Lorcaserin Benzoic Acid Cocrystal Sustained Release
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Solution Overview
Problem
Current solid forms of lorcaserin, such as salts, hydrates, and solvates, face challenges in stability, solubility, and dosing frequency, leading to variations in plasma concentration and the need for multiple daily doses, while cocrystals offer potential advantages but are often developed on a trial-and-error basis without predictable improved properties.
Innovation Solution
A novel cocrystal of lorcaserin hydrochloride and benzoic acid is developed, with a 1:1:1 molar ratio, exhibiting improved stability, solubility, dissolution rate, and bioavailability, suitable for sustained-release formulations, and prepared through methods involving organic solvents like isopropanol and acetone, with specific X-ray diffraction and infrared spectrum characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional solid forms (salts, hydrates, solvates) are used for lorcaserin, then the drug can be formulated, but stability and solubility are insufficient leading to frequent dosing
Solution Approach 1:
The patent applies cocrystal formation by combining lorcaserin hydrochloride with benzoic acid in a 1:1:1 molar ratio to create a composite solid form. This composite structure integrates multiple components with complementary properties, where the cocrystal former (benzoic acid) enhances the stability and solubility of lorcaserin without compromising its pharmacological activity, thereby reducing dosing frequency while maintaining reliable drug performance
Solution Approach 2:
The patent changes the physical and chemical parameters of lorcaserin by forming a cocrystal with specific stoichiometric ratios (1:1:1 molar ratio of lorcaserin:benzoic acid:water). This parameter change in molecular arrangement and intermolecular interactions fundamentally alters the solid-state properties, improving both stability and solubility characteristics to enable less frequent dosing
2Productivity
If salts and solvates are used to improve solubility, then dissolution rate increases, but stability decreases and multiple daily doses are required
Solution Approach 1:
The cocrystal structure creates a stable composite material where lorcaserin hydrochloride and benzoic acid are integrated at the molecular level through weak interactions. This composite maintains high dissolution rate comparable to salts while achieving superior stability that prevents degradation and maintains effective plasma concentrations throughout the dosing interval, eliminating the need for multiple daily doses
Solution Approach 2:
The patent replaces unstable solvates (which have short shelf-life due to solvent volatility and desolvation) with a stable cocrystal structure. The cocrystal uses solid benzoic acid as the cocrystal former instead of volatile organic solvents, creating a stable solid form that maintains its structure and properties over time while still providing rapid dissolution
3Adaptability or versatility
If cocrystals are developed on trial-and-error basis, then novel solid forms can be obtained, but the process is inefficient and properties are not predictable
Solution Approach 1:
The patent uses cocrystal formers (such as benzoic acid) as intermediary substances to systematically explore and optimize solid forms. By selecting appropriate cocrystal formers with known properties and applying systematic screening methods, the development process becomes more efficient and predictable, allowing rational design of cocrystals with desired properties rather than random trial-and-error
Solution Approach 2:
The patent systematically changes parameters such as cocrystal former selection, molar ratios (specifically 1:1:1 ratio), and crystallization conditions to optimize cocrystal properties. This systematic parameter optimization approach transforms the trial-and-error process into a methodical development strategy that predicts and achieves target properties for sustained-release formulations
4Speed
If immediate-release formulations are used, then fast dissolution is achieved, but plasma concentration varies and multiple doses per day are needed
Solution Approach 1:
The cocrystal of lorcaserin hydrochloride and benzoic acid creates a composite material with optimized dissolution characteristics. The structured lattice and intermolecular interactions in the cocrystal enable controlled dissolution that maintains consistent plasma concentrations over an extended period, transforming the immediate-release profile into a sustained-release profile that eliminates peak-trough fluctuations and reduces dosing frequency
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 cocrystal demonstrates enhanced stability and solubility, reducing dosing frequency, maintaining effective plasma concentrations, and improving bioavailability, making it suitable for sustained-release formulations with reduced dependence on coating processes and improved chemical stability.
Implementation Method 1
The weak interaction is defined as neither ionic bond interaction nor covalent bond interaction including such as hydrogen bond, van der Waals forces, π-π interactions and halogen bond
Implementation Method 2
The weak interaction is defined as neither ionic bond interaction nor covalent bond interaction including such as hydrogen bond, van der Waals forces, π-π interactions and halogen bond
Implementation Method 3
The weak interaction is defined as neither ionic bond interaction nor covalent bond interaction including such as hydrogen bond, van der Waals forces, π-π interactions and halogen bond
Implementation Method 4
preparation methods involving organic solvents like isopropanol and acetone
Implementation Method 5
measured using Cu—Kα, radiation, the X-ray powder diffraction pattern of the cocrystal, expressed as 2θ angles, has the following characteristic peaks: 4.5±0.2°, 9.0±0.2°, 12.3±0.2°, 18.0±0.2°, 19.4±0.2° and 23.0±0.2°
Implementation Method 6
measured using Cu—Kα, radiation, the X-ray powder diffraction pattern of the cocrystal
Implementation Method 7
The Fourier transform infrared spectrum of the cocrystal has characteristic peaks at wave numbers of 3384, 2971, 2861, 2524, 2362, 1700, 1595, 1315, 1270, 1119, 946, 818 and 710 cm−1
Data Source
AI summary
The present invention relates to a new type of eutectic crystal of lorcaserin hydrochloride and benzoic acid, when compared with the prior art, the eutectic crystal has the improved properties of good stability, low solubility, and being suitable for the application of controlled-release preparation; the present invention also relates to a method for preparing the eutectic crystal, a pharmaceutical composition thereof and the use thereof in the manufacture of drugs for treating and/or preventing diseases associated with 5HT2C.