CN111437263B

CN111437263B - Corncob total flavone solid dispersion osmotic pump tablet and preparation method thereof

Info

Publication number: CN111437263B
Application number: CN202010180128.6A
Authority: CN
Inventors: 李妍; 张敬卫; 曹珂珂; 李慧; 韩卓
Original assignee: Bengbu College
Current assignee: Bengbu College
Priority date: 2020-03-16
Filing date: 2020-03-16
Publication date: 2022-04-22
Anticipated expiration: 2040-03-16
Also published as: CN111437263A

Abstract

The invention discloses a corncob total flavone solid dispersion osmotic pump tablet and a preparation method thereof: mixing and tabletting the corncob total flavone solid dispersion with osmotic pressure active substances, polyoxyethylene, soluble starch and magnesium stearate to prepare a tablet core, and coating by using a coating solution, wherein the weight of a coating film is controlled to be 5% of that of the tablet core; the tablet core is prepared from the following raw materials in percentage by weight: 40-65% of corncob total flavone solid dispersion, 30-45% of osmotic pressure active substances, 5-10% of polyethylene oxide, 0-1% of magnesium stearate and 0-5% of soluble starch; the osmotically active substance comprises one of sodium chloride, lactose, potassium chloride and mannitol; the coating solution is one of PEG-4000-acetone-CA and PEG-400-ethanol-EC coating solutions. The invention firstly utilizes the solid dispersion technology to improve the dispersion degree of the total flavone and increase the solubility of the fat-soluble components, and then utilizes the osmotic pump controlled release drug delivery system to ensure that the corn total flavone preparation releases drug at a constant speed, thereby reducing the drug administration times and keeping stable blood concentration.

Description

Corncob total flavone solid dispersion osmotic pump tablet and preparation method thereof

Technical Field

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a corncob total flavone solid dispersion osmotic pump tablet and a preparation method thereof.

Background

The corncob is the cob of the corn plant of Gramineae without seeds, has light and flat taste, is used as a medicine for clearing heat and promoting urination, reducing internal heat and expelling toxin, calming the liver and benefiting the gallbladder in ancient times of China, and has obvious effects of promoting urination, reducing blood pressure, reducing blood sugar, enhancing immunity, resisting cancer and the like as proved by modern pharmacological research, and also has certain curative effect on diseases such as nephritis, hepatitis, cholecystitis, gallstone and the like. The corncob contains various nutrient components, such as cellulose, hemicellulose, lignin, starch, amino acid, mineral elements, polyphenol, flavonoids and the like, wherein the flavonoids are the main pharmacological active components.

The flavonoid compounds mainly have the following pharmacological actions: preventing and treating cardiovascular and cerebrovascular diseases, such as atherosclerosis, fragility reduction, permeability improvement, blood lipid and cholesterol reduction, and coronary blood flow increase; anti-inflammatory and immune-modulating effects: acting on normal mitosis process of cells, regulating secretion process of intercellular interaction, and inhibiting release of slow-response inflammatory substance from mast cells and basophils; antibacterial and antiviral effects; anti-tumor and anti-cancer effects: the flavonoid compound has obvious functions of resisting oxidation and free radicals, and the two have obvious correlation, and the stronger the capacity of resisting free radicals and oxidative stress, the greater the functions of resisting the tumor and resisting the cancer; improving the action of the reproductive system: the flavonoid compound, especially isoflavone, has a chemical structure similar to that of estrogen, has remarkable physiological effects of estrogen-like, has an action mechanism similar to that of natural estrogen, and can be competitively combined with the natural estrogen in vivo until the activity of estrogen is regulated; liver protection: the ketone compound has certain protective effect on liver injury caused by various reasons.

Based on the above, the corncob total flavonoids have good effects on preventing and treating cardiovascular diseases, diabetes, nephritis, hepatitis and the like, and in the prior art, although technologies for extracting the corncob total flavonoids are disclosed, such as response surface optimization corncob flavonoids extraction process research [ J ], norlixin, jiachanghong and the like, food industry science and technology, 2014 and 02, such as separation of sweet corncob flavonoids [ J ], wangxin, xietnan and the like by an ethanol-ammonium sulfate aqueous phase system, and Chinese food additives, 2018 and 01, so far, no relevant reports on development of corncob total flavonoids pharmaceutical preparations are found. The invention discloses a corncob total flavone solid dispersion osmotic pump tablet and a preparation method thereof, in order to further improve the clinical application value of corncob flavone and promote the modernized development of a traditional Chinese medicine preparation.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a corncob total flavone solid dispersion osmotic pump tablet and a preparation method thereof.

The technical scheme of the invention is summarized as follows:

an osmotic pump tablet of a solid dispersion of corncob total flavonoids: mixing and tabletting the corncob total flavone solid dispersion with osmotic pressure active substances, polyoxyethylene, soluble starch and magnesium stearate to prepare a tablet core, and coating by using a coating solution, wherein the weight of a coating film is controlled to be 5% of that of the tablet core;

the tablet core is prepared from the following raw materials in percentage by weight:

the osmotically active substance comprises one of sodium chloride, lactose, potassium chloride and mannitol;

the coating liquid is one of polyethylene glycol 4000-acetone-cellulose acetate or polyethylene glycol 400-ethanol-ethyl cellulose coating liquid; wherein, the formula of the coating liquid of the polyethylene glycol 4000-acetone-cellulose acetate is as follows: 6g of polyethylene glycol 4000+ cellulose acetate is dissolved in 97% (v/v) acetone of each 100mL, wherein the dosage of the polyethylene glycol 4000 is 10-30% of that of the cellulose acetate; the formula of the polyethylene glycol 400-ethanol-ethyl cellulose coating solution is as follows: 3.9g of polyethylene glycol 400+ ethyl cellulose is dissolved in 100mL of 95% (v/v) ethanol, and the dosage of polyethylene glycol 4000 is 10-30% of that of cellulose acetate.

Preferably, the osmotic pump tablet is prepared by mixing and tabletting a corncob total flavone solid dispersion with sodium chloride, polyethylene oxide, soluble starch and magnesium stearate to prepare a tablet core, and then coating is carried out by using a coating solution, wherein the weight of a coating film is controlled to be 5% of that of the tablet core;

the coating liquid is a polyethylene glycol 400-ethanol-ethyl cellulose coating liquid, and the formula is as follows: 3.9g of polyethylene glycol 400+ ethyl cellulose are dissolved in 100mL of 95% (v/v) ethanol, and the amount of polyethylene glycol 4000 is 30% of the amount of ethyl cellulose.

A preparation method of a corncob total flavone solid dispersion osmotic pump tablet comprises the following steps:

s1: extracting total flavonoids of corncobs: cleaning and drying corncobs, crushing the corncobs into 100 meshes, adding 1: adding 85% ethanol solution into 25g/mL of the feed-liquid ratio, soaking at 50 deg.C for 1h, ultrasonic extracting for 1h, filtering, eluting with macroporous resin, and vacuum drying to obtain total flavone extract of corn cob;

s2: preparing a solid dispersion: adding the total flavone extract and PVP K30 carrier into anhydrous ethanol, ultrasonic dissolving, heating in 90 deg.C water bath to volatilize solvent, vacuum drying the precipitate, pulverizing to 60 mesh to obtain total flavone solid dispersion, and storing in a dryer;

s3: preparing a tablet core: uniformly mixing the corncob total flavone solid dispersion, sodium chloride, polyethylene oxide and soluble starch, sieving with a 60-mesh sieve, adding a proper amount of 75% ethanol to wet and bond main and auxiliary materials, preparing a soft material, sieving with a 20-mesh sieve, granulating, drying at 50 ℃ for 0.5h, sieving with a 20-mesh sieve, grading, adding magnesium stearate, and tabletting to obtain a tablet core;

s4: coating treatment: and (3) putting the tablet core into a coating pan, coating under the conditions that the temperature is 50 ℃, the rotating speed is 30r/min and the spraying speed is 2.5mL/min, and drying at 50 ℃ for 10h when the weight of a coating film is 5 percent of the weight of the tablet core to obtain the total flavone solid dispersion osmotic pump tablet.

The invention has the beneficial effects that:

1. the invention firstly utilizes the solid dispersion technology and the osmotic pump type controlled release technology to prepare the corncob total flavone oral medicament, because the corn total flavone components are complex and the water solubility is poor, the solid dispersion technology is firstly utilized to improve the dispersion degree of the corn total flavone and increase the solubility of the fat-soluble components, and then the osmotic pump controlled release drug delivery system is utilized to ensure that the corn total flavone preparation releases drug at a constant speed, the drug administration times are reduced, the patient compliance is increased, the stable blood concentration is kept, and the drug effect is more durable.

2. The total flavone solid dispersion osmotic pump tablet prepared by the invention has the characteristics that the drug solubility and the accumulated dissolution rate are similar to zero-order drug release within 24 hours, the release rates can reach more than 85 percent, and the total flavone solid dispersion osmotic pump tablet conforms to the national quality standard of the sustained and controlled release preparation; the finished product is stable in a high-temperature environment, is insensitive to illumination, is easy to absorb moisture and dissolve, and is suitable for being stored in a dry environment.

Drawings

FIG. 1 is a flow chart of a method for preparing a corncob total flavone solid dispersion osmotic pump tablet;

FIG. 2 is a graph of rutin standard curve;

FIG. 3 is a graph showing the effect of different osmotic pressure active substances on the release of drugs from an osmotic pump tablet of a solid dispersion of total flavonoids in corncobs;

FIG. 4 is a graph showing the effect of NaCl content on drug release from an osmotic pump tablet of total flavonoids in corn cob solid dispersion;

FIG. 5 is a graph showing the comparison of PEG-4000-acetone-CA and PEG-400-ethanol-EC coating solutions for drug release from an osmotic pump tablet of total flavonoids in corncobs;

FIG. 6 is a graph showing the effect of different PEG-400 contents in PEG-400-ethanol-EC coating solution on drug release from an osmotic pump tablet of total flavonoids in corncobs solid dispersion;

FIG. 7 is a line graph showing the solubility and cumulative dissolution rate of the corncob total flavone solid dispersion osmotic pump tablet prepared in example 12.

Detailed Description

The present invention is further described in detail below with reference to examples so that those skilled in the art can practice the invention with reference to the description.

The scheme provides a corncob total flavone solid dispersion osmotic pump tablet: mixing and tabletting the corncob total flavone solid dispersion with osmotic pressure active substances, polyoxyethylene, soluble starch and magnesium stearate to prepare a tablet core, and coating by using a coating solution, wherein the weight of a coating film is controlled to be 5% of that of the tablet core;

the coating liquid is one of polyethylene glycol 4000-acetone-cellulose acetate or polyethylene glycol 400-ethanol-ethyl cellulose coating liquid; wherein, the formula of the coating liquid of the polyethylene glycol 4000-acetone-cellulose acetate is as follows: 6g of polyethylene glycol 4000+ cellulose acetate is dissolved in 97% (v/v) acetone of each 100mL, wherein the dosage of the polyethylene glycol 4000 is 10-30% of that of the cellulose acetate; the formula of the polyethylene glycol 400-ethanol-ethyl cellulose coating solution is as follows: every 100mL of 95% (v/v) ethanol is dissolved with 3.9g of polyethylene glycol 400+ ethyl cellulose, and the dosage of polyethylene glycol 4000 is 10-30% of that of the ethyl cellulose.

The scheme also provides a preparation method of the corncob total flavone solid dispersion osmotic pump tablet, which comprises the following steps:

The total flavone solid dispersion osmotic pump tablet prepared by the method is subjected to in-vitro determination and analysis test

Establishment of a Standard Curve

Precisely weighing rutin control 10mg in 50mL volumetric flask, adding appropriate amount of purified water, ultrasonic treating to dissolve completely, and diluting to constant volume to obtain 0.2 mg/mL^-1Rutin standard solution. Respectively placing 0,1, 2, 3, 4, 5, and 6mL of the reference solution in 25mL volumetric flask, adding water to 6mL, and adding 5% NaNO₂Shaking the solution 1mL, standing for 6min, adding 10% Al (NO)₃)₃Mixing 1mL of the solution, standing for 6min, adding 10mL of 4% NaOH solution, adding water to a constant volume to a scale, shaking up, standing for 15min, and measuring the light absorption at 510 nm.

FIG. 2 is a graph showing the standard rutin concentration of 0.008 ug/mL, as can be seen from FIG. 2^-1～0.04ug·mL^-1The time is in a linear relationship with the absorbance. And (3) drawing a standard curve by using the concentration (C) to the absorbance (A) to obtain a linear regression equation: c ═ 0.083A +0.0003 (R)²＝0.9996)。

Determination of total flavone content in corncob

Referring to 'Chinese pharmacopoeia' 2015 edition, the content determination method of osmotic pump controlled release tablets comprises the following steps: taking 20 tablets of the product, carefully removing the coating film,grinding, precisely weighing a medicament equivalent to 20mg of corncob total flavonoids, adding about 10mL of water into a 100mL volumetric flask, wetting, shaking up, adding 60mL of ethanol, performing ultrasonic dissolution at 35 ℃ for 5min, cooling to room temperature, adding ethanol for diluting to a scale, shaking up, filtering, precisely weighing 2mL of subsequent filtrate, adding water into a 25mL volumetric flask to 6mL, adding 5% NaNO₂Shaking the solution 1mL, standing for 6min, adding 10% Al (NO)₃)₃Mixing 1mL of the solution, standing for 6min, adding 10mL of 4% NaOH solution, adding water to a constant volume to a scale, shaking up, and standing for 15 min. The absorbance was measured at 510 mn. Precisely weighing appropriate amount of corncob total flavone reference substance, dissolving in ethanol, diluting, and making into 10 ug/mL^-1The solution is measured and calculated by the same method to obtain the product.

Determination of recovery

According to the verification guiding principle of an analysis method in 'Chinese pharmacopoeia' 2015 edition, respectively and precisely weighing 10mg, 12.5mg and 15mg of total flavonoids in corncobs, preparing a solid dispersion, weighing main and auxiliary materials according to the proportion of 50% of the total flavonoids in the corncobs, 40% of sodium chloride, 7% of polyethylene oxide, 0.5% of magnesium stearate and 2.5% of soluble starch, adding 100mL of water for constant volume, shaking uniformly, filtering with a 0.45um microporous membrane, precisely weighing 1mL of filtrate, adding 50mL of water for constant volume, measuring according to a content measuring method, calculating the relative deviation, judging whether the recovery rate meets the requirement, and calculating the relative deviation according to a formula:

the measurement results are shown in table 1:

TABLE 1 recovery results

As can be seen from Table 1, when the corn cob total flavone content is 75%, 100% and 125%, RDS is less than or equal to 2, so the drug recovery rate meets the requirement.

Determination of release degree of total flavonoids in corncobs

Measuring the drug release behavior of the total flavone solid dispersion osmotic pump tablet, according to a release rate measurement method (XD second method in appendix II of 2010 edition of Chinese pharmacopoeia), taking 100ml of degassed purified water as a dissolution medium, rotating at 100 r/min and at (37 +/-0.5) DEG C, sampling 5ml of the degassed purified water at 2 nd, 4 th, 6 th, 8 th, 10 th and 12 th hours respectively, filtering, and immediately supplementing water with the same temperature and volume in a dissolution cup. Taking 1ml of the subsequent filtrate, placing in a 10ml measuring flask, adding water to dilute to scale, shaking up, measuring absorbance at 360nm wavelength according to Chinese pharmacopoeia ultraviolet spectrophotometry, making a standard curve, and further calculating the release percentage.

Examples 1-4 study on the influence of different osmotic pressure active substances on drug release of total flavone solid dispersion osmotic pump tablets

The osmotic pressure active substances of examples 1 to 4 were sodium chloride, lactose, potassium chloride and mannitol, respectively, and the non-osmotic pressure active substance was set as a blank control group, and an equivalent amount of soluble starch was substituted.

Example 1

Tablet core formula of osmotic pump tablet

Reagent	Total flavone solid dispersion	NaCl	PEO	Magnesium stearate	Solubility in waterStarch
						Percent by weight/%)	50	40	7	0.5	2.5
Dosage per mg	150	120	21	1.5	7.5

PEG-4000-acetone-CA coating liquid formula

Reagent	97% (v/v) acetone	CA	PEG-4000	PEG-4000/CA
					Dosage of	200mL	10g	2g		20％

Example 2

Tablet core formula of osmotic pump tablet

Reagent	Total flavone solid dispersion	Lactose	PEO	Magnesium stearate	Soluble starch
						Percent by weight/%)	50	40	7	0.5	2.5
Dosage per mg	150	120	21	1.5	7.5

PEG-4000-acetone-CA coating liquid formula

Reagent	97% (v/v) acetone	CA	PEG-4000	PEG-4000/CA
					Dosage of	200mL	10g	2g		20％

Example 3

Tablet core formula of osmotic pump tablet

Reagent	Total flavone solid dispersion	KCl	PEO	Magnesium stearate	Soluble starchPowder
						Percent by weight/%)	50	40	7	0.5	2.5
Dosage per mg	150	120	21	1.5	7.5

PEG-4000-acetone-CA coating liquid formula

Example 4

Tablet core formula of osmotic pump tablet

Reagent	Total flavone solid dispersion	Mannitol	PEO	Magnesium stearate	Soluble starch
						Percent by weight/%)	50	40	7	0.5	2.5
Dosage per mg	150	120	21	1.5	7.5

PEG-4000-acetone-CA coating liquid formula

Reagent	97% (v/v) acetone	CA	PEG-4000	PEG-4000/CA
					Dosage of	200mL	10g	2g		20％

FIG. 3 is a graph showing the effect of different osmotic pressure active substances on drug release of an osmotic pump tablet of corn cob total flavone solid dispersion in examples 1-4: as can be seen from FIG. 3, NaCl was most favorable for drug release. The solubility of the lactose is greatly influenced by the temperature, the alpha-lactose solubility and the beta-lactose solubility are increased along with the rise of the temperature, and the lactose solubility is limited and is not enough to improve the sufficient osmotic pressure when simulating the constant temperature in the body; mannitol is used as a high-permeability tissue dehydrating agent, has good solubility, is adhered to starch when dissolved, and is not easy to release medicine components of a tablet core; the KCl solubility is greatly influenced by temperature, so that the storage and transportation of the medicament are not facilitated; NaCl has stable chemical property, can stably provide osmotic pressure, and is cheap and easy to obtain. Thus, the osmotically active substance is preferably NaCl by comparative analysis.

Example 1 and examples 5 to 7 study the influence of NaCl content on drug release of total flavone solid dispersion osmotic pump tablets

The NaCl contents of examples 1 and 5 to 7 were 40%, 30%, 35% and 45%, respectively, and the amount of NaCl was controlled by the amount of the soluble starch added as a filler.

Example 5

Tablet core formula of osmotic pump tablet

Reagent	Total flavone solid dispersion	NaCl	PEO	Magnesium stearate	Soluble starch
						Percent by weight/%)	50	30	7	0.5	12.5
Dosage per mg	150	90	21	1.5	37.5

PEG-4000-acetone-CA coating liquid formula

Reagent	97% (v/v) acetone	CA	PEG-4000	PEG-4000/CA
					Dosage of	200mL	10g	2g		20％

Example 6

Tablet core formula of osmotic pump tablet

Reagent	Total flavone solid dispersion	NaCl	PEO	Magnesium stearate	Soluble starch
						Percent by weight/%)	50	35	7	0.5	7.5
Dosage per mg	150	105	21	1.5	22.5

PEG-4000-acetone-CA coating liquid formula

Reagent	97% (v/v) acetone	CA	PEG-4000	PEG-4000/CA
					Dosage of	200mL	10g	2g		20％

Example 7

Tablet core formula of osmotic pump tablet

PEG-4000-acetone-CA coating liquid formula

Reagent	97% (v/v) acetone	CA	PEG-4000	PEG-4000/CA
					Dosage of	200mL	10g	2g		20％

FIG. 4 is a graph showing the effect of NaCl of different contents on drug release of osmotic pump tablets containing total flavonoids in corncobs in examples 1 and 5 to 7: as can be seen from FIG. 4, the dosage of sodium chloride has a significant effect on the drug release of the corncob total flavone solid dispersion controlled-release tablet. As the NaCl in the tablet core is dissolved to form a high osmotic pressure area, when the solvent continuously enters the osmotic pump, the osmotic pressure in the medicine is continuously increased, and enough power is provided for the release of the medicine. When the NaCl content is 40%, the drug release rate is relatively stable, and the release rate reaches more than 85% in 24 hours. Therefore, the NaCl content is preferably 40%.

Examples 1 and 8 study on the influence of coating solution types on drug release of total flavone solid dispersion osmotic pump tablets

Example 1 PEG-4000-acetone-CA coating solution and example 8 PEG-400-ethanol-EC coating solution

Example 8

Tablet core formula of osmotic pump tablet

Reagent	Total flavone solid dispersion	NaCl	PEO	Magnesium stearate	Soluble starch
						Percent by weight/%)	50	40	7	0.5	2.5
Dosage per mg	150	120	21	1.5	7.5

PEG-400-ethanol-EC coating liquid formula

Reagent	95% (v/v) ethanol	EC	PEG-400	PEG-400/EC
					Dosage of	200mL	6.5g	1.3g	20％

FIG. 5 is a graph showing the comparison of PEG-4000-acetone-CA and PEG-400-ethanol-EC coating solutions in example 1 and example 8 for drug release of corncob total flavone solid dispersion osmotic pump tablets: as can be seen from FIG. 5, the cumulative release rate of the PEG-400-ethanol-EC coated drug is more stable, the release efficiency is higher, and the release rate meets the zero-order release condition, while the drug release of the PEG-4000-acetone-CA coated finished product is obviously reduced in later unit time. Because the boiling point of the acetone is low and the volatilization is fast, when the coating liquid is sprayed on the tablet core, the acetone is volatilized rapidly, molecules at the moment are not connected closely, crossed or wound into a compact coating film in the future, only a discontinuous coating film can be formed, and the intricate coating film forms an independent space structure, so that the coating is not uniform, enough power can be provided for the release of the medicine due to the high NaCl content in the medicine in the first 12h, the medicine release rate is reduced gradually due to the formation of the independent space in 16h to 24h, and only 5 percent of the medicine is released in 8 h. Therefore, the coating solution is preferably a PEG-400-ethanol-EC system.

Example 8-12 Studies on the influence of PEG-400 content in PEG-400-ethanol-EC coating solution on drug release of total flavonoids solid dispersion osmotic pump tablets

In examples 8-12, the amounts of PEG-400 were 20%, 10%, 15%, 25% and 30% of the EC amount, respectively, and the core formulation was consistent with that of example 8.

Example 9

PEG-400-ethanol-EC coating liquid formula

Example 10

PEG-400-ethanol-EC coating liquid formula

Reagent	95% (v/v) ethanol	EC	PEG-400	PEG-400/EC
					Dosage of	200mL	6.783g	1.017g	15％

Example 11

PEG-400-ethanol-EC coating liquid formula

Reagent	95% (v/v) ethanol	EC	PEG-400	PEG-400/EC
					Dosage of	200mL	6.24g	1.56g	25％

Example 12

PEG-400-ethanol-EC coating liquid formula

Reagent	95% (v/v) ethanol	EC	PEG-400	PEG-400/EC
					Dosage of	200mL	6g	1.8g	30％

FIG. 6 is a graph showing the effect of different PEG-400 contents in the PEG-400-ethanol-EC coating solutions of examples 8 to 12 on drug release of an osmotic pump tablet of total flavonoids in corncobs solid dispersion: as can be seen from FIG. 6, different amounts of PEG-400 significantly affect the cumulative release rate of the drug, and the release rate of the drug per unit time increases with the increase of the amount of PEG-400, so the amount of PEG-400 is preferably 30% of the EC amount.

In summary, example 12 is a preferred formulation for preparing an osmotic pump tablet of a total flavonoids in corn cob solid dispersion, which comprises the following steps:

tablet core formula of osmotic pump tablet

PEG-400-ethanol-EC coating liquid formula

Reagent	95% (v/v) ethanol	EC	PEG-400	PEG-400/EC
					Dosage of	200mL	6.0g	1.8g	30％

Determination of drug solubility and cumulative dissolution Rate for corncob Total Flavonoids solid Dispersion osmotic Pump tablets prepared in example 12

Solubility test: 2 tablets of the corn total flavone solid dispersion controlled-release tablet prepared in example 12 were taken and heated in 200mL of artificial gastric fluid at a constant temperature of 37.5 ℃, 2mL of the tablet was taken every 4 hours for absorbance measurement, the drug solubility was calculated, and the original solution was supplemented with the same volume of artificial gastric fluid at the same temperature. (according to the preparation method of Chinese pharmacopoeia (SGF), taking 16.4mL of dilute hydrochloric acid, adding 800mL of water and 10g of pepsin, shaking up, adding water to the scales.)

Cumulative dissolution rate test: taking 2 corn total flavone solid dispersion controlled release tablets, placing in a 500mL artificial gastric juice drug dissolution instrument, setting the rotating speed at 90 r.min^-1And (3) taking 2mL of liquid every 4h at the temperature of 37.5 ℃, carrying out absorbance determination, calculating the cumulative dissolution rate of the medicine, and simultaneously supplementing the artificial gastric juice with the same temperature and volume to the original solution.

FIG. 7 is a line graph of drug solubility and cumulative dissolution: as can be seen from FIG. 7, the solubility of the drug was substantially consistent with the cumulative dissolution rate, which is slightly different from 4h to 20h, mainly because the drug was not released outside the coating in time after part of the drug was dissolved, and the content measured by the cumulative dissolution rate was slightly lower than the dissolution rate. Within 24h, the drug solubility and the accumulated dissolution rate are close to the zero-order drug release characteristic, the release rates can reach more than 85 percent, and the quality standard of the sustained and controlled release preparation in China is met.

Stability test of the corncob Total Flavonoids solid Dispersion osmotic Pump tablets prepared in example 12

High humidity test: 20 tablets of the solid dispersion osmotic pump tablet prepared in example 12 were taken and placed in a drug stabilizer at 25 ℃ and a relative humidity of 75% (saturated NaCl solution) and 92.5% (saturated KNO)₃Solution), the test results are as follows:

TABLE 2 high humidity 75% sample appearance, 24h drug release rate

TABLE 3 high humidity 92.5% sample appearance, 24h drug release rate

As is clear from tables 2 and 3, the total flavone solid dispersion osmotic pump tablets are easy to absorb moisture and dissolve, and since the water-soluble pore-forming agent is contained in the coating film of the osmotic pump tablets, the moisture absorption rate is 5% or less, and the drug release rate is slightly lowered, the product is unstable in a high-humidity environment, and therefore, it is recommended to store the product in a dry environment.

High-temperature test: 20 sheets of the solid dispersion osmotic pump tablet prepared in example 12 were placed in a high temperature environment of 60 ℃ for 10d, samples were taken at 0d, 5d and 10d, and the appearance and the 24-hour release rate (%) of the drug were measured, and the test results are shown in Table 4:

TABLE 4 Effect of high temperature test on drug stability

As can be seen from Table 4, the release of the total flavone solid dispersion osmotic pump tablet is slightly accelerated in the high temperature environment of 60 ℃, but all within the limit specified by the osmotic pump sustained release tablet, which indicates that the product is relatively stable in the high temperature environment and is not affected by the high temperature environment.

And (3) illumination test: 20 tablets of the solid dispersion osmotic pump tablet prepared in example 12 were tested under 4500lx illumination intensity, and the appearance and the cumulative release rate of the drug in 24h were measured by sampling at 0d, 5d and 10d, respectively, and the test results are shown in table 5:

TABLE 5 Effect of illumination intensity on drug stability

As can be seen from Table 5, the solid dispersion osmotic pump tablets did not change significantly under 4500lx light treatment, so the product was stable under light conditions and was not affected by light intensity.

While embodiments of the invention have been disclosed above, it is not limited to the applications listed in the description and the embodiments, which are fully applicable in all kinds of fields of application of the invention, and further modifications may readily be effected by those skilled in the art, so that the invention is not limited to the specific details without departing from the general concept defined by the claims and the scope of equivalents.

Claims

1. An osmotic pump tablet of corncob total flavone solid dispersion is characterized in that: mixing and tabletting the corncob total flavone solid dispersion with osmotic pressure active substances, polyoxyethylene, soluble starch and magnesium stearate to prepare a tablet core, and coating by using a coating solution, wherein the weight of a coating film is controlled to be 5% of that of the tablet core;

40-65% of corncob total flavone solid dispersion

30-45% of osmotic pressure active substance

5-10% of polyoxyethylene

0 to 1 percent of magnesium stearate

0-25% of soluble starch;

the osmotic pressure active substance is sodium chloride;

the coating liquid is polyethylene glycol 400-ethanol-ethyl cellulose coating liquid; wherein, the formula of the polyethylene glycol 400-ethanol-ethyl cellulose coating solution is as follows: dissolving 3.9g of polyethylene glycol 400+ ethyl cellulose in 100mL of 95% (v/v) ethanol, wherein the dosage of the polyethylene glycol 400 is 30% of that of the ethyl cellulose;

the preparation method of the corncob total flavone solid dispersion osmotic pump tablet comprises the following steps:

2. The corncob total flavone solid dispersion osmotic pump tablet according to claim 1, wherein: mixing and tabletting the corncob total flavone solid dispersion with sodium chloride, polyoxyethylene, soluble starch and magnesium stearate to prepare a tablet core, and coating by using a coating solution, wherein the weight of a coating film is controlled to be 5% of that of the tablet core;

corncob total flavone solid dispersion 50%

40 percent of sodium chloride

Polyethylene oxide 7%

Magnesium stearate 0.5%

2.5 percent of soluble starch;

the coating liquid is a polyethylene glycol 400-ethanol-ethyl cellulose coating liquid, and the formula is as follows: 3.9g of polyethylene glycol 400+ ethyl cellulose was dissolved in 100mL of 95% (v/v) ethanol, the amount of polyethylene glycol 400 being 30% of the amount of cellulose acetate.

3. The preparation method of the corncob total flavone solid dispersion osmotic pump tablet as claimed in any one of claims 1 to 2, comprising the steps of: