Prasugrel Base Tablets Stabilized by Hydrotropic Polymer Matrix
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Solution Overview
Problem
Prasugrel base pharmaceutical compositions are sensitive to moisture, temperature, and oxygen, leading to instability and reduced bioavailability compared to its salts, particularly the hydrochloride salt, which complicates the formulation of stable and effective immediate-release tablets.
Innovation Solution
Micronization of prasugrel base combined with a strongly hydrophilic auxiliary agent system that provides a hydrotropic environment, allowing for the creation of bioequivalent tablets to marketed hydrochloride-containing tablets, maintaining dissolution and bioavailability profiles throughout the shelf life without the need for grinding with hydrophilic polymers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If prasugrel base is used as active ingredient, then manufacturing cost is reduced and formulation flexibility is improved, but stability deteriorates due to sensitivity to moisture, temperature and oxygen
Solution Approach 1:
The patent introduces hydrophilic polymers (starch, cellulose derivatives, or their combinations) as intermediary substances that create a protective microenvironment around prasugrel base particles. These polymers absorb moisture and form a barrier against oxygen and temperature fluctuations, thereby stabilizing the prasugrel base without requiring conversion to salt forms. This mediator approach allows the use of prasugrel base while maintaining stability.
Solution Approach 2:
The invention creates a composite formulation system combining prasugrel base with specific hydrophilic polymer matrices. The composite structure integrates the active ingredient with protective polymer networks that provide both mechanical stability and chemical protection. This composite approach enables the formulation to maintain stability characteristics comparable to salt forms while retaining the advantages of using prasugrel base.
2Quantity of substance
If prasugrel base is used instead of salts, then solubility improves, but stability deteriorates due to sensitivity to environmental factors
Solution Approach 1:
Hydrophilic polymers serve as intermediary substances that enhance the solubility of prasugrel base while simultaneously providing stability. The polymers form solubilizing complexes with prasugrel base and create a protective matrix that shields the active ingredient from moisture, oxygen, and temperature effects. This dual-function mediator approach resolves the contradiction between improved solubility and maintained stability.
Solution Approach 2:
The invention changes the physical and chemical parameters of the formulation system by introducing polymers with specific functional groups that can interact with prasugrel base. These parameter changes include modifying the microenvironmental pH, water activity, and molecular interactions within the formulation, thereby achieving both enhanced solubility and improved stability of prasugrel base.
3Quantity of substance
If prasugrel base is used, then bioavailability is improved compared to salts, but dissolution profile becomes inconsistent during storage
Solution Approach 1:
The patent applies preliminary action by pre-organizing prasugrel base within a structured polymer matrix during formulation. The hydrophilic polymers are pre-positioned to surround and protect prasugrel base particles, creating a stable dispersion pattern that prevents aggregation and maintains consistent dissolution characteristics throughout storage. This preliminary structuring ensures bioavailability is maintained over time.
Solution Approach 2:
The invention achieves homogeneity by creating a uniform distribution of prasugrel base within the hydrophilic polymer matrix. The formulation process ensures consistent mixing and dispersion, resulting in a homogeneous product where every particle of prasugrel base is equally protected and solubilized by the polymer network. This homogeneity maintains consistent dissolution and bioavailability profiles during storage.
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 approach results in stable prasugrel base tablets with consistent bioavailability and dissolution profiles over six months, avoiding transformation into a less soluble form and ensuring bioequivalence with hydrochloride-containing tablets, thus addressing the stability and solubility challenges of prasugrel base.
Implementation Method 1
a strongly hydrophilic auxiliary agent system which provides a hydrotropic environment
Data Source
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AI summary
Prasugrel containing quickly released stable oral pharmaceutical compositions containing micronized prasugrel base, and starch or a starch derivative, and processes for the preparation thereof, and the use thereof for treating atherothrombotic events of patients suffering from acute coronary syndrome in which patients were subjected to percutaneous.