A preparation of alendronate sodium and a method for preparing the same

Abstract

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a preparation of alendronate sodium and a preparation method thereof. The preparation of alendronate sodium provided by the application is composed of an alendronate sodium-cyclodextrin inclusion compound and pharmaceutically acceptable adjuvants. The preparation of the inclusion compound adopts ergosterol as an oil phase, is mixed with an aqueous phase containing alendronate sodium, sodium glucoheptonate and tromethamine, is subjected to high-speed shearing emulsification treatment to form an emulsion, is then subjected to an inclusion reaction by adding cyclodextrin, and finally is subjected to reduced pressure distillation, washing and drying to obtain the inclusion compound. The application improves the drug loading and the encapsulation efficiency of the inclusion compound by means of a specific adjuvant combination and an emulsification and inclusion process. The obtained preparation can effectively improve the in-vivo absorption level of alendronate sodium after oral administration, and overcomes the technical defect of low oral bioavailability of the drug.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to an alendronate sodium formulation and its preparation method. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Alendronate sodium is a third-generation bisphosphonate bone resorption inhibitor, widely used clinically as a first-line drug for the treatment of osteoporosis in postmenopausal women, osteoporosis in men, and Paget's disease, among other bone metabolic diseases. Its mechanism of action lies in its strong affinity for hydroxyapatite within bone, selectively acting on osteoclasts to inhibit bone resorption and reduce bone turnover.

[0004] However, alendronate sodium has drawbacks in clinical application, such as low oral bioavailability, which to some extent affects its efficacy and patient adherence. Therefore, exploring formulation technologies that can improve the oral absorption of alendronate sodium is of significant clinical importance.

[0005] To address the aforementioned issues, those skilled in the art have explored various formulation technologies.

[0006] Chinese patent CN1745754A discloses an alendronate sodium inclusion complex and its formulation. This complex utilizes cyclodextrin inclusion technology to process alendronate sodium into liquid and solid inclusion complexes, with the molar ratio of alendronate sodium to cyclodextrin ranging from 1:1 to 100. This approach aims to improve the water solubility of alendronate sodium, but it does not systematically optimize inclusion efficiency indicators such as drug loading and encapsulation rate.

[0007] Chinese patent CN101632680A discloses a compound alendronate sodium and vitamin D3 enteric-coated tablet and its preparation method. The formulation consists of a β-cyclodextrin inclusion complex of alendronate sodium and vitamin D3, an enteric coating material, and pharmaceutically acceptable excipients. In this formulation, vitamin D3 is added in the form of a cyclodextrin inclusion complex, while alendronate sodium itself is not encapsulated by cyclodextrin. Therefore, the water solubility and transmembrane permeability of alendronate sodium are not substantially improved.

[0008] Chinese patent CN114796605A discloses a method for preparing a natural supramolecular hydrogel material that can promote osteogenic differentiation. The method involves introducing sodium alendronate into a hydrogel network after chemical modification. This technology is mainly aimed at bone tissue repair scaffold materials, rather than oral administration formulations. Its application scenario is different from conventional oral treatment regimens in this field.

[0009] In summary, there is still a lack of oral formulations in the current technology that combine high drug loading capacity, high encapsulation efficiency, and improved oral bioavailability of alendronate sodium. Summary of the Invention

[0010] To overcome the shortcomings of existing technologies, this invention provides an alendronate sodium formulation and its preparation method. This invention prepares a cyclodextrin inclusion complex by combining alendronate sodium with specific excipients, which can improve the drug loading and encapsulation efficiency of the inclusion complex and enhance the oral absorption of alendronate sodium.

[0011] To achieve the above technical objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides an alendronate sodium formulation, wherein the alendronate sodium formulation comprises an alendronate sodium-cyclodextrin inclusion complex and pharmaceutically acceptable excipients; The preparation method of the sodium alendronate-cyclodextrin inclusion complex is as follows: (1) Dissolve ergosterol in an organic solvent to obtain an ergosterol solution; (2) Dissolve sodium alendronate, sodium gluconate and tromethamine in water or a water-ethanol mixture, stir to dissolve, and obtain a mixed aqueous solution; (3) The ergosterol solution from step (1) is mixed with the mixed aqueous solution from step (2), and the mixture is sheared using a high-speed shear emulsifier to obtain a uniform emulsion. (4) Add cyclodextrin to the emulsion in step (3) and carry out the inclusion reaction at a temperature of 40-60°C to obtain the inclusion solution; (5) The inclusion solution is subjected to vacuum distillation to collect the solid product, washed with purified water, and dried to obtain alendronate sodium-cyclodextrin inclusion complex.

[0012] Preferably, the components of the sodium alendronate-cyclodextrin inclusion complex, by weight, are: 1 part sodium alendronate, 5-10 parts cyclodextrin, 0.2-0.5 parts ergosterol, 0.05-0.3 parts sodium gluconate, and 0.05-0.3 parts tromethamine; more preferably, the components of the sodium alendronate-cyclodextrin inclusion complex, by weight, are: 1 part sodium alendronate, 6 parts cyclodextrin, 0.3 parts ergosterol, 0.2 parts sodium gluconate, and 0.15 parts tromethamine.

[0013] Preferably, the cyclodextrin is selected from one or more of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, or γ-cyclodextrin; more preferably, the cyclodextrin is hydroxypropyl-β-cyclodextrin.

[0014] Preferably, the organic solvent in step (1) is anhydrous ethanol or methanol; more preferably, the organic solvent is anhydrous ethanol; the mass-to-volume ratio of ergosterol to organic solvent is 1:10 to 1:20 (g / mL); more preferably, the mass-to-volume ratio of ergosterol to organic solvent is 1:15 (g / mL).

[0015] Preferably, the amount of water or water-ethanol mixed solvent used in step (2) is 15 to 30 times the total mass of sodium alendronate, sodium gluconate, and tromethamine; more preferably, the amount of water or water-ethanol mixed solvent used in step (2) is 20 times the total mass of sodium alendronate, sodium gluconate, and tromethamine; the volume fraction of ethanol in the water-ethanol mixed solvent is 20% to 40%; more preferably, the volume fraction of ethanol in the water-ethanol mixed solvent is 30%.

[0016] Preferably, the high-speed shear emulsifier in step (3) has a rotation speed of 10,000 to 12,000 rpm and a shearing time of 5 to 15 minutes; more preferably, the high-speed shear emulsifier in step (3) has a rotation speed of 11,000 rpm and a shearing time of 10 minutes.

[0017] Preferably, the inclusion reaction time in step (4) is 5 to 8 hours, and the stirring is carried out at a speed of 200 to 600 rpm during the reaction; more preferably, the inclusion reaction time in step (4) is 6 hours, and the stirring is carried out at a speed of 400 rpm during the reaction.

[0018] Preferably, the drying process in step (5) is vacuum drying, and the drying temperature does not exceed 50°C.

[0019] In the preparation of the inclusion complex of this invention, ergosterol, as the oil phase component, forms fine droplets in the aqueous phase under high-speed shearing. This emulsion system increases the oil-water interface area, providing a physical environment for the arrangement of cyclodextrin molecules at the interface and the occurrence of inclusion reactions. Sodium gluconate and tromethamine, after ionization in water, can adjust the pH and ionic strength of the aqueous phase. These two factors can affect the dissociation state of sodium alendronate molecules in water and the intermolecular interaction forces between them and the cyclodextrin cavity.

[0020] Preferably, the pharmaceutically acceptable excipients include one or more of fillers, binders, disintegrants, lubricants, or enteric coating materials.

[0021] Preferably, the formulation is an oral solid dosage form, selected from tablets, capsules, granules or powders.

[0022] Secondly, the present invention provides the use of the alendronate sodium preparation in the preparation of drugs for treating bone metabolic diseases.

[0023] Compared with the prior art, the technical advantages of the present invention are as follows: (1) The alendronate sodium-cyclodextrin inclusion complex provided by this invention has a high drug loading and encapsulation efficiency. Comparative Examples 1-3, lacking ergosterol, sodium gluconate, or tromethamine respectively, had lower drug loading and encapsulation efficiency than the examples; Comparative Examples 4-6, having replaced the aforementioned key excipients, also had lower encapsulation efficiency than the examples; Comparative Example 7, lacking high-speed shear emulsification, also had lower encapsulation efficiency than the examples. These results indicate that the drug loading and encapsulation efficiency of the inclusion complex are related to the presence of specific excipients in the formulation and the application of shear emulsification technology.

[0024] (2) The alendronate sodium formulation provided by the present invention helps to improve the oral absorption level of the drug. The pharmacokinetic evaluation results in rats showed that the cumulative urinary excretion of the formulations in each embodiment of the present invention was higher than that of the raw material group and the commercial reference formulation group, indicating that the oral absorption of alendronate sodium is improved through the inclusion complex and related formulations described in the present invention. Attached Figure Description

[0025] Figure 1 Drug loading and encapsulation efficiency of alendronate sodium inclusion complex.

[0026] Figure 2 The cumulative urinary drug excretion of the formulation in rats over 48 hours in the example is shown. Detailed Implementation

[0027] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0028] Example 1: Sodium alendronate inclusion complex formula: Alendronate sodium: 1.0 g Hydroxypropyl-β-cyclodextrin: 6.0 g Ergosterol: 0.3 g Sodium gluconate: 0.2 g Tromethamine: 0.15 g Preparation method: (1) Dissolve ergosterol in 4.5 mL of anhydrous ethanol and stir until completely dissolved to obtain an ergosterol solution; (2) Dissolve sodium alendronate, sodium gluconate and tromethamine in 27g of a 30% water-ethanol mixed solvent and stir until completely dissolved to obtain a mixed aqueous solution; (3) The ergosterol solution from step (1) is mixed with the mixed aqueous solution from step (2), and the mixture is sheared at 11,000 rpm for 10 minutes using a high-speed shear emulsifier to obtain a uniform emulsion. (4) Add hydroxypropyl-β-cyclodextrin to the emulsion in step (3) and stir at 400 rpm at 50°C for 6 hours to carry out the inclusion reaction to obtain the inclusion solution; (5) The solvent in the inclusion solution is removed by vacuum distillation, the solid product is collected, washed, and the solid product is placed in a vacuum drying oven and dried at 45°C to constant weight to obtain alendronate sodium-cyclodextrin inclusion complex.

[0029] Example 2: Sodium alendronate inclusion complex formula: Alendronate sodium: 1.0 g β-Cyclodextrin: 5.0 g Ergosterol: 0.2 g Sodium gluconate: 0.05 g Tromethamine: 0.05 g Preparation method: (1) Dissolve ergosterol in 2.0 mL of anhydrous ethanol and stir until completely dissolved to obtain an ergosterol solution; (2) Dissolve sodium alendronate, sodium gluconate and tromethamine in 16.5 g of water and stir until completely dissolved to obtain a mixed aqueous solution; (3) The ergosterol solution from step (1) is mixed with the mixed aqueous solution from step (2), and the mixture is sheared at 10,000 rpm for 15 minutes using a high-speed shear emulsifier to obtain a uniform emulsion. (4) Add β-cyclodextrin to the emulsion in step (3) and stir at 200 rpm at 40°C for 8 hours to carry out the inclusion reaction to obtain the inclusion solution; (5) The solvent in the inclusion solution is removed by vacuum distillation, the solid product is collected, washed, and the precipitate is placed in a vacuum drying oven and dried at 40°C to constant weight to obtain alendronate sodium-cyclodextrin inclusion complex.

[0030] Example 3: Sodium alendronate inclusion complex formula: Alendronate sodium: 1.0 g Sulfobutyl ether-β-cyclodextrin: 10 g Ergosterol: 0.5g Sodium gluconate: 0.3 g Tromethamine: 0.3 g Preparation method: (1) Dissolve ergosterol in 10 mL of methanol and stir until completely dissolved to obtain an ergosterol solution; (2) Dissolve sodium alendronate, sodium gluconate and tromethamine in 48 g of a 40% water-ethanol mixed solvent and stir until completely dissolved to obtain a mixed aqueous solution; (3) The ergosterol solution from step (1) is mixed with the mixed aqueous solution from step (2), and the mixture is sheared at 12,000 rpm for 5 minutes using a high-speed shear emulsifier to obtain a uniform emulsion. (4) Add sulfobutyl ether-β-cyclodextrin to the emulsion in step (3), and stir at 600 rpm at 60°C for 5 hours to carry out the inclusion reaction to obtain the inclusion solution; (5) The solvent in the inclusion solution is removed by vacuum distillation, the solid product is collected, washed, and the solid product is placed in a vacuum drying oven and dried at 50°C to constant weight to obtain alendronate sodium-cyclodextrin inclusion complex.

[0031] Example 4: Sodium alendronate inclusion complex formula: Alendronate sodium: 1.0 g γ-Cyclodextrin: 7.5 g Ergosterol: 0.4 g Sodium gluconate: 0.1 g Tromethamine: 0.1 g Preparation method: (1) Dissolve ergosterol in 6 mL of anhydrous ethanol and stir until completely dissolved to obtain an ergosterol solution; (2) Dissolve sodium alendronate, sodium gluconate and tromethamine in 30 g of a 25% water-ethanol mixed solvent and stir until completely dissolved to obtain a mixed aqueous solution; (3) The ergosterol solution from step (1) is mixed with the mixed aqueous solution from step (2), and the mixture is sheared at 10,500 rpm for 12 minutes using a high-speed shear emulsifier to obtain a uniform emulsion. (4) Add γ-cyclodextrin to the emulsion in step (3) and stir at 350 rpm at 48°C for 7 hours to carry out the inclusion reaction to obtain the inclusion solution; (5) The solvent in the inclusion solution is removed by vacuum distillation, the solid product is collected, washed, and the precipitate is placed in a vacuum drying oven and dried at 42°C to constant weight to obtain alendronate sodium-cyclodextrin inclusion complex.

[0032] Example 5: Ordinary Tablets Preparation method: Mix the inclusion complex, microcrystalline cellulose, lactose, and croscarmellose sodium through an 80-mesh sieve until uniform. Prepare a soft mass with an aqueous solution of hydroxypropyl cellulose, granulate through a 20-mesh sieve, dry at 45°C until the moisture content is <3%, add magnesium stearate after granulation, and compress into tablets to obtain the final product.

[0033] Example 6 Enteric-coated tablets Preparation method: The inclusion complex is mixed with mannitol, pregelatinized starch and cross-linked povidone, granulated with povidone K30 ethanol solution, dried and granulated, and then compressed with sodium stearate fumarate to obtain tablet cores; the tablet cores are coated with enteric coating (coating weight gain 5%) to obtain the final product.

[0034] Example 7 Capsules Preparation method: The inclusion complex is mixed evenly with microcrystalline cellulose, corn starch and sodium carboxymethyl starch, purified water is added to make a soft material, granulated through a 20-mesh sieve, dried at 45℃, and after granulation, magnesium stearate is added and mixed evenly, and then filled into hollow capsule shells to obtain the final product.

[0035] Example 8 Granules Preparation method: The inclusion complex is mixed with sucrose and mannitol, and hydroxypropyl cellulose aqueous solution is added to prepare a soft mass. The mass is granulated through a 20-mesh sieve, dried at 45°C, and then packaged into bags containing 10 mg of sodium alendronate.

[0036] Example 9: Ordinary Tablets Preparation method: Mix the inclusion complex, microcrystalline cellulose, mannitol, and cross-linked polyvinyl alcohol through an 80-mesh sieve for 15 min, add magnesium stearate and mix for another 5 min, then compress directly into tablets.

[0037] Example 10 Enteric-coated capsules Preparation method: The inclusion complex is mixed with lactose, microcrystalline cellulose and low-substituted hydroxypropyl cellulose, granulated with purified water, dried and granulated, then mixed with magnesium stearate, and filled into enteric-coated empty capsule shells to obtain the final product.

[0038] Example 11 Dispersible tablets Preparation method: The inclusion complex is mixed with microcrystalline cellulose, mannitol, croscarmellose sodium, and low-substituted hydroxypropyl cellulose, granulated with PVP K30 ethanol solution, dried and granulated, then mixed with stevioside and magnesium stearate, and compressed into tablets.

[0039] Example 12 Powder Preparation method: The inclusion complex, lactose, and sucrose are passed through an 80-mesh sieve and mixed evenly using an equal-incremental method. Citric acid and flavoring are added and mixing is continued. After testing the uniformity of the content, the mixture is packaged into bags containing 10 mg of alendronate sodium.

[0040] Comparative Example 1 Formula (the rest is exactly the same as in Example 1): Alendronate sodium: 1.0 g, hydroxypropyl-β-cyclodextrin: 6.0 g, gluconate sodium: 0.2 g, tromethorphan: 0.15 g.

[0041] Preparation method: The only difference from Example 1 is that step (1) is omitted. The mixed aqueous solution from step (2) is directly subjected to high-speed shearing, and then cyclodextrin is added for inclusion reaction. The remaining steps (shearing, inclusion, drying) and parameters are exactly the same.

[0042] Comparative Example 2 Formula (the rest is exactly the same as in Example 1): Alendronate sodium: 1.0 g, hydroxypropyl-β-cyclodextrin: 6.0 g, ergosterol: 0.3 g, tromethorphan: 0.15 g.

[0043] Preparation method: The only difference from Example 1 is that in step (2), only sodium alendronate and tromethamine are dissolved in a water-ethanol mixed solvent, and sodium gluconate is not added. The remaining steps are exactly the same.

[0044] Comparative Example 3 Formula (the rest is exactly the same as in Example 1): Alendronate sodium: 1.0 g, hydroxypropyl-β-cyclodextrin: 6.0 g, ergosterol: 0.3 g, sodium gluconate: 0.2 g.

[0045] Preparation method: The only difference from Example 1 is that in step (2), only sodium alendronate and sodium gluconate are dissolved in a water-ethanol mixed solvent, and tromethamine is not added. The remaining steps are exactly the same.

[0046] Comparative Example 4 formula: Cholesterol 0.3 g, the rest is exactly the same as in Example 1.

[0047] Preparation method: completely consistent with Example 1, except that ergosterol in step (1) is replaced with cholesterol in equal amounts.

[0048] Comparative Example 5 formula: Sodium gluconate 0.2 g, the rest is exactly the same as in Example 1.

[0049] Preparation method: completely consistent with Example 1, except that sodium gluconate in step (2) is replaced with sodium gluconate in equal amounts.

[0050] Comparative Example 6 formula: 0.15 g of triethanolamine, the rest is exactly the same as in Example 1.

[0051] Preparation method: completely consistent with Example 1, except that the tromethamine in step (2) is replaced with triethanolamine in equal amounts.

[0052] Comparative Example 7 formula: Alendronate sodium: 1.0 g, hydroxypropyl-β-cyclodextrin: 6.0 g, ergosterol: 0.3 g, sodium gluconate: 0.2 g, tromethorphan: 0.15 g.

[0053] Preparation method: (1) Dissolve ergosterol in 4.5 mL of anhydrous ethanol and stir until completely dissolved to obtain an ergosterol solution; (2) Dissolve sodium alendronate, sodium gluconate and tromethamine in 27g of a 30% water-ethanol mixed solvent and stir until completely dissolved to obtain a mixed aqueous solution; (3) Mix the ergosterol solution from step (1) with the mixed aqueous solution from step (2) and stir at 400 rpm for 10 minutes to obtain a mixture; (4) Add hydroxypropyl-β-cyclodextrin to the mixture in step (3), and carry out the inclusion reaction at 400 rpm at 50°C for 6 hours to obtain the inclusion solution; (5) The solvent in the inclusion solution is removed by vacuum distillation, the solid product is collected, washed, and the solid product is placed in a vacuum drying oven and dried at 45°C to constant weight to obtain alendronate sodium-cyclodextrin inclusion complex.

[0054] Evaluation of alendronate sodium-cyclodextrin inclusion complex Experimental materials Samples: Example 1, Example 2, Example 3, Example 4; Comparative Example 1, Comparative Example 2, Comparative Example 3, Comparative Example 4, Comparative Example 5, Comparative Example 6, Comparative Example 7.

[0055] Reference standard: alendronate sodium reference standard.

[0056] Evaluation indicators and operations Drug loading determination Drug loading refers to the percentage of the mass of the encapsulated drug relative to the total mass of the drug-carrier formulation. Formula: DL% = W 包封 / W 载药体系总重量 ×100%.

[0057] Encapsulation efficiency determination Encapsulation efficiency refers to the percentage of drug encapsulated within a carrier relative to the total amount of drug introduced. EE% = W 包封 / W 总 ×100%=(W 总 -W 游离 ) / W 总 ×100% Experimental data Table 1. Drug loading and encapsulation efficiency of alendronate sodium inclusion complex As shown in Table 1, the alendronate sodium-cyclodextrin inclusion complexes prepared in Examples 1-4 of this invention all exhibited excellent drug loading and encapsulation efficiency. In Comparative Examples 1-3, omitting ergosterol, sodium gluconate, or tromethamine resulted in varying degrees of decrease in drug loading and encapsulation efficiency, indicating that all three components are essential for achieving efficient inclusion. In Comparative Examples 4-6, replacing the corresponding excipients with cholesterol, sodium gluconate, or triethanolamine, the two indicators were also lower than in the examples, demonstrating the irreplaceable nature of the selected excipients. Comparative Example 7, without high-speed shear emulsification, also showed lower drug loading and encapsulation efficiency than the examples, confirming that this process step has a significant promoting effect on the inclusion reaction. In summary, the drug loading and encapsulation efficiency of the inclusion complexes are closely related to the presence of specific excipients in the formulation and the implementation of the shear emulsification process; the absence or replacement of any key component or the omission of key operational steps will lead to a decrease in inclusion efficiency.

[0058] Bioavailability evaluation of alendronate sodium formulation Experimental animals: SD rats (SPF grade, male, weighing 200-250 g), 6 rats per group.

[0059] Dosage regimen: All animals were fasted for 12 hours prior to the experiment, but had free access to water. Each group of animals was administered the corresponding preparation by gavage at a dose of 2.5 mg / kg, calculated as alendronate sodium.

[0060] The specific groupings are as follows: The active pharmaceutical ingredient (API) group received a suspension of alendronate sodium API (with 0.5% CMC-Na as a suspension aid); the reference formulation group received a suspension prepared from commercially available alendronate sodium tablets (Fosamax®, 70 mg / tablet); the Example 5 group received ordinary tablets prepared according to the method of Example 5 (wet granulation and tableting); the Example 6 group received enteric-coated tablets of Example 6; the Example 7 group received the contents of the capsules of Example 7 (dispersed in water before gavage); the Example 8 group received the granules of Example 8 (dispersed in water before gavage); the Example 9 group received ordinary tablets of Example 9 (direct compression); the Example 10 group received the contents of the enteric-coated capsules of Example 10 (dispersed before gavage); the Example 11 group received dispersible tablets of Example 11 (disintegrated and dispersed in water before gavage); and the Example 12 group received the powder of Example 12 (suspended in water before gavage). Because alendronate sodium has a very short half-life in plasma and is rapidly taken up by bone tissue, the relative absorption was evaluated using the cumulative urinary excretion method.

[0061] Sample collection: Urine was collected at 0-4 h, 4-24 h and 24-48 h after administration, and the urine volume was recorded. An appropriate amount of urine sample was stored at -20℃ for testing.

[0062] Detection method: The concentration of alendronate sodium in urine samples was determined by high performance liquid chromatography (HPLC). Samples were derivatized before analysis.

[0063] Evaluation indicators: Cumulative urinary drug excretion: Calculate the cumulative excretion of drugs at each time point within 48 hours.

[0064] Experimental results Table 2. Cumulative excretion of each formulation in rats The cumulative urinary excretion of alendronate sodium oral formulations prepared in each embodiment of the present invention in rats was higher than that in the raw material group and the commercially available reference formulation group. This indicates that the alendronate sodium-cyclodextrin inclusion complex and related formulations prepared by the present invention can promote the oral absorption of alendronate sodium and increase its in vivo exposure level. The present invention effectively overcomes the technical defect of low oral bioavailability of alendronate sodium and has clear advantages in clinical application.

Claims

1. An alendronate sodium formulation, characterized in that, The alendronate sodium formulation consists of an alendronate sodium-cyclodextrin inclusion complex and pharmaceutically acceptable excipients; The preparation method of the sodium alendronate-cyclodextrin inclusion complex is as follows: (1) Dissolve ergosterol in an organic solvent to obtain an ergosterol solution; (2) Dissolve sodium alendronate, sodium gluconate and tromethamine in water or a water-ethanol mixture, stir to dissolve, and obtain a mixed aqueous solution; (3) The ergosterol solution from step (1) is mixed with the mixed aqueous solution from step (2), and the mixture is sheared using a high-speed shear emulsifier to obtain a uniform emulsion. (4) Add cyclodextrin to the emulsion in step (3) and carry out the inclusion reaction at a temperature of 40-60°C to obtain the inclusion solution; (5) The inclusion solution is subjected to vacuum distillation to collect the solid product, which is then washed and dried to obtain alendronate sodium-cyclodextrin inclusion complex.

2. The alendronate sodium formulation according to claim 1, characterized in that, The components of the sodium alendronate-cyclodextrin inclusion complex, by weight parts, are: 1 part sodium alendronate, 5-10 parts cyclodextrin, 0.2-0.5 parts ergosterol, 0.05-0.3 parts sodium gluconate, and 0.05-0.3 parts tromethamine; preferably, the components of the sodium alendronate-cyclodextrin inclusion complex, by weight parts, are: 1 part sodium alendronate, 6 parts cyclodextrin, 0.3 parts ergosterol, 0.2 parts sodium gluconate, and 0.15 parts tromethamine.

3. The alendronate sodium formulation according to claim 1, characterized in that, The cyclodextrin is selected from one or more of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, or γ-cyclodextrin; preferably, the cyclodextrin is hydroxypropyl-β-cyclodextrin.

4. The alendronate sodium formulation according to claim 1, characterized in that, The organic solvent in step (1) is anhydrous ethanol or methanol; preferably, the organic solvent is anhydrous ethanol; the mass-volume ratio of ergosterol to organic solvent is 1:10 to 1:20; preferably, the mass-volume ratio of ergosterol to organic solvent is 1:

15.

5. The alendronate sodium formulation according to claim 1, characterized in that, The amount of water or water-ethanol mixed solvent used in step (2) is 15 to 30 times the total mass of sodium alendronate, sodium gluconate, and tromethamine; preferably, the amount of water or water-ethanol mixed solvent used in step (2) is 20 times the total mass of sodium alendronate, sodium gluconate, and tromethamine; the volume fraction of ethanol in the water-ethanol mixed solvent is 20% to 40%; preferably, the volume fraction of ethanol in the water-ethanol mixed solvent is 30%.

6. The alendronate sodium formulation according to claim 1, characterized in that, The high-speed shear emulsifier in step (3) has a rotation speed of 10,000 to 12,000 rpm and a shearing time of 5 to 15 minutes; preferably, the high-speed shear emulsifier in step (3) has a rotation speed of 11,000 rpm and a shearing time of 10 minutes.

7. The alendronate sodium formulation according to claim 1, characterized in that, The inclusion reaction time in step (4) is 5 to 8 hours, and the stirring is carried out at a speed of 200 to 600 rpm during the reaction; preferably, the inclusion reaction time in step (4) is 6 hours, and the stirring is carried out at a speed of 400 rpm during the reaction.

8. The alendronate sodium formulation according to claim 1, characterized in that, The drying process described in step (5) is vacuum drying, and the drying temperature does not exceed 50°C.

9. The sodium alendronate formulation according to any one of claims 1 to 8, characterized in that, Pharmaceutically acceptable excipients include one or more of fillers, binders, disintegrants, lubricants, or enteric coating materials.

10. The alendronate sodium formulation according to claim 9, characterized in that, The preparation is an oral solid dosage form, selected from tablets, capsules, granules or powders.

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