Dabigatran Etexilate Mesylate Crystal Forms M and N
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Solution Overview
Problem
Current crystal forms of dabigatran etexilate mesylate lack optimal chemical and physical stability, affecting their suitability for pharmaceutical formulations, particularly in terms of leaching time, biological release, and processing adaptability.
Innovation Solution
Development of new crystal forms M and N with specific X-Ray powder diffraction and infrared absorption spectra, along with a controlled crystallization method using ethanol/ethyl acetate mixed solvents and seed crystals, to enhance stability and processing efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing crystal forms of dabigatran etexilate mesylate are used, then the drug can be manufactured, but the chemical and physical stability is insufficient, affecting pharmaceutical formulation quality
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing new crystal forms (Forms A, B, C, D, G, H, and III) of dabigatran etexilate mesylate with distinct X-ray diffraction patterns, melting points, and stability characteristics. Each crystal form represents a different physical state parameter that optimizes specific pharmaceutical properties, thereby resolving the contradiction between stability and formulation adaptability.
Solution Approach 2:
The patent employs composite materials by creating semihydrate crystal forms that incorporate water molecules into the crystal lattice structure. This composite approach combines the active pharmaceutical ingredient with water in a defined stoichiometric ratio, resulting in enhanced chemical and physical stability while maintaining bioavailability, thus addressing the formulation suitability issue.
2Manufacturing precision
If multiple crystal forms are developed, then stability and processing properties improve, but the complexity of characterizing and selecting the optimal form increases
Solution Approach 1:
The patent applies segmentation by systematically categorizing and characterizing each crystal form with unique identification parameters including specific X-ray diffraction peak patterns, melting points, and solubility characteristics. This segmentation approach allows researchers and manufacturers to select the appropriate crystal form based on specific formulation requirements without being overwhelmed by the complexity of all possible forms.
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 new crystal forms exhibit improved chemical stability, reproducible processing, and enhanced dissolution rates, with crystal form N showing stability in 95% ethanol solutions, making them suitable for pharmaceutical applications.
Implementation Method 1
The X-Ray powder diffractogram of the crystal form M of the dabigatran etexilate mesylate of the present invention has characteristic peaks at the following 2θ diffraction angles: 5.7±0.2°, 6.2±0.2°, 11.2±0.2°, 12.4±0.2°, 18.2±0.2°, 21.4±0.2°, 21.8±0.2° and 23.6±0.2°.
Implementation Method 2
the infrared absorption spectrum of the crystal form M of the dabigatran etexilate mesylate has absorption peaks at about 3433.73 cm−1, 3319.45 cm−1, 2957.35 cm−1, 2931.08 cm−1, 2862.04 cm−1, 1743.33 cm−1, 1732.42 cm−1, 1650.10 cm−1, 1614.11 cm−1, 1586.80 cm−1, 1572.31 cm−1
Implementation Method 3
The Differential Scanning calorimetry (DSC) thermogram of the crystal form M of the dabigatran etexilate mesylate of the present invention has a maximum absorption peak within the range of 145-150° C.
Implementation Method 4
The TGA thermogram of the crystal form M of the dabigatran etexilate mesylate of the present invention shows a weight loss of 0.6-1.8% within the temperature range of 50-150° C.
Data Source
AI summary
The present invention relates to novel crystal forms M and N of dabigatran etexilate mesylate and preparation method and uses thereof, wherein the X-Ray powder diffractogram of the crystal form M has characteristic peaks at the following 2θ diffraction angles: 5.7±0.2°, 6.2±0.2°, 11.2±0.2°, 12.4±0.2°, 18.2±0.2°, 21.4±0.2°, 21.8±0.2° and 23.6±0.2°; and the X-Ray powder diffractogram of the crystal form N has characteristic peaks at the following 2θ diffraction angles: 6.0±0.2°, 11.8±0.2°, 18.2±0.2°, 21.6±0.2°, 24.4±0.2°, 27.7±0.2° and 29.7±0.2°. The crystal forms of the present invention have excellent properties in the aspects of leaching time, biological release, chemical stability and processing adaptability.