Micronized Prasugrel Composition for Dissolution and Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing prasugrel formulations face challenges with low solubility, chemical instability, and polymorphic instability, necessitating improved dissolution rates and stability properties, while current processes are costly and industrially inefficient.
Innovation Solution
Micronization of prasugrel with a water-insoluble hydrophilic excipient, such as crospovidone, in the presence of less than 50% water-soluble hydrophilic polymer, resulting in a composition with enhanced chemical and polymorphic stability and dissolution rate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If prasugrel is formulated with water-soluble hydrophilic polymers to improve dissolution rate, then dissolution rate is improved, but chemical stability and polymorphic stability deteriorate
Solution Approach 1:
The patent uses water-insoluble hydrophilic excipients (croscarmellose sodium, crospovidone, sodium starch glycolate) as intermediary substances during micronization to improve dissolution rate without compromising stability. These excipients act as mediators that enhance wetting and dissolution properties while maintaining the crystalline structure and chemical integrity of prasugrel, unlike water-soluble polymers that cause instability.
Solution Approach 2:
The patent changes the solubility parameter of the hydrophilic excipient from water-soluble to water-insoluble form. By selecting excipients that are hydrophilic but water-insoluble (such as croscarmellose sodium and crospovidone), the formulation achieves improved dissolution kinetics through hydrophilic interaction while preventing the chemical and polymorphic degradation associated with water-soluble polymer systems.
2Speed
If conventional micronization processes are used to improve dissolution rate, then dissolution rate is improved, but manufacturing cost and process complexity increase
Solution Approach 1:
The patent employs self-service micronization where prasugrel is micronized directly with the water-insoluble hydrophilic excipient in a single step without requiring separate preprocessing of the active ingredient. This integrated approach eliminates multiple manufacturing steps, reduces equipment requirements, and lowers overall process complexity while achieving the desired dissolution rate improvement.
Solution Approach 2:
The patent merges the micronization process with the formulation process by combining prasugrel with water-insoluble hydrophilic excipients in a single micronization step. This consolidation of operations simplifies the manufacturing workflow, reduces processing time, and decreases manufacturing costs compared to conventional approaches that require separate micronization and formulation steps.
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 process yields prasugrel compositions with improved chemical and polymorphic stability and dissolution properties, offering a more economical and industrially feasible solution.
Implementation Method 1
the presence of the water-insoluble hydrophilic excipient, stabilizes the crystalline form of prasugrel
Implementation Method 2
micronization of prasugrel with a water-insoluble hydrophilic excipient
Data Source
AI summary
The present invention relates to a process for the micronization of prasugrel, to prasugrel formulations for micronization, to micronized prasugrel compositions obtained or obtainable by the process of the invention and compositions comprising thereof (e.g. granulates or tablets). It further relates to the pharmaceutical use of said compositions, in particular in the treatment of coagulation disorders. More specifically, said process for obtaining a micronized prasugrel composition comprises: a) mixing prasugrel with a water-insoluble hydrophilic excipient, optionally in combination with other excipients; and b) micronizing the composition obtained in a).