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Isotretinoin crystal form II and its preparation method and use

A tretinoin and crystal form technology, applied in the field of isotretinoin crystal form II and its preparation, can solve the problems of low bioavailability and poor stability of isotretinoin

Active Publication Date: 2022-04-08
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Aiming at the problems of poor stability and low bioavailability of isotretinoin in clinical use, through polymorphic research, it is hoped to find new crystal forms that can improve bioavailability and physical and chemical stability

Method used

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  • Isotretinoin crystal form II and its preparation method and use
  • Isotretinoin crystal form II and its preparation method and use
  • Isotretinoin crystal form II and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Mix 1 g of isotretinoin (Aladdin Company, batch number K2011169, purity ≥ 98%) in 40 mL of acetone, stir with a magnetic stirrer at 800 rpm, and dissolve completely at 50° C. Continue to stir and cool to 4°C to obtain a suspension, which is filtered and dried under reduced pressure at room temperature. The crystal form II was obtained as 0.93 g of yellow crystalline powder with a yield of 93%.

[0047] The X-ray powder diffraction (XRPD) figure of the isotretinoin crystal form II of embodiment 1 is shown in figure 1 ; Thermogravimetric analysis (TG) diagram see figure 2 ; Differential scanning calorimetry (DSC) diagram see image 3 ; Infrared spectrum (IR) figure see Figure 4 .

[0048] Detected by a single crystal X-ray diffractometer, the crystal form II of isotretinoin in Example 1 is a triclinic crystal system, the space group is P-1, and the unit cell parameters are: a=8.032(6), b=12.554(15 ), c=17.931(13); α=90.93(4), β=97.90(2), γ=95.07(4); the unit cell v...

Embodiment 2

[0052] Mix 1 g of isotretinoin in 40 mL of methyl ethyl ketone, add a magnetic stirring bar to stir at 800 rpm, and dissolve completely at 50°C. Continue to stir and cool to 4°C to obtain a suspension, which is filtered and dried under reduced pressure at 20-30°C. The crystal form II was obtained as 0.91 g of yellow crystalline powder with a yield of 91%.

[0053] The X-ray powder diffraction (XRPD) pattern of gained product and figure 1 similar.

Embodiment 3

[0055] Mix 500mg of isotretinoin in 20mL of acetone, add a magnetic stir bar to stir at 600rpm, and heat to 50°C to dissolve completely. Slowly volatilize at 20-30°C and dry under reduced pressure. The crystal form II was obtained as 410 mg of yellow crystalline powder with a yield of 82%.

[0056] The X-ray powder diffraction (XRPD) pattern of gained product and figure 1 similar.

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Abstract

Disclosed is isotretinoin crystal form II and its preparation method and application. The crystal form II was characterized by XRD, IR, DSC, TGA and other means. The powder diffraction pattern obtained by the X-ray powder diffraction method of Cu Kα for the crystal form II has diffraction peaks at the following 2θ angles: 6.94°±0.2°, 9.89°±0.2°, 11.03°±0.2°, 13.99°±0.2 °, 16.27°±0.2°, 18.30°±0.2°, 18.62°±0.2°, 19.92°±0.2°, 22.25°±0.2°, 24.64°±0.2°, 28.66°±0.2°. The isotretinoin crystal form II of the present invention has better chemical stability and better dissolution performance, and is a more suitable pharmaceutical crystal form.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical solid chemistry, and specifically relates to isotretinoin crystal form II and its preparation method and application. Background technique [0002] In recent years, with the development of drug design and high-throughput screening technology, the proportion of poorly soluble drugs is increasing, and the problem of polymorphic forms of drugs has become increasingly prominent. Polymorphism refers to the phenomenon that a substance forms two or more solid forms due to the different conformation or arrangement of molecules in the crystal lattice. The definition of polymorph can be divided into two ways: narrow sense and broad sense. Polymorphism in the narrow sense refers to a substance that has the same chemical composition but differs in the way the molecules of the substance are arranged in the crystal. The generalized polymorph also includes amorphous and solvate (pseudopolymorph). For s...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C403/20A61K31/203A61P17/10A61P17/00A61P37/08
CPCC07C403/20A61P17/10A61P17/00A61P37/08C07B2200/13C07C2601/16
Inventor 梅雪锋程银祥王建荣荣晓义
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI