Tiacumicin B Crystalline Polymorphs for Stable Antibiotic Delivery
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Solution Overview
Problem
Current treatments for antibiotic-associated diarrhea, particularly caused by C. difficile, Staphylococcus aureus, and C. perfringens, are inadequate in efficacy and economic burden, with a need for more stable and effective antibiotic forms to manage bacterial infections.
Innovation Solution
A novel crystalline polymorphic form of a 18-membered macrolide compound, characterized by specific X-ray diffraction patterns and melting points, is developed for use in treating antibiotic-associated diarrhea, offering broad-spectrum antibiotic activity and improved stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibiotic formulations are used, then treatment of antibiotic-associated diarrhea can be provided, but efficacy is inadequate and economic burden is high
Solution Approach 1:
The patent applies parameter changes by transitioning from conventional antibiotic formulations to a specific crystalline polymorphic form of tiacumicin B. This polymorphic form exhibits superior stability and bioavailability characteristics, directly improving treatment efficacy while reducing the economic burden through more effective dosing and reduced treatment failure rates.
Solution Approach 2:
The invention utilizes phase transitions by identifying and utilizing a specific crystalline polymorphic form of tiacumicin B. The patent describes the transition from conventional formulations to this optimized polymorphic form, which has distinct crystal lattice structure that enhances stability and bioavailability, thereby resolving the contradiction between efficacy and economic burden.
2Reliability
If different polymorphs of a drug are used, then bioavailability may vary, but it becomes difficult to determine the optimal dose and ensure consistency
Solution Approach 1:
The patent resolves this contradiction by establishing a specific crystalline polymorphic form with defined physical parameters (melting point of 143-145°C, specific XRD pattern). This standardized parameter set eliminates variability in bioavailability and simplifies dosage determination, as the optimal dose can be consistently calculated based on the known bioavailability of this specific polymorph.
3Ease of manufacture
If a kinetically favored polymorph is used, then the drug may be easier to manufacture initially, but it may convert to thermodynamically more stable polymorph during storage causing tablet breakdown
Solution Approach 1:
The patent applies preliminary action by directly producing the thermodynamically stable crystalline polymorphic form of tiacumicin B during the manufacturing process. By establishing the correct crystal lattice structure from the outset through controlled crystallization conditions, the product is pre-stabilized against polymorphic transitions during storage, eliminating the risk of tablet breakdown while maintaining manufacturing feasibility.
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
The novel crystalline form effectively treats and prevents bacterial infections, including those caused by toxin-producing strains, by enhancing bioavailability and stability, thereby reducing the economic and clinical burdens associated with antibiotic-associated diarrhea.
Implementation Method 1
The polymorphic behavior of a compound can be of crucial importance in pharmacy and pharmacology. Polymorphs are, by definition, crystals of the same molecule having different physical properties as a result of the order of the molecules in the crystal lattice.
Implementation Method 2
characterized by a powder x-ray diffraction pattern with at least peaks at diffraction angles 2θ of 7.7°, 15.0°, and 18.8° ± 0.2
Data Source
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AI summary
The invention relates to novel forms of compounds displaying broad spectrum antibiotic activity, especially crystalline polymorphic forms and amorphous forms of such compounds, compositions comprising such crystalline polymorphic forms and amorphous forms of such compounds, processes for manufacture and use thereof. The compounds and compositions of the invention are useful in the pharmaceutical industry, for example, in the treatment or prevention of diseases or disorders associated with the use of antibiotics, chemotherapies, or antiviral therapies, including, but not limited to, colitis, for example, pseudo-membranous colitis; antibiotic associated diarrhea; and infections due to Clostridium difficile ("C. difficile"), Clostridium perfringens ("C. perfringens"), Staphylococcus species, for example, methicillin-resistant Staphylococcus, or Enterococcus including Vancomycin-resistant enterococci.