CN106236728A - A kind of oseltamivir phosphate decentralized capsule and preparation method thereof - Google Patents

Abstract

The invention provides an oseltamivir phosphate dispersible capsule and a preparation method thereof. The oseltamivir phosphate dispersible capsule contains 5.0-45.0% oseltamivir phosphate and 0.1%-5.0% sweetener and other pharmaceutically acceptable excipients, wherein the sweetener is sucralose, aspartame or a mixture thereof. The oseltamivir phosphate dispersible capsules provided by the present invention can be added to fluid food and taken together, and are suitable for infants or children. At the same time, the capsules have good taste, good stability, and are easy to carry and store. On the other hand, the present invention also provides a method for preparing the oseltamivir phosphate dispersed capsules, which is safe, easy to operate and suitable for industrial production.

Description

A kind of oseltamivir phosphate dispersed capsule and preparation method thereof

technical field

The invention relates to the field of pharmaceutical preparations, in particular to a oseltamivir phosphate dispersed capsule and a preparation method thereof.

Background technique

Oseltamivir phosphate, chemical name (-)-(3R,4R,5S)-4-acetamide-5-amino-3-(1-ethylpropoxy)cyclohexene-1-carboxylate ethyl ester phosphate. The chemical structural formula is as follows:

Developed and launched by Roche, Switzerland, oseltamivir phosphate has strong neuraminidase inhibitory activity and is effective against influenza A and B viruses. Information on its properties and preparation methods are disclosed in WO 1998007685 A1 and WO1996026933 A1 .

The currently marketed dosage forms of oseltamivir phosphate include granules, capsules, and dry suspensions. Granules or dry suspensions are suitable for preparation into liquid preparations before use, which is convenient for the elderly, children and people who are not suitable for swallowing. However, oseltamivir phosphate is a drug with a particularly bitter taste, so its pharmaceutical composition is difficult to swallow.

Chinese patent CN 101389323 B discloses a pharmaceutical composition, which contains excipients and oseltamivir phosphate, wherein the excipients are selected from the group with an equilibrium moisture content of 1% by weight or less at 25°C and a relative humidity of 70%. One or more kinds of sugar and sugar alcohol, and the content of glucose and mannose contained in the sugar and sugar alcohol are each 0.01% by weight or less. In order to suppress the bitter taste of the pharmaceutical composition, a large amount of sweeteners (such as sucrose or stevia extract) are also added in the invention to cover the bitter taste.

Chinese patent CN 1820774 B discloses a oseltamivir phosphate granule and its preparation method, the granule contains 1.97-19.8% by weight of oseltamivir phosphate, 75.0-97.5% by weight of diluent, 0.1-5.0 % by weight binder, and 1.0-5.0% by weight of food flavor, sweetener and/or food coloring.

Contents of the invention

Summary of the invention

In the prior art described above, sweeteners such as sucrose, stevia extract and sodium saccharin are used in the disclosed examples, but after these disclosed sweeteners are used in combination with oseltamivir phosphate, although they can The bitter taste of oseltamivir phosphate is masked, but it will affect the stability of oseltamivir phosphate in the prescription, resulting in rapid growth of impurities in the oseltamivir phosphate composition, which is not conducive to the long-term storage and safe use of the drug.

The invention provides a dispersible capsule of oseltamivir phosphate, which is different from ordinary oral capsules. The dispersible capsule of oseltamivir phosphate can add the contents of the capsule to fluid food (juice, milk, etc.) , jam, etc.) taken together, can be a good solution to children's drug problems. However, oseltamivir phosphate has a very bitter taste, and it is unacceptable for children to mix it with fluid food directly. Therefore, it is necessary to add an appropriate taste-masking agent while ensuring the stability of the oseltamivir phosphate dispersible capsules. Therefore, it is worth looking forward to seeking a prescription for oseltamivir phosphate that is good in taste, easy to carry and excellent in stability and is convenient for children to use.

The present inventors have found a dispersible capsule of oseltamivir phosphate with good taste, portability and excellent stability after sufficient research on the crystal form of oseltamivir phosphate and through many experiments and explorations. Since the dispersible capsules are mainly used for children by mixing the medicine in the capsules with fluid food, it is very necessary to mask the taste of the dispersible capsules. Very unexpectedly, the present invention found that when using sucralose or aspartame as sweetener, the taste of oseltamivir phosphate dispersible capsules can be effectively corrected, and at the same time, it has excellent stability.

Here, one aspect of the present invention provides a dispersible capsule of oseltamivir phosphate;

Another aspect provides a preparation method for preparing the oseltamivir phosphate dispersible capsules.

Definition of Terms

"%" in the present invention refers to mass percentage unless otherwise specified.

"RRT" in the present invention refers to the relative retention time in chromatographic analysis and detection unless otherwise specified.

"v/v" in the present invention refers to the volume ratio unless otherwise specified.

The specific numerical values involved in the present invention refer to the numerical values ±5%.

Detailed description of the invention

The invention provides a dispersible capsule of oseltamivir phosphate, which contains oseltamivir phosphate, a sweetener and other pharmaceutically acceptable excipients, wherein the sweetener is sucralose or aspartame sweet.

The present invention also provides a dispersible capsule of oseltamivir phosphate, which contains oseltamivir phosphate, a sweetener and other pharmaceutically acceptable excipients, wherein the sweetener is sucralose, aspirin Batam or mixtures thereof.

Wherein the content of the oseltamivir phosphate is 5.0%-45.0%, and the content of the sweetener is 0.1%-5.0%.

The content of oseltamivir phosphate described therein is 30 mg, 45 mg or 75 mg, calculated according to oseltamivir.

The pharmaceutically acceptable auxiliary materials mentioned therein can be one or more of fillers, binders, disintegrants, glidants, lubricants, pH regulators and food flavors.

The fillers described therein can be, but are not limited to, lactose, microcrystalline cellulose, mannitol, sorbitol, maltitol, xylitol, corn starch, dextrin, maltodextrin, pregelatinized starch, sucrose and gelatin. one or more of. Wherein preferred one or more in sorbitol, maltitol or mannitol.

The binder described therein can be but not limited to one of methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, povidone, microcrystalline cellulose and low-substituted hydroxypropylcellulose species or several. Of these, hydroxypropylmethylcellulose or povidone is preferred.

The disintegrant described therein can be but not limited to one or more of croscarmellose sodium, crospovidone, sodium carboxymethyl starch, corn starch and low-substituted hydroxypropyl cellulose . Among them, croscarmellose sodium or crospovidone is preferred.

The glidant mentioned therein can be, but not limited to, colloidal silicon dioxide or talc or a mixture thereof.

The lubricant described therein may be but not limited to sodium stearate fumarate, magnesium stearate, calcium stearate, zinc stearate, sucrose stearate, hydrogenated vegetable oil, stearic acid, colloidal dioxide One or more of silicon, talc and polyethylene glycol 6000. Among them, sodium stearate fumarate is preferred.

Wherein said pH adjuster can be but not limited to the mixture of citric acid and its hydrate and its pharmaceutically acceptable salt, dihydrogen citrate alkali metal salt, sodium lactate or sodium succinate, preferably monohydrate citric acid and sodium citrate combination.

The food flavor described therein can be but not limited to one or more of peach flavor, sweet orange flavor, strawberry flavor, cream flavor, apple flavor, pineapple flavor and banana flavor. Wherein preferred peach essence or sweet orange essence.

In some embodiments, the oseltamivir phosphate dispersible capsules of the present invention comprise 10.0%-40.0% oseltamivir phosphate, 0.5%-5.0% sweetener and other pharmaceutically acceptable excipients, wherein The sweetener is sucralose or aspartame.

In some embodiments, the oseltamivir phosphate dispersible capsules of the present invention comprise 10.0%-40.0% oseltamivir phosphate, 0.5%-5.0% sweetener and other pharmaceutically acceptable excipients, wherein The sweetener is sucralose, aspartame or a mixture thereof.

In some embodiments, the oseltamivir phosphate dispersible capsules of the present invention comprise 10.0%-40.0% oseltamivir phosphate, 45.0%-85.0% filler, and 0%-5.0% disintegration Agent, 1.0%~4.0% binder, 0.5%~5.0% sweetener, 0.5%~5.0% pH regulator, 0.5%~2.0% lubricant, 0.2%~2.0% glidant , can further contain 0.1%-1.0% food flavor, wherein the sweetener is sucralose or aspartame.

In some embodiments, the oseltamivir phosphate dispersible capsules of the present invention comprise 10.0%-40.0% oseltamivir phosphate, 45.0%-85.0% filler, and 0%-5.0% disintegration Agent, 1.0%~4.0% binder, 0.5%~5.0% sweetener, 0.5%~5.0% pH regulator, 0.5%~2.0% lubricant, 0.2%~2.0% glidant , can further contain 0.1%-1.0% food flavor, wherein the sweetener is sucralose, aspartame or a mixture thereof.

In some embodiments, the oseltamivir phosphate dispersible capsules of the present invention comprise 10.0%-40.0% oseltamivir phosphate, 45.0%-85.0% filler, and 0%-5.0% disintegration Agent, 1.0%~4.0% binder, 0.5%~5.0% sweetener, 0.5%~5.0% pH regulator, 0.5%~2.0% lubricant, 0.2%~2.0% glidant , can further contain 0.1% to 1.0% food flavor; wherein the filler is one or more of mannitol, sorbitol and maltitol, and the disintegrant is cross-linked sodium carboxymethyl cellulose or cross-linked sodium carboxymethyl cellulose Lipovidone, binder is povidone or hypromellose, sweetener is sucralose or aspartame, pH regulator is a mixture of citric acid monohydrate and sodium citrate, lubricant It is sodium stearate fumarate, the glidant is talcum powder or colloidal silicon dioxide, and the food flavor is peach flavor or sweet orange flavor.

In some embodiments, the oseltamivir phosphate dispersible capsules of the present invention comprise 10.0%-40.0% oseltamivir phosphate, 45.0%-85.0% filler, and 0%-5.0% disintegration Agent, 1.0%~4.0% binder, 0.5%~5.0% sweetener, 0.5%~5.0% pH regulator, 0.5%~2.0% lubricant, 0.2%~2.0% glidant , can further contain 0.1% to 1.0% food flavor; wherein the filler is one or more of mannitol, sorbitol and maltitol, and the disintegrant is cross-linked sodium carboxymethyl cellulose or cross-linked sodium carboxymethyl cellulose Lipovidone, the binder is povidone or hydroxypropylmethylcellulose, the sweetener is sucralose, aspartame or a mixture thereof, the pH adjuster is a mixture of citric acid monohydrate and sodium citrate , the lubricant is sodium stearate fumarate, the glidant is talcum powder or colloidal silicon dioxide, and the food flavor is peach flavor or sweet orange flavor.

In some embodiments, the oseltamivir phosphate dispersible capsules of the present invention comprise 10.0%-40.0% oseltamivir phosphate, 45.0%-85.0% filler, 0%-5.0% cross-linking Sodium carboxymethylcellulose, 1.0%-4.0% povidone, 0.5%-3.0% sucralose, 0.5%-5.0% mixture of citric acid monohydrate and sodium citrate, 0.5%-2.0% stearin Sodium fumarate, 0.2%-2.0% talcum powder and 0.1%-1.0% peach essence; wherein the filler is one or more of sorbitol, mannitol and maltitol.

In some embodiments, the oseltamivir phosphate dispersible capsules of the present invention comprise 10.0%-40.0% oseltamivir phosphate, 45.0%-85.0% sorbitol and maltitol, 0%-5.0% Crospovidone, 1.0%~4.0% hypromellose, 1.0%~3.0% aspartame, 0.5%~5.0% mixture of citric acid monohydrate and sodium citrate, 0.5%~2.0% Sodium stearate fumarate, 0.2% to 2.0% colloidal silicon dioxide and 0.1% to 1.0% peach essence.

On the other hand, the present invention also provides a kind of preparation method for preparing described oseltamivir phosphate dispersible capsule, described method comprises the following steps:

a) respectively adding oseltamivir phosphate, filler, disintegrant, binder and pH regulator into a granulation pot and premixing uniformly to prepare a premix;

b) dissolving the sweetener in purified water to prepare a granulation solution, the purified water accounting for 17.0% to 23.0% of the premix;

c) adding the granulation liquid to the pre-mixture for wet granulation, drying and sieving to obtain dry granules;

d) Then add a lubricant and a glidant to the dry granules, mix them evenly, and prepare them into capsules.

Wherein, in the step d) of the preparation method, food essence or sweetener and essence can also be added to the dry granules, mixed evenly, and prepared into capsules.

detailed description

In order to enable those skilled in the art to better understand the technical solutions of the present invention, some non-limiting examples are further disclosed below to further describe the present invention in detail.

The reagents used in the present invention can be purchased from the market or can be prepared by the methods described in the present invention.

Example 1

Preparation prescription:

Preparation

The batch size is 1.5kg, which is 6000 capsules according to the 75mg specification. Add oseltamivir phosphate, sorbitol, maltitol, croscarmellose sodium, povidone, citric acid monohydrate, and sodium citrate into the granulation pot and pre-mix evenly according to the prescription amount. Dissolving the sucralose in the proportion of the prescription in the water accounting for 17%-23% of the premix to obtain a granulation solution, which is added into the granulation solution by a peristaltic pump for granulation; dried by a fluidized bed, and then passed through a sieve for granulation. In the dry granules, add talc, sodium stearate fumarate and peach flavor, mix well. Fill the blended granules into the capsule shell, fill 250 mg blended granules with a specification of 75 mg, fill 150 mg blended granules with a specification of 45 mg, and fill 100 mg blended granules with a specification of 30 mg to obtain a dispersed capsule.

Example 2

Preparation prescription:

Element content Oseltamivir Phosphate 39.40% Sorbitol 24.40% Maltitol 24.40% Crospovidone 2.00% Sodium citrate 3.00% Citric Acid Monohydrate 1.00% Hypromellose 2.00% aspartame 2.00% talcum powder 0.50% Sodium stearate fumarate 1.00% Peach Essence 0.30%

Prepare with reference to the preparation method of Example 1

Example 3

Preparation prescription:

Prepare with reference to the preparation method of Example 1

Example 4

Preparation prescription:

Element content Oseltamivir Phosphate 39.40% Mannitol 45.30% Croscarmellose Sodium 2.00% Sodium citrate 4.00% Citric Acid Monohydrate 0.80% Sucralose 5.00% povidone 2.00% talcum powder 0.50% Sodium stearate fumarate 1.00%

Prepare with reference to the preparation method of Example 1

Example 5

Preparation prescription:

Prepare with reference to the preparation method of Example 1

Example 6

Preparation prescription:

Element content Oseltamivir Phosphate 14.78% Sorbitol 34.71% Maltitol 34.71% Crospovidone 5.00% Sodium citrate 1.00% Citric Acid Monohydrate 0.30% Sucralose 0.50% povidone 4.00% talcum powder 2.00% Sodium stearate fumarate 2.00% Peach Essence 1.00%

Prepare with reference to the preparation method of Example 1

Example 7

Preparation prescription:

Prepare with reference to the preparation method of Example 1

Example 8

Preparation prescription:

Element content Oseltamivir Phosphate 9.85% Sorbitol 80.55% Crospovidone 3.00% Sodium citrate 0.60% Citric Acid Monohydrate 0.20% povidone 3.00% aspartame 1.00% talcum powder 0.50% Sodium stearate fumarate 1.00% Sweet Orange Flavor 0.30%

Prepare with reference to the preparation method of Example 1

Example 9

Preparation prescription:

Element content Oseltamivir Phosphate 39.40% Mannitol 45.30% Croscarmellose Sodium 2.00% Sodium citrate 4.00% Citric Acid Monohydrate 1.00% Sucralose 4.00% Povidone 2.00% talcum powder 0.50% Sodium stearate fumarate 1.30% Peach Essence 0.50%

Prepare with reference to the preparation method of Example 1

Example 10

Preparation prescription:

Element content Oseltamivir Phosphate 39.40% Mannitol 45.80% Croscarmellose Sodium 2.00% Sodium citrate 4.00% Citric Acid Monohydrate 1.00% Sucralose 2.00% aspartame 2.00% Povidone 2.00% talcum powder 0.50% Sodium stearate fumarate 1.00% Peach Essence 0.30%

Prepare with reference to the preparation method of Example 1

Comparative example 1

Preparation prescription:

Element content Oseltamivir Phosphate 39.40% Sorbitol 23.40% Maltitol 23.40% Croscarmellose Sodium 3.00% Sodium citrate 3.00% Citric Acid Monohydrate 1.00% sodium saccharin 3.00% Povidone 2.00% colloidal silicon dioxide 0.50% Sodium stearate fumarate 1.00% Peach Essence 0.30%

Prepare with reference to the preparation method of Example 1

Comparative example 2

Preparation prescription:

Prepare with reference to the preparation method of Example 1

Comparative example 3

Preparation prescription:

Element content Oseltamivir Phosphate 39.40% Sorbitol 23.40% Maltitol 23.40% Croscarmellose Sodium 3.00% Sodium citrate 3.00% Citric Acid Monohydrate 1.00% stevia 3.00% povidone 2.00% colloidal silicon dioxide 0.50% Sodium stearate fumarate 1.00% Peach Essence 0.30%

Prepare with reference to the preparation method of Example 1

Experimental example 1

The oseltamivir phosphate dispersible capsules obtained in the above-mentioned Examples 1-10 and Comparative Examples 1-3 were subjected to a stability test in accordance with the guidelines for the stability of raw materials and pharmaceutical preparations in Appendix XIX of the Chinese Pharmacopoeia 2010 Edition, and the experimental conditions were as follows:

The samples were packaged in PVC/PVDC-AL aluminum-plastic blister packs; at a temperature of 40°C and a relative humidity of 75%; after the 0th day, the third month, and the sixth month, random inspections were performed to investigate the impurities of the samples.

Analytical detection conditions:

Chromatographic column: Waters Xbridge C8, 5μm, 4.6mm×250mm

Detection wavelength: 207nm

Column temperature: 50°C

Flow rate: 1.2mL/min

Injection volume: 20μL

Running time: about 35min

Post run: 3min.

gradient:

time (min) Mobile phase A, v/v mobile phase B, v/v Mobile phase C, v/v 0 75 15 10 5.0 75 15 10 5.1 60 30 10 35 60 30 10

Mobile phase A: Weigh 6.80 g of potassium dihydrogen phosphate, dissolve it in 1 L of ultrapure water, mix well, adjust the pH to 6.0 with potassium hydroxide, filter with a 0.45 μm water filter, and sonicate.

Mobile Phase B: Methanol

Mobile Phase C: Acetonitrile

The data summary under accelerated stability is as follows:

In Example 1, Examples 3-7, and Example 9, the types and proportions of the fillers were changed, and the prescription ratio of the bulk drug was adjusted; the ratio of the pH regulator was adjusted; the prescription ratio of the sweetener was adjusted; and The influence of flavor on prescription was investigated. The results showed that after 6 months of accelerated conditions, using sucralose as a sweetener prescription, the impurity stability of oseltamivir phosphate dispersible capsules was good, and the compatibility between sucralose and raw materials was good, which brought Unexpected results with other sweeteners.

In Example 2 and Example 8, aspartame was used as the sweetener, and the prescription ratios of raw materials and sweeteners were adjusted in the two prescriptions. The results showed that the prescription of aspartame as the sweetener, The impurity stability of Tasvir dispersible capsules is also very good.

In Example 10, the combination of two sweeteners, aspartame and sucralose, was used. The results showed that the stability of the oseltamivir phosphate dispersed capsules was also good when the two sweeteners were used in combination.

Comparative Example 1, using sodium saccharin as a sweetener, the stability of the accelerated 6-month is poor, and the impurity with RRT=1.43 reaches 0.28% in the accelerated 6-month period, compared to the oseltamivir phosphate in Examples 1-10 Dispersed capsules, impurity growth is too fast, impurity stability is poor.

Comparative example 2, using acesulfame potassium as a sweetener, the stability is poor for 6 months after acceleration, and the impurity with RRT=0.19 and RRT=1.43 increases rapidly under the accelerated condition, and the impurity with RRT=1.43 is 1.48% when accelerated for 6 months . Using acesulfame-K as the sweetener, compared with the oseltamivir phosphate dispersible capsules in Examples 1-10, the impurity increases too fast and the risk of stability is high.

In comparative example 3, using stevioside as a sweetener, the stability was poor for 6 months after acceleration, and the impurity with RRT=0.19 and RRT=1.43 grew faster under accelerated conditions, and the impurity with RRT=1.43 was 0.69% during the 6-month acceleration. Using stevia as the sweetener, compared with the oseltamivir phosphate dispersible capsules of Examples 1-10, the impurity increases too fast and the risk of stability is high.

Experimental example 2

By evaluating the mouthfeel, evaluate the taste-masking effect of the oseltamivir phosphate dispersible capsules prepared in Examples 3-5, 7-8 and Example 10, the specific method is as follows:

Add the oseltamivir phosphate dispersible capsules prepared in Examples 3 to 5, 7 to 8 and Example 10 into 200 mL of milk, test the taste of milk, recruit 25 volunteers, and each volunteer takes it in 6 days For milk with different prescriptions, the order in which each volunteer took milk was randomly arranged. The results of the survey of the subjects are as follows:

According to the taste test, the oseltamivir phosphate dispersible capsules provided in Examples 1-10 can very effectively correct the bitter taste of oseltamivir phosphate, and are easily accepted by the subjects.

In summary, as described in the above examples,

The Oseltamivir Phosphate Dispersible Capsules provided by the present invention have a good mouthfeel, compared with the reference preparation obtained by using sweeteners other than sucralose or aspartame in the comparative example, the impurities are relatively stable during storage It has a good effect on the preservation of drugs and the safety of medication.

The method of the present invention has been described through preferred embodiments, and relevant persons can obviously make changes or appropriate changes and combinations to the methods and applications described herein within the content, spirit and scope of the present invention to realize and apply the technology of the present invention . Those skilled in the art can refer to the content of this article to appropriately improve the process parameters to achieve. In particular, it should be pointed out that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.

Claims (20)

1. an oseltamivir phosphate decentralized capsule, comprises oseltamivir phosphate, sweeting agent and other is pharmaceutically acceptable auxiliary Material, wherein said sweeting agent is sucralose or aspartame.

2. an oseltamivir phosphate decentralized capsule, comprises oseltamivir phosphate, sweeting agent and other is pharmaceutically acceptable auxiliary Material, wherein said sweeting agent is sucralose, aspartame or its mixture.

Oseltamivir phosphate decentralized capsule the most according to claim 1, the content of wherein said oseltamivir phosphate It is 5.0%～45.0%；The content of described sweeting agent is 0.1%～5.0% or 0.5%～5.0%.

Oseltamivir phosphate decentralized capsule the most according to claim 3, wherein said oseltamivir phosphate content is 30mg, 45mg or 75mg, based on Oseltamivir.

Oseltamivir phosphate decentralized capsule the most according to claim 3, wherein said pharmaceutically acceptable adjuvant is One or more in filler, binding agent, disintegrating agent, fluidizer, lubricant, pH adjusting agent and edible essence.

Oseltamivir phosphate decentralized capsule the most according to claim 5, comprises the department of phosphoric acid Austria of 10.0%～40.0% His Wei, the filler of 45.0%～85.0%, the disintegrating agent of 0%～5.0%, the binding agent of 1.0%～4.0%, 0.5%～ The sweeting agent of 5.0%, the pH adjusting agent of 0.5%～5.0%, the lubricant of 0.5%～2.0%, the fluidizer of 0.2%～2.0% Agent, wherein said sweeting agent is sucralose or aspartame.

Oseltamivir phosphate decentralized capsule the most according to claim 6, further comprises the food of 0.1%～1.0% Use essence.

8., according to the arbitrary oseltamivir phosphate decentralized capsule described in claim 5～7, wherein said filler is breast Sugar, microcrystalline Cellulose, mannitol, sorbitol, maltose alcohol, xylitol, corn starch, dextrin, maltodextrin, pregelatinated form sediment One or more in powder, sucrose and gelatin.

9., according to the arbitrary oseltamivir phosphate decentralized capsule described in claim 5～7, wherein said binding agent is methyl In cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvidone, microcrystalline Cellulose and low-substituted hydroxypropyl cellulose One or more.

10., according to the arbitrary oseltamivir phosphate decentralized capsule described in claim 5～7, wherein said disintegrating agent is to hand over One in connection sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, corn starch and low-substituted hydroxypropyl cellulose Or it is several.

11. according to the arbitrary oseltamivir phosphate decentralized capsule described in claim 5～7, and wherein said fluidizer is glue Body silicon dioxide or Pulvis Talci or its mixture.

12. according to the arbitrary oseltamivir phosphate decentralized capsule described in claim 5～7, and wherein said lubricant is hard Fat acid fumaric acid sodium, magnesium stearate, calcium stearate, zinc stearate, sucrose stearate, hydrogenated vegetable oil, stearic acid, colloid two One or more in silicon oxide, Pulvis Talci and polyethylene glycol 6000.

13. according to the arbitrary oseltamivir phosphate decentralized capsule described in claim 5～7, and wherein said pH adjusting agent is Citric acid and the mixture of hydrate salt pharmaceutically acceptable with it, dihydrogen citrate alkali metal salt, sodium lactate or succinic acid Sodium.

14. according to the oseltamivir phosphate decentralized capsule described in claim 5 or 7, and wherein said edible essence is water honey One or more in Fructus Persicae essence, orange flavor, strawberry essence, cream flavour, apple essence, flavoring pineapple essence and flavoring banana essence.

15. 1 kinds of oseltamivir phosphate decentralized capsules, comprise the oseltamivir phosphate of 10.0%～40.0%, 45.0%～ The filler of 85.0%, the disintegrating agent of 0%～5.0%, the binding agent of 1.0%～4.0%, the sweeting agent of 0.5%～5.0%, The pH adjusting agent of 0.5%～5.0%, the lubricant of 0.5%～2.0%, the fluidizer of 0.2%～2.0% and 0.1%～ The edible essence of 1.0%；Wherein said filler is one or more in mannitol, sorbitol and maltose alcohol, disintegrate Agent is cross-linking sodium carboxymethyl cellulose or polyvinylpolypyrrolidone, and binding agent is polyvidone or hydroxypropyl methylcellulose, and sweeting agent is three Chlorine sucrose or aspartame, pH adjusting agent is the mixture of citric acid monohydrate and sodium citrate, and lubricant is stearic acid fumaric acid Sodium, fluidizer is Pulvis Talci or silica sol, and edible essence is peach flavor or orange flavor.

16. 1 kinds of oseltamivir phosphate decentralized capsules, comprise the oseltamivir phosphate of 10.0%～40.0%, 45.0%～ The filler of 85.0%, the cross-linking sodium carboxymethyl cellulose of 0%～5.0%, 1.0%～4.0% polyvidone, 0.5%～3.0% Sucralose, the citric acid monohydrate of 0.5%～5.0% and sodium citrate mixture, the stearic acid richness horse of 0.5%～2.0% Acid sodium, the Pulvis Talci of 0.2%～2.0% and 0.1%～the peach flavor of 1.0%；Wherein said filler be sorbitol, One or more in mannitol and maltose alcohol.

17. 1 kinds of oseltamivir phosphate decentralized capsules, comprise the oseltamivir phosphate of 10.0%～40.0%, 45.0%～ The sorbitol of 85.0% and maltose alcohol, the polyvinylpolypyrrolidone of 0%～5.0%, 1.0%～4.0% hydroxypropyl methylcellulose, The aspartame of 1.0%～3.0%, the citric acid monohydrate of 0.5%～5.0% and sodium citrate mixture, 0.5%～2.0% Sodium stearyl fumarate, the silica sol of 0.2%～2.0% and 0.1%～the peach flavor of 1.0%.

The method of the oseltamivir phosphate decentralized capsule that 18. 1 kinds are prepared described in claim 6, comprises the following steps:

A) oseltamivir phosphate, filler, disintegrating agent, binding agent and pH adjusting agent are joined in granulation pot be mixed in advance respectively Even, prepare premix；

B) sweeting agent is dissolved in purified water preparation granulation liquid, and described purified water accounts for the 17.0%～23.0% of premix；

C) granulation liquid is joined in premix and carry out wet granulation, and carry out dried and screened granulate, it is thus achieved that be dried granule；

D) in dry granule, then add lubricant and fluidizer, mix homogeneously, be prepared as capsule；

Wherein said sweeting agent is sucralose or aspartame.

The method of 19. 1 kinds of arbitrary oseltamivir phosphate decentralized capsules prepared described in claim 15～17, including following Step:

A) oseltamivir phosphate, filler, disintegrating agent, binding agent and pH adjusting agent are joined in granulation pot be mixed in advance respectively Even, prepare premix；

B) sweeting agent is dissolved in purified water preparation granulation liquid, and described purified water accounts for the 17.0%～23.0% of premix；

C) granulation liquid is joined in premix and carry out wet granulation, and carry out dried and screened granulate, it is thus achieved that be dried granule；

D) in dry granule, then add edible essence, lubricant and fluidizer, mix homogeneously, be prepared as capsule；

Wherein said sweeting agent is sucralose or aspartame.

20. methods according to claim 19, wherein said d) step is then to add edible perfume in dry granule Essence, lubricant, sweeting agent and fluidizer, mix homogeneously, it is prepared as capsule.