CN113768898A

CN113768898A - Suspended capsule tablet

Info

Publication number: CN113768898A
Application number: CN202111078179.9A
Authority: CN
Inventors: 邓彬; 夏怡然; 严俊; 黄大伟
Original assignee: Shanghai Fosun Xingtai Pharma Technology Co ltd; Jiangsu Wanbang Biopharmaceutical Group Co ltd
Current assignee: Shanghai Fosun Xingtai Pharma Technology Co ltd; Jiangsu Wanbang Biopharmaceutical Group Co ltd
Priority date: 2021-09-14
Filing date: 2021-09-14
Publication date: 2021-12-10
Also published as: WO2023039989A1

Abstract

The invention relates to a suspended capsule tablet, wherein a capsule shell contains a suspended tablet which comprises the following components in percentage by weight: 2-30% of medicine, 10-70% of water-soluble swelling polymer, 0.1-5% of caprylic/capric acid macrogol glyceride, 8-50% of gas generating agent, 10-50% of excipient, 0.1-6% of glidant, 0.1-5% of lubricant and 0-7% of penetration enhancer, wherein the sum of all the components is 100%. After the capsule is immersed in the acid solution, the capsule floats immediately and begins to dissolve gradually, and after water is infiltrated, the surface of the tablet is disintegrated slowly, and the tablet core continues to float. In the absence of a capsule, the surface of the tablet rapidly disintegrates after immersion in an acid solution alone, the drug is rapidly dissolved at an initial stage, and then the gel-forming sustained-release drug is formed. However, when a capsule is added, it is surprisingly found that in the early stage of the dissolution test, the disintegration on the surface of the tablet is greatly reduced, and the dissolution curve of the medicine of some prescriptions is closer to a straight line.

Description

Suspended capsule tablet

Technical Field

The invention relates to a capsule, which contains a suspension tablet and belongs to the field of preparations.

Background

Since gastric floating formulations require rapid penetration of water to produce gas quickly, most effervescent floating systems do not employ film coating techniques, but such effervescent floating systems often suffer from insufficient suspension force due to gas leakage. There are therefore some documents which propose a film coating floating technique.

Patents US8580303 and US8333991 report a dosage form comprising (a) at least one component comprising an aerogenic agent and gabapentin, and (b) at least one hydrophilic film encasing (a). Wherein the hydrophilic membrane expands by swelling, floats on the gastric juice, and is permeable to the gastric juice. Patents US8529955, US8440232 and US8475813 propose a dosage form comprising: gabapentin and a pharmaceutically acceptable tablet core containing excipients, and a semipermeable membrane surrounding the tablet core, the semipermeable membrane comprising a plasticizer and being permeable to gastric fluid but substantially impermeable to insoluble gabapentin. Nilesh Desai et al (AAPS PharmSciTech 2017 Oct; 18 (7): 2626-. However, since drug release requires porous passage through the coating film, the drug must be dissolved in the medium in a molecular state. The insoluble drug particles cannot be released through a film, and the release rate is low when the technology is applied to the drugs.

Sheng-Feng Hung et al (PLoS one.2014: 9 (6): e100321) apply a plasticizer-containing polymeric coating to a multiple unit floating drug delivery system. Vinay Kumar Katakam et al (trop. J. pharm. Res. 4.2014; 13 (4): 489-. However, coating the outside of the core delays the tablet floating time. At the same time, gas generation around the core will hinder drug release and further lead to batch-to-batch dissolution fluctuations.

Ampanart huanga et al (pharmcitech, vol 17, No. 3, 2016, 6) describe a new floating system with a core surrounded by a semi-permeable membrane. The core contains a high proportion of water-insoluble microcrystalline cellulose or gas generant. During dissolution, the gas generated is distributed uniformly in the core (see figures 4 and 8 of the article). The even distribution of this gas within the core or around the film coating will hinder drug release and cause fluctuations in drug release.

Zulfequar a. khan et al (AAPS Pharmsitech, vol 12, No. 4, 12 months 2011) describe a floating tablet that coats a drug-loaded core with a gas-producing layer and a polymer layer. The polymer film can play a role of shielding, and gastric juice is prevented from instantly permeating into the film, so that the conversion of sodium bicarbonate into carbon dioxide is delayed. The medicine is released through the medicine releasing hole. Rania A.H. Ishak ((J Pharm Sci,18(1) 77-100, 2015) considers that the preferred drug candidate for the gastroretentive formulation is a drug that is readily soluble in the acidic environment of stomach-As with Khan, Ranina also considers that the polymer coating should be able to withstand the pressure generated by carbon dioxide to avoid rupture-Sadhana Shahi et al (Asian Journal of Pharmaceutical Technology & Innovation,03 (15); 2015; 32-49) considers that the drug needs to be released from the drug release pores in the tablet polymer film, with a pore size of 600 microns to 1 mm-they also consider that for basic osmotic pump tablets (monolayer osmotic pump tablets), water soluble drugs are preferred-these documents all agree that the coating needs to remain intact, cannot rupture, because of air leakage, suspension forces present problems, but because of the limited pore size in order to achieve the desired release effect, such dosage forms are generally suitable for drugs having good water or gastric acid solubility, and are not suitable for poorly soluble drugs. Because, the coated suspension tablets are extremely difficult to release poorly soluble drugs. We have invented the technology of coating disintegrating suspension tablets and the suspension tablets formed by rapid gelling for application to insoluble drugs. (Chinese patent application No. 20110978396.7) but both showed rapid disintegration on the tablet surface and drug release at the beginning.

Disclosure of Invention

Since most literature and commercially available suspension tablet formulations require coatings, the tablets can only be used for drugs with good water solubility after coating. We have invented the technology of coating disintegrating suspension tablets and the suspension tablet which is quickly formed into gel for applying to the insoluble medicine. (Chinese patent application No. 20110978396.7) but both have an initial rapid disintegration of the tablet surface and release of the drug. In one study we have surprisingly found that the aforementioned problems can be effectively overcome by the incorporation of capsules, modulating the tablet core composition. Based on the above, the invention provides a suspension capsule tablet, which comprises a capsule shell, wherein one or more suspension tablets are contained in the capsule shell, and the suspension tablets comprise the following components in percentage by weight: 2 to 30 percent of medicine, 10 to 70 percent of water-soluble swelling polymer, 0.1 to 5 percent of caprylic/capric acid polyethylene glycol glyceride, 8 to 50 percent of gas generating agent, 10 to 50 percent of excipient, 0.1 to 6 percent of glidant, 0.1 to 5 percent of lubricant, 0 to 7 percent of penetration enhancer, and the sum of all the components is 100 percent.

Except for the capsule, the auxiliary materials are uniformly distributed in the tablet core, and after the tablet is immersed in an acid solution in 0.1N HCl, the initial section of the surface of the tablet rapidly disintegrates to cause the burst release of the medicine and then slowly release the medicine. However, when a capsule is added (tablet in capsule; caplet), surprisingly: in the early stages of the dissolution test, the capsules immediately floated and began to dissolve, the disintegration on the tablet surface was greatly reduced, and the first hours of the drug dissolution profile of some capsule formulations, particularly HPMC capsules, were closer to a straight line (example 2). The invention is suitable for insoluble drugs, and is a product which needs stable drug dissolution rate and achieves ideal dissolution curve effect.

In some specific embodiments, the suspension tablet comprises the following components in percentage by weight: 3 to 15 percent of medicine, 30 to 70 percent of water-soluble swelling polymer, 0.2 to 5 percent of caprylic/capric acid macrogol glyceride, 0.2 to 6 percent of penetration enhancer, 8 to 30 percent of gas generating agent, 15 to 40 percent of excipient, 0.1 to 6 percent of glidant and 0.5 to 5 percent of lubricant, wherein the sum of all the components is 100 percent.

The capsule shell is an HPMC (hydroxypropyl methylcellulose) capsule shell, and can be purchased from the market; the capsule shell needs to be larger than the tablet size.

The medicament of the invention can be suitable for medicaments with any solubility, in particular, the medicament with low solubility in acid can be more suitable for medicaments with low solubility in acid, the medicament with low solubility in acid in the invention refers to medicaments with solubility less than 1mg/ml in hydrochloric acid with pH of 1.2, such as cabozantinib malate, and can also be used for medicaments with better solubility in acid, such as varatinib mesylate. The dosage form can reduce the risk of sudden release of the early-stage medicament and then continuously release the medicament, thereby not only realizing the release requirement, but also avoiding the sudden release of the medicament caused by excessive early-stage disintegration. In some embodiments, drugs with low solubility in acid include, but are not limited to, cabozantinib or a salt thereof, crizotinib or a salt thereof; drugs with relatively good solubility in acids, such as pravastatin mesylate; in some embodiments, a preferred weight ratio is 2% to 15%.

The drug substance of the present invention may be milled or dispersed in a substance prior to forming the dosage form to improve its dissolution rate. In some embodiments, the solid drug may be pulverized to a micron or nanometer scale, for example, the average particle size may be 0.1 microns to 20 microns. In other embodiments, solid dispersion, clathrate, and like techniques may also be employed to improve the dissolution rate. These means may be conventional in the art, for example, Zhi Hui Loh et al (Asian Sciences, volume 10, phase 4, month 7 2015, 255-. Vincent Caron et al (Mixer Mill MM400, Retsch GmbH & Co., Germany) ground at room temperature with a PM 100 high energy planetary Mill (Retsch, Germany) and freeze-ground in a vibrating ball Mill. Methods of molecular dispersion (which here corresponds to solid dispersants) are also described in many scientific articles (e.g.AAPS PharmSci Tech.2013Mar; 14 (1): 464-. Francimix L.Guedes et al (AAPS PharmSci Tech.2011Mar; 12 (1): 401-. The drug and polymer were dissolved in a methanol/chloroform mixture and the solvent was removed by evaporation, freeze drying. The drug is in an amorphous state. Lili fitiani et al (J adv.pharm Technol.). res.2016jul-Sep; 7(3): 105-109), by solvent evaporation method at a pressure of 2: 1. 1: 1 and 1: 2-efavirenz-PVP K30 dispersant was prepared and dried using a freeze dryer. Abhishek Singh et al (advanced drug delivery review, Vol. 100, 2016, 5/1/2016, 27-50) prepare amorphous solid dispersions by spray drying.

In some embodiments of the invention, the percentage by weight of caprylic capric macrogol glycerides is 3-5%. Caprylic capric acid polyethylene glycol glyceride (labrosal) is a mixture composed of a certain proportion of mono, di, and triglyceride and mono and di fatty acid polyethylene glycol ester, a small part of mono, di, and triglyceride of caprylic acid (C8) and capric acid (C10) and most of PEG-8 (molecular weight 400) mono-and di-esters, and can be obtained commercially. The water absorption of the tablet can be increased by adding the caprylic capric acid polyethylene glycol glyceride, and the formation of a gel skeleton is promoted.

In some embodiments of the invention, the gas generant is sodium bicarbonate; in some embodiments, the weight ratio of gas generant is 8-25%; in some embodiments, the gas generant is 9-12% by weight.

In some embodiments of the invention, the water-soluble swelling polymer is selected from hydroxypropyl methylcellulose (hypromellose), carbomers, polyethylene oxide, methylcellulose, gelatin, and other water-soluble polymers with similar high viscosities; in some embodiments, the water-soluble swollen polymer is present in an amount of 35 to 70% by weight and in some embodiments, the water-soluble swollen polymer is present in an amount of 40 to 50% by weight.

In some embodiments, the water-soluble swelling polymer is selected from Hypromellose (HPMC) having a viscosity in the range of 15mpa.s to 4000mpa.s, such as hypromellose E15LV, hypromellose E50, hypromellose K100LV, or hypromellose K4M. Hydroxypropyl methylcellulose (Meiduoxiu)^TM) Is a preferred auxiliary material of a hydrophilic gel framework formula, and is beautiful and beautiful^TMThe medicinal grade hypromellose has multiple selectable viscosity specifications, and can meet the release requirements of medicines with different solubilities. Common CR specifications include E50LV, K100LV, K4M, K15M, K100M, and the like. In some embodiments, the combination of primary water-soluble swelling polymers are hypromellose E series and K series, such as K4M, K15M, and K100M, or water-soluble swelling polymers of similar character to the K series. In some embodiments, the combination of primary water-soluble swelling polymers is hydroxypropyl methylcellulose K100 LV.

In some embodiments, at least two water-soluble swelling polymers are included.

The excipient of the present invention includes, but is not limited to, mannitol, fructose, sucrose, lactose, xylitol, sorbitol, microcrystalline cellulose, calcium carbonate, calcium hydrogen phosphate, tribasic calcium or calcium sulfate, etc. In some embodiments, the excipient is added in an amount of 18-35%. In some embodiments, the excipient is added in an amount of 19-26%.

Penetration enhancers of the invention include, but are not limited to, water soluble salts of inorganic acids such as potassium chloride, potassium sulfate, potassium hydrogen phosphate, sodium hydrogen phosphate and sodium chloride and other organic acids such as citric acid, tartaric acid and the like. The preferred osmolyte is citric acid. In some embodiments, the penetration enhancer is present in an amount of 0.5 to 6% by weight.

Glidants of the invention include, but are not limited to, silicon dioxide, magnesium trisilicate, tribasic calcium phosphate, calcium silicate, magnesium silicate and other materials known to those of ordinary skill in the art. In some embodiments, the glidant is added in an amount of 5-6%.

The lubricant according to the present invention may be selected from, but is not limited to, those conventionally known in the art, such as sodium stearyl fumarate, magnesium stearate, aluminum or calcium stearate, or zinc stearate, polyethylene glycol, glyceryl monostearate, glyceryl behenate, mineral oil, sodium stearyl fumarate, stearic acid, hydrogenated vegetable oil, or talc. In some embodiments, the lubricant is added in an amount of 0.5 to 2.5%. In some embodiments, the lubricant is added in an amount of 0.5 to 1.5%.

The disintegrant according to the present invention may be selected from, but is not limited to, those conventionally known in the art, such as croscarmellose sodium. The disintegrant may or may not be added.

The suspension tablets of the invention may or may not be coated, preferably without coating, but if coated, in some embodiments of the invention the coating comprises 10% to 85% of a water-insoluble polymer and 20% to 80% of a water-soluble polymer, the sum of the components being 100%, the dosage range of the coating having less effect on the effect of the invention, being adjusted within this range to achieve the effect of the invention. The water-insoluble polymer is cationic polymethyl methacrylate (commercial product, e.g. EUDRAGIT)

And EUDRAGIT

) Preferably, the amount is in the range of 10% to 50%. Water-soluble polymers include, but are not limited to, polysaccharides (e.g., maltodextrin), alkyl celluloses (e.g., methylcellulose or ethylcellulose), cellulose acetates, hydroxyalkyl celluloses (e.g., hydroxypropyl cellulose or hydroxypropyl methylcellulose), polyvinylpyrrolidone, gum arabic, sucrose, gelatin, shellac, cellulose acetates, phthalates, lipids, synthetic resins, acrylic polymers, cellulose acetate copolymers, and the like,

Coating systems, polyvinyl alcohol (PVA), copolymers of vinylpyrrolidone and vinyl acetate (e.g. in

Sold under the trade name) or methacrylic acid-based polymers (e.g. as in

Those sold under the brand name). These may be applied from aqueous or non-aqueous systems or a combination of aqueous and non-aqueous systems as the case may be. May also be included with additives and film formers to provide a more satisfactory film. These additives may include plasticizers, channeling agents, anti-tacking (anti-tacking) agents, fillers, polishing agents, opacifying agents, etc., all of which may be commonly used in the art, for example, the plasticizer may be dibutyl phthalate, triethyl citrate, polyethylene glycol (PEG), etc.; the channeling agent may be a surfactant, short chain water soluble polymer, salt, or the like; the antisticking agent can be pulvis Talci, stearic acid, magnesium stearate, colloidal silicon dioxide, etc.; the filler can be talcum powder, precipitated calcium carbonate and the like; the polishing agent can be bee wax, carnauba wax, synthetic chlorinated wax, etc.; opacifying agents such as titanium dioxide and the like. All of these additives may be used at levels well known to those skilled in the art.

The invention also discloses a method for preparing the suspension tablet, which comprises the steps of mixing the caprylic capric acid polyethylene glycol glyceride with the flow aid to form particles, or mixing the caprylic capric acid polyethylene glycol glyceride with the medicine and the flow aid to form particles, then mixing the particles with other tablet core materials, tabletting, and optionally coating.

The specific procedures involved in the preparation process of the present invention may be according to conventional methods in the art. For example, the tablet core of the present invention may be formed by direct compression, granulation-compression, pellet-compression or equivalent methods. In direct compression, the raw materials are mixed thoroughly and placed in a compression mold and compressed to form tablets. In granulation, the formulation solution is sprayed onto a mixture of "granules" and excipients to form granules. The particles are dried and milled to the desired particle size distribution. The granules are then mixed with other excipients and placed in a compression mold and compressed to form tablets. Techniques for preparing tablets are described in Remington "s Pharmaceutical Sciences, (Arthur Osol, editor), 1553-. Particle coating using a fluidized bed is reported in U.S. patent No. 8,282,957, which describes particle spray coating using a spray drying process. U.S. patent No. 8,911,766 describes particle spray coating using solvent evaporation techniques. Some other alternative methods may be used to coat the particles or microparticles of the present invention. Tablet cores coated with a coating pan, fluidized bed or similar equivalent apparatus. Disc coating may be a convenient method of film coating the core. The tablet cores are placed in a pan, the pan is rotated, and the semipermeable polymer solution is sprayed onto the tablet cores. Other spraying techniques, such as air suspension (fluidized bed) are also contemplated. The core was suspended in air in a fluidized bed, and the core was sprayed with the polymer solution, in effect circulating through a Wurster column. Panning procedures may be found in the united states. Patent application No. 20060099262. The air suspension procedure is described in U.S. patent No.2,799,241. am. pharm. assoc, volume 48, page 451-; and ex, volume 49, pages 82-84 (1960), supra.

The invention has the beneficial effects that:

most of the suspension tablet products on the market require coatings and are only suitable for drugs with good water solubility. I have invented the technology of coating disintegrating suspension tablets and the suspension tablet which can be quickly formed into gel for application in insoluble medicine. (Chinese patent application No. 20110978396.7) in the dissolution test, there were both cases where the tablet surface rapidly disintegrated and the drug was released at the initial stage. However, when a capsule is added (tablet in capsule; caplet), surprisingly: in the early stages of the dissolution test, the capsules immediately floated and began to gradually dissolve, the disintegration at the surface of the tablets was greatly reduced, and the first hours of the drug dissolution profile of some of the capsule tablet formulations were closer to a straight line (example 2). The medicament of the invention can be suitable for medicaments with any solubility, in particular, the medicament with low solubility in acid can be more suitable for medicaments with low solubility in acid, the medicament with low solubility in acid in the invention refers to medicaments with solubility less than 1mg/ml in hydrochloric acid with pH of 1.2, such as cabozantinib malate, and can also be used for medicaments with better solubility in acid, such as varatinib mesylate.

The name of the present invention is defined as follows, if not otherwise specified:

"optional" or "optionally" means that the subsequently described event may or may not occur, such that the description includes instances where the event occurs and instances where it does not.

The singular forms (e.g., "a," "an," and "the") included in the claims include plural references unless explicitly stated or the context clearly dictates otherwise. On the other hand, the singular form "ONE" does not include plural references.

"consisting of" is a transitional phrase used in the claims of this invention. "consisting of … … excludes any element, step, or ingredient not specified in the claims.

The term "carbonate" may be exchanged for "bicarbonate", which may be a carbonate or bicarbonate (bicarbonate).

The suspension tablet, the tablet and the tablet core of the invention all refer to the suspension tablet placed in the capsule if not specifically stated.

Unless otherwise specified,% of the present invention means weight percentage.

Drawings

FIG. 1 is the data for the results of example 1, wherein: FIG. 1a is a drug dissolution comparison of the formula 1 suspension tablet and gelatin capsule tablet of example 1. FIG. 1b is a drug dissolution comparison of the formulated HPMC capsule tablet of example 1.

FIG. 2 is the data of the results of example 2, wherein: figure 2a is a comparison of the drug dissolution of the HPMC and gelatin capsule tablets of formula 2a of example 2. Figure 2b is a comparison of the drug dissolution of the HPMC and gelatin caplets of formula 2a of example 2. Figure 2c is a comparison of the drug dissolution of the HPMC and gelatin capsule tablets of formulation 2c of example 2.

Detailed Description

The foregoing examples are illustrative embodiments of the present invention and are illustrative only. Variations and modifications may be made by those skilled in the art without departing from the spirit and scope of the invention. All such modifications and variations are intended to be included herein within the scope of this disclosure.

The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified.

Example 1

1 batch was prepared. The tablet core formulation is shown in table 1 below (mass percent):

[ TABLE 1 ]

Prescription number	Prescription one
		Drug content, mg	60
Cabozantinib malate%	11.12
		Hydroxypropyl methylcellulose E50 LV%	43.88
Caprylic capric acid macrogol glyceride%	4.00
		Sodium bicarbonate,%)	9.00
Microcrystalline cellulose 102%	24.50
		Silicon dioxide content	6.00
Citric acid content	0.50
		Magnesium stearate,%)	1.00
Tablet weight, mg	540

Tablet core: the caprylic capric acid polyethylene glycol glyceride is weighed according to the prescription amount, is quickly mixed with silicon dioxide to form particles, then is mixed with other materials, and the uniformly mixed tablets are tabletted by a rotary tablet machine. The tablet core of formula one was completed.

And (3) filling capsules: the tablet core of prescription one is put into capsules with different specifications and sizes. The supplier of the capsules is suzhou capsules. The standard specifications of the capsule are selected according to the size of the tablet core, and are respectively 000, 00 and 0 from large to small, and the capsule with the same transverse diameter also has the extra-long specification.

As a result:

adopting Chinese pharmacopoeia paddle method 50rpm dissolution condition, dissolution medium 0.1NHCl + 0.2% Tween 80, volume 900mL, suspension tablet begins floating in one minute, and capsule tablet floats at the beginning. The dissolution data were determined and the results are shown in table 3; FIGS. 1a and 1b show: therefore, the HPMC capsule shell selected by the invention can effectively reduce the disintegration condition of the surface of the tablet at the initial stage of a dissolution experiment.

[ TABLE 2 ] dissolution data

Example 2

3 batches were prepared. The formulation is shown in table 3 below:

[ TABLE 3 ]

The procedure was as in example 1.

As a result:

adopting Chinese pharmacopoeia paddle method 50rpm dissolution condition, dissolution medium 0.1NHCl + 0.2% Tween 80, volume 900mL, suspension tablet begins floating in one minute, and capsule tablet floats at the beginning. The dissolution data were determined and the results are shown in table 5; fig. 2a, fig. 2b and fig. 2 c: therefore, the HPMC capsule shell selected by the invention can effectively reduce the disintegration condition on the surface of the tablet at the initial stage of a dissolution experiment.

[ TABLE 4 ] dissolution data

Claims

1.A capsule is characterized by comprising a capsule shell, wherein one or more suspension tablets are contained in the capsule shell, and the suspension tablets comprise the following components in percentage by weight: 2-30% of medicine, 10-70% of water-soluble swelling polymer, 0.1-5% of caprylic/capric acid macrogol glyceride, 8-50% of gas generating agent, 10-50% of excipient, 0.1-6% of glidant, 0.1-5% of lubricant and 0-7% of penetration enhancer, wherein the sum of all the components is 100%; the preferred suspending tablet comprises the following components in percentage by weight: 3 to 15 percent of medicine, 30 to 70 percent of water-soluble swelling polymer, 0.2 to 5 percent of caprylic capric acid macrogol glyceride, 0.2 to 6 percent of penetration enhancer, 8 to 30 percent of gas generating agent, 15 to 40 percent of excipient, 0.1 to 6 percent of glidant and 0.5 to 5 percent of lubricant, and the sum of all components is 100 percent.

2. The capsule according to claim 1, wherein the capsule shell is an HPMC capsule shell, and the capsule shell is larger than the tablet size.

3. The capsule according to claim 1, wherein the suspension tablet is uncoated.

4. The capsule according to claim 1, wherein the drug is cabozantinib or a salt thereof, rivastigmine or a salt thereof, crizotinib or a salt thereof; the preferred weight percentage of the drug is 2% -15%.

5. The capsule according to claim 1, wherein the caprylic capric acid macrogol glyceride is 3-5% by weight.

6. The capsule of claim 1, wherein the gas generant is sodium bicarbonate; the preferred weight ratio of gas generant is 8-25%, more preferably 9-12%.

7. The capsule according to claim 1, wherein the water-soluble swelling polymer is selected from hypromellose, carbomer, polyethylene oxide, methylcellulose, or gelatin; preferably, the water-soluble swelling polymer is selected from hypromellose with viscosity ranging from 15mpa.s to 4000 mpa.s; more preferably, the water-soluble swelling polymer is selected from hypromellose E15, hypromellose E50, hypromellose K100LV or hypromellose K4M; preferably, the weight ratio of the water-soluble swelling polymer is 35 to 70%, more preferably 40 to 50%.

8. The capsule according to claim 1, wherein the excipients comprise mannitol, fructose, sucrose, lactose, xylitol, sorbitol, microcrystalline cellulose, calcium carbonate, dibasic calcium phosphate, tribasic calcium or calcium sulfate; preferably, the excipient is added in an amount of 18-35%, more preferably 19-26%.

9. The capsule according to claim 1, wherein the penetration enhancer comprises a water-soluble salt of an inorganic acid or an organic acid; preferably, the water-soluble salt of an inorganic acid comprises potassium chloride, potassium sulfate, potassium hydrogen phosphate, sodium hydrogen phosphate or sodium chloride; the organic acid comprises citric acid or tartaric acid; preferably, the weight ratio of the penetration enhancer is 0.5-6%.

10. The capsule of claim 1, wherein said glidant comprises silicon dioxide, magnesium trisilicate, tribasic calcium phosphate, calcium silicate, or magnesium silicate; preferably, the addition amount of the glidant is 5-6%.

11. The capsule of claim 1, wherein said lubricant comprises sodium stearyl fumarate, magnesium stearate, aluminum stearate, calcium stearate, zinc stearate, polyethylene glycol, glyceryl monostearate, glyceryl behenate, mineral oil, sodium stearyl fumarate, stearic acid, hydrogenated vegetable oil, or talc; preferably, the lubricant is added in an amount of 0.5% to 2.5%, more preferably 0.5 to 1.5%.

12. The capsule according to claim 1, wherein the suspension tablet is prepared by: mixing the caprylic capric acid polyethylene glycol glyceride and the glidant to form particles, or mixing the caprylic capric acid polyethylene glycol glyceride, the medicine and the glidant to form particles, mixing the particles with other tablet core materials, and tabletting.