Fluorohydrocortisone acetate tablet and preparation process thereof

Abstract

The invention discloses a hydrocortisone acetate tablet and a preparation process thereof, and the hydrocortisone acetate tablet comprises the following components in percentage by mass: 0.08-0.12% of hydrocortisone acetate, 0.05-0.12% of magnesium stearate, 0.05-0.12% of magnesium stearate, 0.05-0.12% of magnesium stearate, and the balance of magnesium stearate. 80 to 95% of lactose monohydrate; 2-8% of directly pressed corn starch; 0.2%-1.0% of a flow aid; the fluhydrocortisone acetate tablet is prepared by the following method: mixing the fluhydrocortisone acetate, the lactose monohydrate and the directly-pressed corn starch, and then sieving the mixture; and adding the flow aid and the lubricant, mixing, and tabletting. The simple and convenient direct pressing process is adopted, simplicity, convenience and stability are achieved, material and labor cost can be reduced, and large-scale production is facilitated. The pharmaceutical composition is simple in prescription, good in flowability and good in dissolution reproducibility, in-vivo bioavailability can be improved, and the pharmaceutical composition has the same or better safety and curative effect as those of an original pharmaceutical composition.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and in particular relates to a fludrocortisone acetate tablet and its preparation process. Background Technology

[0002] Fludrocortisone acetate, also known as 9α-fludrocortisone, 9α-fluorocortisol, flucortisone, 9α-fludrocortisol, fludrocortisone, 9α-fluorocortisol acetate, and 9α-fluorohydrocortisone acetate, is mainly used for replacement therapy in adrenocortical insufficiency and can also be used topically for skin diseases such as allergic dermatitis, contact dermatitis, seborrheic dermatitis, and eczema. Its active ingredient has the chemical name 9-Fluoro-11β, 17, 21-trihydroxypregn-4-ene-3, 20-dione 21-acetate, and its chemical structure is as follows:

[0003] The original research process for fludrocortisone acetate tablets involved wet granulation, a complex process. Furthermore, the original formulation was complicated, particularly the corn starch, which required hot water slurry preparation, making it unsuitable for large-scale production and resulting in high material and labor costs. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to overcome the deficiencies and defects mentioned in the background art above, and to provide a fludrocortisone acetate tablet and its preparation process.

[0005] To solve the above-mentioned technical problems, the technical solution proposed by this invention is as follows: A fludrocortisone acetate tablet comprising, by weight percentage, the following components, totaling 100%: Fludrocortisone acetate 0.08~0.12%; Lactose monohydrate 80-95%; Direct-pressed corn starch 2-8%; Flow aid 0.2~1.0%; Lubricant 0.2~1.5%; The fludrocortisone acetate tablets are prepared by the following method: fludrocortisone acetate, lactose monohydrate, and direct-pressed corn starch are mixed and then sieved; a gliding agent and a lubricant are added and mixed, and then the mixture is compressed into tablets.

[0006] As a further improvement, the fludrocortisone acetate has a D90 of <20 micrometers and a D50 of <10 micrometers.

[0007] As a further improvement, the flow aid is talc and / or silica.

[0008] As a further improvement, the lubricant is one or more of magnesium stearate, hydrogenated castor oil, and sodium stearate.

[0009] A method for preparing the fludrocortisone acetate tablets of the present invention includes the following steps: (1) Mix fludrocortisone acetate, lactose monohydrate, and direct-pressed corn starch, and then sieve; (2) Add glidin and lubricant, mix, and then compress into tablets.

[0010] As a further improvement, in step (1), the mixing speed is 5~15 rpm and the mixing time is 10~40 min.

[0011] As a further improvement, the sieve mesh size in step (1) is 20~60 mesh.

[0012] As a further improvement, in step (2), the mixing speed is 5~15 rpm and the mixing time is 5~20 min.

[0013] As a further improvement, the tableting pressure in step (2) is 20~60N.

[0014] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The present invention uses lactose monohydrate as a filler, which has good flowability and compressibility. After being compressed into tablets, it can form a smooth and dense surface, which can effectively delay the rapid penetration of moisture in the air and avoid the finished product from absorbing moisture. In addition, its water solubility does not affect the dissolution of the drug, which is beneficial to improving the bioavailability of the tablets.

[0015] (2) The present invention adopts a simpler direct pressure process. The direct pressure process is simple and stable, which is conducive to reducing material and labor costs, facilitating large-scale production, and can significantly reduce energy consumption, manpower and material waste.

[0016] (3) The formulation of this invention is simple, has good fluidity, and good dissolution reproducibility, which is beneficial to improving bioavailability in vivo. It also has the same or better safety and efficacy as the original drug. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 It is the cumulative dissolution curve in a medium with a pH of 1.2; Figure 2This is the cumulative dissolution curve in a medium with a pH of 4.5. Detailed Implementation

[0019] To facilitate understanding of the present invention, the present invention will be described more fully and in detail below with reference to the accompanying drawings and preferred embodiments, but the scope of protection of the present invention is not limited to the following specific embodiments.

[0020] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art. The technical terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the invention.

[0021] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0022] In some specific embodiments, the fludrocortisone acetate tablets of the present invention comprise, by weight percentage, the following components, totaling 100%: Fludrocortisone acetate 0.08~0.12%; Filler: lactose monohydrate 80-95%; Disintegrant: 2-8% of directly compressed corn starch; Flow aid 0.2~1.0%; Lubricant 0.2~1.5%.

[0023] The active ingredient, fludrocortisone acetate, has specific particle size characteristics: D90 < 20 micrometers and D50 < 10 micrometers. Larger particle sizes result in slower dissolution and affect absorption in the body.

[0024] The filler lactose monohydrate gives the formulation granules excellent flowability and compressibility. Furthermore, its water-soluble properties allow for rapid dissolution of the active ingredient. Too little lactose is detrimental to tableting, while too much is detrimental to tablet dissolution.

[0025] Direct-pressed corn starch, a disintegrant, has weaker disintegrant properties than sodium carboxymethyl starch, thus preventing rapid tablet disintegration and excessive dissolution. Small dosages result in slow disintegration and dissolution, while large dosages lead to rapid disintegration and dissolution. Both rapid and slow dissolution negatively impact therapeutic efficacy.

[0026] Fly flow aids, such as talc and silica, can improve the flowability of the formulation, promote uniform mixing, and improve tablet uniformity. Insufficient amounts will affect the flowability of the formulation, thus impacting tablet uniformity.

[0027] Lubricants such as magnesium stearate, hydrogenated castor oil, and sodium stearate can improve the compressibility of tablets and contribute to the stability of the tableting process. Too little lubricant is detrimental to the stability of the tableting process, as excessive hydrophobicity can affect tablet dissolution.

[0028] If necessary, other excipients may be added to the above composition, such as sweeteners (e.g., aspartame, stevioside, etc.), colorants (e.g., yellow iron oxide, red iron oxide, etc.), stabilizers (e.g., citric acid, lactic acid, malic acid, etc.), and pH adjusters (e.g., sodium bicarbonate, fumaric acid, citric acid, etc.).

[0029] If desired, the above composition may also contain other suitable active ingredients.

[0030] In some specific embodiments, the method for preparing fludrocortisone acetate tablets of the present invention includes the following steps: (1) Mix fludrocortisone acetate, lactose monohydrate as filler, and corn starch as disintegrant. Mix at 5-15 rpm for 10-40 min, then sieve. This step affects the uniformity of mixing, which in turn affects the uniformity, safety, and efficacy of the tablets. Insufficient mixing speed and time will affect the uniformity of mixing.

[0031] If the material is not sieved, the screen mesh size is 20~60 mesh. There may be lumps in the material. If it is not sieved, it may affect the uniformity of mixing.

[0032] (2) Add the glidant and lubricant and mix at a speed of 5-15 rpm for 5-20 min, then compress the tablet. This step affects the uniformity of lubricant mixing, and uneven mixing affects tablet stability.

[0033] The tableting pressure is 20~60N. This step affects the tablet hardness, which in turn affects the tablet's brittleness and dissolution. If the hardness is too low, the tablet will not be firm enough and will easily break. If the hardness is too high, it will affect the tablet's disintegration and thus its dissolution.

[0034] The composition of each embodiment is shown in the table below (unit: %):

[0035] Example 1 4000 tablets were made, each containing approximately 100mg. Tablet preparation method: Weigh out the amounts of API, filler, disintegrant, gliding agent and lubricant for each prescription according to the table above; Mix the API with other components except for the gliding agent and lubricant using a multi-directional motion mixer at a speed of 5-15 rpm for 30 minutes.

[0036] The above materials are sieved through a 40-mesh sieve. Then, the flow aid and lubricant are added and mixed at a speed of 5-15 rpm for 15 minutes.

[0037] Tablets are compressed using a rotary tablet press at a pressure of 20N.

[0038] Example 2 4000 tablets were made, each containing approximately 100mg. Tablet preparation method: Weigh out the amounts of API, filler, disintegrant, gliding agent and lubricant for each prescription according to the table above; Mix the API with other components except for the gliding agent and lubricant using a multi-directional motion mixer at a speed of 5-15 rpm for 30 minutes.

[0039] The above materials are sieved through a 40-mesh sieve. Then, the flow aid and lubricant are added and mixed at a speed of 5-15 rpm for 15 minutes.

[0040] Tablets are compressed using a rotary tablet press at a pressure of 60 N.

[0041] The dissolution curves of Examples 1-2 and the original drug are as follows: Figure 1 and Figure 2 As can be seen, the dissolution data is basically consistent with the original study, and Example 2 has a higher dissolution rate.

[0042] Example 3 4000 tablets were made, each containing approximately 100mg. Tablet preparation method: Weigh out the amounts of API, filler, disintegrant, gliding agent and lubricant for each prescription according to the table above; Mix the API with other components except for the gliding agent and lubricant using a multi-directional motion mixer at a speed of 5-15 rpm for 10 minutes.

[0043] The above materials are sieved through a 40-mesh sieve. Then, the flow aid and lubricant are added and mixed at a speed of 5-15 rpm for 20 minutes.

[0044] Tablets are compressed using a rotary tablet press at a pressure of 40N.

[0045] Example 4 4000 tablets were made, each containing approximately 100mg. Tablet preparation method: Weigh out the amounts of API, filler, disintegrant, gliding agent and lubricant for each prescription according to the table above; Mix the API with other components except for the gliding agent and lubricant using a multi-directional motion mixer at a speed of 5-15 rpm for 30 minutes.

[0046] The above materials are sieved through a 40-mesh sieve. Then, the flow aid and lubricant are added and mixed at a speed of 5-15 rpm for 15 minutes.

[0047] Tablets are compressed using a rotary tablet press at a pressure of 20N.

[0048] Example 5 4000 tablets were made, each containing approximately 100mg. Tablet preparation method: Weigh out the amounts of API, filler, disintegrant, gliding agent and lubricant for each prescription according to the table above; Mix the API with other components except for the gliding agent and lubricant using a multi-directional motion mixer at a speed of 5-15 rpm for 30 minutes.

[0049] The above materials are sieved through a 40-mesh sieve. Then, the flow aid and lubricant are added and mixed at a speed of 5-15 rpm for 15 minutes.

[0050] Tablets are compressed using a rotary tablet press at a pressure of 20N.

[0051] This invention uses lactose monohydrate as a filler, which has good flowability and compressibility. After compression into tablets, it forms a smooth and dense surface, effectively delaying the rapid penetration of moisture from the air and preventing moisture absorption by the finished product. Furthermore, its water solubility ensures it does not affect drug dissolution, thus improving tablet bioavailability. This invention employs a simpler direct compression process, which is simple and stable, reducing material and labor costs, facilitating large-scale production, and significantly reducing energy consumption, labor, and material waste. The formulation of this invention is simple, with good flowability and good dissolution reproducibility, which is beneficial for improving in vivo bioavailability. It also exhibits the same or better safety and efficacy as the original drug.

[0052] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention in any way. Therefore, any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention should fall within the protection scope of the present invention.

Claims

1. A fludrocortisone acetate tablet, characterized in that, Including the following components by mass percentage, totaling 100%: Fludrocortisone acetate 0.08~0.12%; Lactose monohydrate 80-95%; Direct-pressed corn starch 2-8%; Flow aid 0.2~1.0%; Lubricant 0.2~1.5%; The fludrocortisone acetate tablets are prepared by the following method: fludrocortisone acetate, lactose monohydrate, and direct-pressed corn starch are mixed and then sieved; a gliding agent and a lubricant are added and mixed, and then the mixture is compressed into tablets.

2. The fluhydrocortisone acetate tablets according to claim 1, characterized in that, The fluhydrocortisone acetate has a D90 of <20 micrometers and a D50 of <10 micrometers.

3. The fluhydrocortisone acetate tablets according to claim 1, characterized in that, The flow aid is talc and / or silica.

4. The fluhydrocortisone acetate tablets according to claim 1, characterized in that, The lubricant is one or more of magnesium stearate, hydrogenated castor oil, and sodium stearate.

5. A method for preparing fludrocortisone acetate tablets according to any one of claims 1 to 4, characterized in that, Includes the following steps: (1) Mix fludrocortisone acetate, lactose monohydrate, and direct-pressed corn starch, and then sieve; (2) Add glidin and lubricant, mix, and then compress into tablets.

6. The method for preparing fludrocortisone acetate tablets according to claim 5, characterized in that, Step (1) Mixing speed 5~15 rpm, mixing time 10~40 min.

7. The method for preparing fludrocortisone acetate tablets according to claim 5, characterized in that, The sieve mesh size in step (1) is 20~60 mesh.

8. The method for preparing fludrocortisone acetate tablets according to claim 5, characterized in that, Step (2) Mixing speed 5~15 rpm, mixing time 5~20 min.

9. The method for preparing fludrocortisone acetate tablets according to claim 5, characterized in that, The tableting pressure in step (2) is 20~60N.

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