High-stability watered pill as well as preparation method and application thereof

Abstract

The invention provides a high-stability watered pill as well as a preparation method and application thereof, and the preparation method of the watered pill comprises the following steps: S1, mixing starch and water, and performing ultrasonic stirring to obtain paste; s2, medicine powder is sprayed into the paste, the spraying distance is 1-7 cm, the pressure is 1-7 bar, the airflow speed is 1-7 m / s, stirring is conducted to form a ball, and a material ball is obtained; s3, carrying out microwave preheating treatment on the material block to obtain a pretreated material block; s4, the pretreated material balls are twisted into strips on a pill twisting bottom plate, then the strips roll in a groove path, and watered pills are obtained; and S5, the watered pills are subjected to high-pressure auxiliary curing for 15-45 min under the pressure of 35-75 MPa and then subjected to normal-pressure drying for 10-30 h at the temperature of 25-55 DEG C, and the target high-stability watered pills are obtained. The prepared watered pill is moderate in hardness, good in viscosity, stable in finished product quality, good in uniformity and solubility, high in stability, long in quality guarantee period and easy to produce on a large scale, and has practical significance.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical materials technology, and in particular to a highly stable water pill, its preparation method, and its application. Background Technology

[0002] Water pills, also known as water-coated pills, are small spherical pills made by using cold boiled water, medicinal juice, or other liquids as binders (wetting agents) to form finely powdered medicines. Water pills developed from decoctions, initially made by mixing the decoction of one part of the medicine with the finely powdered medicine of another part of the prescription and forming pills by dripping water. Later, it gradually evolved to use various water-soluble liquids as binders and a coating method to form all or part of the finely powdered medicines in the prescription into small pills.

[0003] The preparation process of the pan-based method is as follows: raw material preparation, molding, shaping, capping, drying, pellet selection, quality inspection, and packaging. The following problems are prone to occur during the production process: 1. It is difficult to control the stable quality of the finished water pellets, and unevenness is likely to occur; 2. Capping may cause unevenness or cracks on the surface of the water pellets, affecting their stability; 3. If drying is not well controlled, it will lead to uneven drying of the water pellets, affecting their strength and quality; 4. Pellet selection is inefficient, difficult, and time-consuming. These problems affect the final quality, stability, and production efficiency of the water pellets and require strict control.

[0004] Therefore, it is necessary to develop a preparation process that produces water pellets with moderate hardness, good viscosity, high stability, stable quality, good uniformity and solubility, short dispersibility, and ease of large-scale production, which is of practical significance. Summary of the Invention

[0005] In view of this, the present invention proposes a highly stable water pellet, its preparation method and application.

[0006] The technical solution of this invention is implemented as follows: A method for preparing highly stable water pellets, comprising the following steps: S1. Mix starch and water, and stir ultrasonically to obtain a paste; S2. Spray the drug powder into the paste at a distance of 1-7cm, a pressure of 1-7bar, and an airflow speed of 1-7m / s, and stir until it forms a ball to obtain a material ball; S3. Microwave preheating is performed on the material to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 35-75MPa for 15-45 minutes, and then dried at normal pressure at 25-55℃ for 10-30 hours to obtain the target high-stability water pellets.

[0007] Furthermore, in step S1, the starch is any one of potato starch, sweet potato starch, and wheat flour; the mass ratio of starch to water is 5-6:20.

[0008] Furthermore, in step S1, the ultrasonic stirring temperature is 15-25℃, the power is 10-20KHz, and the time is 40-60min.

[0009] Furthermore, in step S2, the mass ratio of the paste to the drug powder is 1.25-1.3:1.

[0010] Furthermore, in step S2, the drug powder is passed through a 100-120 mesh sieve.

[0011] Furthermore, in step S2, the spraying distance is 2-6 cm, the pressure is 1-5 bar, and the airflow velocity is 2-5 m / s; the shape of the material clump is such that the compressed clump does not crack or disperse.

[0012] Furthermore, in step S3, the microwave preheating treatment is performed at 40-50℃ and 200-300W for 30-40 minutes.

[0013] Furthermore, in step S5, the pressure of the high-pressure assisted curing is 40-60 MPa, the time is 20-40 min, and the temperature is 20-30℃; the temperature of the normal pressure drying is 30-50℃, and the time is 12-24 h.

[0014] A highly stable water pellet is prepared by the method described above.

[0015] Application of a highly stable water pellet in the preparation of drug delivery carriers.

[0016] Compared with the prior art, the beneficial effects of the present invention are: 1. The water pills prepared by this invention have moderate hardness, good viscosity, stable finished product quality, good uniformity, solubility and high stability, short dissolution time, long shelf life, are easy to mass-produce, have good market prospects and have practical significance.

[0017] 2. The paste produced by ultrasonically stirring a specific type of starch and a specific ratio of starch and water in this invention exhibits excellent adhesion when forming clumps with drug powder, preventing breakage during strip forming. The drug powder, after sieving (100-120 mesh), is fine, has good absorption, and easily forms clumps, thus improving production efficiency. Ultrasonic stirring enhances the uniformity and fineness of the paste, prevents agglomeration, and improves the solubility and uniformity of the final product. This invention uses a spraying process to mix the drug powder with the paste to form clumps, improving the stability and uniformity of the clumps and preventing drug powder aggregation. Microwave preheating of the clumps further strengthens the bond between the drug powder and the clumps, further improving the stability of the water pills.

[0018] 3. This invention combines high-pressure assisted curing and normal-pressure drying to form highly stable water pellets. The high pressure enhances the strength and stability of the water pellets in a short time, making them denser and more uniform, thus improving the structure and stability of the water pellets. The preparation process is simple and the scrap rate of the finished product is low. Detailed Implementation

[0019] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention.

[0020] Unless otherwise specified, the experimental methods used in the embodiments of this invention are all conventional methods.

[0021] Unless otherwise specified, all materials and reagents used in the embodiments of this invention are commercially available.

[0022] Example 1 A method for preparing highly stable water pellets, comprising the following steps: S1. Mix potato starch and water at a mass ratio of 27:100, and ultrasonically stir for 50 minutes at 15KHz and 20℃ to obtain a paste. S2. According to the mass ratio of 1.27:1, spray the drug powder that has passed through a 110-mesh sieve (spraying distance of 4cm, pressure of 3bar, airflow speed of 3m / s) into the paste, stir it into a ball, and continue stirring until it does not crack or disperse when squeezed to obtain the material ball; S3. Preheat the material in a microwave oven at 45℃ and 250W for 35 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 50MPa and 25℃ for 30min, and then dried at 40℃ and normal pressure for 18h to obtain the target high-stability water pellets.

[0023] Example 2 A method for preparing highly stable water pellets, comprising the following steps: S1. Mix sweet potato starch and water in a mass ratio of 1:4, and ultrasonically stir for 40 minutes at 10KHz and 15℃ to obtain a paste. S2. According to the mass ratio of 1.25:1, spray the drug powder that has passed through a 100-mesh sieve (spraying distance of 2cm, pressure of 1bar, airflow speed of 2m / s) into the paste and stir until it forms a ball. Continue stirring until it does not crack or disperse when squeezed to obtain the material ball. S3. Preheat the material in a microwave oven at 40℃ and 200W for 30 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 40MPa and 20℃ for 20min, and then dried at 30℃ and normal pressure for 12h to obtain the target high-stability water pellets.

[0024] Example 3 A method for preparing highly stable water pellets, comprising the following steps: S1. Mix wheat flour and water in a mass ratio of 3:10, and ultrasonically stir for 60 minutes at 20KHz and 25℃ to obtain a paste. S2. According to the mass ratio of 1.3:1, spray the drug powder that has passed through a 120-mesh sieve (spraying distance of 6cm, pressure of 5bar, airflow speed of 5m / s) into the paste, stir it into a ball, and continue stirring until it does not crack or disperse when squeezed to obtain the material ball; S3. Preheat the material in a microwave oven at 50℃ and 300W for 40 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 60MPa and 30℃ for 40min, and then dried at 50℃ and normal pressure for 24h to obtain the target high-stability water pellets.

[0025] Comparative Example 1 The difference from Example 1 is that potato starch is replaced with corn starch, otherwise it is the same as Example 1.

[0026] The preparation method of the highly stable water pills in this comparative example includes the following specific steps: S1. Mix corn starch and water at a mass ratio of 27:100 and ultrasonically stir for 50 minutes at 15KHz and 20℃ to obtain a paste. S2. According to the mass ratio of 1.27:1, spray the drug powder that has passed through a 110-mesh sieve (spraying distance of 4cm, pressure of 3bar, airflow speed of 3m / s) into the paste, stir it into a ball, and continue stirring until it does not crack or disperse when squeezed to obtain the material ball; S3. Preheat the material in a microwave oven at 45℃ and 250W for 35 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 50MPa and 25℃ for 30min, and then dried at 40℃ and normal pressure for 18h to obtain the target water pellets.

[0027] Comparative Example 2 The difference from Example 1 is that ultrasonic stirring is absent; instead, it is cooked over a low flame. Otherwise, it is the same as Example 1.

[0028] The preparation method of the highly stable water pills in this comparative example includes the following specific steps: S1. Mix potato starch and water at a mass ratio of 27:100 and cook at 40℃ for 50 minutes to obtain a paste. S2. According to the mass ratio of 1.27:1, spray the drug powder that has passed through a 110-mesh sieve (spraying distance of 4cm, pressure of 3bar, airflow speed of 3m / s) into the paste, stir it into a ball, and continue stirring until it does not crack or disperse when squeezed to obtain the material ball; S3. Preheat the material in a microwave oven at 45℃ and 250W for 35 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 50MPa and 25℃ for 30min, and then dried at 40℃ and normal pressure for 18h to obtain the target water pellets.

[0029] Comparative Example 3 The difference from Example 1 is that step S2 is replaced by conventional mixing instead of spraying; otherwise, it is the same as Example 1.

[0030] A method for preparing highly stable water pellets, comprising the following steps: S1. Mix potato starch and water at a mass ratio of 27:100, and ultrasonically stir for 50 minutes at 15KHz and 20℃ to obtain a paste. S2. According to the mass ratio of 1.27:1, gradually add the paste to the drug powder that has passed through a 110-mesh sieve, stir until it forms a dough, and continue stirring until it does not crack or disperse when squeezed to obtain the dough. S3. Preheat the material in a microwave oven at 45℃ and 250W for 35 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 50MPa and 25℃ for 30min, and then dried at 40℃ and normal pressure for 18h to obtain the target high-stability water pellets.

[0031] Comparative Example 4 The difference from Example 1 is that the microwave preheating treatment in step S3 is missing; otherwise, it is the same as Example 1.

[0032] A method for preparing highly stable water pellets, comprising the following steps: S1. Mix potato starch and water at a mass ratio of 27:100, and ultrasonically stir for 50 minutes at 15KHz and 20℃ to obtain a paste. S2. According to the mass ratio of 1.27:1, spray the drug powder that has passed through a 110-mesh sieve (spraying distance of 4cm, pressure of 3bar, airflow speed of 3m / s) into the paste, stir it into a ball, and continue stirring until it does not crack or disperse when squeezed to obtain the material ball; S3. Roll the material into strips on the rolling plate, then roll it in the groove to obtain water balls; S4. The water pellets are subjected to high-pressure assisted curing at 50MPa and 25℃ for 30min, and then dried at 40℃ and normal pressure for 18h to obtain the target high-stability water pellets.

[0033] Comparative Example 5 The difference from Example 1 is that step S5 is ordinary drying, while the rest is the same as in Example 1.

[0034] The preparation method of the highly stable water pills in this comparative example includes the following specific steps: S1. Mix potato starch and water at a mass ratio of 27:100, and ultrasonically stir for 50 minutes at 15KHz and 20℃ to obtain a paste. S2. According to the mass ratio of 1.27:1, spray the drug powder that has passed through a 110-mesh sieve (spraying distance of 4cm, pressure of 3bar, airflow speed of 3m / s) into the paste, stir it into a ball, and continue stirring until it does not crack or disperse when squeezed to obtain the material ball; S3. Preheat the material in a microwave oven at 45℃ and 250W for 35 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. Dry the water pellets at 60℃ for 18 hours to obtain the target water pellets.

[0035] Comparative Example 6 The difference from Example 1 is that the mass ratio of paste to drug powder is 1:1, while everything else is the same as in Example 1.

[0036] A method for preparing highly stable water pellets, comprising the following steps: S1. Mix potato starch and water at a mass ratio of 27:100, and ultrasonically stir for 50 minutes at 15KHz and 20℃ to obtain a paste. S2. According to the mass ratio of 1:1, spray the drug powder that has passed through a 110-mesh sieve (spraying distance of 4cm, pressure of 3bar, airflow speed of 3m / s) into the paste, stir it into a ball, and continue stirring until it does not crack or disperse when squeezed to obtain the material ball; S3. Preheat the material in a microwave oven at 45℃ and 250W for 35 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 50MPa and 25℃ for 30min, and then dried at 40℃ and normal pressure for 18h to obtain the target water pellets.

[0037] Comparative Example 7 The difference from Example 1 is that the drug powder is passed through a 90-mesh sieve; otherwise, it is the same as Example 1.

[0038] The preparation method of the highly stable water pills in this comparative example includes the following specific steps: S1. Mix potato starch and water at a mass ratio of 27:100, and ultrasonically stir for 50 minutes at 15KHz and 20℃ to obtain a paste. S2. According to the mass ratio of 1.27:1, spray the drug powder that has passed through a 90-mesh sieve (spraying distance of 4cm, pressure of 3bar, airflow speed of 3m / s) into the paste, stir it into a ball, and continue stirring until it does not crack or disperse when squeezed to obtain the material ball; S3. Preheat the material in a microwave oven at 45℃ and 250W for 35 minutes to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 50MPa and 25℃ for 30min, and then dried at 40℃ and normal pressure for 18h to obtain the target water pellets.

[0039] Test case The water pills prepared in Examples 1-3 and Comparative Examples 1-7 were tested, and the testing criteria are shown in Table 1. The test results are shown in Table 2.

[0040] Table 1

[0041] Table 2

[0042] As can be seen from Table 2, the water pills prepared by the process flow of Examples 1-3 of the present invention have qualified all indicators, can significantly shorten the dissolution time, the prepared water pills have moderate softness and hardness, good viscosity, stable finished product quality, good uniformity, solubility and high stability, long shelf life of finished product and easy to mass-produce.

[0043] Comparative Example 1 differs from Example 1 in that potato starch was replaced with corn starch, resulting in some indicators failing to meet standards. This indicates that a paste made from a specific ratio of potato starch and water can form a clump with the drug powder that exhibits good adhesion and does not break when rolled into strips. Comparative Example 2 differs from Example 1 in that it lacks ultrasonic stirring, i.e., it uses ordinary low-heat stirring, resulting in some indicators failing to meet standards. This indicates that ultrasonic stirring can improve the uniformity and fineness of the paste, prevent agglomeration, and improve the solubility and uniformity of the subsequent finished product. Comparative Example 3 differs from Example 1 in that step S2, instead of spraying, is replaced with conventional mixing, resulting in some indicators failing to meet standards. Comparative Example 4 differs from Example 1 in that it lacks the microwave preheating treatment in step S3, resulting in some indicators failing to meet standards. Comparative Example 5 differs from Example 1 in that step S5 is ordinary drying, resulting in some indicators failing to meet standards. This indicates that the combination of high-pressure assisted curing and normal-pressure drying can form highly stable water pellets. High pressure can improve the strength and stability of the water pellets in a short time, making them denser and more uniform, thus improving the structure and stability of the water pellets. The difference between Comparative Example 6 and Example 1 is that the mass ratio of paste to drug powder is 1:1, which resulted in some indicators failing to meet the standards. This indicates that only water pills prepared with paste and drug powder in a specific ratio can meet all the requirements. The difference between Comparative Example 7 and Example 1 is that the drug powder is sieved through a 90-mesh sieve. This indicates that sieved drug powder is fine, has good absorption effect, is easy to form into clumps, and helps to improve uniformity and stability.

[0044] In addition, 50 water pills were randomly selected from each of the preparation processes of Examples 1-3 and Comparative Examples 1-7, and the yield was calculated. The yield (%) = number of water pills that meet the standard and have stable quality / total number of water pills × 100%. The statistical results are shown in Table 3.

[0045] Table 3

[0046] As shown in Table 3, the yield of water pills obtained by the preparation processes of Examples 1-3 of this invention all reached 100%. Compared with Comparative Examples 1-7, the water pills prepared by Examples 1-3 can significantly reduce the scrap rate and have good market prospects. The difference between Comparative Example 1 and Example 1 is that potato starch is replaced with corn starch; the difference between Comparative Example 2 and Example 1 is that ultrasonic stirring is omitted, i.e., ordinary low-heat stirring is used; the difference between Comparative Example 3 and Example 1 is that step S2 is replaced by conventional mixing instead of spraying; the difference between Comparative Example 4 and Example 1 is that microwave preheating treatment in step S3 is omitted; the difference between Comparative Example 5 and Example 1 is that step S5 is ordinary drying; the difference between Comparative Example 6 and Example 1 is that the mass ratio of paste to drug powder is 1:1; the difference between Comparative Example 7 and Example 1 is that the drug powder is passed through a 90-mesh sieve; the yield of water pills in Comparative Examples 1-7 all decreased.

[0047] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing highly stable water pellets, characterized in that, The specific steps include: S1. Mix starch and water, and stir ultrasonically to obtain a paste; S2. Spray the drug powder into the paste at a distance of 1-7cm, a pressure of 1-7bar, and an airflow speed of 1-7m / s, and stir until it forms a ball to obtain a material ball; S3. Microwave preheating is performed on the material to obtain a pretreated material. S4. Roll the pretreated material into strips on the pellet rolling base plate, and then roll it in the groove to obtain water pellets; S5. The water pellets are subjected to high-pressure assisted curing at 35-75MPa for 15-45 minutes, and then dried at normal pressure at 25-55℃ for 10-30 hours to obtain the target high-stability water pellets.

2. The method for preparing a highly stable water pellet as described in claim 1, characterized in that, In step S1, the starch is any one of potato starch, sweet potato starch, and wheat flour; the mass ratio of starch to water is 5-6:

20.

3. The method for preparing highly stable water pellets as described in claim 1, characterized in that, In step S1, the ultrasonic stirring temperature is 15-25℃, the power is 10-20KHz, and the time is 40-60min.

4. The method for preparing a highly stable water pellet as described in claim 1, characterized in that, In step S2, the mass ratio of the paste to the drug powder is 1.25-1.3:

1.

5. The method for preparing highly stable water pellets as described in claim 1, characterized in that, In step S2, the drug powder is passed through a 100-120 mesh sieve.

6. The method for preparing a highly stable water pellet as described in claim 1, characterized in that, In step S2, the spraying distance is 2-6cm, the pressure is 1-5bar, and the airflow velocity is 2-5m / s; the shape of the material clump is such that the compressed clump does not crack or disperse.

7. The method for preparing a highly stable water pellet as described in claim 1, characterized in that, In step S3, the microwave preheating treatment is performed at 40-50℃ and 200-300W for 30-40 minutes.

8. The method for preparing highly stable water pellets as described in claim 1, characterized in that, In step S5, the pressure of the high-pressure assisted curing is 40-60 MPa, the time is 20-40 min, and the temperature is 20-30℃; the temperature of the normal pressure drying is 30-50℃, and the time is 12-24 h.

9. A highly stable water pellet, characterized in that, It is prepared by the preparation method according to any one of claims 1-8.

10. The application of the highly stable water pellet of claim 9 in the preparation of a drug delivery carrier.

Images