JPS615027A - Sustained release solid pharmaceutical - Google Patents

Abstract

PURPOSE:A solid pharmaceutical of a physiologically active substance, e.g. a medicine, containing noncrystallized starch. CONSTITUTION:A sustained release solid pharmaceutical obtained by incorporating noncrystallized starch, e.g. starch prepared by partially or completely depriving the crystallinity of crystalline starch such as potato starch or sweet potato starch, with a physiologically active substance e.g. a medicine, and if necessary an excipient, colorant, binder, flavoring agent, etc. The dosage form thereof is tablet, troche, capsule or granule, etc. The content of the noncrystallized starch in the pharmaceutical is suitably selected from the duration of the drug effect, noncrystallinity of the noncrystallized starch, presence or absence of an additive, etc., but preferably 5-99.9% based on the total pharmaceutical. EFFECT:The release time of the main drug can be adjusted without influence of pH of the digestive juice nor bile. The pharmaceutical can be mass-produced, and the cost is reduced without adversely affecting the living body.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to sustained release solid preparations. For more details, please see j
The present invention relates to a sustained-release solid preparation for physiologically active substances such as pharmaceuticals, which is characterized by containing assembled starch.

``Prior Art'' Conventionally, various methods have been used for formulations and their manufacturing methods to sustain the release of drugs from the formulation and maintain the efficacy of the drugs for a long time. There are also methods for coating drug crystals, granules, and tablets with cellulose derivatives, and methods for chemically bonding drugs with polymeric compounds (e.g., [Basic Drug Development Course XI Pharmaceutical Manufacturing Methods (Part 1) Jll, pp. 7-123 (
Published by Chidai Shokan in 1972), Patent Publication No. 1 in 1982
Publication No. 8694, Published Patent Publication No. 11051 of 1982
3 Publication, Publication Patent Publication No. 500495 of 1982, etc.).

[Problems to be Solved by the Invention] The conventional method described above has a complicated manufacturing process and is expensive, and may also require organic solvents such as methylene chloride and chloroform. It has the disadvantage that it is difficult to remove. Furthermore, it is difficult to control the drug release rate, and the pl of digestive fluid in the body
The release rate varies considerably depending on factors such as hydroxide and bile, and the expected sustained effect may not be obtained.

The present inventor completed the present invention as a result of intensive research into a formulation that does not require a complicated manufacturing process and can accurately control the release rate.

Means for Solving the Problems] The present invention relates to a sustained-release solid preparation characterized by containing amorphous starch. More specifically, the present invention involves mixing physiologically active substances such as pharmaceuticals with amorphous starch, adding excipients, coloring agents, binders, flavoring agents, etc. as necessary, and using a conventional method. The present invention relates to a sustained-release solid preparation that is molded.

The amorphous starch used in the present invention refers to starch in which the crystallinity of crystalline starch has been partially or substantially completely lost. Examples of methods for making crystalline starch amorphous include pulverization using a mill, pregelatinization, spray drying, freeze drying, and rapid precipitation using sudden changes in temperature or solvent composition. Crystalline starches used as raw materials include potato starch, → potato starch, corn starch, waxy corn starch, rice starch, glutinous rice starch, wheat starch,
Examples include barley starch, tapioca starch, pomegranate starch, kolyang starch, and kudzu starch.

The sustained-release solid preparation of the present invention may contain excipients, colorants, binders, flavoring agents, and the like, as required. These additives include conventional additives that can be used in pharmaceutical preparations, and are added in appropriate amounts according to conventional methods depending on the purpose.

The sustained-release solid preparation of the present invention is prepared by adding the active ingredient, amorphous starch, and, if necessary, additives such as those mentioned above, and mixing them uniformly. , obtained by formulating. The formulation method is not particularly limited, and can be carried out according to conventional methods, such as tabletting, capsule filling, granulation, etc., to form blocks into desired solid formulations such as tablets, troches, capsules, and granules. can.

The release rate of the main drug in the sustained-release solid preparation of the present invention depends on the solubility of the drug in water, but also depends on the content of amorphous starch, the type and content of additives such as excipients, and the shape of the preparation. It can be arbitrarily adjusted depending on formulation conditions such as size and compression.

The content of amorphous starch in the sustained-release solid preparation of the present invention is not particularly limited, and may be appropriately selected depending on the desired duration of medicinal efficacy, the degree of amorphousness of the amorphous starch, the presence or absence of the additives, etc. However, it is desirable that the content ranges from about 5% to 99.9% of the total formulation.

The physiologically active substances contained in the formulation of the present invention are for systemic or local disease treatment or for pre-IIJJ, for which the therapeutic effect is expected to be further increased than before by sustained release.
4 or veterinary drugs, such as acetaminophenone, zenacetin, /aspirin, sulvirin, phenylbutacin, mefenano acid, flufenamic acid, ibuprofen, and indomethacin; antipyretic, analgesic, and antiinflammatory drugs; colchicine, probenecin Anti-inflammatory drugs such as: anti-inflammatory enzymes such as alpha-chymotrypsin; anti-inflammatory steroids such as hydrocortisone, prednisone, prednisolone, triamcinolone, dexamethasone, and betamethacin; antihistamicin drugs such as diphenhydramine hydrochloride and chlorpheniramine maleate; Antibiotics, bactericidal agents such as iclin, leucomycin, fradiomycin, penicillin derivatives, cephalosporin derivatives, erythromycin; chemotherapeutic agents such as sulfathiazole, nalisixic acid, local anesthetics such as bensicaine;
Cardiotropes such as digitalis, digoxin, and theophylline;
Vasodilators such as nitrochrycerine and papaverine hydrochloride Antitussive expectorants such as codine diphosphate and ephedrine hydrochloride; Oral disinfectants such as chlorhexidine hydrochloride, domiphene bromide, cetylpyridinium chloride, and ethacridine; Azulene, phenobarin, and vitamin U, etc. Drugs for the gastrointestinal tract; enzymes such as lysozyme chloride and dextranase; hypoglycemic drugs such as insulin; other drugs such as hemostatic drugs, sex hormones, antihypertensive drugs, sedatives, and anti-malignant tumor drugs.

Further, using the sustained-release solid preparation of the present invention, sustained-release preparations having various purposes can be manufactured. For example, by using excipients with low specific gravity, it is possible to form a preparation that floats in the stomach.

For example, when it is desired to release a large amount of the active ingredient at an initial stage, a dry-coated tablet or a multi-layered tablet containing the sustained-release solid preparation of the present invention as a core and layers with a faster release rate of the active ingredient added to the outer layer or upper and lower layers may be used. It can also be a lock.

Furthermore, for example, general film coating, enteric coat ink, etc. can be applied.

The sustained-release solid preparation of the present invention can be used, for example, as a herbicide, an antifungal agent,
It can also be used in sustained release formulations of pesticides such as growth regulators.

1 Effect] j The solid preparation of the present invention containing recombinant starch gradually forms a shell from its surroundings without disintegrating in the digestive juices of the body, and the drug in the preparation is gradually released, reducing the amount released. In addition to being controllable, gel formation is not affected by digestive fluid pl+ or bile, so accurate and sustained effects can be achieved.

[Effects of the Invention] The sustained-release solid preparation of the present invention can be used to adjust the release time of any crude drug by appropriately combining the amount of amorphous starch, dosage form, etc. The release rate can be accurately controlled because it is not affected by digestive fluid PL+ or bile. It does not require any special additions to the manufacturing process, so mass production is possible and can contribute to cost reduction. Amorphous starch has advantages such as being inexpensive and having no adverse effects on living organisms.

[Examples] Example 1 10 g of potato starch (pharmaceutical product) was ground for about 6 hours using a centrifugal rotating ball mill. After thoroughly mixing 5 g of the amorphous starch thus obtained and 5 g of theophylline anhydride, each tablet was made into tablets of 500 mg.

The tablets were placed in a net and suspended in Japanese Pharmacopoeia disintegration test liquid No. 1 (200 ml) heated to 37°C, and the released liquid was stirred with a magnetic cooler. A portion of the released liquid was sampled over time, and the amount of theophylline released was quantified by spectrophotometry.

On the other hand, as a comparative example, 5 g of potato starch before amorphization and 5 g of theophylline anhydride were thoroughly mixed, then tablets were made in the same manner as above, and a release test was conducted.

The results are shown in Table 1.

As is clear from the results in Table 1, the tablet according to the present invention exhibited sustained release, with a release rate of 52% after 8 hours.

Table 1 Example 2 Potato alpha starch 5g and theophylline anhydride 5
Tablets were made in the same manner as in Example 1 using
It's one.

On the other hand, as a comparative example, 1 5 g of unpregelatinized potato tin was thoroughly mixed and then tableted in the same manner as above, and a release test was conducted.

The results are shown in Table 2.

As is clear from the results in Table 2, the tablets made using amorphous starch exhibited long-lasting properties, with a release rate of 44% after 8 hours.
%Met.

Table 2

Claims (1)

[Claims] Sustained-release solid preparation characterized by containing amorphous starch