JPH0749372B2 - Sustained release suppository - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial application] The present invention relates to a sustained release suppository.

[Prior Art] Some drugs that are usually used as suppositories have a medicinal effect for a relatively short period of time, or side effects frequently occur due to rapid transfer into the body. Drugs such as these need to be desensitized. Improvements in this respect were made by using Pluronic F-127 as a base [Chemical and Pharmaceutical Bulletin Vol. 34, page 1801 (1986)] and various additives (cyclodextrin). , Ethyl cellulose, etc.) is a sustained-release base (JP-A-58-172311).

[Problems to be Solved by the Invention] However, since the former is in a sol state at room temperature, it is difficult to take the form of an ordinary solid suppository, and the latter has a problem that the operation becomes complicated.

Further, in the case of a suppository using a water-soluble base, irritation to rectal mucosa is a problem.

[Means for Solving Problems] The present inventors have found that when a sucrose fatty acid ester is incorporated in a small amount (for example, about 20% by weight) into a suppository using a water-soluble base, sustained release of the drug is not observed. Not seen, but 50-90% by weight
The present invention has been completed by finding that the formulation allows sustained release, has low irritation to mucous membranes, is easy to operate during production, and is inexpensive to produce.

That is, the present invention is a suppository containing 50 to 90% by weight of sucrose fatty acid ester and a water-soluble base.

The amount of sucrose fatty acid ester in the sustained release suppository is 50 to 90% by weight, preferably 60 to 75% by weight, based on the suppository.

The sucrose fatty acid ester used in the present invention is sucrose
And higher fatty acids having 8 to 20 carbon atoms (eg palmitic
Acid, stearic acid, etc.) monoesters, diesters,
Polyester or a mixture of these esters.
The HLB value is suitably 8 or less, preferably 6
It is as follows. The shape is powdery or liquid.
Or paste, for example DK ester
(Daiichi Kogyo Seiyaku Co., Ltd.) or Ryotoshi
Rugger ester (Manufactured by Mitsubishi Kasei Foods Co., Ltd.)
can give. When preparing, mix one or more
You may use.

The water-soluble base used in the present invention is one normally used for suppositories, for example, macrogol, MC, CMC-N.
a, glycerogelatin, glycerin and the like. Moreover, you may mix and use these various types.

The medicinal component used in the present invention is a drug usually used for suppositories such as antipyretic analgesics and antibiotics.

In addition to the sucrose fatty acid ester, the water-soluble base, the medicinal component, an antioxidant and a stabilizer can be added to enhance the storage stability. The antioxidant is, for example, tocopher, dibutylhydroxytoluene (BHT) and the like, and the stabilizer is, for example, phosphoric acid, ascorbic acid, citric acid and the like. In addition, a wax component, a gelling agent or the like may be added in order to adjust the hardness and feel of the suppository. The wax component is, for example, hydrogenated castor oil, carbowax, etc., and the gelling agent is, for example, an acrylic acid polymer.

The method for producing the sustained release suppository of the present invention will be described. After mixing and melting the sucrose fatty acid ester and the water-soluble base at 70 to 90 ° C,
Add medicinal ingredients. It is manufactured by adding sufficient stirring so that the sucrose fatty acid ester and the water-soluble base component do not separate, forming an oil-dispersed emulsion in which the sucrose fatty acid ester is the oil phase, filling it in a container, and rapidly cooling it. . The dosage form may be a dosage form suitable for the site of use, and examples of the dosage form used include a dosage form applied to the rectum or vagina.

Examples of the present invention will be shown below, but the present invention is not limited to these examples.

Example 1 DK ester F-20W 50 wt% Macrogol 4000 49 wt% Indomethacin 1 wt% DK ester and Macrogol 4000 were mixed and melted at 70 to 90 ° C, and then indomethacin was added. Add sufficient stirring to prevent DK ester and Macrogol 4000 from separating,
It was prepared by forming an emulsion in oil having an ester as an oil phase, filling a container, and rapidly cooling.

Example 2 DK Ester F-20W 60% by weight Macrogol 4000 39% by weight Indomethacin 1% by weight A suppository was produced in the same manner as in Example 1 except that the above components were used.

Example 3 DK Ester F-10 50% by weight Macrogol 4000 49% by weight Indomethacin 1% by weight A suppository was prepared in the same manner as in Example 1 except that the above components were used.

Example 4 DK Ester F-20W 85% by weight Macrogol 4000 14% by weight Indomethacin 1% by weight A suppository was produced in the same manner as in Example 1 except that the above components were used.

Example 5 DK Ester F-20W 75% by weight Macrogol 40000 24% by weight Indomethacin 1% by weight A suppository was prepared in the same manner as in Example 1 except that the above components were used.

Example 6 DK Ester F-10 55% by weight Macrogol 1540 10% by weight Macrogol 4000 34% by weight Indomethacin 1% by weight According to the same manner as in Example 1, a suppository was produced.

Example 7 Ryoto Sugar Ester S-170 70% by weight Macrogol 6000 29% by weight Phenylpropanolamine chloride 1% by weight A suppository was prepared in the same manner as in Example 1 except that the above components were used.

Reference Example 1 Macrogol 4000 99% by weight Indomethacin 1% by weight After melting Macrogol 4000 at 70 ° C to 90 ° C, indomethacin was added, and the mixture was filled in a container and rapidly cooled to produce a suppository.

Reference Example 2 DK ester F-20W 20% by weight Macrogol 4000 79% by weight Indomethacin 1% by weight A suppository was produced in the same manner as in Example 1 except that the above components were used.

Test Example For the suppositories produced in the above Examples 1, 2, 5 and Reference Examples 1, 2, the method of Muranishi et al. [Pharmaceuticals Vol. 39, No. 1, 1-7, (198
7)], the respective drug release tests were conducted. However, the release liquid is 0.05M, pH 7.0, phosphate buffer 300m, kept at 37 ℃.
was carried out at an inner layer stirring speed of 25 rpm. 1 ml was taken from the release solution over time to obtain 0.05M, pH 7.0 phosphate buffer:
After diluting with 3 ml of 1: 1 solution of ethanol and filtering with a 0.45 μm filter, the concentration of indomethacin was determined by the absorbance at UV320 nm. After collection, 1 ml of 0.05 M, pH 7.0 phosphate buffer was supplemented.

The results of these tests are shown in FIG.

[Effect of the Invention] As is clear from the above description, the suppository of the present invention contains 50 to 90% of sucrose fatty acid ester to control the release of the drug.

Further, the operation at the time of production is simple and the production cost is low, and even though it is a suppository using a water-soluble base, it is mild to mucous membranes.

Further, by using a water-soluble base, in the case of a drug that is difficult to dissolve in an oily base, the dispersibility of the drug is improved and the release from the suppository is kept constant.

[Brief description of drawings]

FIG. 1 shows the release rate of indomethacin suppositories formulated with various proportions of sucrose fatty acid ester.

Claims (1)

[Claims] 1. A sustained-release suppository containing 50 to 90% by weight of sucrose fatty acid ester and a water-soluble base.