JPH0776172B2 - Matrice locks - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention relates to drugs, buffers and waxes as a base,
The present invention relates to a matrix tablet containing a hydrophobic polymer compound or a gel-forming polymer compound, which is used in the medical field.

[Prior Art] A matrix tablet obtained by mixing a drug with a water-insoluble substance such as waxes, hydrophobic polymer compounds or gel-forming polymer compounds and tableting the drug particles with ethyl cellulose or Microcapsules and the like coated with acrylic polymer compounds have been widely studied and some have been put to practical use.

[Problems to be Solved by the Invention] Although a conventional matrix tablet can achieve a sustained drug release effect, the dissolution rate of the drug depends on the solubility of the drug in the digestive fluid. For example, in the case of a basic drug, gastric juice is used. Among them, there is a problem that the dissolution rate increases and the dissolution rate decreases in intestinal fluid.

In addition, since the drug is eluted from the matrix tablet according to the first-order rate equation, the amount of the drug released decreases with the passage of time. Therefore, in the intestinal tract, which is the main absorption site of the drug, for example, in the case of a basic drug, the dissolution of the drug from the matrix tablet is significantly reduced, and there is a problem that the drug effect cannot be sufficiently sustained.

On the contrary, in the case of an acidic drug, the dissolution rate decreases in the gastric juice and increases in the intestinal juice. As described above, since the acidic drug is less likely to be eluted in the stomach, there is a problem that the drug effect is not rapidly exhibited when the drug stays in the stomach for a long time after being taken after eating.

[Means for Solving Problems] As a result of intensive studies conducted by the inventors of the present invention for the purpose of overcoming the above-mentioned problems, in a matrix tablet produced by adding a buffer, the buffer is easily soluble. Nevertheless, the pH in the pores is maintained because it is retained in the matrix pores for a long time.
As a result of constant control, the drug can be continuously eluted without being affected by the pH of the digestive juice, and the elution rate of the drug can be arbitrarily changed by changing the composition of the added buffer. The present invention has been completed by finding that the above can be achieved.

Examples of basic drugs applicable to this invention include metoclopramide base, sulpiride, metoprolol, thiapride, zotepine, cibenzoline, cimetidine, cinnarizine, ephedrine, atropine, pyridoxine,
Examples thereof include codeine, and examples of the acidic drug include voltaren, antibiotics (eg, penicillin-based, cephalosporin-based antibiotics, etc.), etc., but the present invention provides more preferable results when applied to basic drugs. Be done.

The buffer may be a physiologically acceptable substance, for example, citric acid, phthalic acid, tartaric acid, boric acid and salts thereof, primary, secondary or tertiary phosphates (for example,
Amino acids such as monosodium phosphate, dibasic sodium phosphate, dibasic potassium phosphate, dibasic potassium phosphate, etc., glycine and their salts, ammonium chloride, potassium chloride, sodium acetate, etc. or mixtures thereof are used. To be done. Furthermore, hydrates of these buffers can also be used.

The matrix matrix of the present invention can be manufactured by a known method, that is, by mixing a matrix matrix with a drug and a buffer and tableting, but if necessary, lactose, sucrose, mannitol, various starches. Excipients such as or a lubricant such as magnesium stearate may be added.

As the matrix base, waxes (for example, carnauba wax, beeswax, lanolin, hydrogenated soybean oil, hydrogenated castor oil, hydrogenated tallow oil, higher alcohols, paraffins, etc.),
Hydrophobic polymer compounds (for example, ethyl cellulose) and gel-forming polymer compounds (for example, carboxymethyl cellulose, polyvinyl pyrrolidone, hydroxypropyl methyl cellulose, carboxylic acid polysaccharide alginic acid, agar, collagen, etc.) can be mentioned.

The matrix tablets are prepared by heating and melting waxes which are matrix bases, or dissolving polymer compounds in an appropriate solvent, and adding a drug, a buffer and, if necessary, an excipient to these. It can also be produced by kneading, kneading, drying and sieving, mixing the obtained particles with a lubricant and tableting.

The content of the buffer in the matrix tablet needs to be an amount capable of maintaining the buffer effect until the dissolution of the drug from the matrix tablet is completed. Since the ratio of the buffer and the drug in the matrix tablet is related to the diffusion rate of both, the amount of the buffer can be appropriately determined depending on the amount and the nature of the drug, but usually 1 to 10 times the drug weight. This object can be achieved by using an amount of buffer, preferably from 1 to 5 times.

On the other hand, the content of the matrix base in the matrix tablet is not particularly limited, it can be appropriately determined depending on the amount and properties of the drug and buffer used and the intended duration, etc., usually 20 to 80% of the tablet weight, It is preferably 40 to 60%.

[Effects of the Invention] Typical test results are shown below to show the effects of the present invention.

Test tablet A: Matrices tablet obtained in Example 1 below Test tablet B: Matrices tablet obtained in Example 2 below Test tablet C: Matrices tablet obtained in Example 3 below Test tablet D: Production example described below Obtained Matrices Tablets Dissolution test Test method 1: 10th Revised Japanese Pharmacopoeia Dissolution test Paddle method [First solution (pH about 1.2), 900 ml, 37 ° C, 100 r.p.
m] Test method 2: 10th revised Japanese Pharmacopoeia dissolution test method Paddle method [Second liquid (pH about 6.8), 900 ml, 37 ° C, 100 r.p.
m] Test results The following table shows the results of the dissolution test.

From the above test results, it is understood that the matrix tablet of the present invention can continuously elute the drug without being affected by the pH of the eluate, as compared with the matrix tablet containing no buffer (test tablet D).

In addition, it is understood that in the matrix tablet of the present invention, the drug dissolution rate can be adjusted by changing the composition of the buffer.

[Examples] The present invention will be described below with reference to Examples.

Example 1 Paraffin (13 g), metoclopramide base (1.56 g),
Citric acid monohydrate (2.6 g), lactose (7.8 g) and magnesium stearate (1.04 g) were weighed and mixed, and then by direct compression method, a matrix tablet having the following composition per tablet was obtained. Obtained.

Metoclopramide base 15.6 mg Citric acid monohydrate 26 mg Paraffin 130 mg Lactose 78 mg Magnesium stearate 10.4 mg 260 mg Example 2 In the same manner as in Example 1, Matrices tablets having the following composition per tablet were obtained.

Metoclopramide base 15.6 mg Citric acid monohydrate 13 mg Anhydrous sodium phosphate 13 mg Paraffin 130 mg Lactose 78 mg Magnesium stearate 10.4 mg 260 mg Example 3 In the same manner as in Example 1, the following composition was prepared per tablet. A matrix tablet having the above was obtained.

Metoclopramide base 15.6 mg Anhydrous dibasic sodium phosphate 26 mg Anhydrous dibasic potassium phosphate 26 mg Paraffin 130 mg Lactose 52 mg Magnesium stearate 10.4 mg 260 mg Production Example Similar to Example 1, each tablet has the following composition. I got a matrix tablet.

Metoclopramide base 15.6 mg Paraffin 130 mg Lactose 104 mg Magnesium stearate 10.4 mg 260 mg

Claims (2)

[Claims] 1. A matrix tablet containing a drug, a buffer and a wax, a hydrophobic polymer or a gel-forming polymer as a base. 2. The matrix tablet according to claim 1, wherein the drug is a basic drug.