Ketoprofen Lysine Co-Crystal Form 4 for Faster Dissolution
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Solution Overview
Problem
Current Ketoprofen formulations face challenges with poor solubility and dissolution rates, leading to bioavailability issues, particularly in treatments requiring high dosages and long-term administration, and existing co-crystals like Ketoprofen Lysine Salt exhibit low crystallinity and high particle size, affecting hygroscopicity and flowability.
Innovation Solution
The formation of a co-crystal of Ketoprofen Lysine (Form 4) under specific conditions, characterized by higher crystallinity, lower particle size, and improved dissolution rate, achieved through a process involving a non-saturated solution of Ketoprofen in solvents like 2-methyl-1-propanol and ethyl acetate, mixed with solid lysine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Ketoprofen is used as free acid in pharmaceutical compositions, then it shows high tolerability and widespread clinical use, but it has poor water solubility and dissolution rate leading to bioavailability problems
Solution Approach 1:
The patent changes the physical-chemical parameters of Ketoprofen by forming a co-crystal with Lysine, transforming it from a poorly soluble free acid into a co-crystal form with improved solubility and dissolution rate while maintaining the active pharmaceutical ingredient's identity
Solution Approach 2:
The patent creates a composite material system by forming a co-crystal between Ketoprofen and Lysine, where two different compounds are combined in a stoichiometric ratio to produce a new material with superior solubility properties compared to pure Ketoprofen
2Ease of manufacture
If Ketoprofen Lysine Salt is prepared using non-saturated solutions, then the preparation process is simple, but the resulting co-crystal shows low crystallinity and high particle size affecting hygroscopicity and flowability
Solution Approach 1:
The patent modifies the crystallization parameters by using saturated or supersaturated solutions instead of non-saturated solutions, and by controlling temperature and solvent evaporation rates to achieve high crystallinity and appropriate particle size in the co-crystal product
3Quantity of substance
If high dosage Ketoprofen is administered for long-term treatment, then it effectively treats serious inflammatory conditions, but poor solubility limits bioavailability and absorption
Solution Approach 1:
The patent changes the dissolution kinetics parameter by forming a co-crystal that dissolves faster and more completely, enabling better absorption and bioavailability even at high dosages required for serious inflammatory conditions
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
Ketoprofen Lysine co-crystal Form 4 demonstrates enhanced dissolution rates and better taste, making it suitable for rapid and effective administration in treating pain and inflammatory diseases.
Implementation Method 1
Pharmaceutical co-crystallization has attracted great amount of academic, industrial and therapeutic interests by co-crystallization of two or more pure compounds with crystal engineering to create a new functional material
Implementation Method 2
Co-crystals can be defined as a stoichiometric multi-component system formed between two or more compounds, which are solid under ambient conditions, connected by non-covalent and non-ionic interactions
Implementation Method 3
preparing a non-saturated solution of Ketoprofen in a solvent selected from 2-methyl-1-propanol and ethyl acetate
Data Source
AI summary
The present invention refers to a co-crystal of Ketoprofen Lysine named Form 4, a pharmaceutical composition comprising said co-crystal, a process for its preparation and to its use in the treatment of pain and inflammatory diseases.