Anhydrous Monosodium Crystal Form for High-Density Formulation
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Solution Overview
Problem
Monohydrous crystals of monosodium N-(2-ethylsulfonylamino-5-trifluoromethyl-3-pyridyl)cyclohexane carboxamide have a needle-like shape, leading to low density and poor fluidity, making formulation difficult.
Innovation Solution
Development of an anhydrous crystal form with high bulk density and tapped density, characterized by specific X-ray diffraction peaks and infrared absorption bands, suitable for formulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monohydrous crystal is used, then the compound has phospholipase A2 inhibitory effects and is useful as anti-inflammatory agent, but the needle-like shape leads to low density and poor fluidity making formulation difficult
Solution Approach 1:
The patent changes the hydration state parameter from monohydrous to anhydrous form, which fundamentally alters the crystal morphology from needle-like to granular, thereby improving fluidity while preserving the pharmacological activity
Solution Approach 2:
The patent creates a new crystal form (anhydrous crystal) that combines the beneficial pharmacological properties of the original compound with improved physical properties (high density, good fluidity), effectively creating a composite material with multiple desirable characteristics
2Stability of the object's composition
If monohydrous crystal is used, then the compound maintains its chemical structure and activity, but the low bulk density results in bulky formulation and poor handleability
Solution Approach 1:
The patent changes the water content parameter from 4.28% (monohydrous) to essentially 0% (anhydrous), which causes a dramatic increase in bulk density from low to high, reducing the volume occupied while maintaining chemical integrity
Solution Approach 2:
The patent removes the water of crystallization from the monohydrous crystal structure, extracting the harmful component (water causing needle-like morphology) while retaining the active pharmaceutical ingredient with its essential chemical structure
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 anhydrous crystal exhibits excellent fluidity and handleability, enabling efficient formulation and stable production of high-density formulations with improved solubility and absorbability.
Implementation Method 1
the powder X-ray diffraction pattern of the anhydrous crystal obtained by using Cu—Kα as a radiation source at a tube voltage of 30 kV and a tube current of 30 mA includes at least one peak at a diffraction angle of 2θ±0.2° selected from the group consisting of 7.3, 10.9, 11.5, 14.5, 15.6, 18.3, 19.0, 19.7, 21.7, 23.7, 26.0, 32.3, 33.5, 34.3, 40.6 and 44.6
Implementation Method 2
which has an absorption band at at least one wavelength of wavelengths 3,345±10, 2,930±10, 2,850±10, 1,660±10, 1,615±10, 1,560±10, 1,520±10, 1,460±10, 1,430±10, 1,350±10, 1,330±10, 1,280±10, 1,240±10, 1,200±10, 1,140±10, 1,115±10, 1,090±10, 1,000±10, 940±10, 910±10, 855±10, 820±10, 780±10, 770±10, 740±10 and 690±10 cm−1 in an infrared absorption spectrum
Data Source
AI summary
The present invention provides a novel crystal of monosodium N-(2-ethylsulfonylannino-5-trifluoronnethyl-3-pyridyl)cyclohexane carboxamide that has a high density, particularly a high bulk density and/or tapped density, and that is suitable for formulation. More specifically, provided is an anhydrous crystal of monosodium N-(2-ethylsulfonylannino-5-trifluoronnethyl-3-pyridyl)cyclohexane carboxamide.