CN103432088B - Albendazole large tablets and preparation technology thereof - Google Patents

Abstract

The invention discloses albendazole large tablets and a preparation technology thereof. The large albendazole tablets comprise 25wt% of glucosyl beta-cyclodextrin and 41.6wt% of albendazole as well as various auxiliary materials such as starch, apple green, brilliant blue, talcum powder, magnesium stearate and aluminium hydroxide. The preparation technology comprises the following steps of: preparation of starch slurry and a glucosyl beta-cyclodextrin inclusion compound of the albendazole, mixing, pelleting and tabletting. The albendazole large tablets have the advantages that the glucosyl beta-cyclodextrin inclusion compound is used for inclusion of the albendazole so as to improve the slow-release effect and the bioavailability of the albendazole, so that the effective haemoconcentration plasma concentration time of medicines is prolonged, the problem of difficulty in absorption by gastrointestinal tracts is solved, and the pharmaceutical effect is improved; the forming effect of the large tablets is good by the reasonable distribution of the contents of the components in the albendazole large tablets in combination with an inclusion process. The preparation technology is simple and convenient to operate. The albendazole large tablets are used for treating nematodosis in cattle gastrointestinal tracts in clinic, the expelling rate reaches 100%, after the albendazole large tablets are taken for 7 days, the negative conversion ratio and decrement rate of eggs are respectively 86.7% and 98.9%, after 14 days, the negative conversion ratio and the decrement rate reach 100% respectively, and the parasite expelling effect of the albendazole large tablets is obviously superior to those of medicine control groups.

Description

Albendazole bolus and preparation technology thereof

Technical field

The present invention relates to the technical field of albendazole preparation for animals, particularly relate to a kind of albendazole bolus and preparation technology thereof.

Background technology

Albendazole system benzimidazoles derivative, be white or off-white powder, odorless, tasteless, water insoluble, be slightly soluble in acetone or chloroform, its in vivo rapid metabolization be sulfoxide, sulfone alcohol and 2-amine sulfone alcohol.The polymerization of parasite intestinal wall cell cytosol microtubule system is suppressed to intestinal nematodes selectivity and irreversibility, block it to absorb the picked-up of multiple nutrients and glucose, polypide endogenous glycogen is caused to be exhausted, and suppress fumaric reductase system, stop the generation of adenosine triphosphate, cause polypide to survive and to breed.

Veterinary is in Clinical practice, and albendazole is benzimidazole anthelmintic drug the most widely, not only has efficiently multiple nematicide, and also has stronger dispel effect to some trematodiasis and cestode.The albendazole tablet of current research report is mainly conventional tablet, use rear gastrointestinal absorption poor, bioavailability is low, effective haemoconcentration is held time shorter, thus make the drug effect of Albenza not good, hold time to extend effective haemoconcentration, the mode that those skilled in the art generally adopt albendazole is prepared into Emulsion or suspension formulations carries out injection administration.In the Albenza that simultaneously now studies have reported that, albendazole content is lower, mostly be the little weight tablet of 0.025g-0.5g/ sheet, the Albenza of this small dimension is very inconvenient on the livestock animals that the body weight such as cattle are larger, dispensing quantity is more, therefore need to research and develop a kind of dispensing quantity few, veterinary clinic is conveniently applied to the high-load albendazole anthelmintic abnormity bolus of the large domestic animals such as cattle.Owing to changing the content specification of Albenza, compared with little content specification tablet, there is fabricating technology difficulty relatively large, the easy part when tabletting sticking, the problems such as molding effect is bad, and part mass index is as defective in disintegration time, and gastrointestinal absorption is difficult.

Summary of the invention

In view of this, the invention provides a kind of albendazole bolus and preparation technology thereof, the bioavailability of albendazole can be improved, solve that large stretch of albendazole molding effect is bad, part mass index is as defective in disintegration time, gastrointestinal tract is difficult to the problems such as absorption.

For solving above technical problem, technical scheme of the present invention is, provide a kind of albendazole bolus, described albendazole comprises glucityl beta-schardinger dextrin-.

Described glucityl beta-schardinger dextrin-by can improve after inclusion technique technique enclose albendazole medicine slow release effect, increase blood density of medicine hold time and improve bioavailability; Strengthen the stability of medicine; Reduce the toxic and side effects of medicine; For taste masking, protection against the tide with make liquid medicine solidification.Glucityl beta-schardinger dextrin-, compared with other enclose material, has water-soluble good, inclusion rate advantages of higher, is more suitable for the enclose of water-insoluble drug especially albendazole.

Preferably, the constituent of described albendazole bolus, according to mass ratio range, comprising:

Moisture controls within 5%.

Preferably, the specification of described albendazole bolus is 39 × 17 × 9.5mm (long × wide × high).

A preparation technology for albendazole bolus, comprises the steps:

A, take starch 10 parts by weight, and take light green 1.13 parts respectively, light blue 0.37 part, add a small amount of water after three's mixing and stir, then add 25 parts of waters for injection, to stir with steam punching in gel, obtain starch slurry for subsequent use;

B, get glucityl beta-schardinger dextrin-25 parts, join in 30 parts of waters for injection, be heated to 60-80 DEG C, after stirring and dissolving, then add albendazole 41.6 parts, under 60-65 DEG C of condition, stir 1.5-2 hour, drying under reduced pressure, to Han Shui Liang≤5%, obtains the glucityl Benexate Hydrochloride of albendazole;

C, dry gained clathrate is positioned in mixer, add Pulvis Talci 10 parts again, after being uniformly mixed 15 minutes, adding starch 6.4 parts, remix 15 minutes, add the starch slurry made in steps A again, be uniformly mixed and be prepared into soft material, granulate, dry grain, add magnesium stearate 0.2 part, aluminium hydroxide 0.3 part mixing granulate, compression molding.

Compared with prior art, tool of the present invention has the following advantages:

Adopt glucityl beta-cyclodextrin inclusion compound albendazole, improve slow release effect and the bioavailability of albendazole, thus the effective blood concentration time course of prolong drug, solve the problem that gastrointestinal tract is difficult to absorb, increase drug effect.The content of the various component of reasonable distribution albendazole bolus, and in conjunction with clathrate process, make the good forming effect of bolus, quality index is qualified, preparation technology is simple, easy to operate.

Detailed description of the invention

In order to make those skilled in the art understand technical scheme of the present invention better, below in conjunction with specific embodiment, the present invention is described in further detail.

Below in conjunction with embodiment, the specific embodiment of the present invention is further described.Following examples only for technical scheme of the present invention is clearly described, and can not limit the scope of the invention with this.

A preparation technology for albendazole bolus, comprises the steps:

A, take starch 10Kg by weight, and take light green 1.13Kg respectively, light blue 0.37Kg, add a small amount of water after three's mixing and stir, then add 25Kg water for injection, to stir with steam punching in gel, obtain starch slurry for subsequent use;

B, get glucityl beta-schardinger dextrin-25Kg, join in 30Kg water for injection, be heated to 60-80 DEG C, after stirring and dissolving, then add albendazole 41.6Kg, under 60-65 DEG C of condition, stir 1.5-2 hour, drying under reduced pressure, to Han Shui Liang≤5%, obtains the glucityl Benexate Hydrochloride of albendazole;

C, dry gained clathrate is positioned in mixer, add Pulvis Talci 10Kg again, after being uniformly mixed 15 minutes, add starch 6.4Kg, remix 15 minutes, add the starch slurry made in steps A again, be uniformly mixed and be prepared into soft material, granulate, dry grain, add magnesium stearate 0.2Kg, aluminium hydroxide 0.3Kg mixing granulate, namely compression molding obtains the albendazole bolus of good forming effect.

The specification of every a slice albendazole bolus is: 39 × 17 × 9.5mm, punch die: long 39mm × wide 17mm, and without word drift, equipment is rushed in 11 punchings, 21.Obtain the special-shaped bolus that tablet is 6g weight, packaging.Detect according to the regulation of " People's Republic of China's veterinary drug allusion quotation ", obtain the quality index such as the disintegration time of whole albendazole bolus qualified, disintegration time reaches less than 3 minutes.

So the constituent of the albendazole bolus obtained and content thereof, count by weight: glucityl beta-schardinger dextrin-25%, starch 16.4%, albendazole 41.6%, light green 1.13%, light blue 0.37%, Pulvis Talci 10%, magnesium stearate 0.2%, aluminium hydroxide 0.3, moisture control within 5%.

Below gained albendazole bolus clinical practice test of the present invention is described:

1 materials and methods

1.1 trial drug

Albendazole Special-shaped sheet, i.e. albendazole bolus of the present invention, specification 6g, 2500mg tabletting sticking, Chengdu Qiankun Animal Drug Industry Co., Ltd. produces.Lot number, 20130102.

1.2 control drug

Albendazole tablet, specification 250mg, Sichuan Qian Xing animal pharmaceutical estate company limited produces, through the product that is up to the standards.

1.3 experimental animals and medication

Choose certain cattle farm and infect the serious cattle 90 of nematicide, be divided into drug test group, drug control group, blank group etc. 3 groups, often organize 30, three groups of test cattle are fed management under similarity condition.

Drug test group: oral albendazole Special-shaped sheet, dosage is 15mg/kg body weight.

Drug control group: oral albendazole sheet, dosage is 15mg/kg body weight.

Blank group: not administration of falling ill.

1.4 test method

The previous day is just carried out egg count to the test cattle manure that primary election infects nematicide serious in test, check worm's ovum number (PEG) contained by every g feces, and by above-mentioned medication administration, each group of 7 days upon administration, 14 days acquisition test cattle manure just carries out egg count, checks worm's ovum number (PEG) contained by every g feces.

1.5 efficacy determination

Negative rate on the egg=(worm's ovum turn out cloudy number of animals/experimental animal number) × 100%.

Redution of eggs=[before (before anthelmintic after PEG-anthelmintic PEG)/anthelmintic PEG] × 100%.

2 result of the tests

Result of the test shows, the expeling rate of albendazole Special-shaped sheet to cattle gastrointestinal nematode parasites reaches 100%, medication after 7 days Negative rate on the egg and Redution of eggs be respectively 86.7% and 98.9%, reach 100% after 14 days, anthelminthic effect is obviously better than drug control group.The results are shown in Table 1, table 2.

Table 1 Redution of eggs (%)

Table 2 Negative rate on the egg (%)

Claims (3)

1. an albendazole bolus, is characterized in that, described albendazole bolus is made up of the component of following percentage by weight:

2. albendazole bolus as claimed in claim 1, it is characterized in that, the specification of described albendazole bolus is 39 × 17 × 9.5mm.

3. the preparation technology of the albendazole bolus as described in any one of claim 1 to 2, is characterized in that, comprise the steps:

A, take starch 10 parts by weight, and take light green 1.13 parts respectively, light blue 0.37 part, add a small amount of water after three's mixing and stir, then add 25 parts of waters for injection, to stir with steam punching in gel, obtain starch slurry for subsequent use;

B, get glucityl beta-schardinger dextrin-25 parts, join in 30 parts of waters for injection, be heated to 60-80 DEG C, after stirring and dissolving, then add albendazole 41.6 parts, under 60-65 DEG C of condition, stir 1.5-2 hour, drying under reduced pressure, to Han Shui Liang≤5%, obtains the glucityl Benexate Hydrochloride of albendazole;

C, dry gained clathrate is positioned in mixer, add Pulvis Talci 10 parts again, after being uniformly mixed 15 minutes, adding starch 6.4 parts, remix 15 minutes, add the starch slurry made in steps A again, be uniformly mixed and be prepared into soft material, granulate, dry grain, add magnesium stearate 0.2 part, aluminium hydroxide 0.3 part mixing granulate, compression molding.