JPS5865213A - Soft capsule preparation containing dl-2-(4,8,12- trimethyltridecyl)-2,5,7,8-tetramethyl-6-chromanyl nicotinate - Google Patents

Abstract

PURPOSE:To provide a soft capsule preparation stable even after long-term storage, free from separation and seepage of the active component, absorbable easily through the digestive tracts by oral administration, and having rapid drug action, by using a mixture of the titled active component and an oily solvent as the encapsulated liquid. CONSTITUTION:100pts.wt. of dl-2-(4,8,12-trimethyltridecyl)-2,5,7,8-tetramethyl-6- chromanyl nicotinate (active component) widely used as a remedy for hyperlipemia, arteriosclerosis, etc. is mixed with 40-200pts.wt. of an oily solvent which is liquid at normal temperature and has excellent compatibility to the active component, e.g. vegetable oil, medium-chain fatty oil (especially 8-10C medium chain fatty oil), etc. The mixture is used as an encapsulation liquid, and filled in the skin of a soft capsule by conventional process. Addition of 4-12pts.wt. of an absorbefacient such as polysorbate 80, lecithin, etc. to the mixture remarkably increases the absorbability of the active component.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is extremely stable in the distribution process of commercially available medical products, has good gastrointestinal absorption, and has superior effects (1/ -2-(4,8,1
2-trimethyltridecyl)-2,5,7,8-tetramethyl-6-chromanylnicotinate soft capsules K
Seki-1-ru.

d71! -2-(4,8,12-1-limethyltridecino-1)-2,5,7,8-tetramethyl-6-chromanyl nichinate is widely used in the treatment of hyperlipidemia, arteriosclerosis, etc. The melting point of this medicine is approximately 68° (
1, and its properties are a pale oily wax-like solid.When making hard capsules or granules, they are first adsorbed onto an adsorbent, and then made into granules using an excipient. (Requires steps such as t'.

For this reason, Fp-appetizer formulations have disadvantages such as a large dosage form and a complicated manufacturing process.

Furthermore, as mentioned above, it has a low melting point, so if it goes through a normal distribution process and is exposed to a fairly high temperature, (11-2-(4,8,12-trimethyltridecyl) )-2,5,7,8-tetramethyl-6-chromacono1
Nicotinate melts and becomes liberated from the granules to the surface.

As a result, due to the phase change from solid to liquid or from liquid to solid, the phenomenon of uneven distribution of the drug is observed, and in severe cases, there may be a phenomenon of leakage to the outside from the joint site of the hard capsule.

Therefore, the present inventor conducted intensive research to overcome such drawbacks and found that dl-2-(4*8+12-trimethyltridecyl)-2,5,7,8-titrame, 1,000 ru6
- Soft capsules containing chromanyl nicotinate mixed with an oily solvent as an internal solution are stable even during long-term storage, and all of the above drawbacks are solved, and more surprisingly, oral The present invention was completed based on the discovery that when administered, the drug is well absorbed from the gastrointestinal tract and the onset of drug efficacy is extremely rapid.

The oil-based solvent of the present invention is normally oily and dl-
2-(4,8,12-1-limethyltridecyl)-2,
It has excellent compatibility with 5,7,8-tetramethyl-6-chromanylnicotinate, is pharmaceutically acceptable, and has good foaming properties, such as patterned oils such as soybean oil, sesame oil, or medium-chain oils. Although fatty oils may be used, medium-chain fatty oils having 8 to 10 carbon atoms are particularly preferred.

dl-2-C4,8,12-)limethyltridecyl)-
The above effects can be achieved by simply blending the above oily solvent with 2,5,7,8-tetramethyl-6-chromanyl nicotinate, but if an absorption enhancer such as polysorbate 80 or lecithin is further blended. The above absorption is significantly increased.

The oily solvent blended into the internal solution of the present invention is dl-2-(4
,8,12-trimethyltridinno[)-2,5,7,
8-tetramethyl-6-chromanyl nicotinate 100
40 to 200 parts (by weight), and the absorption enhancer is preferably 4 to 12 parts.

The capsules of the present invention obtained in this way have better absorption than conventional hard capsules, and since they are formulated into soft capsules as an oil and fat solution, the dl-2-
(4,8,12-)trimethyltridine)-2,5,7
, 8-Tetramethyl-6-chromanylnicotinate has very good uniformity and dispersibility, and since it is a transparent capsule, it is beautiful and the contamination of foreign substances can be seen at a glance, giving patients a sense of security. There is. Furthermore, the free age and leakage of d-2-(4,8,12-1-limethyltritecyl)-2,5,7,8-tetramethyl-6-chromanylnicotinate in the other formulations mentioned above. It has the advantages of being completely dissolved, disintegrating, dissolving, gj, tl, and being easy for patients to administer.

Next, an example will be given and explained.

Example 1 d-2-(4,8,12-)limethyltridecyl)-
An internal solution is prepared by mixing 100 parts of 2,5,7,8-tetramethyl-6-chromanyl nicotinate, 5 parts of polysorbate 80, 10 parts of soybean lecithin, and 45 parts of Panacet 810 (manufactured by NOF Corporation). 160 mg of this internal liquid is filled into soft capsule shells according to a conventional method to obtain soft capsules.

that's all Applicant: Tokai Capsule Co., Ltd.

Claims (1)

[Claims] 1-2-(4,8,12-)limethyltridenyl)-2
, 5,7,8-tetramethyl-6-chromanyl nicotinate and an oily solvent.