CN115177595A

CN115177595A - Oxagolide sodium tablet and preparation method thereof

Info

Publication number: CN115177595A
Application number: CN202210788466.7A
Authority: CN
Inventors: 谢俊; 黄彦博; 黄春玉; 刘文一; 李剑
Original assignee: Jinling Pharmaceutical Co ltd
Current assignee: Jinling Pharmaceutical Co ltd
Priority date: 2022-07-06
Filing date: 2022-07-06
Publication date: 2022-10-14

Abstract

The invention discloses an oxa-rogue sodium tablet which takes oxa-rogue sodium as a medicine or an active ingredient and a pharmaceutical excipient containing a super disintegrantMixing the compositions, granulating, tabletting and/or coating to obtain tablets suitable for oral administration; the super disintegrant is selected from one or more of croscarmellose sodium, sodium carboxymethyl starch, crospovidone and low-substituted hydroxypropyl cellulose. The selected super-disintegrant not only has super-strong disintegration and anticoagulation, but also can overcome the phenomena of fusion, sticking and the like of granules containing the oxagoril sodium caused by high-speed tabletting; the super disintegrant has no carbonate ion, and can not be orally taken

When the carbonate meets gastric acid, a large amount of carbon dioxide is instantaneously generated to bring side effects or adverse reactions such as flatulence and the like; the oxagolide sodium tablet is hardly influenced by the acidity in the stomach, and the dissolution curve is stable.

Description

Oxagolide sodium tablet and preparation method thereof

Technical Field

The invention belongs to the field of pharmacy, and mainly relates to an oxa-lagog natrium tablet and a preparation method thereof.

Background

Oxagolide sodium (Elagolix, CAS number: 832720-36-2) is a gonadotropin releasing hormone (GnRH) antagonist developed by Albvie corporation, and is mainly used for clinically relieving symptoms of uterine myoma, endometriosis and the like of adult women.

In the development of oral tablets of oxalagril sodium, albervol company found that there were at least two problems (CN 11169892A, CN 111246850A): 1. when the loracarbef sodium is orally applied in a solid dosage form, gel formation is prone to happen, particularly when the solid preparation does not contain proper anti-gelling agents, the gel formation is prone to happen, the formed gel limits the dissolution of the loracarbef sodium, and finally, the bioavailability of the loracarbef sodium among patients and in the patients can be greatly changed; 2. oxalagrol sodium may degrade to form compounds with lactam structures. The pharmaceutical composition of the sodium oxagolide + sodium carbonate can reduce the gel formation of the sodium oxagolide and/or reduce the generation of lactam degradation products, so as to maintain the safety and efficacy of the product.

Aiming at the 'two problems' in CN 1116988992A and CN111246850A and a solution thereof, the Aibervis company develops an oxalago natrium tablet:

(150mg、200mg)。

the inventors have determined that by looking up the physicochemical properties of loracarbef sodium and its Biopharmaceutical Classification System (BCS) and listing them in table 1: (1) The oxagolide sodium is low-melting-point amorphous powder, and is easy to melt and stick when heated (50-60 ℃); (2) the oxalagogrel sodium is a BCS III medicament: high solubility, low permeability, i.e. the solubility of oxa-degril sodium is high and independent of the pH of the physiological medium in the gastrointestinal tract, but its absorption is limited (low permeability or low absorption of the drug). Therefore, in the pharmaceutical field, the pharmaceutical excipients which may interfere with the absorption of the low-permeability or low-absorption drug of oxadegril sodium, such as polyols (mannitol, sorbitol, polyethylene glycol) and surfactants, should be avoided as much as possible as the formulation components; (3) In pharmacy, the bioavailability of low-absorption medicines in a human body is often highly variable.

Table 1: physicochemical Properties and Biopharmaceutical Classification System (BCS) of Oxagolide sodium

The inventor inquires through

The bioavailability and the coefficient of variation of oxagoril sodium in the specification are shown in table 2. The inventors further determined based on table 2: oxa-rogine sodium is a low permeability or low absorption drug and has a large variability in bioavailability (20-30%). Thus, in oxa-rogatide sodiumIn the prescription composition of the tablet, the addition of pharmaceutical excipients which interfere with the absorption of the oxadegril sodium, such as polyols (mannitol, sorbitol, polyethylene glycol), surfactants and the like, should be avoided as much as possible.

Table 2: is administered orally

Is of high bioavailability

Biopharmaceutical parameters	Oxagoli sodium (Elagolix)
		Bioavailability of the active ingredient	30％～50％
Coefficient of Variation (CV)	20％～30％

The inventor inquires through

The compositions of the prescription listed in the specification are subjected to reverse quantitative analysis, and the mass fractions of the compositions of the prescription are listed in Table 3.

Table 3:

prescription composition, mass fraction and prescription analysis thereof

Prescription composition	Mass fraction (%)	Prescription analysis
			Oxagolide sodium salt	35	Medicine (active ingredient)
Sodium carbonate	17	Alkaline auxiliary material, disintegrant and anticoagulant
			Mannitol	34	Excipient
Pregelatinized starch	10	Excipient and disintegrant
			Povidone	3	Adhesive agent
Magnesium stearate	1	Lubricant agent

The inventors can determine based on table 3: (1) In

In the prescription composition, the key auxiliary material is sodium carbonate which can overcome the defect of oxa-roglyme sodium in CN 1116988992A and CN111246850A"at least two problems" of "the pharmaceutical composition, but in the pharmaceutical composition, sodium carbonate is not only used to overcome" at least two problems "of" oxa-goril sodium; (2) In the pharmacy, mannitol is often used as an excipient for dry granulation and tabletting, but mannitol is a pharmaceutically accepted interference; (3) In pharmacy, mannitol possibly influences the absorption of low-permeability medicines, and is commonly recognized in the industry, and if mannitol is required to be used in the prescription composition, the dosage is controlled to be the minimum dosage; (4) Pharmaceutically, povidone is commonly used as a binder, with povidone K30 being the most commonly used type. (5) Magnesium stearate is a commonly used hydrophobic lubricant in pharmacy; if the mass fraction of magnesium stearate in the prescription composition is too large (> 1%), the hardness of the tablet and the dissolution of the drug may be affected; (6) From, to

The characteristics of various auxiliary materials selected in the prescription composition can be presumed, and the product is prepared by dry granulation and tabletting.

Disclosure of Invention

In pharmacy and the prescription composition of tablets, besides medicaments or active ingredients, the pharmaceutical composition generally also comprises other functional pharmaceutical excipients: disintegrants, excipients (diluents, fillers), binders, lubricants, and the like.

The disintegrant is a pharmaceutical excipient which rapidly disintegrates in an aqueous medium, thereby rapidly dissolving the drug. In the pharmacy, except for the slow-release tablets or the tablets with certain special purposes, the components of the tablet prescription are provided with a certain mass fraction (2-10%) of disintegrant.

Disintegrating agents are generally classified into general disintegrating agents and super disintegrating agents according to the strength of the disintegrating ability. Common disintegrating agents mainly include dry starch, sugar powder, effervescent disintegrating agent (sodium carbonate, sodium bicarbonate, or citric acid, tartaric acid), etc.; the common super disintegrant is mainly croscarmellose sodium (CCMC-Na), sodium carboxymethyl starch (CMS-Na), crospovidone (PVPP), low substituted hydroxypropyl cellulose (L-HPC), etc.

The main mechanism of action of the disintegrant is: (1) Capillary action, namely when the tablet meets an aqueous medium, the disintegrant enables water to rapidly enter the inside of the tablet through capillary action, so that the whole tablet is broken up; (2) The disintegrating agent has water absorption expansibility, so that the binding force of the tablet is damaged and the tablet is disintegrated; (3) The tablet has gas generating effect, if sodium carbonate, sodium bicarbonate and/or citric acid, tartaric acid and other auxiliary materials are added into the tablet prescription, when the tablet meets gastric acid and/or water, carbon dioxide is generated, so that the volume of the tablet is expanded and the tablet is disintegrated.

Excipients are pharmaceutical excipients that form the basic skeleton of a tablet. Common excipients include starch, microcrystalline cellulose, lactose, mannitol, inorganic salts, and the like.

The adhesive is a pharmaceutical excipient which is prepared by bonding raw and auxiliary material powder into granules so as to facilitate tabletting. The adhesive can be liquid (wetting agent), and commonly used is water, ethanol-water and the like; or solid powder, which often also has the functions of excipient and/or disintegrant, such as hypromellose, hyprolose, povidone, gelatin, sodium alginate, etc.

The lubricant is a pharmaceutical excipient for improving the flowability of the prescription composition. The commonly used lubricant comprises magnesium stearate, calcium stearate, talcum powder, micro silica gel, sodium dodecyl sulfate, hydrogenated vegetable oil, etc.

The invention aims to solve the two problems of CN 1116988992A and CN111246850A, and is different from the problems

The prescription measures of (1): (1) By using super disintegrant instead of

The effervescent disintegrant in the prescription composition overcomes at least two problems existing in the oxalagril sodium in CN 1116988992A and CN 111246850A; (2) Replacement with non-polyol excipients

The excipient mannitol in the prescription composition can remove the possibly influenced absorption of the loragol sodium to the maximum extentCollecting auxiliary materials; and/or (3) replacement of talc powder by hydrophilic lubricant

The hydrophobic lubricant magnesium stearate in the prescription composition overcomes the defects caused by excessive magnesium stearate.

The purpose of the invention is realized by the following technical scheme:

the tablets are tablets suitable for oral administration, which are prepared by mixing oxagolide sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super-disintegrant and then granulating, tabletting and/or coating.

The mass ratio of the oxalagril sodium to the super-disintegrant is 35-35, preferably 35-35.

In the oxa-rogue sodium tablet, the mass fraction of the oxa-rogue sodium is 35%.

The pharmaceutical excipient composition of the present invention refers to a powder which is used in the production of a drug or the formulation of a prescription, has been reasonably evaluated in terms of safety, and contains no biological activity in a pharmaceutical preparation, in addition to a drug or an active ingredient.

The pharmaceutical adjuvant composition comprises super disintegrant, excipient, adhesive, lubricant, etc. The pharmaceutical adjuvant composition does not contain excipients which are possibly influencing the absorption of the oxadiargyl sodium in the gastrointestinal tract, such as mannitol, sorbitol, polyethylene glycol, surfactants and the like, and does not contain lubricants which are possibly influencing the tabletting of the oxadiargyl sodium, such as magnesium stearate, calcium stearate, hydrogenated vegetable oil and the like.

The super disintegrant is selected from one or more of croscarmellose sodium (CCMC-Na), sodium carboxymethyl starch (CMS-Na), crospovidone (PVPP) and low-substituted hydroxypropyl cellulose (L-HPC), preferably one or more of croscarmellose sodium, sodium carboxymethyl starch or crospovidone having the same cation as that of sodium oxarogrel, and more preferably croscarmellose sodium. The super disintegrant with the same cation as the oxalaggrin sodium is selected, so that the stability of the oxalaggrin sodium is facilitated.

The mass fraction of the super disintegrant is 1-20%, preferably 10-20%, more preferably 12-18%.

The excipient is selected from one or more of microcrystalline cellulose, starch, lactose, inorganic salt and the like, and is preferably one or the combination of microcrystalline cellulose and starch.

The mass fraction of the excipient is 25-40%.

The adhesive is selected from one or more of water, ethanol water, pregelatinized starch, povidone, hydroxypropyl cellulose, gelatin, sodium alginate, powdered sugar and the like, preferably one or more of pregelatinized starch, povidone and hydroxypropyl methylcellulose, more preferably one or a combination of two of pregelatinized starch and povidone K30, and when the adhesive is the combination of pregelatinized starch and povidone K30, the mass ratio of the pregelatinized starch to the povidone K30 is 10-10.

The mass fraction of the adhesive is 10-25%.

The lubricant is selected from one or more of talcum powder, superfine silica gel powder, magnesium stearate, calcium stearate and the like, preferably the talcum powder and the superfine silica gel powder, and more preferably the talcum powder.

The mass fraction of the lubricant is 1-3%.

As a more specific technical scheme of the oxa-goril sodium tablet, the oxa-goril sodium tablet is prepared by mixing oxa-goril sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super disintegrant, and then granulating and tabletting the mixture to prepare the tablet suitable for oral administration; the mass fraction of the raw and auxiliary materials is as follows, and the total amount of the raw and auxiliary materials is 100%:

as another more specific technical scheme of the oxa-gol sodium tablet, the invention provides the oxa-gol sodium tablet which is a coated tablet suitable for oral administration and prepared by mixing oxa-gol sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super-disintegrant, and then granulating, tabletting and coating; the mass fraction of the raw and auxiliary materials is as follows, and the total mass of the raw and auxiliary materials is 100%:

the coating material is selected from

Premixing common coating powder, specifically selected from

85F630048-CN，

85F640105-CN; the mass fraction of the coating material is 2-3%. The oxagoril sodium coated tablet is prepared by adopting common coating equipment to carry out conventional operation.

Another object of the present invention is to provide a method for preparing the oxalagrol sodium tablet, which comprises: crushing the raw material drug of the oxagoril sodium, sieving the crushed raw material drug with a 80-mesh sieve, and sieving the medicinal auxiliary material with the 80-mesh sieve; weighing raw and auxiliary materials according to the prescription, mixing, granulating and tabletting to obtain the oxa-gol natrium tablet.

The granulation is dry granulation or wet granulation.

As a further preferable technical scheme of the preparation method of the present invention, the tablets further comprise a coating, and the tablets are coated with the oxagoril sodium, which is suitable for oral administration.

And with

In contrast, the present inventionThe oxagoid sodium tablet can at least obtain the following beneficial effects:

(1) Besides the super-strong disintegration and anticoagulation effects, the selected super-disintegrant can overcome the phenomena of fusion, sticking and the like of granules containing the oxagoli sodium caused by high-speed tabletting, so that the continuous and smooth production of tablets is facilitated, and the uniformity and the attractiveness of the content of the tablets can be increased.

(2) The selected super disintegrating agent has no carbonate ions, and oral administration can not occur

When the carbonate meets gastric acid, a large amount of carbon dioxide is instantaneously generated to bring side effects or adverse reactions such as flatulence and the like.

(3) When the patient takes the medicine before or after meals, the acidity in stomach is different

Contains sodium carbonate with a mass fraction of about 17 percent

The different rates of disintegration, thus causing the different dissolution rates of oxalagogrel, and the variability of the curative effect of the patients or among the patients; the oxalagogelix sodium tablet is hardly influenced by the acidity in the stomach, and the dissolution curve is stable.

(4) The formula of the oxalagrol sodium tablet of the invention does not contain

The highest amount of mannitol (mass fraction: 37%, table 3) in the formulation composition, so as to avoid as much as possible interfering with formulation factors of BCS class III, sodium oxalagonate absorbed in the intestinal tract.

(5) The invention is to

The hydrophobic lubricant magnesium stearate in the prescription composition is replaced by the hydrophilic lubricant talcum powder, so that the problem of hardness in the granulating process can be avoidedLoose particles and difficult tabletting caused by excessive magnesium stearate or uneven mixing.

(6) The preparation method of the oxalago sodium tablet is simple in steps and high in yield.

Drawings

FIG. 1 is an electron micrograph of granules obtained by dry granulation in example 1.

Fig. 2 is a microscopic view of the granules obtained by dry granulation in example 1.

Fig. 3 is a micrograph of the oxarogatide sodium tablet of example 1 after standing for 1 hour in 0.1mol hydrochloric acid.

Fig. 4 is a dissolution profile of the oxalagogelix sodium tablets of example 1 at various phs.

Fig. 5 is an electron micrograph of granules prepared by wet granulation in example 2.

Fig. 6 is a microscopic image of the granules obtained by wet granulation in example 2.

Fig. 7 is a micrograph of the oxarogatide sodium tablet of example 2 left to stand in 0.1mol hydrochloric acid for 1 hour.

Fig. 8 is a dissolution profile of the oxalagonidine sodium tablets of example 2 at various phs.

Fig. 9 is a dissolution profile of the oxalagrol sodium tablet of example 3.

Fig. 10 is a dissolution profile of the oxalagrol sodium tablet of example 4.

Fig. 11 is a dissolution profile of the oxalagrol sodium tablet of example 5.

Fig. 12 is a dissolution profile of the oxalagrol sodium tablet of example 6.

Detailed Description

In order to make the technical solution of the present invention more clearly understood, the technical solution of the present invention is further described in detail with reference to specific examples, but the examples of the present invention are not to be construed as limiting the scope of the present invention.

Tablet manufacturing equipment: the device comprises a grinder, a mixer, a dry-method granulator, a swing-type granulator, an air-blast drying box, a rotary tablet press and a high-efficiency coating machine.

Example 1

Prescription:

the lorago sodium tablet of the embodiment is prepared by a dry granulation method, and the steps are as follows:

step (1), pretreatment: crushing the sodium oxalagogride, and sieving the crushed sodium oxalagogride with a 80-mesh sieve; sieving the auxiliary materials with a 80-mesh sieve;

step (2), weighing: weighing raw and auxiliary materials according to the prescription amount;

step (3), granulating: putting the oxalagogrel sodium, the croscarmellose sodium, the microcrystalline cellulose, the pregelatinized starch and the povidone K30 into a mixer, mixing, performing dry granulation by using a dry granulator according to the process shown in Table 4, observing particles by using a scanning electron microscope (model: flexSEM-1000-II), wherein an electron microscope picture of the particles is shown in figure 1, and observing the particles by using a microscope (model: XSP-200X), and a micrographic picture of the particles is shown in figure 2;

table 4: dry granulation process parameters

Granulating process	Granulation parameters
		Speed of filling	6.00HZ
Speed of sheet pressing	10.00HZ
		Speed of granulation	20.00HZ
Mesh aperture	14 mesh

Step (4), total mixing: mixing the granules prepared in the step (3) with talcum powder;

step (5), tabletting: adding the totally mixed materials into a rotary tablet machine, adjusting the loading (450 mg) and tabletting (8-10 kg of hardness) to obtain the oxagoril tablet.

The oxalagrol sodium tablet of this example was left to stand in 0.1mol hydrochloric acid for 1 hour, and the micrograph is shown in fig. 3.

Dissolution test method: according to the technical guideline for dissolution test of common oral solid preparation and determination method of dissolution rate and release rate (0931 of the four-part general rule of 2020 edition of Chinese pharmacopoeia), hydrochloric acid solution with pH of 1.2, citrate buffer solution with pH of 4.5, phosphate buffer solution with pH of 6.8 and purified water are respectively used as dissolution media, the volume of the dissolution media is 900ml, the rotating speed is 50rpm, samples are respectively taken at 5, 10, 15, 20, 25, 30 and 45min, the absorbance (n = 6) is determined at the wavelength of ultraviolet 274nm, the dissolution curve is shown in figure 4, and it can be seen that the dissolution of the sodium loratadine in the sodium loratadine tablet is hardly influenced by pH, and the dissolution curve (pH of 1.2, 4.5, 6.8 and purified water) is stable.

The influence factor test results are shown in table 5, and it can be seen from table 5 that the amount of the oxalagrilamide impurities is not increased.

Table 5: experimental results of influencing factors

Conditions of	Theeragolide lactam%	Maximum unknown impurity%	Total impurities%
				Day
0	0.01	0.03	0.04
				60 ℃ for 10 days	0.01	0.03	0.04
4500LX + -500LX for 10 days	0.01	0.03	0.04
				45 ℃ and 75% RH for 10 days	0.01	0.03	0.05

Example 2

Prescription:

the lorago sodium tablet of the embodiment is prepared by a wet granulation method, and the steps are as follows:

step (3), slurry preparation: dissolving polyvidone K30 in purified water, and stirring to obtain a pulp solution with polyvidone K30 concentration of 5% (w/w);

step (4), granulating: putting the oxagoril sodium, the croscarmellose sodium, the microcrystalline cellulose and the pregelatinized starch into a mixer, and adding the prepared slurry to prepare a soft material; then placing the soft material in a swing type granulator, granulating (with 14 mesh sieve), drying (< 50 ℃), grading to obtain dry granules, observing the granules by using a scanning electron microscope (model: flexSEM-1000-II), wherein the particle electron microscope picture is shown in figure 5, and observing the granules by using a microscope (model: XSP-200X), and the particle micrograph is shown in figure 6;

step (5), tabletting: and (4) mixing the dry granules prepared in the step (4) with talcum powder, and tabletting (the hardness is 8-10 kg) to obtain the oxa-goril sodium tablet.

The oxalagrol sodium tablet of this example was left to stand in 0.1mol hydrochloric acid for 1 hour and the micrograph is shown in fig. 7.

By observing micrographs of granules (electron micrographs and micrographs) and tablets obtained by dry granulation in example 1 and kept standing in 0.1mol of hydrochloric acid for 1 hour, and micrographs of granules (electron micrographs and micrographs) and tablets obtained by wet granulation in example 2 and kept standing in 0.1mol of hydrochloric acid for 1 hour, there was no difference in sensitivity between them.

The dissolution rate of the loratadine sodium tablet of this example was measured (n = 6) by referring to the dissolution rate measurement method of example 1, and the dissolution curve is shown in fig. 8, and it can be seen that the dissolution rate of loratadine sodium in the loratadine sodium tablet is hardly affected by pH.

The results of the influence factor test are shown in table 6, and it is known that the impurity content of the oxagolide is not increased.

Table 6: experimental results of influence factors

Condition	Theeragolide lactam%	Maximum unknown impurity%	Total impurities%
				Day
0	0.01	0.03	0.04
				60 ℃ for 10 days	0.01	0.03	0.04
4500LX + -500LX for 10 days	0.01	0.03	0.04
				45 ℃ and 75% RH for 10 days	0.01	0.03	0.05

Example 3

Prescription:

the lorago sodium tablet of this example was prepared by dry granulation, which was the same as example 1.

The dissolution of the oxalagrine tablet of this example was measured (n = 6) by the dissolution test method of example 1, and the dissolution curve is shown in fig. 9, and it can be seen that the dissolution of the oxalagrine in the oxalagrine tablet is hardly affected by pH.

The results of the influence factor test are shown in table 7, and it is understood that the impurity content of the oxagolide is not increased.

Table 7: experimental results of influencing factors

Condition	Oxagolide lactam%	Maximum unknown impurity%	Total impurities%
				Day
0	0.01	0.03	0.04
				60 ℃ for 10 days	0.01	0.03	0.04
4500LX + -500LX for 10 days	0.01	0.03	0.04
				45 ℃ and 75% RH for 10 days	0.01	0.03	0.05

Example 4

Prescription:

referring to example 1, an oxaregamide tablet was prepared by a dry granulation method, and the oxaregamide tablet was coated:

preparing a coating solution: taking prescription amount

85F630048-CN, adding purified water to prepare 10% suspension, and continuously stirring;

coating: and (3) putting the oxagoril tablets into a high-efficiency coating pot, and performing conventional coating operation until the coating solution is used up to obtain the oxagoril coated tablets.

The dissolution of the oxalagril sodium-coated tablet of this example was measured (n = 6) by the dissolution test method of example 1, and the dissolution curve is shown in fig. 10, and it can be seen that the dissolution of oxalagril sodium in the oxalagril sodium-coated tablet is hardly affected by pH.

The influence factor test results are shown in table 8, and it can be seen that the amount of the oleanolic amide impurities is not increased.

Table 8: experimental results of influencing factors

Example 5

Prescription:

referring to example 4, an oxalaggrin sodium tablet was prepared by dry granulation, and the oxalaggrin sodium tablet was coated to prepare an oxalaggrin sodium coated tablet.

Referring to the dissolution test method of example 1, the dissolution rate (n = 6) of the loracarbef tablet of this example was measured, and the dissolution curve is shown in fig. 11, and it can be seen that the dissolution of loracarbef sodium in the loracarbef coated tablet was hardly affected by pH.

The results of the influence factor test are shown in table 9, and it is understood that the impurity content of the oxagolide is not increased.

Table 9: experimental results of influence factors

Condition	Theeragolide lactam%	Maximum unknown impurity%	Total impurities%
				Day
0	0.01	0.03	0.04
				60 ℃ for 10 days	0.01	0.03	0.04
4500LX + -500LX for 10 days	0.01	0.03	0.04
				45 ℃ and 75% RH for 10 days	0.02	0.03	0.05

Example 6

Prescription:

referring to example 4, an oxaregamide tablet was prepared by dry granulation, and the oxaregamide tablet was coated to obtain an oxaregamide-coated tablet.

The dissolution rate (n = 6) of the tablets coated with loracarbef of this example was measured by the dissolution rate measurement method of example 1, and the dissolution curve is shown in fig. 12, and it can be seen that the dissolution rate of loracarbef in the tablets coated with loracarbef was hardly affected by pH.

The influence factor test results are shown in table 10, and it is known that the amount of the oleanolic amide impurities is not increased.

Table 10: experimental results of influencing factors

Condition	Oxagolide lactam%	Maximum unknown impurity%	Total impurities%
				Day
0	0.01	0.03	0.04
				60 ℃ for 10 days	0.01	0.03	0.04
4500LX + -500LX for 10 days	0.01	0.03	0.04
				45 ℃ and 75% RH for 10 days	0.02	0.03	0.05

Claims

1. An oxagoril tablet characterized by: the tablet is prepared by mixing the oxadegril sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing the super-disintegrant, and then granulating, tabletting and/or coating the mixture.

2. The oxarogatide tablet according to claim 1, wherein: the mass ratio of the oxalagril sodium to the super-disintegrant is 35-35, preferably 35-35.

3. The oxalagrol sodium tablet of claim 1, wherein: the pharmaceutical adjuvant composition comprises a super disintegrant, an excipient, a binder and a lubricant, but does not contain an excipient which can affect the absorption of the oxa-gol sodium in the gastrointestinal tract and does not contain a lubricant which can affect the tabletting of the oxa-gol sodium.

4. The oxarogine sodium tablet according to claim 1 or 3, characterized in that: the super disintegrant is selected from one or more of croscarmellose sodium, sodium carboxymethyl starch, crospovidone and low-substituted hydroxypropyl cellulose, and preferably one or more of croscarmellose sodium, sodium carboxymethyl starch or crospovidone.

5. The oxalagrol sodium tablet of claim 3, wherein: the excipient is selected from one or more of microcrystalline cellulose, starch, lactose and inorganic salt, preferably one or a combination of microcrystalline cellulose and starch.

6. The oxarogine sodium tablet of claim 3, wherein: the adhesive is selected from one or more of water, ethanol water, pregelatinized starch, povidone, hydroxypropyl cellulose, gelatin, sodium alginate and powdered sugar, preferably one or more of pregelatinized starch, povidone and hydroxypropyl methylcellulose, and more preferably one or a combination of two of pregelatinized starch and povidone K30.

7. The oxalagrol sodium tablet of claim 3, wherein: the lubricant is selected from one or more of talcum powder, superfine silica powder, magnesium stearate and calcium stearate, preferably the talcum powder and the superfine silica powder, and more preferably the talcum powder.

8. The oxalagrol sodium tablet of claim 1, wherein: the coating material is selected from

Premixing common coating powder.

9. The oxalagrol sodium tablet is characterized in that: the tablets are prepared by mixing oxagolide sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super-disintegrant, and then granulating and tabletting; wherein the mass fraction of the raw materials and the auxiliary materials is as follows:

10. the oxagolide sodium tablet is characterized in that: the coated tablet is prepared by mixing oxagolide sodium serving as a medicine or an active ingredient with a pharmaceutical adjuvant composition containing a super-disintegrant, and then granulating, tabletting and coating; wherein the mass fraction of the raw materials and the auxiliary materials is as follows: