CN113069423A

CN113069423A - Baroswarriol orally disintegrating tablet and preparation method thereof

Info

Publication number: CN113069423A
Application number: CN202110002226.5A
Authority: CN
Inventors: 汪志辉; 黄心; 游劲松; 黄芳芳
Original assignee: Sunshine Lake Pharma Co Ltd
Current assignee: Sunshine Lake Pharma Co Ltd
Priority date: 2020-01-04
Filing date: 2021-01-04
Publication date: 2021-07-06
Anticipated expiration: 2041-01-04
Also published as: CN113069423B

Abstract

The invention relates to a baloxavir disoproxil orally disintegrating tablet and a preparation method thereof, belonging to the field of pharmaceutical preparations. The oral disintegrating tablet of the baloxavir disoproxil comprises the baloxavir disoproxil, crospovidone, low-substituted hydroxypropyl cellulose and one or more other auxiliary materials. The preparation method comprises the steps of sieving, mixing, tabletting and the like. The orally disintegrating tablet provided by the invention has the advantages of good compressibility, good taste, moderate hardness, simple preparation process, low cost and good administration compliance, and is beneficial to children, the elderly, bedridden patients and dysphagia patients and people who have difficulty in getting water.

Description

Baroswarriol orally disintegrating tablet and preparation method thereof

Technical Field

The invention relates to the field of pharmaceutical preparations, in particular to a Baroswarriol orally disintegrating tablet and a preparation method thereof.

Background

Baroxavir disoproxil (chemical name { (12aR) -12- [ (11S) -7, 8-difluoro-6, 11-dihydrodibenzo [ b, e ] thiepin-11-yl ] -6, 8-dioxo-3, 4,6,8,12,12 a-hexahydro-1H- [1,4] oxazino [3,4-c ] pyrido [2,1-f ] [1,2,4] triazin-7-yl } oxy) methyl carbonate) is a drug against influenza A and B viruses.

The currently marketed baclofloxacin ester dosage forms mainly comprise tablets and powder, no products are marketed for baclofloxacin ester orally disintegrating tablets, and no patents and documents for baclofloxacin ester orally disintegrating tablets are searched, but the tablets and powder are inconvenient for children, old people, bedridden patients and patients with dysphagia and people who have difficulty in taking water.

The preparation process of orally disintegrating tablets is more, and the common preparation process mainly comprises the following steps: the orally disintegrating tablets prepared by the first three methods have short disintegration time and good taste, but need large-scale equipment such as a freeze dryer and a spray dryer, have more steps and long time consumption, and need organic solvents and the like, so that a series of environmental protection problems are caused while a large amount of labor expenditure is required, and the preparation cost of the orally disintegrating tablets is greatly increased. When the powder direct compression method is used for preparing the orally disintegrating tablets, the process is simple and easy to implement, but the mouth feel of the orally disintegrating tablets is greatly influenced by the flowability, compressibility and the like of auxiliary materials, and the requirements on the types and the content of the auxiliary materials are higher, so that the qualified Baloxapite orally disintegrating tablets need to contain proper auxiliary materials and proper content.

Therefore, in order to solve the problems of inconvenient administration of the baclofloxacin ester preparation for children, old people, bedridden patients and patients with dysphagia and people who have difficulty in taking water, and the problems of high cost and poor taste in the preparation of the baclofloxacin ester orally disintegrating tablet, the baclofloxacin ester orally disintegrating tablet with low cost, simple process and good taste and the preparation method thereof are needed.

Disclosure of Invention

In order to solve the problems, the invention provides a Baroswarriol orally disintegrating tablet and a preparation method thereof.

In one aspect, the present invention provides an orally disintegrating tablet of bacloxavir hydrochloride.

A baclofloxacin ester orally disintegrating tablet comprises baclofloxacin ester, mannitol, crospovidone, low-substituted hydroxypropyl cellulose and one or more other auxiliary materials.

The content of the bacloxavir ester can be 8 wt% to 40 wt% relative to the total mass of the bacloxavir ester orally disintegrating tablet. In some embodiments, the amount of baroxavir ester is from 8 wt% to 30 wt% relative to the total mass of the orally disintegrating tablet of baroxavir ester. In some embodiments, the bacloxavir ester is present in an amount from 10 wt% to 30 wt% relative to the total mass of the bacloxavir ester orally disintegrating tablet. In some embodiments, the amount of baroxavir ester is 15 wt% to 20 wt% relative to the total mass of the oral disintegrating tablet of baroxavir ester.

The mannitol may be contained in an amount of 39 wt% to 81 wt% with respect to the total mass of the oral disintegrating tablet of baclovir. In some embodiments, the mannitol is present in an amount of 45 wt% to 60 wt% relative to the total mass of the oral disintegrating tablet of baclovir. In some embodiments, the mannitol is present in an amount of 50 wt% to 55 wt% relative to the total mass of the oral disintegrating tablet of baclovir.

The content of crospovidone may be 5 wt% to 15 wt% with respect to the total mass of the oral disintegrating tablet of baclovir pivoxil. In some embodiments, the crospovidone is present in an amount of 8 wt% to 10 wt% relative to the total mass of the orally disintegrating tablet of baclovir.

The content of the low-substituted hydroxypropylcellulose can be 3 wt% -7 wt% relative to the total mass of the oral disintegrating tablet of bacloxavir hydrochloride. In some embodiments, the low-substituted hydroxypropylcellulose is present in an amount of 5 wt% to 6 wt% relative to the total mass of the orally disintegrating tablet of bacloxavir.

The bacloxavir ester orally disintegrating tablet may not contain at least one of microcrystalline cellulose, lactose, sucrose, sorbitol, and maltitol. In some embodiments, the orally disintegrating tablets of baclofloxacin are free of microcrystalline cellulose, which facilitates improved taste of the orally disintegrating tablets of baclofloxacin. In some embodiments, the baclofloxacin ester orally disintegrating tablet does not contain saccharides such as lactose and sucrose, and is convenient for a diabetic patient to take. In some embodiments, the orally disintegrating tablets of bacloxavir disoproxil do not comprise sorbitol and/or maltitol, which is beneficial for improving the compressibility of the orally disintegrating tablets of bacloxavir disoproxil. In some embodiments, the orally disintegrating tablets of baclofloxacin ester do not contain microcrystalline cellulose, sorbitol, and maltitol, which is beneficial for improving the mouth feel and compressibility of the orally disintegrating tablets of baclofloxacin ester. In some embodiments, the orally disintegrating tablet of baclofloxacin ester does not contain microcrystalline cellulose, lactose, sucrose, sorbitol and maltitol, which is beneficial to improving the taste and compressibility of the orally disintegrating tablet of baclofloxacin ester and is also beneficial to the administration of diabetics.

The mannitol may include at least one selected from mannitol 200SD, mannitol 100SD, mannitol M200, and mannitol M100.

The adjuvant may include at least one selected from a lubricant and an odorant.

The lubricant may include at least one selected from magnesium stearate, sodium fumarate stearate, and colloidal silica.

The taste-modifying agent may comprise at least one selected from aspartame, sucralose, steviol glycosides, sodium saccharin, eradicant, tartaric acid, citric acid and malic acid.

The preparation process of the orally disintegrating tablet can be a powder direct tabletting method; the direct powder tabletting method is simple to operate, and is beneficial to environmental protection and cost reduction.

In some embodiments of the invention, a baclovir ester orally disintegrating tablet comprises baclovir ester, mannitol, crospovidone, low substituted hydroxypropylcellulose, and one or more other excipients; the baclofloxacin ester orally disintegrating tablet does not contain at least one of microcrystalline cellulose, lactose, sucrose, sorbitol and maltitol; the scheme is beneficial to improving the taste and compressibility of the oral disintegrating tablet of the baclofloxacin ester and is also beneficial to the taking of diabetics.

In some embodiments of the invention, a baclovir ester orally disintegrating tablet comprises baclovir ester, mannitol, crospovidone, low substituted hydroxypropylcellulose, and one or more other excipients; the content of the baroxavir ester is 8-40 wt% relative to the total mass of the baroxavir ester orally disintegrating tablet; the content of the mannitol is 39-81 wt%; the content of the crospovidone is 5 wt% -15 wt%; the content of the low-substituted hydroxypropyl cellulose is 3 wt% -7 wt%, and the scheme is favorable for disintegration of the orally disintegrating tablet.

In some embodiments of the invention, a baclovir ester orally disintegrating tablet comprises baclovir ester, mannitol, crospovidone, low substituted hydroxypropylcellulose, and one or more other excipients; the preparation process of the orally disintegrating tablet is a powder direct tabletting method; the scheme is simple to operate, and is beneficial to environmental protection and cost reduction.

In some embodiments of the invention, a baclovir ester orally disintegrating tablet comprises baclovir ester, mannitol, crospovidone, low substituted hydroxypropylcellulose, and one or more other excipients; the content of the baroxavir ester is 8-40 wt% relative to the total mass of the baroxavir ester orally disintegrating tablet; the content of the mannitol is 39-81 wt%; the content of the crospovidone is 5 wt% -15 wt%; the content of the low-substituted hydroxypropyl cellulose is 3-7 wt%; the preparation process of the orally disintegrating tablet is a powder direct tabletting method; the technical scheme is simple to operate, quick in disintegration, beneficial to environmental protection and cost reduction, and capable of solving the problems of poor flowability of auxiliary materials and poor compressibility in a direct powder tabletting method.

In some embodiments of the invention, a baclovir ester orally disintegrating tablet comprises baclovir ester, mannitol, crospovidone, low substituted hydroxypropylcellulose, and one or more other excipients; the baclofloxacin ester orally disintegrating tablet does not contain at least one of microcrystalline cellulose, lactose, sucrose, sorbitol and maltitol; the content of the baroxavir ester is 8-40 wt% relative to the total mass of the baroxavir ester orally disintegrating tablet; the content of the mannitol is 39-81 wt%; the content of the crospovidone is 5 wt% -15 wt%; the content of the low-substituted hydroxypropyl cellulose is 3-7 wt%; the scheme is beneficial to improving the disintegration, the taste and the compressibility of the oral disintegrating tablet of the baloxavir disoproxil and is also beneficial to the taking of diabetics.

In some embodiments of the invention, a baclovir ester orally disintegrating tablet comprises baclovir ester, mannitol, crospovidone, low substituted hydroxypropylcellulose, and one or more other excipients; the baclofloxacin ester orally disintegrating tablet does not contain at least one of microcrystalline cellulose, lactose, sucrose, sorbitol and maltitol; the content of the baroxavir ester is 8-40 wt% relative to the total mass of the baroxavir ester orally disintegrating tablet; the content of the mannitol is 39-81 wt%; the content of the crospovidone is 5 wt% -15 wt%; the content of the low-substituted hydroxypropyl cellulose is 3-7 wt%; the preparation process of the orally disintegrating tablet is a powder direct tabletting method; the scheme is beneficial to improving the disintegration, the taste and the compressibility of the orally disintegrating tablet of the baloxavir disoproxil; is beneficial for the diabetic to take; the method is simple to operate, is beneficial to environmental protection and cost reduction, and can solve the problems of poor flowability of auxiliary materials, poor compressibility in a direct powder tabletting method and the like.

In another aspect, the present invention provides a process for preparing the aforementioned orally disintegrating tablets of baroxavir.

A process for preparing the aforementioned oral disintegrating tablets of baloxavir, comprising the steps of:

1) sieving the baloxavir disoproxil, the mannitol, the crospovidone, the low-substituted hydroxypropyl cellulose and other auxiliary materials respectively;

2) according to the content of the prescription, the baloxavir disoproxil and the mannitol are uniformly mixed, then the crospovidone and the low-substituted hydroxypropyl cellulose with the prescription amount are added and uniformly mixed, and then other auxiliary materials are added and uniformly mixed to obtain mixed powder;

3) tabletting the mixed powder obtained in the step 2) to obtain the baculoxavir disoproxil orally disintegrating tablet.

And sieving the mannitol, the disintegrant and other auxiliary materials respectively by using a sieve with a sieve pore of not more than 0.250 mm.

The baroxavir disoproxil is sieved by a sieve with a mesh no larger than 0.125 mm.

Advantageous effects

Compared with the prior art, the invention has the following beneficial effects:

(1) the orally disintegrating tablet of the baloxavir disoproxil does not contain microcrystalline cellulose, which is beneficial to improving the taste of the orally disintegrating tablet of the baloxavir disoproxil; the baclofloxacin ester orally disintegrating tablet does not contain saccharides such as lactose, sucrose and the like, and is beneficial to the administration of diabetics; the oral disintegrating tablet of baloxavir disoproxil does not contain sorbitol and maltitol; the compressibility of the oral disintegrating tablet of the baloxavir disoproxil is improved; the orally disintegrating tablet of the baloxavir disoproxil does not contain microcrystalline cellulose, sorbitol and maltitol, and is favorable for improving the taste and compressibility of the orally disintegrating tablet of the baloxavir disoproxil; the oral disintegrating tablet of the baclofloxacin ester does not contain microcrystalline cellulose, lactose, sucrose, sorbitol and maltitol, is favorable for improving the taste and compressibility of the oral disintegrating tablet of the baclofloxacin ester, and is also favorable for the diabetics to take.

(2) Preparing the oral disintegrating tablet of the baloxavir disoproxil by adopting a powder direct compression method; the preparation method is simple to operate, and is beneficial to environmental protection and cost reduction.

(3) The oral disintegrating tablet of the baloxavir disoproxil is prepared from the baloxavir disoproxil, mannitol, crospovidone and low-substituted hydroxypropyl cellulose, wherein the contents of the components in the oral disintegrating tablet are respectively 8-40 wt% of the baloxavir disoproxil, 39-81 wt% of the mannitol, 5-15 wt% of the crospovidone and 3-7 wt% of the low-substituted hydroxypropyl cellulose.

(4) The obtained orally disintegrating tablet has higher disintegration rate than sorbitol and maltitol by using mannitol as filler.

(5) The disintegrating agent is crospovidone and low-substituted hydroxypropyl cellulose, and the obtained orally disintegrating tablet has higher disintegrating speed than the orally disintegrating tablet prepared by sodium carboxymethyl starch and croscarmellose sodium.

(6) Mannitol is adopted as a filling agent, and crospovidone and low-substituted hydroxypropyl cellulose are adopted as disintegrating agents, so that the mannitol and the low-substituted hydroxypropyl cellulose can cooperate with each other, the disintegration speed of the obtained orally disintegrating tablet can be improved more favorably, and unexpected technical effects are achieved.

(7) The preparation method of the baclofloxacin ester orally disintegrating tablet is simple to operate, and is beneficial to environmental protection and cost reduction.

(8) The prepared baroxavir pivoxil prepared by the scheme of the invention has the advantages of good dissolution rate, high disintegration speed, convenient administration, good taste, simple preparation and the like.

Description of the terms

In the present invention, mg means mg, g means g,% means% mm means mm, pH means pH, min means minute, h means hour, DEG C means centigrade, rpm means rpm, N means hardness unit "ox", mol/L means mol per liter, and W/W means weight ratio.

The term "weight percent" or "percent by weight" or "wt%" is defined as the weight of an individual component in a formulation divided by the total weight of all components of the formulation and multiplied by 100. In some cases, if the formulation has an outer coating, the total weight may include or exclude the coating weight.

In the description of the present invention, it is to be understood that the terms "first", "second" and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implying any number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present invention, "a plurality" means two or more unless specifically defined otherwise. In the description herein, references to the description of the terms "some embodiments," "examples," "specific examples," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.

Detailed Description

The embodiment of the invention discloses a Baroswarriol orally disintegrating tablet and a preparation method thereof. Those skilled in the art can modify the process parameters appropriately to achieve the desired results with reference to the disclosure herein. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods of the present invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications of the methods described herein, as well as appropriate variations and combinations of the methods described herein, may be made to implement and use the techniques of the present invention without departing from the spirit and scope of the invention.

Example 1:

the prescription of the composition is as follows: as shown in table 1.

Table 1: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil by using a sieve with sieve holes not larger than 0.125 mm, and respectively sieving the auxiliary materials by using a sieve with sieve holes not larger than 0.250 mm; weighing the sieved baclovir disoproxil and mannitol 200SD according to the prescription content, uniformly mixing, adding the crospovidone and the low-substituted hydroxypropyl cellulose in the prescription content, uniformly mixing, finally adding the sucralose and the magnesium stearate in the prescription content, uniformly mixing, and tabletting to obtain the baclovir disoproxil orally disintegrating tablets.

Example 2

The prescription of the composition is as follows: as shown in table 2.

Table 2: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil by using a sieve with sieve holes not larger than 0.125 mm, and respectively sieving the auxiliary materials by using a sieve with sieve holes not larger than 0.250 mm; and weighing and mixing the sieved baroxavir disoproxil and mannitol 200SD according to the prescription content, then adding the crospovidone and the low-substituted hydroxypropyl cellulose in the prescription content, mixing uniformly, finally adding the sucralose and the magnesium stearate in the prescription content, mixing uniformly, and tabletting to obtain the baroxavir disoproxil orally disintegrating tablets.

Example 3

The prescription of the composition is as follows: as shown in table 3.

Table 3: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

Example 4

The prescription of the composition is as follows: as shown in table 4.

Table 4: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil by using a sieve with sieve holes not larger than 0.125 mm, and respectively sieving the auxiliary materials by using a sieve with sieve holes not larger than 0.250 mm; and weighing and mixing the screened baroxavir disoproxil and the mannitol 100SD according to the prescription content, then adding the crospovidone and the low-substituted hydroxypropyl cellulose in the prescription content, mixing uniformly, finally adding the sucralose and the magnesium stearate in the prescription content, mixing uniformly, and tabletting to obtain the baroxavir disoproxil orally disintegrating tablets.

Experimental example 5:

the prescription of the composition is as follows: as shown in table 5.

Table 5: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil by using a sieve with sieve holes not larger than 0.125 mm, and respectively sieving the auxiliary materials by using a sieve with sieve holes not larger than 0.250 mm; and weighing and mixing the screened baroxavir disoproxil and the mannitol M200 uniformly according to the prescription content, then adding the crospovidone and the low-substituted hydroxypropyl cellulose in the prescription content, uniformly mixing, finally adding the sucralose and the magnesium stearate in the prescription content, uniformly mixing, and tabletting to obtain the baroxavir disoproxil orally disintegrating tablets.

Example 6:

the prescription of the composition is as follows: as shown in table 6.

Table 6: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil by using a sieve with sieve holes not larger than 0.125 mm, and respectively sieving the auxiliary materials by using a sieve with sieve holes not larger than 0.250 mm; and weighing and mixing the screened baroxavir disoproxil and the mannitol M100 uniformly according to the content of the prescription, then adding the crospovidone and the low-substituted hydroxypropyl cellulose in the content of the prescription, uniformly mixing, finally adding the sucralose and the magnesium stearate in the content of the prescription, uniformly mixing, and tabletting to obtain the baroxavir disoproxil orally disintegrating tablets.

Comparative example 1:

the prescription of the composition is as follows: as shown in table 7.

Table 7: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil with a sieve pore not larger than 0.125 mm, sieving the auxiliary materials with a sieve pore not larger than 0.250 mm respectively, weighing the sieved baloxavir disoproxil and mannitol according to the prescription content, uniformly mixing, adding the crospovidone with the prescription content, uniformly mixing, finally adding the sucralose and the magnesium stearate with the prescription content, uniformly mixing, and tabletting to obtain the baloxavir disoproxil orally disintegrating tablets.

Comparative example 2:

the prescription of the composition is as follows: as shown in table 8.

Table 8: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil with a sieve pore not larger than 0.125 mm, sieving the auxiliary materials with a sieve pore not larger than 0.250 mm respectively, weighing the sieved baloxavir disoproxil and mannitol according to the prescription content, uniformly mixing, adding the low-substituted hydroxypropyl cellulose with the prescription content, uniformly mixing, finally adding the sucralose and the magnesium stearate with the prescription content, uniformly mixing, and tabletting to obtain the baloxavir disoproxil orally disintegrating tablets.

Comparative example 3:

the prescription of the composition is as follows: as shown in table 9.

Table 9: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

Comparative example 4:

the prescription of the composition is as follows: as shown in table 10.

Table 10: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

Comparative example 5:

the prescription of the composition is as follows: as shown in table 11.

Table 11: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil by using a sieve with a sieve pore not larger than 0.125 mm, sieving the auxiliary materials by using a sieve with a sieve pore not larger than 0.250 mm, weighing the sieved baloxavir disoproxil and microcrystalline cellulose according to the prescription content, uniformly mixing, adding the crospovidone with the prescription content and the low-substituted hydroxypropyl cellulose, uniformly mixing, finally adding the sucralose with the prescription content, uniformly mixing, and tabletting to obtain the baloxavir disoproxil orally disintegrating tablets.

Comparative example 6:

the prescription of the composition is as follows: as shown in table 12.

Table 12: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil with a sieve pore not larger than 0.125 mm, sieving the auxiliary materials with a sieve pore not larger than 0.250 mm respectively, weighing the sieved baloxavir disoproxil and sorbitol according to the prescription content, uniformly mixing, adding the crospovidone and the low-substituted hydroxypropyl cellulose according to the prescription content, uniformly mixing, finally adding the sucralose and the magnesium stearate according to the prescription content, uniformly mixing, and tabletting to obtain the baloxavir disoproxil orally disintegrating tablet.

Comparative example 7:

the prescription of the composition is as follows: as shown in table 13.

Table 13: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil with a sieve pore not larger than 0.125 mm, sieving the auxiliary materials with a sieve pore not larger than 0.250 mm respectively, weighing the sieved baloxavir disoproxil and maltitol according to the prescription content, uniformly mixing, adding the crospovidone and the low-substituted hydroxypropyl cellulose according to the prescription content, uniformly mixing, finally adding the sucralose and the magnesium stearate according to the prescription content, uniformly mixing, and tabletting to obtain the baloxavir disoproxil orally disintegrating tablet.

Comparative example 8:

the prescription of the composition is as follows: as shown in table 14.

Table 14: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baloxavir disoproxil with a sieve pore not larger than 0.125 mm, sieving the auxiliary materials with a sieve pore not larger than 0.250 mm respectively, weighing the sieved baloxavir disoproxil and mannitol according to the prescription content, uniformly mixing, adding the carboxymethyl starch sodium according to the prescription content, uniformly mixing, finally adding the sucralose and the magnesium stearate according to the prescription content, uniformly mixing, and tabletting to obtain the baloxavir disoproxil orally disintegrating tablets.

Comparative example 9:

the prescription of the composition is as follows: as shown in table 15.

Table 15: baroxavirate oral disintegrating tablet prescription

The preparation process comprises the following steps:

sieving the baroxavir disoproxil with a sieve pore not larger than 0.125 mm, sieving the auxiliary materials with a sieve pore not larger than 0.250 mm respectively, weighing the batroxavir ester sieved according to the prescription content, uniformly mixing the batroxavir ester with mannitol, adding the croscarmellose sodium with the prescription content, uniformly mixing, finally adding the sucralose and the magnesium stearate with the prescription content, uniformly mixing, and tabletting to obtain the baroxavir disoproxil orally disintegrating tablet.

Comparative example 10:

referring to the formulation of the original research (trade name: XOFLUZA granules 2% pack; Barosavirate size: 10 mg/bag; manufacturer name: Japanese salt wild pharmacy (Shionogi Co)), the specific composition formulation: as shown in table 16.

Table 16: barosavirate powder prescription

Components	Prescription dose (mg)
		Barosavir ester	10
Mannitol	180
		Maltitol	270
Povidone	0.6
		Hydroxypropyl methylcellulose	15.0
Talcum powder	2.5
		Silica gel micropowder	5.0
Sodium chloride	5.0
		Sucralose	10.0
Orange essence	1.9

The preparation method comprises the following steps:

the preparation method is characterized by preparing the Baroswarriol ester powder by referring to the original prescription. Weighing and mixing the baloxavir ester, the mannitol and the maltitol in the prescription according to the content of the prescription, sieving for 3 times by a 80-mesh sieve, uniformly mixing, adding a povidone aqueous solution, granulating by a 24-mesh sieve, drying for 2h in a 50-DEG C oven, granulating by a 30-mesh sieve, measuring and calculating the actual content of dry particles, adding converted hydroxypropyl methylcellulose, talcum powder, aerosil, sodium chloride, sucralose and orange essence according to the prescription, and mixing for 3min to obtain the powder.

Example 7: comparison of results

The hardness, disintegration time, hygroscopicity, dissolution rate and taste of the tablets were measured for the orally disintegrating tablets of baclofloxacin ester obtained in examples 1 to 6 and comparative examples 1 to 9, respectively, and the taste of the suspension was measured for the powder of baclofloxacin ester obtained in comparative example 10, and the results are shown in tables 17, 18 and 19.

TABLE 17 results of examples 1-6

TABLE 18 results of comparative examples 1 to 9

TABLE 19 results of comparative example 10

Evaluating items	Comparative example 10
		After being mixed with water, the taste is improved	Sweet without bitter taste, but slightly salty with astringent taste
Dissolution rate (60min)	35％

And (4) analyzing results:

as can be seen from tables 17, 18 and 19:

1) the results of examples 1-6 and comparative example 5 show that the mouth feel and appearance of the obtained baclovir disoproxil orally disintegrating tablet are most satisfactory by using mannitol as a filler; the addition of the microcrystalline cellulose can bring strong hygroscopicity and gritty feeling to the orally disintegrating tablet of the baroxavir disoproxil.

2) The results of examples 1 to 6 and comparative examples 6 to 7 show that the obtained orally disintegrating tablets disintegrate faster with mannitol as a filler than with sorbitol and maltitol.

3) The results of examples 1-6 and comparative examples 8-9 show that the disintegrating speed of orally disintegrating tablets obtained by using crospovidone and low-substituted hydroxypropylcellulose as disintegrating agents is higher than that of orally disintegrating tablets obtained by using sodium carboxymethyl starch and croscarmellose sodium.

4) The results of examples 1 to 6 and comparative examples 6 to 9 show that the use of mannitol as a filler and crospovidone and low-substituted hydroxypropylcellulose as disintegrants can cooperate with each other to more favorably increase the disintegration rate of the resulting orally disintegrating tablets.

5) The results of examples 1-6 and comparative example 10 show that the oral disintegrating tablet of baclofloxacin ester prepared by the invention has similar dissolution rate compared with the original grinding powder, and has better taste and best meets the requirement.

6) From the results of examples 1-6 and comparative examples 1-4, it can be seen that the content of bacloxavir ester is 8 wt% to 30 wt%, the content of mannitol is 39 wt% to 81 wt%, the content of crospovidone is 5 wt% to 15 wt%, and the content of low-substituted hydroxypropylcellulose is 3 wt% to 7 wt%, based on the total weight of the composition, the prepared bacloxavir ester orally disintegrating tablet has no bad taste, good compressibility, moderate hardness of the tablet, similar disintegration time limit to that measured under the <0921> item of the four-part general rule of the chinese pharmacopoeia 2015 edition, excellent disintegration, and dissolution meeting the quality control requirement.

Therefore, the preparation method of the oral disintegrating tablet of the Baroswarriol ester can solve the problems that children, old people, bedridden patients and patients with dysphagia and people who have difficulty in getting water take the preparation of the Baroswarriol ester inconveniently, and the preparation of the oral disintegrating tablet of the Baroswarriol ester has high cost and poor taste; the prepared oral disintegrating tablet of the baroxavir disoproxil has the advantages of good compressibility, good taste, moderate hardness, simple preparation process, low cost and good administration compliance.

While the methods of the present invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications of the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of the present invention within the context, spirit and scope of the invention. Those skilled in the art can modify the process parameters appropriately to achieve the desired results with reference to the disclosure herein. It is expressly intended that all such similar substitutes and modifications which would be obvious to those skilled in the art are deemed to be included within the invention.

Claims

1. The oral disintegrating tablet of the baloxavir disoproxil is characterized by comprising the baloxavir disoproxil, mannitol, crospovidone, low-substituted hydroxypropyl cellulose and one or more other auxiliary materials.

2. The orally disintegrating tablet of baroxavir disoproxil of claim 1, wherein the baroxavir disoproxil is present in an amount of 8 wt% to 40 wt% relative to the total mass of the orally disintegrating tablet of baroxavir disoproxil; and/or the mannitol content is 39-81 wt% relative to the total mass of the oral disintegrating tablet of baclovir disoproxil; and/or the content of the crospovidone is 5-15 wt% relative to the total mass of the Baroswarriol orally disintegrating tablet; and/or the content of the low-substituted hydroxypropyl cellulose is 3-7 wt% relative to the total mass of the oral disintegrating tablet of the baroxavir disoproxil.

3. The baclofloxacin ester orally disintegrating tablet according to any one of claims 1-2, which comprises no at least one of microcrystalline cellulose, lactose, sucrose, sorbitol, and maltitol.

4. The baclosapivir ester orally disintegrating tablet according to any one of claims 1 to 3, wherein the mannitol is selected from at least one of mannitol 200SD, mannitol 100SD, mannitol M200 and mannitol M100.

5. The oral disintegrating tablet of baroxavir ester as claimed in any of claims 1-4, wherein the excipients are selected from at least one of lubricants and corrigents.

6. The baclofloxacin ester orally disintegrating tablet according to claim 5, wherein the lubricant is selected from at least one of magnesium stearate, sodium fumarate stearate, and aerosil; and/or the taste agent is at least one selected from aspartame, sucralose, stevioside, saccharin sodium, canaric acid, tartaric acid, citric acid and malic acid.

7. The baclofloxacin ester orally disintegrating tablet according to any one of claims 1 to 6, wherein the process for preparing the orally disintegrating tablet is a powder direct compression method.

8. A process for preparing an orally disintegrating tablet of baclovir disoproxil as claimed in any of claims 1-6, comprising the steps of:

2) mixing the baloxavir disoproxil and the mannitol uniformly, adding the crospovidone and the low-substituted hydroxypropyl cellulose, mixing uniformly, adding other auxiliary materials, and mixing uniformly to obtain mixed powder;

9. The method according to claim 8, wherein the mannitol, disintegrant and other excipients are sieved through a sieve having a mesh size of no greater than 0.250 mm.

10. The method of claim 8, wherein the bacloxavir ester is sieved using a sieve having a mesh size no greater than 0.125 mm.