Albendazole suspension preparation and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical compositions, in particular to an albendazole suspension preparation and a preparation method thereof.The albendazole suspension preparation is obtained by mixing an albendazole inclusion compound, propylene glycol, a thickener, an emulsifier, a preservative, a stabilizer, a suspending aid, an antioxidant, deionized water and an acidity regulator, the albendazole clathrate compound is prepared from albendazole, chitosan and hydroxypropyl-beta-cyclodextrin, the hydroxypropyl-beta-cyclodextrin has a hydrophilic outer surface and a lipophilic central cavity, and the hydrophobic interaction of the hydroxypropyl-beta-cyclodextrin can accommodate a lipophilic drug albendazole, so that the solubility and the stability of the albendazole can be effectively improved, and the albendazole clathrate compound can be used for preparing a medicine for treating the albendazole. The albendazole clathrate compound has the advantages that the albendazole clathrate compound is prepared from hydroxypropyl-beta-cyclodextrin and chitosan, the chitosan has mucous membrane adhesion, the stagnation time of the albendazole clathrate compound on gastrointestinal mucosa is prolonged by grafting the chitosan to the surface of the hydroxypropyl-beta-cyclodextrin, the absorbability and bioavailability of gastrointestinal tracts are further improved, the albendazole clathrate compound and the hydroxypropyl-beta-cyclodextrin have a synergistic effect, the drug effect of the albendazole is improved, and the albendazole clathrate compound has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical composition technology, and in particular to an albendazole suspension formulation and its preparation method. Background Technology

[0002] With the development of livestock farming, many animals such as pigs, cattle, sheep, and chickens are now raised in intensive, concentrated environments. Under these conditions, parasitic diseases are more likely to develop and spread. Therefore, eliminating internal parasites and promoting healthy animal growth is particularly important. Currently, there are many types of veterinary deworming drugs on the market.

[0003] Albendazole, also known as propylthioimidazole, belongs to the benzimidazole class. Its chemical name is methyl 5-propylthio-1H-benzimidazole-2-carbamate, and its molecular formula is C6H2O. 12 H 15 N3O2S, with a relative molecular weight of 265.0885 and a melting point of 208-210℃, is a broad-spectrum, highly effective, and low-toxicity veterinary anthelmintic. It exhibits high activity against nematodes, schistosomes, and tapeworms, and significantly inhibits egg development. It also has a marked exterminant effect on various nematodes, schistosomes, tapeworms, and cysticercosis that parasitize animals. After being metabolized in the body into sulfoxides or sulfones, it inhibits the parasite's absorption of glucose, leading to glycogen depletion, or inhibits the fumarate reductase system, hindering ATP production and preventing parasite survival and reproduction. Albendazole is not only highly effective against adult worms but also has a strong killing effect on immature worms, larvae, and eggs.

[0004] Because albendazole is a poorly soluble substance, insoluble in water and most organic solvents, and only soluble in certain acids, its application is greatly limited. Currently, products using albendazole as the main ingredient are available in various dosage forms, including powders, tablets, and suspensions. The most widely used albendazole tablets are inconvenient for livestock. In livestock use, the administration process is cumbersome, easily causing vomiting and resulting in inaccurate dosage, affecting the deworming effect. Furthermore, tablets require wetting and disintegration before slow release and absorption, have a long peak time, slow action, and low bioavailability. Powders are mixed with feed, but uneven mixing and intake due to feed type, particle size, and feed intake can lead to insignificant deworming effects. Suspensions offer better administration routes than tablets and powders, but due to the poor solubility of albendazole, the bioavailability of ordinary suspensions remains very low.

[0005] Suspensions are non-homogeneous liquid preparations formed by dispersing poorly soluble solid drugs in a dispersion medium in a particulate state. The drug particles in suspensions are generally between 0.5 and 10 μm, with some as small as 0.1 μm and others as large as 50 μm or larger.

[0006] In the prior art, patent document CN108992402A discloses an albendazole suspension and its preparation method. Each 100ml of suspension contains the following components measured by volume percentage: 10%-20% albendazole, 12%-16% emulsifier, 0.013%-0.015% thickener, 1%-1.5% stabilizer, 5.5%-6% suspending agent, 0.25%-0.3% preservative, acidity regulator, and the remainder is filled with water. This invention solves the problems of existing albendazole tablets being difficult to feed to livestock, cumbersome to operate, and prone to causing vomiting. It can also be diluted with water in any proportion and has a good suspension effect. However, albendazole has low solubility, and its absorption rate and bioavailability in the gastrointestinal tract still need to be improved.

[0007] Therefore, based on the relevant technologies mentioned above, there is an urgent need to develop an albendazole suspension formulation and its preparation method. Summary of the Invention

[0008] In view of this, the purpose of this invention is to provide an albendazole suspension formulation and its preparation method, so as to solve the problems of low solubility, poor absorption rate and bioavailability of albendazole in the gastrointestinal tract in the prior art.

[0009] To achieve the above objectives, the present invention provides an albendazole suspension formulation and its preparation method.

[0010] An albendazole suspension formulation comprises the following raw materials in parts by weight: 10-15 parts albendazole inclusion complex; 5-7 parts propylene glycol; 0.1-0.2 parts thickener; 12-20 parts emulsifier; 0.3-0.4 parts preservative; 0.2-0.5 parts stabilizer; 2-3 parts suspending agent; 0.5-1 part antioxidant; 165-182 parts deionized water; pH adjuster to adjust the system pH to 6-7. The albendazole inclusion complex was prepared from albendazole, hydroxypropyl-β-cyclodextrin and chitosan.

[0011] Preferably, the albendazole inclusion complex is prepared by the following method: Step A1. Add hydroxypropyl-β-cyclodextrin to a 5% sodium hydroxide solution and stir at 40-50℃ until completely dissolved. Then add epichlorohydrin dropwise, heat to react, and adjust the pH of the system to 7 with 20% hydrochloric acid to obtain mixture A. Step A2. Dissolve chitosan in a 1% acetic acid solution, add mixture A at 42-45℃, adjust the pH of the system to 9-9.5 with a 5% sodium hydroxide solution, and carry out the heating reaction. After the reaction is completed, adjust the pH of the system to 5 with acetic acid, dialyze with deionized water, and freeze dry to obtain compound A. Step A3. Add albendazole to glacial acetic acid and sonicate to obtain solution B. Then dissolve compound A in deionized water to obtain solution C. Add solution B dropwise to solution C at 500-700 rpm and mix thoroughly. Stir at room temperature in the dark for 10-12 hours. Centrifuge, filter, rotary evaporate, and freeze dry at 5000-6000 rpm to obtain the albendazole inclusion complex.

[0012] Preferably, the ratio of hydroxypropyl-β-cyclodextrin, sodium hydroxide solution, and epichlorohydrin used in step A1 is 5-8.5g:40-70mL:6-7.5mL; The heating reaction is carried out at a temperature of 45-53℃ for 4-5 hours.

[0013] Preferably, the ratio of chitosan to acetic acid solution in step A2 is 2-3g:100-150mL; The heating reaction is carried out at a temperature of 65-70℃ for 10-12 hours.

[0014] Preferably, the ratio of albendazole to glacial acetic acid in step A3 is 200-300 mg: 20-30 mL; The ratio of compound A to deionized water is 1-1.5g:100-150mL.

[0015] Preferably, the emulsifier is obtained by mixing Tween 80 and poloxamer 188 in a mass ratio of 2-4:1; The antioxidant is at least one of anhydrous sodium sulfite, sodium thiosulfate, thiourea, sodium bisulfite, and sodium formaldehyde sulfoxylate.

[0016] Preferably, the suspending agent is polyvinyl alcohol; The thickener is hydroxypropyl methylcellulose.

[0017] Preferably, the stabilizer is polyvinylpyrrolidone; The preservative is at least one of thimerosal and boric acid.

[0018] Preferably, the acidity regulator is PBS buffer.

[0019] A method for preparing an albendazole suspension formulation includes the following steps: Step S1. Add deionized water to propylene glycol and stir evenly at 70-80℃. Add suspending agent and albendazole inclusion complex and stir evenly to form a suspension. Mix the emulsifier by high-speed shear for 2-3 minutes at a speed of 17000-20000 rpm to obtain suspension A. Step S2. Add preservatives, antioxidants, thickeners and stabilizers to suspension A, and adjust the pH of the system to 6-7 with an acidity regulator. After stirring evenly, pass the mixture through a high-speed shear mixing emulsifier for 2-3 minutes at a speed of 17000-20000 rpm to obtain the albendazole suspension formulation.

[0020] The beneficial effects of this invention are: This invention provides an albendazole suspension formulation and its preparation method. The method involves mixing albendazole inclusion complex, propylene glycol, thickener, emulsifier, preservative, stabilizer, suspending agent, antioxidant, deionized water, and acidity regulator to prepare an albendazole suspension formulation with good solubility, high gastrointestinal absorption, and high bioavailability. The albendazole inclusion complex is prepared from albendazole, chitosan, and hydroxypropyl-β-cyclodextrin. Hydroxypropyl-β-cyclodextrin has a hydrophilic outer surface and a lipophilic central cavity; its hydrophobic interaction can accommodate the lipophilic drug albendazole, thereby effectively improving the solubility and stability of albendazole. Chitosan has mucosal adhesion properties; by grafting it onto the surface of hydroxypropyl-β-cyclodextrin, it prolongs the retention time of the albendazole inclusion complex on the gastrointestinal mucosa, thereby improving gastrointestinal absorption and bioavailability. The two components work synergistically to enhance the efficacy of albendazole, demonstrating broad application prospects compared to existing technologies. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments.

[0022] The sources and properties of some of the raw materials used in this invention are as follows: Example 1: A method for preparing an albendazole suspension formulation, comprising the following steps: S1. Add 5g of hydroxypropyl-β-cyclodextrin to 40mL of 5% sodium hydroxide solution and stir at 40℃ until completely dissolved. Then add 6mL of epichlorohydrin and heat at 45℃ for 4h. Adjust the pH of the system to 7 with 20% hydrochloric acid to obtain mixture A. S2. Dissolve 2g of chitosan in 100mL of 1% acetic acid solution, add mixture A at 42℃, adjust the pH of the system to 9 with 5% sodium hydroxide solution, heat the reaction at 65℃ for 10h, after the reaction is completed, adjust the pH of the system to 5 with acetic acid, dialyze with deionized water, and freeze dry to obtain compound A; S3. Add 200 mg of albendazole to 20 mL of glacial acetic acid and sonicate to obtain solution B. Then dissolve 1 g of compound A in 100 mL of deionized water to obtain solution C. Add solution B dropwise to solution C at 500 rpm and mix well. Stir at room temperature in the dark for 10 h. Centrifuge, filter, rotary evaporate, and freeze dry at 5000 rpm to obtain the albendazole inclusion complex. S4. Add 165g of deionized water to 5g of propylene glycol and stir evenly at 70℃. Add 2g of polyvinyl alcohol and 10g of albendazole inclusion complex and stir evenly to form a suspension. Pass the mixture through a high-speed shear mixing emulsifier for 2 minutes at a speed of 17000 rpm to obtain suspension A. S5. Add 0.3g thimerosal, 0.5g sodium thiosulfate, 0.1g hydroxypropyl methylcellulose and 0.2g polyvinylpyrrolidone to suspension A, adjust the pH of the system to 6 with PBS buffer, stir evenly, and then pass through a high-speed shear mixing emulsifier for 2 minutes at a speed of 17000 rpm to obtain albendazole suspension preparation.

[0023] Example 2: A method for preparing an albendazole suspension formulation, comprising the following steps: S1. Add 5.5g of hydroxypropyl-β-cyclodextrin to 45mL of 5% sodium hydroxide solution and stir at 42℃ until completely dissolved. Then add 6.5mL of epichlorohydrin and heat at 47℃ for 4h. Adjust the pH of the system to 7 with 20% hydrochloric acid to obtain mixture A. S2. Dissolve 2.2g of chitosan in 110mL of 1% acetic acid solution, add mixture A at 42℃, adjust the pH of the system to 9 with 5% sodium hydroxide solution, heat the reaction at 67℃ for 10.5h, after the reaction is completed, adjust the pH of the system to 5 with acetic acid, dialyze with deionized water, and freeze dry to obtain compound A; S3. Add 220 mg of albendazole to 22 mL of glacial acetic acid and sonicate to obtain solution B. Then dissolve 1.1 g of compound A in 110 mL of deionized water to obtain solution C. Add solution B dropwise to solution C at 550 rpm and mix well. Stir at room temperature in the dark for 10.5 h. Centrifuge at 5200 rpm, filter, rotary evaporate, and freeze dry to obtain albendazole inclusion complex. S4. Add 168g of deionized water to 5.3g of propylene glycol and stir evenly at 72℃. Add 2.2g of polyvinyl alcohol and 11g of albendazole inclusion complex and stir evenly to form a suspension. Pass the mixture through a high-speed shear mixing emulsifier for 2 minutes at a speed of 17500rpm to obtain suspension A. S5. Add 0.32g thimerosal, 0.6g sodium thiosulfate, 0.12g hydroxypropyl methylcellulose and 0.25g polyvinylpyrrolidone to suspension A, adjust the pH of the system to 6 with PBS buffer, stir evenly, and then pass through a high-speed shear mixing emulsifier for 2 minutes at a speed of 17500 rpm to obtain albendazole suspension preparation.

[0024] Example 3: A method for preparing an albendazole suspension formulation, comprising the following steps: S1. Add 6g of hydroxypropyl-β-cyclodextrin to 50mL of 5% sodium hydroxide solution and stir at 44℃ until completely dissolved. Then add 6.5mL of epichlorohydrin and heat at 48℃ for 4.5h. Adjust the pH of the system to 7 with 20% hydrochloric acid to obtain mixture A. S2. Dissolve 2.4 g of chitosan in 120 mL of 1% acetic acid solution, add mixture A at 43 °C, adjust the pH of the system to 9 with 5% sodium hydroxide solution, heat the reaction at 68 °C for 11 h, after the reaction is completed, adjust the pH of the system to 5 with acetic acid, dialyze with deionized water, and freeze dry to obtain compound A; S3. Add 240 mg of albendazole to 24 mL of glacial acetic acid and sonicate to obtain solution B. Then dissolve 1.2 g of compound A in 120 mL of deionized water to obtain solution C. Add solution B dropwise to solution C at 600 rpm and mix well. Stir at room temperature in the dark for 11 h. Centrifuge, filter, rotary evaporate, and freeze dry at 5400 rpm to obtain albendazole inclusion complex. S4. Add 170g of deionized water to 5.5g of propylene glycol and stir evenly at 74℃. Add 2.4g of polyvinyl alcohol and 12g of albendazole inclusion complex and stir evenly to form a suspension. Pass the mixture through a high-speed shear mixing emulsifier for 3 minutes at a speed of 18000rpm to obtain suspension A. S5. Add 0.34g thimerosal, 0.6g sodium thiosulfate, 0.14g hydroxypropyl methylcellulose and 0.3g polyvinylpyrrolidone to suspension A, adjust the pH of the system to 6 with PBS buffer, stir evenly, and then pass through a high-speed shear mixing emulsifier for 2 minutes at a speed of 18000 rpm to obtain albendazole suspension preparation.

[0025] Example 4: A method for preparing an albendazole suspension formulation, comprising the following steps: S1. Add 7.5g of hydroxypropyl-β-cyclodextrin to 550mL of 5% sodium hydroxide solution and stir at 46℃ until completely dissolved. Then add 7mL of epichlorohydrin and heat at 50℃ for 4.5h. Adjust the pH of the system to 7 with 20% hydrochloric acid to obtain mixture A. S2. Dissolve 2.6 g of chitosan in 130 mL of 1% acetic acid solution, add mixture A at 45 °C, adjust the pH of the system to 9.5 with 5% sodium hydroxide solution, heat at 70 °C for 11.5 h, after the reaction is completed, adjust the pH of the system to 5 with acetic acid, dialyze with deionized water, and freeze dry to obtain compound A; S3. Add 260 mg of albendazole to 26 mL of glacial acetic acid and sonicate to obtain solution B. Then dissolve 1.3 g of compound A in 130 mL of deionized water to obtain solution C. Add solution B dropwise to solution C at 600 rpm and mix well. Stir at room temperature in the dark for 11.5 h. Centrifuge, filter, rotary evaporate, and freeze dry at 5600 rpm to obtain the albendazole inclusion complex. S4. Add 175g of deionized water to 6g of propylene glycol and stir evenly at 76℃. Add 2.6g of polyvinyl alcohol and 13g of albendazole inclusion complex and stir evenly to form a suspension. Pass the mixture through a high-speed shear mixing emulsifier for 3min at a speed of 19000rpm to obtain suspension A. S5. Add 0.36g thimerosal, 0.8g sodium thiosulfate, 0.16g hydroxypropyl methylcellulose and 0.4g polyvinylpyrrolidone to suspension A, adjust the pH of the system to 7 with PBS buffer, stir evenly, and then pass through a high-speed shear mixing emulsifier for 3 minutes at a speed of 17000 rpm to obtain albendazole suspension formulation.

[0026] Example 5: A method for preparing an albendazole suspension formulation, comprising the following steps: S1. Add 7.5g of hydroxypropyl-β-cyclodextrin to 60mL of 5% sodium hydroxide solution and stir at 48℃ until completely dissolved. Then add 7mL of epichlorohydrin and heat at 50℃ for 4.5h. Adjust the pH of the system to 7 with 20% hydrochloric acid to obtain mixture A. S2. Dissolve 2.6 g of chitosan in 140 mL of 1% acetic acid solution, add mixture A at 45 °C, adjust the pH of the system to 9.5 with 5% sodium hydroxide solution, heat at 70 °C for 12 h, after the reaction is completed, adjust the pH of the system to 5 with acetic acid, dialyze with deionized water, and freeze dry to obtain compound A; S3. Add 280 mg of albendazole to 28 mL of glacial acetic acid and sonicate to obtain solution B. Then dissolve 1.4 g of compound A in 140 mL of deionized water to obtain solution C. Add solution B dropwise to solution C at 650 rpm and mix well. Stir at room temperature in the dark for 12 h. Centrifuge, filter, rotary evaporate, and freeze dry at 5800 rpm to obtain the albendazole inclusion complex. S4. Add 180g of deionized water to 6.5g of propylene glycol and stir evenly at 78℃. Add 2.8g of polyvinyl alcohol and 14g of albendazole inclusion complex and stir evenly to form a suspension. Pass the mixture through a high-speed shear mixing emulsifier for 3 minutes at a speed of 19000rpm to obtain suspension A. S5. Add 0.38g thimerosal, 0.9g sodium thiosulfate, 0.18g hydroxypropyl methylcellulose and 0.45g polyvinylpyrrolidone to suspension A, adjust the pH of the system to 7 with PBS buffer, stir evenly, and then pass through a high-speed shear mixing emulsifier for 3 minutes at a speed of 19000 rpm to obtain albendazole suspension preparation.

[0027] Example 6: A method for preparing an albendazole suspension formulation, comprising the following steps: S1. Add 8.5g of hydroxypropyl-β-cyclodextrin to 70mL of 5% sodium hydroxide solution and stir at 50℃ until completely dissolved. Then add 7.5mL of epichlorohydrin and heat at 53℃ for 5h. Adjust the pH of the system to 7 with 20% hydrochloric acid to obtain mixture A. S2. Dissolve 3g of chitosan in 150mL of 1% acetic acid solution, add mixture A at 45℃, adjust the pH of the system to 9.5 with 5% sodium hydroxide solution, heat the reaction at 70℃ for 12h, after the reaction is completed, adjust the pH of the system to 5 with acetic acid, dialyze with deionized water, and freeze dry to obtain compound A; S3. Add 300 mg of albendazole to 30 mL of glacial acetic acid and sonicate to obtain solution B. Then dissolve 1.5 g of compound A in 150 mL of deionized water to obtain solution C. Add solution B dropwise to solution C at 700 rpm and mix well. Stir at room temperature in the dark for 12 h. Centrifuge, filter, rotary evaporate, and freeze dry at 6000 rpm to obtain the albendazole inclusion complex. S4. Add 182g of deionized water to 7g of propylene glycol and stir evenly at 80℃. Add 3g of polyvinyl alcohol and 15g of albendazole inclusion complex and stir evenly to form a suspension. Pass the mixture through a high-speed shear mixing emulsifier for 3min at a speed of 20000rpm to obtain suspension A. S5. Add 0.4g thimerosal, 1g sodium thiosulfate, 0.2g hydroxypropyl methylcellulose and 0.5g polyvinylpyrrolidone to suspension A, adjust the pH of the system to 7 with PBS buffer, stir evenly, and then pass through a high-speed shear mixing emulsifier for 3 minutes at a speed of 20,000 rpm to obtain albendazole suspension preparation.

[0028] Comparative Example 1: This comparative example differs from Example 1 only in that "albendazole inclusion complex" is replaced with "albendazole". All other steps and parameters are the same, and will not be repeated here. The final product is an albendazole suspension.

[0029] Comparative Example 2: This comparative example differs from Example 1 only in that “hydroxypropyl-β-cyclodextrin” is replaced with “β-cyclodextrin”. All other steps and parameters are the same, and will not be repeated here. The final product is albendazole suspension.

[0030] Comparative Example 3: S1. Add 200 mg albendazole to 20 mL of glacial acetic acid, sonicate to obtain solution A, and completely dissolve 2 g of hydroxypropyl-β-cyclodextrin in 20 mL of deionized water to obtain solution B. Mix solution A and solution B and let stand until the solution is clear. After sonication, let stand in a refrigerator at 4 °C for 12 h and then remove the organic solvent by rotary evaporation. Finally, dissolve the obtained product in water, filter, and freeze dry under reduced pressure to obtain albendazole inclusion complex. S2. Add 165g of deionized water to 5g of propylene glycol and stir evenly at 70℃. Add 2g of polyvinyl alcohol and 10g of albendazole inclusion complex and stir evenly to form a suspension. Pass the mixture through a high-speed shear mixing emulsifier for 2 minutes at a speed of 17000 rpm to obtain suspension A. S3. Add 0.3g thimerosal, 0.5g sodium thiosulfate, 0.1g hydroxypropyl methylcellulose and 0.2g polyvinylpyrrolidone to suspension A, adjust the pH of the system to 6 with PBS buffer, stir evenly, and then pass through a high-speed shear mixing emulsifier for 2 minutes at a speed of 17000 rpm to obtain albendazole suspension preparation.

[0031] Performance testing: redistribution The suspensions prepared in Examples 1-6 and Comparative Examples 1-3 were poured into 10ml stoppered graduated cylinders, shaken vigorously for 1 minute, and then placed at room temperature. After 10 days, the 10ml stoppered graduated cylinder containing the suspension was rotated 180 degrees, inverted once, and paused for 5 seconds; this was recorded as one shake. The number of shakes required to redisperse the suspension into a homogeneous system was recorded. Fewer shakes indicate easier dispersion and better redispersibility of the dry suspension. Grade A represents 1-3 shakes, Grade B represents 3-5 shakes, Grade C represents 5-7 shakes, Grade D represents 7-9 shakes, and Grade E represents no redispersibility after 10 shakes. Parasite control test: 100 mL of albendazole suspension prepared in Examples 1-6 and Comparative Examples 1-3 were diluted with 500 kg of water to obtain 9 groups of drugs. Sheep in the same flock naturally infected with nematodes, fly larvae, scabies mites and schistosomiasis were randomly divided into 10 groups. The 9 groups of drugs were fed to the sheep in the same flock. One group of sheep was set as a blank group and did not receive the drug. The parasite conversion rate of each group of sheep was recorded as the deworming rate. Drug content determination: The albendazole suspensions prepared in Examples 1-6 and Comparative Examples 1-3 were tested according to the "Veterinary Drug Quality Standards - 2017 Edition Chemical Drugs Volume".

[0032] Table 1. Summary of experimental data from Examples 1-6 and Comparative Examples 1-3

[0033] Table 2 Summary of experimental data from Examples 1-6 and Comparative Examples 1-3

[0034] Data Analysis: As can be seen from Tables 1 and 2, the albendazole suspension prepared by this invention has better anthelmintic properties, higher bioavailability, and better solubility. This may be because the albendazole inclusion complex is prepared from albendazole, chitosan, and hydroxypropyl-β-cyclodextrin. Hydroxypropyl-β-cyclodextrin has a hydrophilic outer surface and a lipophilic central cavity. Its hydrophobic interaction can accommodate the lipophilic drug albendazole, thereby effectively improving the solubility and stability of albendazole. Chitosan has mucosal adhesion properties. By grafting onto the surface of hydroxypropyl-β-cyclodextrin, it prolongs the retention time of the albendazole inclusion complex on the gastrointestinal mucosa, thereby improving the absorption and bioavailability of the gastrointestinal tract. The two have a synergistic effect, thus improving the efficacy of albendazole.

[0035] 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 the invention is limited to these examples; within the framework of the invention, 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 the different aspects of the invention as described above, which are not provided in detail for the sake of brevity.

[0036] This invention is intended to cover all such substitutions, modifications, and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this invention should be included within the scope of protection of this invention.

Claims

1. An albendazole suspension formulation, characterized in that, Includes the following quantities of raw materials: 10-15 parts albendazole inclusion complex; 5-7 parts propylene glycol; 0.1-0.2 parts thickener; 12-20 parts emulsifier; 0.3-0.4 parts preservative; 0.2-0.5 parts stabilizer; 2-3 parts suspending agent; 0.5-1 part antioxidant; 165-182 parts deionized water; pH adjuster to adjust the system pH to 6-7. The albendazole inclusion complex was prepared from albendazole, hydroxypropyl-β-cyclodextrin and chitosan.

2. The albendazole suspension formulation according to claim 1, characterized in that, The albendazole inclusion complex is prepared as follows: Step A1. Add hydroxypropyl-β-cyclodextrin to a 5% sodium hydroxide solution and stir at 40-50℃ until completely dissolved. Then add epichlorohydrin dropwise, heat to react, and adjust the pH of the system to 7 with 20% hydrochloric acid to obtain mixture A. Step A2. Dissolve chitosan in a 1% acetic acid solution, add mixture A at 42-45℃, adjust the pH of the system to 9-9.5 with a 5% sodium hydroxide solution, and carry out the heating reaction. After the reaction is completed, adjust the pH of the system to 5 with acetic acid, dialyze with deionized water, and freeze dry to obtain compound A. Step A3. Add albendazole to glacial acetic acid and sonicate to obtain solution B. Then dissolve compound A in deionized water to obtain solution C. Add solution B dropwise to solution C at 500-700 rpm and mix thoroughly. Stir at room temperature in the dark for 10-12 hours. Centrifuge, filter, rotary evaporate, and freeze dry at 5000-6000 rpm to obtain the albendazole inclusion complex.

3. The albendazole suspension formulation according to claim 2, characterized in that, The ratio of hydroxypropyl-β-cyclodextrin, sodium hydroxide solution, and epichlorohydrin used in step A1 is 5-8.5g:40-70mL:6-7.5mL; The heating reaction is carried out at a temperature of 45-53℃ for 4-5 hours.

4. The albendazole suspension formulation according to claim 2, characterized in that, The ratio of chitosan to acetic acid solution used in step A2 is 2-3g:100-150mL; The heating reaction is carried out at a temperature of 65-70℃ for 10-12 hours.

5. The albendazole suspension formulation according to claim 2, characterized in that, The ratio of albendazole to glacial acetic acid in step A3 is 200-300 mg: 20-30 mL; The ratio of compound A to deionized water is 1-1.5g:100-150mL.

6. The albendazole suspension formulation according to claim 1, characterized in that, The emulsifier is obtained by mixing Tween 80 and Poloxamer 188 in a mass ratio of 2-4:1; The antioxidant is at least one of anhydrous sodium sulfite, sodium thiosulfate, thiourea, sodium bisulfite, and sodium formaldehyde sulfoxylate.

7. The albendazole suspension formulation according to claim 1, characterized in that, The suspending agent is polyvinyl alcohol; The thickener is hydroxypropyl methylcellulose.

8. The albendazole suspension formulation according to claim 1, characterized in that, The stabilizer is polyvinylpyrrolidone; The preservative is at least one of thimerosal and boric acid.

9. The albendazole suspension formulation according to claim 1, characterized in that, The acidity regulator is PBS buffer.

10. The method for preparing the albendazole suspension formulation according to any one of claims 1-9, characterized in that, Includes the following steps: Step S1. Add deionized water to propylene glycol and stir evenly at 70-80℃. Add suspending agent and albendazole inclusion complex and stir evenly to form a suspension. Mix the emulsifier by high-speed shear for 2-3 minutes at a speed of 17000-20000 rpm to obtain suspension A. Step S2. Add preservatives, antioxidants, thickeners and stabilizers to suspension A, and adjust the pH of the system to 6-7 with an acidity regulator. After stirring evenly, mix the emulsifier by high-speed shearing for 2-3 minutes at a speed of 17000-20000 rpm to obtain the albendazole suspension formulation.

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