Fenoprofen calcium composition and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a fenoprofen calcium composition and a preparation method, the fenoprofen calcium composition comprises the following components by weight: 63-80% of fenoprofen calcium, 5-20% of a filler, 7-15% of a disintegrating agent composition, 3-6% of an adhesive, 0.5-2% of a lubricant, and 0.1-2% of a surfactant; the disintegrating agent composition comprises dry starch and a disintegrating agent, wherein the disintegrating agent comprises one or more of sodium carboxymethyl starch, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose and croscarmellose sodium; the weight ratio of the dry starch to the disintegrating agent is 1: (0.5-3); the disintegration efficiency and the dissolution rate of the composition can be effectively improved.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a fenprofen calcium composition and its preparation method. Background Technology

[0002] Fennoprofen calcium is a nonsteroidal anti-inflammatory drug with antipyretic, analgesic, and anti-inflammatory effects. It reduces the synthesis of inflammatory mediators such as prostaglandins by inhibiting cyclooxygenase, thereby controlling swelling and pain in local tissues caused by prostaglandins.

[0003] CN201510041175.1 discloses a fenoprofen calcium pharmaceutical composition, with the following mass percentages of each component: fenoprofen calcium 68%, sodium carboxymethyl starch 22%, and hydroxypropyl cellulose 9%. Because fenoprofen calcium active pharmaceutical ingredient constitutes a large proportion of the formulation and has a low density, its material properties result in poor compressibility of samples prepared using conventional formulations. Even if tablets can be formed, the disintegration time is long, affecting the release of the active pharmaceutical ingredient and thus impacting the bioavailability of the formulation. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a nonprofen calcium composition and a preparation method, which effectively improves the disintegration efficiency and dissolution rate of the composition.

[0005] This invention provides a fenofofen calcium composition comprising the following components in weight percentage: Fenolprofen calcium: 63~80% Filler: 5~20% Disintegrant composition: 7~15% Adhesive: 3~6% Lubricant: 0.5~2% Surfactant: 0.1~2%; The disintegrant composition comprises dry starch and a disintegrant, wherein the disintegrant comprises one or more of sodium carboxymethyl starch, crospovidone, low-substituted hydroxypropyl cellulose, and crospovidone carboxymethyl cellulose; the weight ratio of the dry starch to the disintegrant is 1:0.5~3.

[0006] Preferably, the components include the following components in weight percentage: Fenolofen calcium: 68~80% Filler: 5~15% Disintegrant composition: 7~15% Adhesive: 5~6% Lubricant: 0.5~1% Surfactant: 0.1~2%.

[0007] Preferably, the disintegrant is crospovidone or low-substituted hydroxypropyl cellulose.

[0008] Preferably, the weight ratio of the dry starch to the disintegrant is 1:0.5~1.5.

[0009] Preferably, the filler includes one or more of pregelatinized starch, microcrystalline cellulose, mannitol, and lactose.

[0010] Preferably, the adhesive comprises one or more of povidone, carboxymethyl cellulose, and hydroxypropyl methylcellulose.

[0011] Preferably, the lubricant includes one or more of stearic acid, magnesium stearate, calcium stearate, and talc.

[0012] Preferably, the surfactant includes one or more of sodium dodecyl sulfate, Tween 80, and poloxamer.

[0013] Preferably, the dosage form of the nonoprofen calcium composition is a tablet.

[0014] This invention provides a method for preparing the aforementioned fenoprofen calcium composition, wherein the fenoprofen calcium composition is in tablet form, and the steps are as follows: Each component is pulverized and sieved. All components except lubricant, surfactant, and dry starch are added to a wet granulator. The aqueous solution of surfactant is used as a wetting agent to form a soft mass. The mass is stirred (time controlled at 3-5 min) and granulated. The granulated material is dried and then sized. Lubricant and dry starch are added, the mixture is mixed, and then pressed into tablets.

[0015] The beneficial effects of this invention are that the disintegrants of this invention employ a combination of two disintegrants with different mechanisms of action, which can significantly improve the disintegration of the fenprofen calcium composition without affecting the release of the active pharmaceutical ingredient. The mechanism of action of dry starch as a disintegrant is mainly capillary action, utilizing its hydrophilic properties to allow water to rapidly diffuse throughout the formulation in the early stages of disintegration, creating conditions for subsequent swelling. The main principle of sodium carboxymethyl starch, crospovidone, low-substituted hydroxypropyl cellulose, and crospovidone carboxymethyl cellulose as disintegrants is swelling action, which, in conjunction with capillary action, can significantly improve disintegration efficiency.

[0016] This invention addresses the problem of difficult sample disintegration by employing a combination of two disintegrants with different principles, while also increasing the release of active pharmaceutical ingredients and improving the bioavailability of the formulation.

[0017] The formulation process of this invention is simple and easy to operate, and it solves the problems of product compressibility, disintegration, and dissolution. It has a wide range of applications and strong production feasibility. Detailed Implementation

[0018] Example 1 A fenolofen calcium composition, the formulation of which is as follows:

[0019] The preparation method is as follows: 1) The raw material drug is pulverized and sieved.

[0020] 2) Add the fenoprofen calcium, mannitol, crospovidone, and povidone K30 from the prescription to a wet granulator, add Tween-80 to purified water as a wetting agent, prepare a soft mass, and stir and shear for 3 minutes.

[0021] 3) After the granulated material is dried in an oven at 55°C, it is granulated, and dry starch and magnesium stearate are added. The mixture is then pressed into tablets.

[0022] Example 2 A fenolofen calcium composition, the formulation of which is as follows:

[0023] The preparation method is the same as in Example 1. Specifically, it follows the preparation method of this invention (each component is pulverized and sieved; all components except lubricant, surfactant, and dry starch are added to a wet granulator; an aqueous solution of the surfactant is used as a wetting agent to form a soft mass; stirring is performed (time controlled at 3-5 min); granulation is then carried out; the granulated material is dried and sized; lubricant and dry starch are added; the mixture is then pressed into tablets). When the raw material inputs differ in different examples and comparative proportions, the corresponding raw materials are adjusted according to the above principles. The same applies below.

[0024] Example 3 A fenolofen calcium composition, the formulation of which is as follows:

[0025] The preparation method is the same as in Example 1.

[0026] Comparative Example 1 A fenolofen calcium composition, the formulation of which is as follows:

[0027] The preparation method is the same as in Example 1.

[0028] Comparative Example 2 A fenolofen calcium composition, the formulation of which is as follows:

[0029] The preparation method is the same as in Example 1.

[0030] Comparative Example 3 A fenolofen calcium composition, the formulation of which is as follows:

[0031] The preparation method is the same as in Example 1.

[0032] Comparative Example 4 A fenolofen calcium composition, the formulation of which is as follows:

[0033] The preparation method is the same as in Example 1.

[0034] Hardness and disintegration time were tested according to the general rules of the Chinese Pharmacopoeia, and dissolution rate in water for 30 minutes was tested according to the Japanese Orange Book. The results are shown in the table below.

[0035]

[0036] As can be seen from the table above, using a combination of dry starch with one or more of sodium carboxymethyl starch, crospovidone, low-substituted hydroxypropyl cellulose, and crospovidone carboxymethyl cellulose, and controlling the weight ratio of the two, can significantly improve tablet hardness, reduce disintegration time, and increase dissolution rate compared to using dry starch alone, using too much dry starch, or using other disintegrant combinations that do not contain dry starch.

[0037] Those skilled in the art should understand that the discussion of any of the above embodiments is merely exemplary and is not intended to imply that the scope of protection of this application is limited to these examples; under the concept of this application, the technical features of the above embodiments or different embodiments can also be combined, the steps can be implemented in any order, and there are many other variations of different aspects of one or more embodiments of this application as described above, which are not provided in detail for the sake of brevity.

[0038] One or more embodiments in this application are intended to cover all such substitutions, modifications, and variations that fall within the broad scope of this application. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of one or more embodiments in this application should be included within the protection scope of this application.

Claims

1. A non-norprofen calcium composition, characterized in that, The components include the following components by weight percentage: Fenolprofen calcium: 63~80% Filler: 5~20% Disintegrant composition: 7~15% Adhesive: 3~6% Lubricant: 0.5~2% Surfactant: 0.1~2%; The disintegrant composition comprises dry starch and a disintegrant, wherein the disintegrant comprises one or more of sodium carboxymethyl starch, crospovidone, low-substituted hydroxypropyl cellulose, and crospovidone carboxymethyl cellulose; the weight ratio of the dry starch to the disintegrant is 1:0.5~3.

2. The non-norprofen calcium composition as described in claim 1, characterized in that, The components include the following components by weight percentage: Fenolofen calcium: 68~80% Filler: 5~15% Disintegrant composition: 7~15% Adhesive: 5~6% Lubricant: 0.5~1% Surfactant: 0.1~2%.

3. The non-norprofen calcium composition as described in claim 1, characterized in that, The disintegrant is crospovidone or low-substituted hydroxypropyl cellulose.

4. The non-norprofen calcium composition as described in claim 1, characterized in that, The weight ratio of the dry starch to the disintegrant is 1:0.5~1.

5.

5. The nonoprofen calcium composition according to any one of claims 1-4, characterized in that, The filler includes one or more of pregelatinized starch, microcrystalline cellulose, mannitol, and lactose.

6. The nonoprofen calcium composition according to any one of claims 1-4, characterized in that, The adhesive includes one or more of polyvinylpyrrolidone, carboxymethyl cellulose, and hydroxypropyl methylcellulose.

7. The nonoprofen calcium composition according to any one of claims 1-4, characterized in that, The lubricant includes one or more of stearic acid, magnesium stearate, calcium stearate, and talc.

8. The nonoprofen calcium composition according to any one of claims 1-4, characterized in that, The surfactant includes one or more of sodium dodecyl sulfate, Tween 80, and poloxamer.

9. The nonoprofen calcium composition according to any one of claims 1-4, characterized in that, The dosage form of the nonoprofen calcium composition is tablets.

10. A method for preparing a nonoprofen calcium composition as described in any one of claims 1-9, characterized in that, The dosage form of the fenofofen calcium composition is tablets, and the steps are as follows: Each component is pulverized and sieved. All components except lubricant, surfactant, and dry starch are added to a wet granulator. An aqueous solution of surfactant is used as a wetting agent to form a soft mass. The mass is stirred and granulated. The granulated material is dried and then sized. Lubricant and dry starch are added, the mixture is mixed, and then pressed into tablets.

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