JP2019001730A - Stable oral pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral pharmaceutical composition containing one or more pharmaceutically active ingredients selected from cetirizine which suppresses decomposition and discoloration by light, an optically active isomer thereof, or a pharmaceutically acceptable salt thereof. It contains one or more pharmaceutically active ingredients and colorants selected from cetirizine, optically active isomers thereof or pharmaceutically acceptable salts thereof, in particular iron oxide, blue aluminum lake and yellow aluminum lake. An oral pharmaceutical composition in which decomposition and discoloration due to light are suppressed. [Selection diagram] None

Description

  The present invention relates to an oral drug containing one or more pharmaceutically active ingredients selected from cetirizine, optically active isomers thereof, or pharmaceutically acceptable salts thereof, particularly levocetirizine hydrochloride, in which decomposition and discoloration by light are suppressed. A composition is provided.

  Levocetirizine hydrochloride is known as a compound that suppresses the production of histamine. Currently, a pharmaceutical composition containing levocetirizine hydrochloride is sold as a film-coated tablet and a syrup dosage form under the trade name Xyzal (registered trademark).

  Currently, as a report on the stability of levocetirizine hydrochloride, it is disclosed that polyols such as mannitol are incompatible with levocetirizine hydrochloride (Patent Document 1). In addition, by preparing a preparation containing levocetirizine and a pH adjuster and adjusting the preparation to a pH of 4 to 7 when the preparation is made into a 5 wt% aqueous suspension or 5 wt% aqueous solution, alcohols such as polyols are used. It has been disclosed that the reactivity with respect to the product can be suppressed and the stability can be improved (Patent Document 2).

Japanese Patent No. 4724367 JP 2006-094364 A

  However, these findings are only shown for the storage stability of levocetirizine hydrochloride, and do not mention a method for suppressing decomposition and discoloration by light.

  Currently, pharmaceutical compositions containing one or more pharmaceutically active ingredients selected from cetirizine, optically active isomers thereof or pharmaceutically acceptable salts thereof, in particular levocetirizine hydrochloride, are degraded under the influence of light irradiation. I found a new problem of being promoted and causing discoloration. In particular, with regard to discoloration, it was confirmed that there are problems not only in the influence of light irradiation but also in an environment where no light exists.

  As a result of diligent research to solve the above-mentioned problems, the present inventors have found that oral pharmaceutical compositions containing one or more pharmaceutically active ingredients selected from cetirizine, optically active isomers thereof, or pharmaceutically acceptable salts thereof. It was found that the problem of decomposition and discoloration due to light can be solved simultaneously by adding a colorant to the product, and further studies were made to complete the present invention.

  Surprisingly, according to the present invention, a simple method of simply blending a colorant with one or more pharmaceutically active ingredients selected from cetirizine, optically active isomers thereof or pharmaceutically acceptable salts thereof. , Light degradation and discoloration can be suppressed.

  In the oral pharmaceutical composition of the present invention, the colorant is not particularly limited, and for example, iron oxide, edible tar pigment, natural pigment and the like can be used. In the present invention, preferred colorants are yellow ferric oxide, ferric oxide, blue aluminum lake and yellow aluminum lake. Most preferred are yellow ferric oxide and ferric oxide. Moreover, the coloring agent of this invention should just be mix | blended with an oral pharmaceutical composition, and the method of the addition is not specifically limited.

  In the oral pharmaceutical composition of the present invention, the blending amount of the colorant is not particularly limited as long as the effect of the present invention is exerted. For example, the blending amount of the colorant is preferably 0.03 parts by weight, more preferably 0.05 parts by weight as the lower limit value when the weight of the oral pharmaceutical composition is 100 parts by weight. is there. As an upper limit, Preferably it is 1 weight part, More preferably, it is 0.2 weight part. In addition, when the weight of the active ingredient is 100 parts by weight, the lower limit is preferably 0.6 parts by weight, and more preferably 1 part by weight. As an upper limit, Preferably it is 20 weight part, More preferably, it is 4 weight part.

  The dosage form of the oral pharmaceutical composition of the present invention may be any dosage form as long as it is a preparation for oral use, and is not particularly limited. Examples thereof include jelly, gummi, dry syrup, powder, granule, Fine granules, chewable preparations, tablets, film-coated tablets and the like can be mentioned, preferably tablets, and more preferably tablets orally disintegrating tablets.

  The oral pharmaceutical composition of the present invention is a range that does not impair the effects of the present invention, other than one or more pharmaceutically active ingredients and colorants selected from cetirizine, optically active isomers thereof, or pharmaceutically acceptable salts thereof. In addition, carriers or additives generally used in the manufacture of pharmaceuticals and foods may be included. As the carrier or additive, for example, an excipient, a binder, a disintegrant, a sweetener, a corrigent, a fluidizing agent, a lubricant, a fragrance and the like can be used as appropriate.

  In the oral pharmaceutical composition of the present invention, the excipient is not particularly limited. However, when the dosage form is an orally disintegrating tablet, water-soluble or water-affinity is preferable in consideration of mouthfeel and the like. For example, lactose hydrate, mannitol, sorbitol, xylitol, trehalose, cyclodextrin, sucrose, isomalt, partially pregelatinized starch, crystalline cellulose, anhydrous calcium hydrogen phosphate, calcium carbonate and the like can be used in appropriate combination.

  In the oral pharmaceutical composition of the present invention, the binder is not particularly limited, and for example, hydroxypropylcellulose, hypromellose, gelatin, pregelatinized starch, polyvinylpyrrolidone and the like can be used.

  In the oral pharmaceutical composition of the present invention, the disintegrant is not particularly limited. For example, crystalline cellulose, crospovidone, carmellose, low-substituted hydroxypropylcellulose, carmellose calcium, croscarmellose sodium, carboxymethyl starch sodium, partial alpha Modified starch, hydroxypropyl starch and the like can be used.

  In the oral pharmaceutical composition of the present invention, the sweetening agent is not particularly limited. And its extract, glycyrrhizic acid, sweet tea, aspartame, stevia, thaumatin, sodium citrate and the like can be used.

  In the oral pharmaceutical composition of the present invention, the corrigent is not particularly limited, and for example, cyclodextrin, citric acid, sodium citrate, tartaric acid, DL-malic acid, glycine, DL-alanine and the like can be used.

  In the oral pharmaceutical composition of the present invention, the fluidizing agent is not particularly limited. For example, hydrous silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, synthetic hydrotalcite, dry aluminum hydroxide gel, kaolin, calcium silicate , Magnesium aluminate metasilicate, talc and the like can be used.

  In the oral pharmaceutical composition of the present invention, the lubricant is not particularly limited, and examples thereof include magnesium stearate, calcium stearate, sodium stearyl fumarate, stearic acid, talc, sodium lauryl sulfate, hydrogenated vegetable oil, microcrystalline wax, shoal. Sugar fatty acid esters, polyethylene glycol, and the like can be used.

  In the oral pharmaceutical composition of the present invention, the flavor is not particularly limited, and examples thereof include strawberry flavor, apple flavor, tropical fruit flavor, dairy flavor, tea flavor, citrus flavor, coffee flavor and cherry flavor. Can be used.

  The oral pharmaceutical composition of the present invention can be produced by a conventional method according to the dosage form of the preparation. For example, when the dosage form is a tablet, the powder mixture of the components of the oral pharmaceutical composition is produced as it is or by compression molding by a conventional method through steps such as mixing, granulation, and sizing as necessary. Can do.

  It does not specifically limit as a mixer which can be used in said mixing, A well-known mixer can be used.

  Moreover, it does not specifically limit about the granulation method, For example, a wet granulation method, a dry granulation method, etc. are employable. As the granulating apparatus, for example, a known granulating apparatus such as a fluidized bed granulating apparatus, a rolling type granulating apparatus, a Wurster type granulating apparatus or a stirring granulating apparatus may be appropriately selected and used.

  The tableting machine used for tableting is not particularly limited, and a known tableting machine such as a rotary tableting machine or a single tableting machine may be appropriately selected and used.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated concretely, this invention is not limited to these Examples.

  In accordance with the prescription in Table 1 below, levocetirizine hydrochloride, β cyclodextrin (Seldex B-100H (manufactured by Nippon Shokuhin Kako Co., Ltd.)), light anhydrous silicic acid (AdSolider 101 (manufactured by Fuji Silysia Chemical Ltd.)), lactose hydration (Flow rack 100 (Megure Japan Co., Ltd.), lactose DMV 200M (DFE Pharma Co., Ltd.)), Colorant, Carmellose (NS-300 (Nichirin Chemical Co., Ltd.)), Acesulfame potassium (Sanet Pharma Grade D (MC Foods Specialties Co., Ltd.)), sucralose (Sucralose (P) (manufactured by Saneigen FFI Co., Ltd.)) and a fragrance were mixed uniformly. Sodium stearyl fumarate (PRUV (manufactured by JRS PHARMA)) was further added and mixed to the mixture, and the mixture was compression molded to contain the levocetirizine hydrochloride-containing oral cavity of Examples 1-4 and Comparative Example 1 Disintegrating tablets were obtained.

  A stability test was performed on the preparations of Examples 1 to 4 and Comparative Example 1. The stability test was carried out by storing each orally disintegrating tablet under a hermetic condition at 60 ° C. for 3 weeks or by light irradiation under a condition of 1.2 million lux · hr. The samples were evaluated by a color difference test (spectral colorimeter SE-2000 Nippon Denshoku Industries Co., Ltd.) and a purity test (high performance liquid chromatography 30A series Shimadzu Corporation).

  Table 2 shows the evaluation results for each specimen irradiated with light under conditions of 1.2 million lx · hr.

  From the results of Table 2, as compared with Comparative Example 1 that does not contain a colorant, the samples of Examples 1 to 4 had a low ratio of total affinity after light irradiation, and the result that discoloration was also suppressed was obtained.

  Table 3 shows the evaluation results regarding specimens stored for 3 weeks under airtight conditions at 60 ° C.

  From the results in Table 3, it was confirmed that even in the absence of light irradiation, the orally disintegrating tablet discolored in Comparative Example 1. From this result, it was confirmed that in the composition containing levocetirizine hydrochloride, the phenomenon of discoloration was caused not only by the influence of light but also by the influence of the storage over time in an environment without light. Surprisingly, this test revealed that the present invention has an effect of effectively suppressing such discoloration over time.

  The present invention provides an oral pharmaceutical composition containing one or more pharmaceutically active ingredients selected from cetirizine, optically active isomers thereof, or pharmaceutically acceptable salts thereof in which degradation and discoloration by light are suppressed. And has industrial applicability in the field of pharmaceuticals and the like.

Claims (9)

An oral pharmaceutical composition comprising one or more pharmaceutically active ingredients selected from cetirizine, an optically active isomer thereof, or a pharmaceutically acceptable salt thereof, and a coloring agent. The oral pharmaceutical composition according to claim 1, wherein the pharmaceutically active ingredient is levocetirizine hydrochloride. The oral pharmaceutical composition according to any one of claims 1 and 2, wherein the colorant is one or more additives selected from iron oxide, blue aluminum lake and yellow aluminum lake. The oral pharmaceutical composition according to any one of claims 1 to 3, comprising 0.03 to 1 part by weight of a coloring agent relative to 100 parts by weight of the oral pharmaceutical composition. The oral pharmaceutical composition according to claim 1, wherein decomposition by light is suppressed. The oral pharmaceutical composition according to claim 1, wherein discoloration is suppressed. The oral pharmaceutical composition according to claim 1, wherein the colorant is contained in the uncoated tablet portion of the tablet. An oral pharmaceutical composition is an orally disintegrating tablet, The oral pharmaceutical composition of any one of Claims 1-7. In order to suppress degradation and coloring due to light, an oral pharmaceutical composition contains cetirizine, an optically active isomer thereof, or one or more pharmaceutically active ingredients selected from pharmaceutically acceptable salts thereof and a coloring agent, A method for producing the pharmaceutical composition.