JP2003104887A - Aranidipine-containing composition stable to light - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a light-stable drug preparation free from the defect of aranidipine easily decompositing with light and with time. SOLUTION: Aranidipine in a drug preparation is stabilized by adding titanium oxide and yellow iron sesquioxide. The amount of titanium oxide is 131.1 pts.wt. based on the aranidipine and that of the yellow iron sesquioxide is 10.0 pts.wt. based on the active substance. The decrease of drug in the drug preparation with light can be prevented by the method to improve the light stability of the preparation.

Description

Detailed Description of the Invention

[0001]

This invention relates to pyridine compounds, especially
It relates to a light-stabilized composition of alanidipine, and more particularly to a light-stable solid composition obtained by coating alanidipine with a coating solution containing titanium oxide, yellow iron sesquioxide and the like.

[0002]

Alanidipine is a known compound,
It is used as a therapeutic agent for hypertension. However, since alanidipine is a dihydropyridine compound, it has a property that it is easily decomposed by light and its efficacy as an active substance decreases. Therefore, even if a dihydropyridine compound is used as a solid preparation, it is affected by light and gradually undergoes an oxidation reaction, causing a change in appearance such as a lighter yellow color. There was a problem with the conversion. Therefore, conventionally, a method of adding an appropriate antioxidant to prevent oxidation, a method of enclosing a deoxidizer during packaging, a method of minimizing contact with outside air, and the like have been adopted. As a result of various studies aimed at obtaining a stable formulation also for alanidipine, as a carrier of purified sucrose (granulated sugar), alanidipine, an enteric polymer film base, and a water-insoluble polymer film base were used to facilitate the preparation of alanidipine. Although granules are manufactured by the solid dispersion method for the purpose of solubilization, the stability to light could not be maintained.

[0003]

As a method of solving the problem of being unstable to light and gradually oxidizing, it is generally estimated that the addition of an antioxidant as an additive is easy. But,
In the case of poorly soluble compounds such as alanidipine, the antioxidants that can be used are limited. The present invention provides a stable alanidipine-containing composition that does not use an antioxidant.

[0004]

[Means for Solving the Problems] In order to maintain the pharmaceutical characteristics of existing granules (solubilization of the drug substance by the solid dispersion method) and to obtain the target pharmaceutical preparation, the nuclear granule production method is the same as that of the existing granules. As a result of various studies aimed at obtaining a light stable alanidipine preparation, the present inventor completed the present invention by applying a coating containing a light-shielding agent and a coloring agent. That is, the present invention contains a pyridine compound which is characterized by spraying a coating solution containing a colorant and a light-shielding agent onto a preparation in which a pyridine compound which is unstable to light, particularly alanidipine, is solid-dispersed with an appropriate excipient. A method of photostabilizing a composition.
Hereinafter, the present invention will be described in detail.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Colorants added to a solid containing alanidipine which is unstable to light in the present invention include, for example, Edible Yellow No. 5, iron sesquioxide, yellow sesquioxide, and the like. It is 0.05 to 1.0% by weight. Moreover, titanium oxide is mentioned as a light-shielding agent, and its compounding amount is suitably 6.0 to 15.0% by weight. And as a film forming agent, hydroxypropylmethyl cellulose 2910,
Methacrylic acid copolymer LD and the like can be mentioned, but the compounding amount thereof is 3.5 to 7.0% by weight in the preparation.

The stable composition in the present invention may be any solid dosage form, and may be a suitable excipient, binder, lubricant, disintegrating agent, solubilizing agent, surfactant, stabilizer. , A stable preparation that can be orally administered as a pharmaceutical by adding a preservative, a corrigent, a coloring agent, and the like, such as tablets, powders, fine granules, granules, and capsules.

[0007]

EFFECT OF THE INVENTION Since the alanidipine-containing composition of the present invention is stabilized by suppressing its decomposition, it is useful as a light-stable alanidipine-containing composition that can be stored for a long period of time.

The present invention will be described in more detail below with reference to experimental examples and examples, but the present invention is not limited to these experimental examples and examples.

[0009]

Examples Example 1 Hydroxypropyl methylcellulose 2910 99.99. By using 1000 parts by weight of nuclear granules containing alanidipine as a carrier.
5 parts by weight, 49.8 parts by weight of Macrogol 6000 and 149.3 parts by weight of titanium oxide were coated on the surface of the carrier with purified water and dried to obtain an alanidipine-containing composition.

Example 2 Hydroxypropylmethylcellulose 2910 3 with 829.2 parts by weight of nuclear granules containing alanidipine as a carrier
2.7 parts by weight, Macrogol 6000 8.2 parts by weight,
61.2 parts by weight of titanium oxide, 61.3 parts by weight of talc, and 2.4 parts by weight of Yellow No. 5 were coated on the surface of the carrier with purified water and dried to obtain an alanidipine-containing composition.

Example 3 Hydroxypropyl methylcellulose 2910 3 with 829.2 parts by weight of core granules containing alanidipine as a carrier
2.7 parts by weight, Macrogol 6000 8.2 parts by weight,
Titanium oxide 61.2 parts by weight, talc 61.3 parts by weight, yellow 5 1.6 parts by weight, iron sesquioxide 0.8 parts by weight, yellow iron sesquioxide 1.0 parts by weight were used with purified water to prepare a carrier surface. Was coated and dried to obtain an alanidipine-containing composition.

Example 4 Hydroxypropyl methylcellulose 29107 with 745.3 parts by weight of nuclear granules containing alanidipine as a carrier
3.2 parts by weight, Macrogol 6000 18.3 parts by weight, titanium oxide 137.2 parts by weight, talc 61.3
By weight, 1.0 part by weight of yellow ferric oxide was coated on the surface of the carrier with purified water and dried to obtain an alanidipine-containing composition.

Example 5 Hydroxypropyl methylcellulose 2910 6 with 741.5 parts by weight of core granules containing alanidipine as a carrier
9.9 parts by weight, Macrogol 6000 17.5 parts by weight, titanium oxide 131.1 parts by weight, yellow ferric sesquioxide 1
A carrier surface was coated with 0.0 parts by weight of purified water and dried to obtain an alanidipine-containing composition.

Example 6 Using 741.5 parts by weight of core granules containing alanidipine as a carrier, 69.9 parts by weight of methacrylic acid copolymer LD, 17.5 parts by weight of Macrogol 6000, and titanium oxide 1
31.1 parts by weight and 10.0 parts by weight of yellow ferric oxide are coated on the surface of the carrier with purified water and dried,
An alanidipine-containing composition was obtained.

Control Example 1 The existing granules were prepared by using 860 parts by weight of granulated sugar as a carrier.
Methacrylic acid copolymer S 47.5 parts by weight, methacrylic acid copolymer RS 20.0 parts by weight, Macrogol 6000 5.0 parts by weight, and talc 47.5 parts by weight were used as an absolute ethanol / dichloromethane mixture (8: 2). It is a product obtained by applying a coating to the surface of a carrier and drying.

Test Example (Light Stability Test of Formulations Containing Alanidipine) The photostability test was carried out on the formulations of Examples 1 to 6 and Control Example 1. Fluorescent lamp 6000 lux, 240,000 lux, 4
Table 1 shows the appearance and the measurement results of the amount of photodegradation product D-2 produced by irradiation with 80,000 lux.

[0017]

[Table 1]

The appearance of Control Example 1 which was not subjected to the light-shielding treatment did not change, but the amount of the photodegradation product D-2 was large. On the other hand, hydroxypropyl methylcellulose 291
Regarding Examples 1 to 5 in which 0 was used as a film forming agent, Example 1 in which only titanium oxide was added thereto, and titanium oxide,
In Example 2 in which talc and yellow No. 5 were added, and Example 3 in which iron sesquioxide and yellow iron sesquioxide were added to Example 2, light resistance was secured, but discoloration was observed in appearance. . In Example 4 in which the amount of titanium oxide was about twice that in Examples 2 and 3, there was no discoloration, but the photostability was not retained. It was found that in Example 5 in which the amount of yellow ferric oxide was 10 times that of Examples 3 and 4, no discoloration in appearance and light stability was secured.

Claims (3)

[Claims] 1. A light-stable pyridine-based compound containing titanium oxide as a light-shielding agent and edible yellow No. 5, iron sesquioxide, and yellow iron sesquioxide as a coloring agent. 2. A light-stable alanidipine-containing composition containing titanium oxide as a light-shielding agent and edible yellow No. 5, iron sesquioxide, and yellow iron sesquioxide as colorants. 3. The method for producing a stable alanidipine-containing composition according to claim 1, which comprises coating with a coating liquid containing a light-shielding agent and a colorant.