JPH085783B2 - Bromhexine hydrochloride adsorption prevention method - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for preventing adsorption of bromhexine hydrochloride, and more specifically, to prevent adsorption of bromhexine hydrochloride on a plastic laminated aluminum packaging material or a plastic packaging material. Regarding the method.

[Prior Art] Bromhexine hydrochloride is not known to be adsorbed on a plastic laminated aluminum packaging material or a plastic packaging material, or a method for preventing it.

[Problems to be solved by the invention] When solid pharmaceuticals containing bromhexine hydrochloride are used as excipients such as crystalline cellulose and polysaccharides such as starch, bromhexine hydrochloride is adsorbed on a plastic laminated aluminum packaging material such as polyethylene or a plastic packaging material. Content decreases. This phenomenon can be prevented to some extent by using monosaccharides such as mannitol, sorbit, and lactose, and disaccharides, but if multicomponents such as antipyretic analgesics, antihistamines, and antitussives are included, they are contained therein. The existing basic drug further promotes the adsorption of bromhexine hydrochloride on the plastic laminated aluminum packaging material or the plastic packaging material.

Bromhexine hydrochloride is a drug widely used as an excellent expectorant, but its dose is only as small as 4 mg at a time. Therefore, a decrease in the content due to adsorption to the plastic laminated aluminum packaging material or the plastic packaging material during storage affects the drug efficacy, although it is a small amount.

[Means for Solving Problems] As a result of various studies to solve the above problems, the present inventors have found that bromhexine hydrochloride and a basic drug in a solid preparation containing granules of bromhexine hydrochloride and a basic drug, respectively. Or a powder, and by further mixing these granules or powders to form a granule or powder, it was found that bromhexine hydrochloride can be prevented from being adsorbed on a plastic laminated aluminum packaging material or a plastic packaging material, and further The present invention has been completed based on the findings.

In the present invention, the basic drug has a secondary or tertiary ammonium, and as an antipyretic analgesic, antitussive or antihistamine, acetaminophen, ethenzamide, salicylamide, diphenhydramine hydrochloride, phosphate Codeine, noscapine hydrochloride, dl-chlorpheniramine maleate, carbinoxamine maleate, dihydrocodeine phosphate, noscapine and the like can be mentioned.

The plastic laminated aluminum packaging material or plastics used for the plastic packaging material includes acrylonitrile resin, ethylene-vinyl alcohol copolymer, polyvinyl alcohol, polyethylene, polyester, polypropylene and the like. For example, Barex 210 [trade name; manufactured by Mitsui Toatsu Chemicals, Inc.], EVAL [trade name; manufactured by Kuraray Co., Ltd.], Poval [trade name;
Made by Kuraray Co., Ltd., etc.

The preparation of the present invention can be produced, for example, by the following method.

Bromhexine hydrochloride and common excipients such as lactose,
Mannit and the like are manufactured into granules or powders in accordance with the 11th revised Japanese Pharmacopoeia general rules, and basic drugs are also made into granules or powders in accordance with the 11th revised Japanese Pharmacopoeia general rules.
Thereafter, the respective granules or powders are mixed to produce the desired granules or powders. Wrap this in plastic laminated aluminum packaging or plastic container,
Can be a product.

EFFECTS OF THE INVENTION According to the present invention, it is possible to prevent adsorption of bromhexine hydrochloride in granules or powders on plastics in packaging. Therefore, using conventional plastic packaging materials or plastic laminated aluminum packaging materials, bromhexine hydrochloride granules can be used. It is now possible to package a drug or powder into a product.

[Examples] Hereinafter, the present invention will be specifically described with reference to Examples and Test Examples.

Example 1 Formulation A; Bromhexine hydrochloride 4 mg Lactose 491 mg Hydroxypropylcellulose 5 mg Total 500 mg B; Acetaminophen 300 mg dl-Chlorpheniramine maleate 2.5 mg Cloperastine hydrochloride 16 mg Hydroxypropylcellulose 5 mg Lactose 176.5 mg Total 500 mg Granules were obtained according to Japanese Pharmacopoeia General Rules 5.

The respective A and B granules were mixed to obtain the target granule. This granule was filled in a polyethylene laminated aluminum pack.

Example 2 Formulation A; Bromhexine hydrochloride 4 mg Hydroxypropylcellulose 5 mg Sorbitol 291 mg Total 300 mg B; Acetaminophen 300 mg Carbinoxamine maleate 2.5 mg Noscapine hydrochloride 16 mg Hydroxypropylcellulose 5 mg Sorbitol 276.5 mg Total 600 mg According to general rule 5, granules were obtained.

The respective A and B granules were mixed to obtain the target granule. This granule was filled in a polyester laminated aluminum pack.

Example 3 Formulation A; Bromhexine hydrochloride 4 mg Polyvinylpyrrolidone 5 mg Lactose 191 mg Total 200 mg B; Ethenzamide 500 mg Cremastine fumarate 0.12 mg Lysozyme chloride 20 mg Polyvinylpyrrolidone 15 mg Lactose 264.88 mg Total 800 mg I got a powder.

The respective A and B powders were mixed to obtain the target powder. This powder was filled in a polyethylene laminated aluminum pack.

Test Example 1 (Sample) The granules obtained in Examples 1 and 3 were packed in an aluminum packaging material in which Barex 210 [trade name; manufactured by Mitsui Toatsu Chemicals, Inc.] was laminated with 4 mg of bromhexine hydrochloride equivalent. Were designated as samples 1 and 2. In addition, as control products, control products 1 and 2 were prepared by packing granules having the following formulation into an aluminum packaging material laminated with Barex 210 and packing 4 mg of bromhexine hydrochloride.

Formulation of Control Product 1; Bromhexine Hydrochloride 4 mg Acetaminophen 300 mg dl-Chlorpheniramine Maleate 2.5 mg Cloperastine Hydrochloride 16 mg Hydroxypropylcellulose 10 mg Lactose 667.5 mg Total 1000 mg Formulation of Control Product 2; Bromhexine Hydrochloride 4 mg Ethenzamide 500 mg Cremastine Fumarate 0.12 mg Lysozyme chloride 20 mg Polyvinylpyrrolidone 20 mg Lactose 255.88 mg Total 800 mg Samples 1 and 2 and controls 1 and 2 were stored at 50 ° C, and after 1 week, 2 weeks, 3 weeks, and 4 weeks, each packaging material was subjected to chloroform. The extract that had been refluxed for 30 minutes at 50 ° C. was quantified for bromhexine hydrochloride in the Barex membrane under the following conditions.

(Quantitative conditions) 1) Pump; HITACHI 655A-12 [manufactured by Hitachi, Ltd.] 2) Detector; HITACHI 655A [manufactured by Hitachi, Ltd.] 3) Operating conditions; Detector; UV absorption meter Measurement wavelength; 210 nm Detector sensitivity: 0.04 AUFS column; inner diameter 4 mm, length: 150 mm stainless steel tube is filled with octadecylsilylated 5 μm silica gel as a packing material.

Column temperature; 50 ℃ Mobile phase; 1 / of acetonitrile and sodium lauryl sulfate
Mixture of 15M potassium dihydrogen phosphate solution (mixing ratio 520: 480) Flow rate: 1 ml / min Injection rate: Bromhexine hydrochloride concentration 20 μg / ml 10 μm
l Injection (Results) The quantitative results are shown in Table 1 as a percentage with the amount of bromhexine hydrochloride in the sample at the start of the test being 100.

Claims (1)

[Claims] 1. Bromhexine hydrochloride and a basic drug are respectively made into granules or powders, and these granules or powders are further mixed to obtain granules or powders, whereby bromhexine hydrochloride is plastic laminated aluminum packaging material or plastic. A method to prevent adsorption to the packaging material.