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Composition for heat melt extrusion and method for producing heat melt extruded product using same

A hot-melt extrusion and composition technology, which is applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, and pharmaceutical formulas, etc., can solve the problem of drug inactivation, easy hydrolysis and deactivation of drugs or carriers problem to achieve high bioabsorbability

Active Publication Date: 2016-01-27
SHIN ETSU CHEM IND CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0024] However, the method in Patent Document 1 has the following disadvantages: Since water is a poor solvent for poorly water-soluble drugs, water can enhance the crystallinity of the drug and prevent the drug from being amorphized; Inactivation of drugs with adverse properties; and under high humidity conditions, due to the influence of heat and water, the drug or carrier is easily hydrolyzed and becomes inactive

Method used

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  • Composition for heat melt extrusion and method for producing heat melt extruded product using same
  • Composition for heat melt extrusion and method for producing heat melt extruded product using same
  • Composition for heat melt extrusion and method for producing heat melt extruded product using same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1 to 5 and comparative example 1 to 2

[0095] HPMCAS-1 to HPMCAS-7 were pre-dried such that the moisture content was measured to be less than 1 wt%. Using a die diameter of 1 mm, a die height of 10 mm, and an extrusion rate of 50 mm / min, extruded from a die outlet in a vacuum extruder (single-screw piston type melt extruder: Capilograph manufactured by Toyo Seiki Seisaku-sho, Ltd.) The dried HPMCAS-1 to HPMCAS-7 were taken out, and the minimum extrusion temperature of HPMCAS-1 to HPMCAS-7 was measured. The results are shown in Table 3.

[0096] table 3

[0097]

HPMCAS

Glass transition temperature (°C)

Minimum extrusion temperature (°C)

Example 1

HPMCAS-1

70

110

Example 2

HPMCAS-2

81

140

Example 3

HPMCAS-3

94

140

Example 4

HPMCAS-4

101

140

Example 5

HPMCAS-5

112

150

Comparative example 1

HPMCAS-6

85

140

Comparative example 2

HPMCAS-7

126

180

[0098] Th...

Embodiment 6 to 10 and comparative example 3 to 4

[0101] Hot melt extrudates were prepared using the poorly water soluble drug ascorbic acid. Ascorbic acid has a thermal decomposition temperature of 176°C and is a model drug, which raises concerns about inactivation due to thermal decomposition during hot-melt extrusion.

[0102] The respective HPMCAS and ascorbic acid powders were mixed in a mortar at a weight ratio of HPMCAS to ascorbic acid of 1:0.5 to prepare compositions for hot melt extrusion.

[0103] Subsequently, a hot-melt extruder (Thermo Fisher Scientific Inc. The HAAKEMiniLab produced) makes the above mixed powder carry out hot-melt extrusion. The minimum extrusion temperature of the hot-melt extrudate was measured in the same manner as in Example 1. Further, the hot-melt extrudate thus obtained was pulverized at 20000 rpm with a pulverizer (WonderBlender WB-1 produced by Osaka Chemical Co., Ltd.) and sieved through a 30-mesh sieve (opening of 500 μm). The powder thus obtained and the composition for hot-melt ...

Embodiment 11 to 15 and comparative example 5 to 6

[0109] Film test pieces were prepared by using HPMCAS-1 to HPMCAS-7 and subjected to measurement of dissolution time in phosphate buffer. A solution of 16 g of HPMCAS in 64 g of a mixed solvent of dichloromethane and ethanol in a 1:1 weight ratio of dichloromethane to ethanol was cast on a glass plate and dried at room temperature. The resulting film was dried at 80° C. for 2 hours, and cut into test pieces having a thickness of 100 μm, a length of 1 cm, and a width of 1 cm.

[0110] The dissolution time of the test piece was measured according to the disintegration test (auxiliary tube) in the 16th edition of the Japanese Pharmacopoeia. More specifically, one of the test pieces was placed in 1 L of phosphate buffer solution with a pH of 6.0, and the test piece was dissolved to A measurement of the time required to observe the absence of undissolved material. The phosphate buffer has a pH of 6.0, which corresponds to the pH of the digestive fluid in the upper to middle part ...

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Abstract

Provided is a composition for heat melt extrusion, which contains at least a medicament and a hypromellose acetate succinate (HPMCAS) that has a degree of molar substitution of hydroxypropoxy groups of 0.40 or more and a ratio (molar ratio) of acetyl groups to succinyl groups of less than 1.6. Also provided is a method for producing a heat melt extruded product, which comprises at least a step wherein a composition for heat melt extrusion containing at least a medicament and a hypromellose acetate succinate that has a degree of molar substitution of hydroxypropoxy groups of 0.40 or more and a ratio (molar ratio) of acetyl groups to succinyl groups of less than 1.6 is heated, melted and extruded at a heat melt temperature that is not less than the melting temperature of the hypromellose acetate succinate or not less than the temperature at which both the hypromellose acetate succinate and the medicament are melted.

Description

technical field [0001] The present invention relates to a composition for hot melt extrusion and a method for preparing hot melt extrudates by using the composition. Background technique [0002] In recent years, a method for producing a formulation including a step of hot-melt extruding a mixture of a drug and a polymer has attracted attention. [0003] For example, solid dispersions obtained from solidifying poorly water-soluble drugs and polymers by hot-melt extrusion include the drug in an amorphous state and have the drug molecularly dispersed in a polymeric carrier. Such solid dispersions significantly increase apparent solubility and enhance bioavailability. Since hot-melt extrusion can be performed without solvents, it is suitable for drugs that are unstable in water. Not requiring solvent recovery in hot melt extrusion has the advantages of safety, no environmental concerns, saving energy for the solvent recovery step, and improving worker safety. Furthermore, un...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/38A61K9/16A61K9/20
CPCC08B11/193C08B11/20C08B13/00C08L1/32A61K9/146C08J3/201C08J2301/32A61K31/4422A61K31/496A61K47/38
Inventor 藁品彰吾草木史枝菊池一辉尾原荣丸山直亮
Owner SHIN ETSU CHEM IND CO LTD
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