Method of producing drug-containing wax matrix particles, extruder to be used in the method and sustained-release preparation containing cilostazol

A manufacturing method and technology of sustained-release preparations, which are applied in the field of wax-based particle manufacturing, can solve the problems of drug or additive stability damage, wax-based particle preparation technology, solidification, etc., and achieve high biological availability , effective pharmacological effects, and the effect of ensuring sustained release

Inactive Publication Date: 2009-01-07
OTSUKA PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This heating melting spraying method is suitable for forming spherical matrix particle, but there are following disadvantages: (1) must have the large-scale device that is used for spray cooling; ) must carry out temperature control on pipelines, pumps, etc. required to connect storage tanks and spray cooling devices, etc.
Also, a large amount of raw materials must be heat-treated during mass production by the heating melt spray method, and the raw materials are inevitably exposed to high temperatures for a long time, so the stability of drugs or additives may be destroyed by heat
Furthermore, the

Method used

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  • Method of producing drug-containing wax matrix particles, extruder to be used in the method and sustained-release preparation containing cilostazol
  • Method of producing drug-containing wax matrix particles, extruder to be used in the method and sustained-release preparation containing cilostazol
  • Method of producing drug-containing wax matrix particles, extruder to be used in the method and sustained-release preparation containing cilostazol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0152] use figure 2 The extruder of the configuration shown, produces wax matrix particles. As an extruder, the structure and its operating conditions are shown below.

[0153] Extruder type: Twin-screw extruder (KEX-25, manufactured by Kurimoto Iron Works)

[0154] Screw shape: From the downstream side to the upstream side, the shape in which the conveying, kneading, and mixing sections are connected in sequence

[0155] Nozzle: Dual Fluid Nozzle

[0156] Screw part length: Approximately 50cm

[0157] Rotation speed of the screw: 125rpm

[0158] The shape and diameter of the discharge hole of the nozzle: circular, 0.5mm

[0159] The residence time of raw materials in the drum: about 2 minutes

[0160] Drum temperature setting temperature: drum sleeve 1a-1 is 140°C, drum sleeve 1a-2 is 150°C, drum sleeve 1a-3 and 1a-4 are 160°C

[0161] Temperature and introduction speed of spray gas: about 200°C, 25L / min

[0162] Discharge speed per discharge hole of molten kneaded...

Embodiment 2

[0168] As raw materials, 300 g of theophylline, 10 g of ethyl cellulose, and 690 g of fatty acid glyceride (glycerol monobehenate; melting point of about 75° C.) were mixed, and wax was produced under the same conditions as in Example 1 above using the obtained mixed raw material. matrix particles.

[0169] The obtained wax matrix particles were spherical, and when the particle size distribution was measured with a laser diffraction particle size distribution meter (Tohnichi Computer Application), the 10% cumulative diameter was 43 μm, the 50% cumulative diameter (average particle diameter) was 88 μm, and the 90% cumulative diameter was 160 μm, 99% cumulative diameter is 204 μm.

[0170] In addition, it was confirmed that no troubles such as theophylline precipitation in the extruder and liquid clogging occurred during the production process. In addition, the content of theophylline in the obtained wax-based particles was about 100% relative to the theoretical value.

Embodiment 3

[0172] As raw materials, 300 g of theophylline and 700 g of hardened oil (melting point: about 86° C.) were mixed, and using the obtained mixed raw material, wax matrix particles were produced under the same conditions as in Example 1 above.

[0173] The obtained wax matrix particles were spherical, and when the particle size distribution was measured with a laser diffraction particle size distribution meter (Tohnichi Computer Application), the 10% cumulative diameter was 48 μm, the 50% cumulative diameter (average particle diameter) was 96 μm, and the 90% cumulative diameter was 169 μm, 99% cumulative diameter is 221 μm.

[0174] In addition, it was confirmed that no troubles such as theophylline precipitation in the extruder and liquid clogging occurred during the production process. In addition, the content of cilostazol in the obtained wax-based particles was about 100% relative to the theoretical value.

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Abstract

It is intended to provide a method of conveniently producing drug-containing wax matrix particles (in particular, drug-containing wax matrix particles having an average particle diameter of 1 mm or less) through melting and spraying steps without suffering from a jamming failure caused by the recrystallization of the once molten drug. Namely, drug-containing wax matrix particles containing a drug and a wax are produced via the following steps (i) and (ii): (i) the step of feeding the drug and wax as described above into an extruder wherein the temperatures of a barrel (1) and a die have been controlled to a level higher than the melting point of the wax; and (ii) the step of melt-kneading the drug with the wax in the extruder as described above and simultaneously spraying out the melt-kneaded mixture comprising the drug and the wax from a spray nozzle (5), which is attached directly to a die (3) provided at the tip of the barrel (1) in the extruder, into an atmosphere at a temperature lower than the melting point of the wax to thereby form particles.

Description

technical field [0001] The present invention relates to a method for manufacturing wax matrix particles containing medicine. In addition, the present invention relates to an extruder for the manufacture of drug-containing wax-based particles. [0002] The present invention also relates to a sustained-release preparation containing cilostazol. In more detail, the present invention relates to a sustained-release preparation comprising wax-based particles containing cilostazol, which releases cilostazol when administered on an empty stomach and after a meal. Or the difference in blood concentration changes is small, and it has excellent sustained-release properties. Background technique [0003] As oral sustained-release preparations, single-unit types such as tablets and multi-unit types such as granules are known, and a multi-unit type preparation with little inter-individual variation in drug release in vivo and blood concentration distribution is expected. In addition, a...

Claims

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Application Information

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IPC IPC(8): A61J3/06A61K9/14A61K31/4709A61K31/522A61K47/12A61K47/14A61K47/44B01J2/04A61K47/06
CPCB29B7/826B29B7/823B29B7/726B29B7/007B29C48/022B29C48/04B29C48/1472B29C48/397A61K9/1617A61K31/4709
Inventor 友平裕三山口恭生
Owner OTSUKA PHARM CO LTD
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