CN115487163A - Tofacitinib sustained-release preparation and preparation method thereof - Google Patents
Tofacitinib sustained-release preparation and preparation method thereof Download PDFInfo
- Publication number
- CN115487163A CN115487163A CN202110679040.3A CN202110679040A CN115487163A CN 115487163 A CN115487163 A CN 115487163A CN 202110679040 A CN202110679040 A CN 202110679040A CN 115487163 A CN115487163 A CN 115487163A
- Authority
- CN
- China
- Prior art keywords
- tofacitinib
- sustained
- release
- mass
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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Abstract
The invention discloses a tofacitinib sustained-release preparation and a preparation method thereof. The tofacitinib sustained-release preparation comprises a drug-containing tablet core and a sustained-release coating film, wherein the drug-containing tablet core comprises tofacitinib raw material, a filler, a framework material, a disintegrating agent, an adhesive and a lubricant; the slow release coating comprises a film forming material and a pore-foaming agent; the disintegrant comprises sodium carboxymethyl starch. The tofacitinib sustained-release preparation can reduce food effect, achieve sustained-release effect, realize once-daily administration to achieve treatment effect, and is biologically equivalent to a commercially available preparation.
Description
Technical Field
The invention relates to a tofacitinib sustained-release preparation and a preparation method thereof.
Background
Tofacitinib citrate is a novel oral Janus kinase inhibitor developed by the American Giuseppe company, and can effectively inhibit the activity of JAK1 and JAK3 and block the signal conduction of multiple inflammatory cytokines. Is suitable for patients with insufficient treatment effect or intolerance to methotrexateAdult patients with severe active Rheumatoid Arthritis (RA) may be used in combination with methotrexate or other non-bioremediation disease antirheumatic drugs (DMARDs). The chemical name of the derivative is 3- ((3R, 4R) -4-methyl-3- [ methyl- (7H-pyrrolo [2,3-d)]Pyrimidin-4-yl) -amino]-piperidin-1-yl) -3-oxo-propionitrile of formula C 16 H 20 N 6 O, structural formula as follows:
patent CN202010347827.5 discloses an oral sustained release formulation of tofacitinib, under the trade name Xeljanz XR, which is a once-a-day pharmaceutical dosage form with therapeutic effect consistent with the immediate release dosage form Xeljanz. The tofacitinib sustained-release preparation has a problem of incomplete absorption, and the size is adjusted to 11mg so as to be equivalent to a 10mg immediate-release preparation. In addition, the preparation is an osmotic pump punching technology, the process is complex, toxic and harmful organic solvents are used in the preparation process, the problem of organic solvent residue is easy to exist, and certain challenges are brought to the industrial production process of products.
Patent CN202010119445.7 discloses a tofacitinib citrate sustained release tablet and a preparation method thereof, wherein only a skeleton is used. Patent CN201811365133.3 discloses a tofacitinib controlled release tablet, a preparation method and application thereof, and only membrane control is used. The two patents respectively adopt a framework technology and a membrane control technology to prepare the tofacitinib sustained-release preparation, but a single framework or membrane control technology is easy to have a strong food effect and can cause sudden release in vivo to influence the safety.
Patent CN202011512873.2 discloses a tofacitinib citrate sustained release tablet with membrane control and framework dual sustained release. Patent CN201911300186.1 discloses tofacitinib citrate tablets and a preparation method thereof. Both of the two patents adopt a dual sustained release technology of a framework and a membrane control to achieve the stable release of the medicine in vitro, but the two patents do not relate to the problem of food effect.
Disclosure of Invention
The invention aims to overcome the defect that the food effect of a tofacitinib sustained-release preparation in the prior art needs to be improved, and provides the tofacitinib sustained-release preparation and a preparation method thereof. The sustained-release preparation has better sustained-release effect, can reduce food effect, realizes that the treatment effect can be achieved by taking the preparation once every day, and is biologically equivalent to the preparation sold in the market. In addition, the oral sustained-release preparation has simple preparation process, low cost and easy production and amplification.
The invention provides a tofacitinib sustained-release preparation, which comprises a drug-containing tablet core and a sustained-release coating film, wherein the drug-containing tablet core comprises tofacitinib raw material, a filler, a framework material, a disintegrant, an adhesive and a lubricant; the slow release coating comprises a film forming material and a pore-foaming agent; the disintegrant comprises sodium carboxymethyl starch.
In the present invention, the disintegrant is preferably only sodium carboxymethyl starch. The mass of the disintegrant is preferably 4-12%, for example 4%, 8% or 12% of the mass of the drug containing core.
In the invention, the mass ratio of the sustained-release coating film to the drug-containing tablet core can be the conventional mass ratio in the field, and is preferably (2-5): 50, e.g. 3: 50. 1:25 or 1:10.
in the invention, the tofacitinib raw material medicine is tofacitinib or a medicinal derivative thereof, such as tofacitinib (preferably tofacitinib crystal) and/or tofacitinib medicinal salt. The salt of the tofacitinib is preferably tofacitinib citrate. The dosage of the tofacitinib raw material medicine is a therapeutically effective amount, and generally can be 5-20% of the mass of the medicine-containing tablet core, such as 9%.
In the present invention, the filler may be a filler conventional in the art, preferably selected from one or more of lactose, microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, pregelatinized starch, sucrose, dibasic calcium phosphate, starch and dextrin, and more preferably lactose. The amount of filler may be selected from those conventionally used in the art, preferably from 40 to 70%, e.g. 48%, 51%, 54%, 58%, 60% or 63% by mass of the drug containing core.
In the present invention, the matrix material may be a conventional matrix material in the art, and is preferably selected from one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, polyoxyethylene, and sodium carboxymethyl cellulose, and more preferably is hydroxypropyl methylcellulose. The amount of matrix material is selected in accordance with conventional amounts of matrix material in the art, preferably from 10 to 30% by mass of the drug-containing core, for example 17.5%, 20%, 22.5%, 24%, 25% or 26%.
In the present invention, the binder may be a binder conventional in the art, preferably selected from one or more of copovidone, hydroxypropylcellulose, starch and pregelatinized starch, more preferably copovidone. The amount of binder is selected in accordance with the conventional amounts of binder used in the art, preferably from 1 to 10%, for example 6% by mass of the tablet core.
In the present invention, the lubricant may be a lubricant conventional in the art, preferably selected from one or more of magnesium stearate, talc, colloidal silicon dioxide and calcium stearate, and more preferably magnesium stearate. The amount of lubricant used may be selected in accordance with conventional amounts of lubricant used in the art, and is preferably 0.1 to 5%, e.g. 1%, by mass of the drug-containing core.
In the present invention, the film-forming material may be a film-forming material conventional in the art, preferably selected from one or more of an aqueous ethylcellulose dispersion, an aqueous dispersion of 30wt% polyvinyl acetate, a methyl acrylate copolymer, a polyamide and polyethylene, and more preferably an aqueous ethylcellulose dispersion. The amount of the film-forming material may be selected from those conventionally used in the art, and is preferably 40 to 60%, for example 45%, 50% or 53% by mass of the sustained-release coating film.
In the present invention, the pore-forming agent may be a pore-forming agent conventional in the art, preferably a polymer and/or a water-soluble excipient. The polymer is preferably selected from one or more of hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, povidone, crospovidone, copovidone, polyethylene glycol-polyvinyl alcohol, low substituted hydroxypropyl cellulose, starch and pregelatinized starch, more preferably hydroxypropyl methylcellulose. The water soluble excipient is preferably selected from one or more of mannitol, lactose, sorbitol, xylitol and maltitol, more preferably lactose. The amount of the porogen used may be selected according to the amounts conventionally used for porogens in the art. The polymer is preferably used in an amount of 20-50%, for example 30%, 35% or 45% by mass of the sustained-release coating. The amount of the water-soluble excipient is preferably less than or equal to 10%, for example 3%, 5% or 8% by mass of the sustained-release coating film.
In the present invention, the sustained-release coating film may further include other excipients that are conventional in the art, in addition to the film-forming material and the pore-forming agent, and preferably further include one or more of a lubricant, a plasticizer, a colorant, and a surfactant.
Wherein, the lubricant can be a conventional lubricant in the field, preferably selected from one or more of talcum powder, magnesium stearate, calcium stearate, superfine silica powder, kaolin, silicon dioxide and stearic acid, and more preferably talcum powder. The amount of the lubricant is selected according to the conventional amount of the lubricant in the field, and is preferably 1-10%, more preferably 6% of the mass of the sustained-release coating.
Wherein the plasticizer can be a plasticizer conventional in the art, preferably one or more of glycerin, propylene glycol, polyethylene glycol, dimethyl phthalate, diethyl phthalate, dibutyl sebacate, triethyl citrate and tributyl citrate, and more preferably triethyl citrate. The amount of the plasticizer can be selected according to the conventional amount of the plasticizer in the field, and is preferably 1 to 10 percent, and more preferably 6 percent of the mass of the sustained-release coating film.
Wherein the colorant may be a colorant conventional in the art.
Wherein the surfactant may be a surfactant conventional in the art.
The invention also provides a preparation method of the tofacitinib sustained-release preparation, which comprises the following steps: tabletting and coating according to the components of the tofacitinib sustained-release preparation.
Wherein the tabletting is carried out according to the conventional tabletting operation in the field, and specifically comprises the following steps: premixing the components (such as tofacitinib raw material, filler, framework material, disintegrating agent and adhesive) except lubricant, adding lubricant, mixing, and tabletting to obtain the tablet core. The time for the premixing is preferably 10 to 20min, more preferably 15min. The total mixing time is preferably 4-6min, more preferably 5min. The tablet is preferably compressed to control the hardness of the tablet core to be 8-12kg.
Wherein, the coating is carried out according to the conventional coating operation in the field, and specifically comprises the following steps: coating the drug-containing tablet core with a coating solution comprising water, a film-forming material and a pore-forming agent. The water is preferably purified water. The amount of water is that which is conventional in the art.
The above preferred conditions may be combined arbitrarily to obtain preferred embodiments of the present invention without departing from the general knowledge in the art. The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows: the tofacitinib sustained-release preparation can reduce food effect, achieve sustained-release effect, realize once-daily administration to achieve treatment effect, and is biologically equivalent to a commercially available preparation.
Drawings
FIG. 1 is a pharmacokinetic profile of the two formulations of example 13 after administration on an empty stomach;
FIG. 2 is a pharmacokinetic profile of the two formulations of example 13 following ingestion of a meal.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
The percentages in the examples are by mass.
Examples 1 to 6
The tablet core is prepared by direct tabletting, and the weight of the single tablet core containing the medicine is 200mg.
TABLE 1 drug-containing core compositions (mg/tablet) of examples 1-3
TABLE 2 drug-containing core compositions (mg/tablet) of examples 4-6
Table 3 coating compositions of examples 1-6
* Is the solid component in the ethyl cellulose water dispersion. The ethyl cellulose aqueous dispersion is a commercially available auxiliary material, and the manufacturer is Carlekang and the trade name is Sulisi.
The preparation process comprises the following steps:
(1) Pretreatment: sieving the raw materials and adjuvants with 30 mesh sieve respectively;
(2) Pre-mixing: weighing the other components except magnesium stearate, and mixing for 15min;
(3) Total mixing: adding magnesium stearate, and mixing for 5min;
(4) Tabletting: tabletting the totally mixed materials, and controlling the hardness to be 8-12kg;
(5) Coating: the slow release coating film component is prepared into coating liquid, and the weight is increased by 6 percent.
Examples 7 to 9
The tablet core is prepared by direct tabletting, and the weight of a single tablet containing the tablet core is 200mg.
TABLE 4 drug-containing core compositions (mg/tablet) of examples 7-9
Table 5 coating liquid composition of examples 7 to 9 (mass%)
* Is the solid component in the ethyl cellulose water dispersion.
In examples 7, 8 and 9, purified water: the mass ratio of the slow-release coating film is respectively 32: 10. 31, and 3:1.
The preparation process comprises the following steps:
(1) Pretreatment: sieving the raw materials and adjuvants with 30 mesh sieve respectively;
(2) Premixing: weighing the other components except magnesium stearate, and mixing for 15min;
(3) Total mixing: adding magnesium stearate, and mixing for 5min;
(4) Tabletting: tabletting the total mixed materials, and controlling the hardness to be 8-12kg;
(5) Coating: the slow release coating film component is prepared into coating liquid, and the weight is increased by 6 percent.
Release assay:
the release characteristics of the tablets were measured over a 10h time interval according to the dissolution and release assay method of 0931 (second method, 75rpm, 900ml dissolution medium) on the basis of the general rule of the four sections of the "Chinese pharmacopoeia" 2020 edition, and the release in phosphate buffer at pH6.8 was measured in% (in%) at 37 ℃.
TABLE 6 Release (%) versus time (h) for examples 1-9
| Time (h) | 1 | 2.5 | 4 | 10 |
| Example 1 | 8 | 27 | 50 | 96 |
| Example 2 | 12 | 34 | 60 | 97 |
| Example 3 | 15 | 40 | 68 | 99 |
| Example 4 | 10 | 31 | 59 | 98 |
| Example 5 | 12 | 34 | 63 | 97 |
| Example 6 | 12 | 39 | 70 | 98 |
| Example 7 | 12 | 36 | 58 | 97 |
| Example 8 | 10 | 33 | 57 | 96 |
| Example 9 | 13 | 40 | 64 | 99 |
According to the release curves of examples 1 to 9 in table 6, it can be shown that the sustained release preparation of tofacitinib of the present invention can effectively control the drug release to achieve the sustained release effect.
Examples 10 to 12
The tablet core is prepared by direct tabletting, and the weight of the single tablet core containing the medicine is 200mg.
TABLE 7 drug-containing core compositions (mg/tablet) of examples 10-12
TABLE 8 coating compositions for examples 10-12
* Is the solid component in the ethyl cellulose water dispersion.
The preparation process comprises the following steps:
(1) Pretreatment: sieving the raw materials and adjuvants with 30 mesh sieve respectively;
(2) Premixing: weighing the other components except magnesium stearate, and mixing for 15min;
(3) Total mixing: adding magnesium stearate, and mixing for 5min;
(4) Tabletting: tabletting the totally mixed materials, and controlling the hardness to be 8-12kg;
(5) Coating: the sustained-release coating film component was formulated into coating solutions, and the weights of the coatings were 4% (example 10), 8% (example 11), and 10% (example 12), respectively.
Release assay:
the release characteristics of the tablets were measured over a 10h time interval according to the dissolution and release assay method of 0931 (second method, 75rpm, 900ml dissolution medium) on the basis of the general rule of the four sections of the "Chinese pharmacopoeia" 2020 edition, and the release in phosphate buffer at pH6.8 was measured in% (in%) at 37 ℃.
TABLE 9 Release (%) vs. time (h) for examples 10-12
| Time (h) | 1 | 2.5 | 4 | 10 |
| Example 10 | 10 | 29 | 51 | 98 |
| Example 11 | 8 | 24 | 48 | 98 |
| Example 12 | 7 | 21 | 45 | 97 |
According to the release curves of examples 10-12 in table 9 and example 2 in table 6, it can be shown that the weight gain of the sustained-release coating film is between 4% and 10%, and the in vitro release of the tofacitinib sustained-release preparation in the invention has no significant difference, i.e. the invention is easy to produce and amplify, has good reproducibility and can control the release.
Comparative example 1
The invention prepares the drug-containing tablet core by direct tabletting, and the weight of the single-piece drug-containing tablet core is 200mg.
TABLE 10 drug-containing core composition of comparative example 1 (mg/tablet)
Table 11 coating liquid composition of comparative example 1 (mass%)
* Is the solid component in the ethyl cellulose water dispersion.
The preparation process comprises the following steps:
(1) Pretreatment: sieving the raw materials and adjuvants with 30 mesh sieve respectively;
(2) Premixing: weighing the other components except magnesium stearate, and mixing for 15min;
(3) Total mixing: adding magnesium stearate, and mixing for 5min;
(4) Tabletting: tabletting the total mixed materials, and controlling the hardness to be 8-12kg;
(5) Coating: the slow release coating film component is prepared into coating liquid, and the weight is increased by 6 percent.
Release assay:
the release characteristics of the tablets were measured over a 10h time interval according to the dissolution and release assay method of 0931 (second method, 75rpm, 900ml dissolution medium) on the basis of the general rule of the four sections of the "Chinese pharmacopoeia" 2020 edition, and the release in phosphate buffer at pH6.8 was measured in% (in%) at 37 ℃.
TABLE 12 Release (%) of comparative example 1 as a function of time (h)
| Time (h) | 1 | 2.5 | 4 | 10 |
| Release (%) of comparative example 1 | 9 | 26 | 53 | 98 |
The release profiles of comparative example 1 in table 12 and example 1 in table 6 are combined to show that: comparative example 1 and example 1 did not differ significantly in the in vitro release process.
Example 13 Biggee in vivo pharmacokinetic experiments
Healthy adult beagle dogs were randomly divided into 3 groups (example group, comparative example group 1, one at a time) and the experiment was performed alternately. The single administration example group was administered as example 1, and the comparative example group 1 was administered as comparative example 1. Study in vivo pharmacokinetic experiments on fasting and after feeding, respectively, fasting for 12h before the experiment, and administering 150g each of lipid (half fat lean minced pork) to the fed group at the time of the experiment, followed by administration; the fasting group was given 100ml of water, followed by administration. Meals were scheduled simultaneously 8h after dosing. Each group of dogs was tested by collecting 3ml of blood from the great saphenous vein at a predetermined time, anticoagulating the blood with heparin, and sampling plasma samples by low temperature centrifugation. Test formulations T were prepared as the example groups 1 Comparative example group 1 as test preparation T 2 。
TABLE 13 in vivo pharmacokinetic data for two sets of formulations
As can be seen from the results of the in vivo pharmacokinetic experiments in beagle dogs in table 13:
example set (T) 1 ) In the fasting and fed states, C max Has no significant difference with AUC, and has fed state C max And AUC 1.12 and 1.05 times of fasting state, respectively.
Comparative example group 1 (T) 2 ) AUC was not significantly different between fed and fasted states, with the AUC at fed being 1.10 times that of fasted state, but C at fed max Is obviously 1.37 times higher than that of the fasting state.
The results of the drug content test in blood for each time period in the fasting and fed states for T1 and T2 are shown in table 14 and fig. 1-2.
TABLE 14 in vivo Release data for the two sets of formulations
As can be seen from tables 13-14, FIG. 1 and FIG. 2, the food effect is significantly controlled when the disintegrant is sodium carboxymethyl starch at a level of 4% (T1). The T1 release preparation can sufficiently resist gastrointestinal tract and food extrusion in vivo, can reduce food effect, and can achieve the treatment effect by taking the preparation once a day.
The results indicated that the example group exhibited a small food effect in the fed state, and the safety in vivo was high; although the tofacitinib sustained-release tablet in the comparative example can achieve the sustained-release effect in vitro, the tofacitinib sustained-release tablet is released suddenly in vivo after eating, and the food effect is obvious.
Claims (10)
1. The tofacitinib sustained-release preparation is characterized by comprising a drug-containing tablet core and a sustained-release coating film, wherein the drug-containing tablet core comprises tofacitinib raw material, a filler, a framework material, a disintegrant, an adhesive and a lubricant; the slow release coating comprises a film forming material and a pore-foaming agent; the disintegrant comprises sodium carboxymethyl starch.
2. The sustained-release formulation of tofacitinib according to claim 1, wherein said disintegrant is sodium carboxymethyl starch.
3. The sustained-release formulation of tofacitinib according to claim 1 or 2, wherein the disintegrant is present in an amount of 4 to 12%, such as 4%, 8% or 12% by mass of the drug-containing core.
4. The tofacitinib sustained-release preparation according to claim 1, wherein the mass ratio of the sustained-release coating film to the drug-containing core tablet is (2-5): 50, e.g. 3: 50. 1:25 or 1:10.
5. the tofacitinib sustained-release preparation according to claim 1, wherein the tofacitinib drug substance is tofacitinib and/or a salt of tofacitinib drug; the tofacitinib is preferably tofacitinib crystal, and the salt of the tofacitinib medicine is preferably tofacitinib citrate;
and/or the dosage of the tofacitinib raw material medicine is 5-20 percent, such as 9 percent of the mass of the medicine-containing tablet core.
6. The tofacitinib sustained-release formulation according to claim 1, wherein said tofacitinib sustained-release formulation satisfies one or more of the following conditions:
(1) the filler is selected from one or more of lactose, microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, pregelatinized starch, sucrose, calcium hydrogen phosphate, starch and dextrin, preferably lactose;
(2) the amount of the filler is 40-70% of the mass of the drug-containing tablet core, such as 48%, 51%, 54%, 58%, 60% or 63%;
(3) the framework material is selected from one or more of hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, polyoxyethylene and sodium carboxymethyl cellulose, and is preferably hydroxypropyl methyl cellulose;
(4) the dosage of the framework material is 10-30% of the mass of the drug-containing tablet core, such as 17.5%, 20%, 22.5%, 24%, 25% or 26%;
(5) the binder is selected from one or more of copovidone, hydroxypropyl cellulose, starch and pregelatinized starch, preferably copovidone;
(6) the dosage of the adhesive is 1-10 percent, such as 6 percent of the mass of the medicine-containing tablet core;
(7) the lubricant is selected from one or more of magnesium stearate, talcum powder, colloidal silicon dioxide and calcium stearate, and is preferably magnesium stearate;
(8) the amount of lubricant is 0.1-5%, for example 1%, of the mass of the drug-containing tablet core.
7. The tofacitinib sustained-release preparation according to claim 1, wherein said tofacitinib sustained-release preparation satisfies one or more of the following conditions:
(1) the film-forming material is selected from one or more of ethyl cellulose aqueous dispersion, 30wt% polyvinyl acetate aqueous dispersion, polyvinyl acetate, methyl acrylate copolymer, polyamide and polyethylene, and preferably ethyl cellulose aqueous dispersion;
(2) the dosage of the film forming material is 40-60 percent of the mass of the slow release coating film, such as 45 percent, 50 percent or 53 percent;
(3) the pore-foaming agent is a polymer and/or a water-soluble excipient; the polymer is preferably selected from one or more of hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, povidone, crospovidone, copovidone, polyethylene glycol-polyvinyl alcohol, low substituted hydroxypropyl cellulose, starch and pregelatinized starch, more preferably hydroxypropyl methylcellulose; the water-soluble excipient is preferably selected from one or more of mannitol, lactose, sorbitol, xylitol and maltitol, more preferably lactose;
(4) the slow release coating film also comprises one or more of a lubricant, a plasticizer, a coloring agent and a surfactant; the lubricant is preferably selected from one or more of talc, magnesium stearate, calcium stearate, aerosil, kaolin, silicon dioxide and stearic acid, more preferably talc; the plasticizer is preferably one or more of glycerol, propylene glycol, polyethylene glycol, dimethyl phthalate, diethyl phthalate, dibutyl sebacate, triethyl citrate and tributyl citrate, more preferably triethyl citrate.
8. The tofacitinib sustained-release formulation according to claim 7, wherein said tofacitinib sustained-release formulation satisfies one or more of the following conditions:
(1) the amount of the polymer is 20-50% of the mass of the slow-release coating film, such as 30%, 35% or 45%;
(2) the amount of the water-soluble excipient is less than or equal to 10 percent of the mass of the slow-release coating film, such as 3 percent, 5 percent or 8 percent;
(3) the dosage of the lubricant is 1-10% of the mass of the slow-release coating film, and is more preferably 6%;
(4) the dosage of the plasticizer is 1-10% of the mass of the slow release coating film, and is more preferably 6%.
9. A process for the preparation of a sustained release formulation of tofacitinib, as claimed in any one of claims 1 to 8, comprising the steps of: tabletting and coating according to each component of the tofacitinib sustained-release preparation.
10. The method for preparing a tofacitinib sustained-release preparation according to claim 9, wherein the tabletting specifically comprises: premixing the components except the lubricant, adding the lubricant, mixing, and tabletting to obtain the tablet core; the time for premixing is preferably 10-20min, more preferably 15min; the total mixing time is preferably 4-6min, more preferably 5min; the tablet core hardness of the tablet is preferably controlled to be 8-12kg;
and/or the coating operation is specifically as follows: coating the drug-containing tablet core with a coating solution containing water, a film-forming material and a pore-forming agent; the water is preferably purified water.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110679040.3A CN115487163A (en) | 2021-06-18 | 2021-06-18 | Tofacitinib sustained-release preparation and preparation method thereof |
| PCT/CN2022/099114 WO2022262802A1 (en) | 2021-06-18 | 2022-06-16 | Sustained-release preparation of tofacitinib and preparation method therefor |
| TW111122544A TW202300155A (en) | 2021-06-18 | 2022-06-17 | Tofacitinib sustained-release preparation and preparation method thereof |
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| CN202110679040.3A CN115487163A (en) | 2021-06-18 | 2021-06-18 | Tofacitinib sustained-release preparation and preparation method thereof |
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| CN115487163A true CN115487163A (en) | 2022-12-20 |
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| CN202110679040.3A Pending CN115487163A (en) | 2021-06-18 | 2021-06-18 | Tofacitinib sustained-release preparation and preparation method thereof |
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| Country | Link |
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| CN (1) | CN115487163A (en) |
| TW (1) | TW202300155A (en) |
| WO (1) | WO2022262802A1 (en) |
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| CN117562954B (en) * | 2024-01-16 | 2024-04-26 | 江西汇仁药业股份有限公司 | Shenbao tablet preparation and evaluation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2481411A1 (en) * | 2011-01-27 | 2012-08-01 | Ratiopharm GmbH | Oral dosage forms for modified release comprising the JAK3 inhibitor tasocitinib |
| US20120195966A1 (en) * | 2011-01-27 | 2012-08-02 | Frank Sievert | Oral dosage form for modified release comprising a jak3 inhibitor |
| WO2017029587A1 (en) * | 2015-08-19 | 2017-02-23 | Sun Pharmaceutical Industries Limited | Sustained release oral pharmaceutical compositions of tofacitinib |
| CN108066319B (en) * | 2016-11-10 | 2022-01-14 | 江苏先声药业有限公司 | Tofacitinib citrate enteric sustained-release pellet and preparation method thereof |
| CN106389371B (en) * | 2016-11-16 | 2019-03-15 | 杭州朱养心药业有限公司 | tofacitinib citrate pharmaceutical composition |
| CN111150711B (en) * | 2018-11-07 | 2023-04-07 | 上海博志研新药物技术有限公司 | Tofacitinib controlled-release tablet, preparation method and application thereof |
| WO2020194081A1 (en) * | 2019-03-27 | 2020-10-01 | Unichem Laboratories Limited | Extended release composition of tofacitinib |
| CN110787145B (en) * | 2019-12-17 | 2022-03-29 | 南京康川济医药科技有限公司 | Tofacitinib citrate sustained-release tablet and preparation method thereof |
| CN112755000A (en) * | 2021-01-21 | 2021-05-07 | 石药集团欧意药业有限公司 | Tofacitinib citrate sustained-release tablet |
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2021
- 2021-06-18 CN CN202110679040.3A patent/CN115487163A/en active Pending
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2022
- 2022-06-16 WO PCT/CN2022/099114 patent/WO2022262802A1/en active Application Filing
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| WO2022262802A1 (en) | 2022-12-22 |
| TW202300155A (en) | 2023-01-01 |
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