties deteriorate
Solution Approach 1:
The patent applies preliminary action by pre-establishing multiple stable crystalline forms and solvates with characterized properties before pharmaceutical formulation. The crystalline forms are prepared and characterized in advance, allowing selection of the most stable form for each specific application, thereby ensuring both high production yield and crystalline stability without compromise.
3Ease of manufacture
If amorphous or non-crystalline forms are used, then manufacturing simplicity is improved, but filtration properties and mechanical properties deteriorate
Solution Approach 1:
The patent applies parameter changes by providing multiple crystalline forms with distinct physical properties including filtration characteristics and mechanical properties. The crystalline forms offer improved filtration properties and mechanical strength compared to amorphous forms, while maintaining manufacturing feasibility through established crystallization processes.
4Speed
If certain crystalline forms are selected, then dissolution rates are improved, but stability may deteriorate
Solution Approach 1:
The patent applies parameter changes by characterizing multiple crystalline forms with different dissolution rates and stability profiles. This allows formulation scientists to select the optimal crystalline form based on the specific pharmaceutical application requirements, achieving the desired balance between dissolution rate and stability for each particular use case.
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
These crystalline forms provide enhanced stability, reduced water uptake, and improved processing and storage properties, leading to more effective and stable pharmaceutical compositions for treating diseases in animals, with specific forms offering advantages in dissolution rates and stability.
Implementation Method 1
The Form I polymorph may exhibit less water uptake than other solid-state forms of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide under, for example, ambient conditions
Data Source
AI summary
This invention relates to solvated and non-solvated crystalline forms of 20,23-dipiperidinyl-5-O-mycaminosyl-tylonolide, as well as methods for making such crystalline forms, medicaments comprising (or derived from) such crystalline forms, methods for making medicaments comprising (or derived from) such crystalline forms, methods of treatment using such crystalline forms, and kits comprising such crystalline forms.