JP2002322064A - Stable benazepril hydrochloride tablet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enhance the storage stability of a benazepril hydrochloride tablet. SOLUTION: This stable benazepril hydrochloride tablet is obtained by preparing and processing benazepril hydrochloride by using additives not containing an alkali metal and an alkaline earth metal.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND ART Benazepril hydrochloride is known as a drug that inhibits angiotensin converting enzyme (ACE) in vivo, and is clinically used for treatment of hypertension and the like.

[0002] However, this drug contains excipients, disintegrants,
Tableting using conventional additives such as binders and lubricants,
When stored in the form of a formulation, the content of benazepril hydrochloride in the formulation decreases over time.

[0003]

The present inventors have conducted a number of tests and have found that the cause is attributable to the alkali metals and alkaline earth metals contained in the tablets.

[0004] Excipients such as excipients, disintegrants and binders are used in tablets, and representative ones are selected.
100 mg of benazepril hydrochloride was mixed with 100 mg of benazepril hydrochloride in a powder state, stored in a glass bottle at 60 ° C. for one month, and the content of benazepril hydrochloride was measured. The results shown in Table 1 were obtained.

Table 1 Additive content (% when initial value is set to 100) Benazepril hydrochloride alone 99.0 Lactose 99.5 Mannitol 99.8 Microcrystalline cellulose 99.4 Corn starch 98.9 Low substituted hydroxypropylcellulose 99.1 Hydroxypropylcellulose 99.5 Polyvinyl pyrrolidone 99.3 Sucrose fatty acid ester 98 .6 Calcium hydrogen phosphate 89.5 Carboxymethyl cellulose calcium 90.2 Sodium carboxymethyl starch 93.0 Magnesium stearate 89.6

[0006] Based on the above results, the present invention provides a stable benazepril hydrochloride tablet prepared by formulating benazepril hydrochloride with an additive component containing no alkali metal or alkaline earth.

[0007] Additives that can be used as additives such as excipients, disintegrants, binders, lubricants and the like are specified in the Pharmacopoeia and other official publications. Components not containing may be appropriately selected and used.

In general, tablet preparation methods include a method of granulating a mixture of a drug and an additive into granules using a binder solution and tableting, and a dry method including a method of directly tableting the mixture. In the case of the present invention, a dry method is preferred.

The packaging method of the preparation may be a commonly used PTP, moisture-proof PTP, polyethylene bottle, glass bottle, etc., and no special consideration is required.

[0010]

The following non-limiting examples demonstrate the invention.

Example 1 Formulation per tablet: benazepril hydrochloride 5 mg mannitol 120 mg crystalline cellulose 5 mg corn starch 7 mg sucrose fatty acid ester 3 mg計 Total 140mg

The respective components were uniformly mixed and formed into tablets by a conventional direct tableting method.

[0013] The obtained tablets are placed in a PTP, moisture-proof PTP, polyethylene bottle or glass bottle,
The solution was stored for one month under the conditions of ° C. and 75% relative humidity, and the content of benazepril hydrochloride was measured. The results shown in Table 2 were obtained.

Table 2 Packaging style Initial value (%) Content after storage (%) ─────── ───────── ───────────── PTP 100 .1 100.1 Moistureproof PTP Same as above 99.6 Polyethylene bottle Same as above 100.7 Glass bottle Same as above 98.9

Comparative Example 1 Formulation per tablet: benazepril hydrochloride 5 mg lactose 108 mg crystalline cellulose 10 mg calcium hydrogen phosphate 10 mg carboxymethyl cellulose calcium 2 mg hydroxypropyl cellulose 3 mg magnesium stearate 2 mg計 Total 140mg

Hydroxypropylcellulose was dissolved in about 300 ml of water per 12 g to prepare a binder solution. The remaining components except magnesium stearate were mixed, granulated in a fluidized bed granulator using the above binder, dried, and the resulting granules were mixed with magnesium stearate and tableted.

The tablets obtained were stored in the same manner as in Example 1 in various packages under the same conditions, and the content was measured. Table 3 shows the results.

Table 3 Packaging style Initial value (%) Content after storage (%) ─────── ───────── ───────────── PTP 100 8.7 86.1. Moistureproof PTP Same as above 89.3 Polyethylene bottle Same as above 97.4 Glass bottle Same as above 96.6

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Claims (2)

[Claims] 1. A stable benazepril hydrochloride tablet prepared by formulating benazepril hydrochloride with an additive component not containing an alkali metal and an alkaline earth metal. 2. The benazepril hydrochloride tablet according to claim 1, wherein the preparation is a dry tableting method including a direct tableting method.