WO2019208967A1 - Comprimé à enrobage entérique comprenant de l'acide fénofibrique ou un sel pharmaceutiquement acceptable de celui-ci - Google Patents

Comprimé à enrobage entérique comprenant de l'acide fénofibrique ou un sel pharmaceutiquement acceptable de celui-ci Download PDF

Info

Publication number
WO2019208967A1
WO2019208967A1 PCT/KR2019/004601 KR2019004601W WO2019208967A1 WO 2019208967 A1 WO2019208967 A1 WO 2019208967A1 KR 2019004601 W KR2019004601 W KR 2019004601W WO 2019208967 A1 WO2019208967 A1 WO 2019208967A1
Authority
WO
WIPO (PCT)
Prior art keywords
weight
enteric
acid
tablet
pharmaceutically acceptable
Prior art date
Application number
PCT/KR2019/004601
Other languages
English (en)
Korean (ko)
Inventor
최연웅
조상민
기도형
송인호
Original Assignee
한국유나이티드제약 주식회사
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 한국유나이티드제약 주식회사 filed Critical 한국유나이티드제약 주식회사
Publication of WO2019208967A1 publication Critical patent/WO2019208967A1/fr
Priority to PH12020551635A priority Critical patent/PH12020551635A1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin

Definitions

  • the present invention relates to an enteric coated tablet comprising fenofibric acid or a pharmaceutically acceptable salt thereof and a method for preparing the same.
  • fenofibrate 2- [4- (4-chlorobenzyl) phenoxy] -2-methyl-2-propanoic acid, which is used to treat hyperlipidemia.
  • Fenofibric acid the active form of fenofibrate, activates lipoprotein lipase to promote catabolic activity of VLDL-triglycerides and inhibits the activity of acetyl-coA carboxylase to inhibit fatty acid synthesis in the liver. It also reduces the production of small high-density LDL particles at higher risk of developing atherosclerosis and promotes the production of large low-density particles. It also reduces the accumulation of intracellular esterified cholesterol by inhibiting the activity of acetyl-coA cholesterol transferase (Kor. J. Clin. Pharm., Vol. 15, No. 1. 2005).
  • Korean Patent No. 10-1202994 discloses a phenoside capsule filled with fenofibric acid (135 mg) using an alkalizing agent to improve solubility and sustained release granules using ethyl cellulose.
  • One object of the present invention is a core comprising fenofibric acid or a pharmaceutically acceptable salt thereof, a disintegrant and an alkalizing agent for solubilizing poorly soluble fenofibric acid; And an enteric coating layer, wherein the alkalizing agent is to provide an enteric coated tablet containing 0.5 to 2 parts by weight relative to 1 part by weight of fenofibric acid or a pharmaceutically acceptable salt thereof.
  • Another object of the invention is a core comprising fenofibric acid or a pharmaceutically acceptable salt thereof, and a disintegrant; And an enteric coating layer, wherein the disintegrant is to provide an enteric coated tablet comprising 7.5 to 30% by weight based on the total weight of the enteric coated tablet.
  • Another object of the present invention is to prepare a mixture by (a) mixing fenofibric acid or a pharmaceutically acceptable salt, disintegrant, and alkalizing agent thereof; (b) tableting the mixture of step (a) by direct compression to prepare a tablet; And (c) coating the resultant of step (b) with an enteric coating, wherein the disintegrant is mixed in an amount of 7.5 to 30% by weight based on the total weight of the enteric coated tablet.
  • the present invention is a core comprising fenofibric acid or a pharmaceutically acceptable salt thereof; And an enteric coated tablet comprising an enteric coating layer.
  • an alkalizing agent is included as a solubilizer, which increases the microenvironment pH around fenofibric acid upon exposure in vivo and thus the water solubility of fenofibric acid. Increase the bioabsorption rate.
  • the alkalizing agent also increases the solubility of fenofibric acid or its pharmaceutically acceptable salts even in low pH environments.
  • enteric coated tablets that can minimize drug loss in the stomach (pH 1.2) and release the drug in the small intestine.
  • enteric coating tablets according to the present invention were designed by mixing, lubricating and tableting fenofibric acid with a predetermined ratio of disintegrant and then enteric coating.
  • Enteric-coated tablets according to the present invention has a very high bioavailability of the active ingredient since the elution is started in a high pH environment, and can further reduce the production cost because the content of the active ingredient can be further reduced than the prior art.
  • it is excellent in stability during long-term storage in the form of tablets, the size of the tablets can be small, the patient taking convenience can be increased.
  • the core of the enteric coated tablet comprises fenofibric acid or a pharmaceutically acceptable salt thereof.
  • a pharmaceutically acceptable salt herein means a compound that does not impair the biological activity and the properties of the fenofibric acid administered.
  • Non-limiting examples of such pharmaceutically acceptable salts include acids that form non-toxic acid addition salts containing pharmaceutically acceptable anions, such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, and the like.
  • Organic carbon acids such as inorganic acid, tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trichloroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, salicylic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, acid addition salts formed by sulfonic acids such as p-toluenesulfonic acid and the like.
  • carboxylic acid salts include metal salts or alkaline earth metal salts formed by lithium, sodium, potassium, calcium, magnesium, amino acid salts such as lysine, arginine, guanidine, dicyclohexylamine, N Organic salts such as -methyl-D-glucamine, tris (hydroxymethyl) methylamine, diethanolamine, choline and triethylamine and the like.
  • the enteric coated tablets of the present invention may comprise a pharmaceutically effective amount of fenofibric acid or a pharmaceutically acceptable salt thereof.
  • pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, generally in an amount of 0.001 to 1000 mg / kg, preferably 0.05 To 200 mg / kg, more preferably from 0.1 to 100 mg / kg amount may be administered once to several times a day.
  • the specific therapeutically effective amount for a particular patient is determined by the specific composition, including the type and extent of the reaction to be achieved and whether other enteric coated tablets are used, as appropriate, the age, body weight, general health of the patient. It is desirable to apply differently depending on the various factors and similar factors well known in the medical field, including the condition, sex and diet, time of administration, route of administration and rate of composition, duration of treatment, drugs used with or co-specific with the specific composition. .
  • fenofibric acid or a pharmaceutically acceptable salt thereof may be included in the enteric coated tablet at 100-160 mg per unit enteric coated tablet, specifically 100-120 mg per unit enteric coated tablet. Since the enteric coated tablet according to the present invention exhibits excellent bioavailability, it may exhibit a high therapeutic effect even in a small amount compared to the conventional 135 mg / unit enteric coated tablet, and may also reduce side effects.
  • alkalizing agent e.g., sodium EDTA
  • binder e.g., sodium EDTA
  • coating agent e.g., sodium EDTA
  • disintegrant e.g., sodium EDTA
  • fenofibric acid or a pharmaceutically acceptable salt thereof is 5 to 90% by weight, specifically 10 to 75% by weight, based on the total enteric coating tablet weight. %, More specifically, may be included in 10 to 30% by weight, but is not limited thereto.
  • the fenofibric acid or a pharmaceutically acceptable salt thereof may be ground to 10 to 50 mesh, for example, 15 to 40 mesh, or 20 to 35 mesh.
  • the final dissolution rate is improved when used to grind to the size (Fig. 4).
  • the core may be made of a tablet, not a filled capsule.
  • the core may further comprise an alkalizing agent for solubilizing the fenofibric acid active ingredient.
  • the alkalizing agent is used to improve the solubility of the fenofibric acid active ingredient and improve the bioavailability, and to use a material suitable for the preparation of tablets of the present invention with excellent tableting properties, if necessary. It can also be mixed with a conventional alkalizing agent and used.
  • Korean Patent No. 1202994 which is a conventional fenofibric acid pellet formulation as an alkalizing agent for solubilizing fenofibric acid to improve bioavailability, calcium carbonate, calcium hydroxide, dicalcium phosphate, tricalcium phosphate, magnesium carbonate, Magnesium hydroxide, magnesium silicate, magnesium oxide, magnesium aluminate, magnesium aluminum hydroxide, lithium hydroxide, potassium hydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodium hydroxide and the like are known.
  • the present inventors have intensively studied, and when magnesium metasilicate aluminate is added as an alkalizing agent, not only does the water solubility of fenofibric acid increase, but also the adsorptivity, disintegration property, stability as well as compression formation suitable for tablet tableting. It was found that the back was improved.
  • Magnesium metasilicate is used as an antacid that can protect the stomach from gastric ulcers with excellent antacid ability.It can function as an alkalizing agent.It has a large specific surface area and porosity, so it can also be used as an adsorbent, disintegrant and stabilizer. It can also serve as a lubricant to increase fluidity and improve tableting. Thus, it is an alkalizing agent suitable for preparing fenofibric acid tablets according to the present invention.
  • magnesium metasilicate aluminate when magnesium metasilicate aluminate is mixed with magnesium oxide and used as an alkalizing agent, the solubility improvement effect of fenofibric acid is more enhanced than when magnesium metasilicate aluminate is used alone, and the most preferable result is obtained.
  • the pharmaceutical composition according to the present invention is used as an alkalizing agent by mixing together magnesium oxide and magnesium metasilicate aluminate.
  • magnesium metasilicate aluminate (noisin S1) appeared in the solubilization effect, it was more excellent solubilization effect, meta to 1 part by weight of magnesium oxide
  • magnesium silicate aluminate is mixed at 4 to 10 parts by weight and used as an alkalizing agent, it is shown that the bioavailability of the fenofibric acid active ingredient is greatly improved while securing tableting properties and stability.
  • the drug and the alkalizing agent are not released in the gastric fluid and are released after reaching the intestine, thereby reducing the loss of the active ingredient and the alkalizing agent. Therefore, it is possible to maintain the optimum content of the active ingredient and the alkalizing agent to achieve the desired solubility, thereby reducing the production cost and remedy gastrointestinal side effects due to excessive drug content.
  • the alkalizing agent is included in less than the above range, the desired solubility improvement effect may not be obtained.
  • the alkalizing agent of the present invention may be included in an amount of 0.5 to 2 parts by weight, more preferably 0.75 to 1.5 parts by weight, based on 1 part by weight of fenofibric acid or a pharmaceutically acceptable salt thereof.
  • magnesium oxide which is a known alkalizing agent
  • magnesium metasilicate aluminate which is an alkalizing agent and can function as a lubricant, a disintegrant, a stabilizer, and an adsorbent, may be included in an amount of 4 to 10 parts by weight based on 1 part by weight of magnesium oxide.
  • the formulation according to the present invention uses an alkalizing agent in an amount of 0.5 parts by weight or more and 2 parts by weight or less to 1 part by weight of fenofibric acid or a pharmaceutically acceptable salt thereof, and more specifically, magnesium oxide as an alkalizing agent.
  • magnesium metasilicate aluminate in the tablet core may be included in an amount of 4 to 10 parts by weight based on 1 part by weight of magnesium oxide, so that the solubility improving effect is most excellent in the above range, and bioavailability may be greatly improved.
  • the magnesium oxide may effectively increase the solubility of fenofibric acid by acting as an alkalizing agent together with magnesium metasilicate, even though it is included in a relatively small amount compared to magnesium metasilicate.
  • the magnesium oxide may be included in an amount of 0.05 to 0.3 parts by weight based on 1 part by weight of fenofibric acid or a pharmaceutically acceptable salt thereof, and the magnesium metasilicate aluminate may be included in an amount of 0.2 to 1.95 parts by weight.
  • the solubility of the formulation was significantly improved from 0.05 parts by weight, the increase rate of solubility in the range exceeding 0.3 parts by weight This did not increase significantly.
  • the core of the tablet according to the invention may further comprise a disintegrant.
  • the disintegrant contained in the core may lead to rapid disintegration, thereby improving the initial and final dissolution rate of the formulation.
  • the disintegrant is not limited as long as it is intended to promote disintegration in the digestive tract of the body, and any dispersant may be used as long as it is a material commonly used in the art.
  • Non-limiting examples include croscarmellose sodium, sodium starch glycolate, carboxymethyl cellulose-Ca (CMC-Ca), crospovidone, alginic acid, polyvinylpyrrolidone, corn starch, microcrystalline cellulose, hydroxypropyl methylcellulose And it may be selected from the group consisting of hydroxypropyl cellulose, and combinations thereof.
  • the disintegrant may be included in an amount of 0.03 to 30% by weight, specifically 7.5 to 30% by weight, and more specifically 7.5 to 25% by weight based on the total weight of the formulation.
  • the disintegrant may be included in 6.0 to 10.0% by weight based on the total weight of the formulation.
  • the formulation according to an embodiment of the present invention including the enteric coating layer, even if it contains a lot of disintegrant compared to other formulations, it can be prevented from disintegrating before reaching the small intestine.
  • the core may further comprise excipients for direct hits.
  • the excipient for direct hit may be selected from the group consisting of lactose or its hydrate, microcrystalline cellulose, calcium phosphate dibasic, and combinations thereof, but may be used as long as it is a material commonly used in the art without limitation. More preferably, lactose monohydrate and microcrystalline cellulose can be used.
  • the lactose hydrate may be included in an amount of 0.05 to 30 parts by weight based on 1 part by weight of the total enteric coated tablet.
  • lactose monohydrate may be included in an amount of 0.1 to 5 parts by weight, and more specifically 0.15 to 2 parts by weight, based on 1 part by weight of the total enteric coating tablet. If it is included below the weight, the flowability may be lowered and tableting may be lowered. If it is included in an amount exceeding the weight, the size of the tablet may increase, leading to a problem of ease of taking.
  • the core may further comprise a lubricant.
  • the glidant may comprise 0.2% to 2.0% by weight of the total weight (100% by weight) of the enteric coated tablet, more preferably 0.4% to 1.0% by weight.
  • the compression of the tablet does not appear smoothly, and sticking (sticking) may occur when the powder adheres to the surface of the punch, causing a groove on the surface of the tablet.
  • the glidant may be, for example, magnesium stearate, stearic acid, talc, sodium stearyl fumarate, sodium lauryl sulfate, poloxamer or combinations thereof.
  • the core may further comprise a binder for direct acting. Applicant has confirmed that the use of the binder for direct stroke has the effect of reducing the capping (capacitance of peeling the top of the tablet into a hat shape), laminating (phenomena of peeling the tablet into layers) during manufacture.
  • the binder for direct hit may include vinylpyrrolidone-vinyl acetate copolymer, but is not limited thereto, and any binder may be used as long as it is a material commonly used in the art.
  • the binder for direct hit may be copovidone (trade name: collidone VA 64, or collidone VA 64 fine).
  • the core may further comprise a surfactant.
  • a surfactant in the present invention, anionic, cationic, or neutral surfactants can be used to increase the solubility of enteric coated tablets, for example, soluplus (Polyvinyl caprolactam-Polyvinylacetate-Polyoxyetheylen graft copolymer), sodium lauryl sulfate (SLS), Sepitrap 80®polisorbate 80) or Sepitrap 4000® (Microencapsulated polyoxyl 40-hydrogenated castor oil) can be used.
  • soluplus Polyvinyl caprolactam-Polyvinylacetate-Polyoxyetheylen graft copolymer
  • SLS sodium lauryl sulfate
  • Sepitrap 80®polisorbate 80 Sepitrap 4000®
  • Microencapsulated polyoxyl 40-hydrogenated castor oil can be used.
  • the surfactant can be included, for example, at 0.1 or 20% by weight, specifically 0.5 or 15% by weight, more specifically 0.5 to 10% by weight of the enteric coated tablet weight.
  • the enteric coating layer is a layer containing an enteric coating, and may be formed surrounding the core to prevent loss of the core, which is a tablet.
  • the coating agent can be used without limitation so long as it disintegrates in a high pH serous environment.
  • Non-limiting examples include shellac, hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate, cellulose acetate, polyvinyl alcohol phthalate, poly (methacrylic acid-co-methylmethacrylic acid), poly ( Methylacrylic acid-co-methylmethacrylic acid-co-methacrylic acid), poly (methacrylic acid-co-ethylacrylic acid), and combinations thereof.
  • the poly (methacrylic acid-co-methylmethacrylic acid) is Eudragit L 100, Eudragit L100-55, Eudragit L 12.5, Eudragit L 100 P, Eudragit S 100, Selected from the group consisting of Eudragit S 12.5, Eudragit S 100 P, Eudragit L30 D-55, Eudragit FS 30 D, Acryl-EZE (Colorcon), Acryl-EZE (Colorcon) and combinations thereof Can be one.
  • the enteric coating layer may be included in 2.0 wt% to 20 wt%, specifically 4 to 15 wt%, more specifically 4 to 12 wt% of the total weight of the enteric coating tablet. If the coating layer is formed below the above range, undesired release may occur. If the coating layer is formed above the above range, the dissolution rate is decreased and the acid resistance is poor, thereby reducing the bioavailability. May occur.
  • the enteric coated tablet of the present invention may further comprise a primary coating layer comprising a waterproofing agent between the core and the enteric coating layer.
  • the primary coating layer may be included for moisture proof of the disintegrant according to the excessive use of the disintegrant.
  • an enteric coating may be used to prevent core loss by dissolving by moisture over time as it passes through the gastrointestinal tract.
  • the waterproofing agent may be, for example, Opadry II (Colorcon Co., Component: PVA and HPMC-based derivatives), but any waterproofing agent used for moisture proof in the pharmaceutical industry may be used without limitation.
  • the primary coating layer may be included as 0.03 to 30 parts by weight, specifically 0.04 to 1 part by weight based on 1 part by weight of fenofibric acid or a pharmaceutically acceptable salt thereof.
  • the primary coating layer is formed in the range below the moisture-proof effect does not appear sufficiently, and when the primary coating layer is formed in the above range, the dissolution rate is reduced to decrease the bioavailability.
  • the enteric coating layer of the present invention may further comprise Opadry II.
  • the first coating layer and the enteric coating layer may be included in the enteric coating tablet in a weight ratio of 1: 0.01 to 1: 10, specifically 1: 0.05 to 1: 5 weight ratio.
  • the primary coating layer is formed in the range below the moisture-proof effect does not appear sufficiently, and when the primary coating layer is formed in the above range, the dissolution rate is reduced to decrease the bioavailability.
  • the enteric coated tablet according to the invention may further comprise conventional pharmaceutically acceptable additives and adjuvants.
  • conventional pharmaceutically acceptable additives and adjuvants are as follows:
  • Antioxidants such as phenol (tocopherol and also vitamin E and vitamin-ETPGS (d-alpha-tocopheryl polyethylene glycol 1000 succinate)), butylhydroxyanisol, butylhydroxytoluene, octyl and dodecyl gallate ), Organic acids (ascorbic acid, citric acid, tartaric acid, lactic acid) and salts and esters thereof
  • Wetting agents such as salts of fatty acids, fatty acid alkyl sulfates, fatty acid alkyl sulfonates, linear alkylbenzenesulfonates, fatty acid alkyl polyethylene glycol ether sulfates, fatty acid alkyl polyethylene glycol ethers, alkylphenol polyethylene glycol ethers, alkyl polyglycosides, fatty acids N-methylglucamide, polysorbate, sorbitan fatty acid esters and poloxamers,
  • Isosortic agents such as sodium chloride, glucose or glycerol
  • Colorants such as iron oxide, carotenoids, etc.
  • -Commonly used additives such as pharmaceutically acceptable diluents, lubricants, pH adjusting agents, antifoams, dissolution aids, buffers, bacteriostatic agents and the like.
  • the enteric coated tablets according to the invention may comprise, in addition to fenofibric acid, additionally pharmaceutically active ingredients.
  • the enteric coated tablet of the present invention may include a powder form, and is preferably prepared in the form of a solid enteric coated tablet, but is not impossible to prepare in the form of a liquid and is not excluded from the scope of rights.
  • the enteric coated tablets of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations.
  • the term "administration" refers to introducing the pharmaceutical composition of the present invention to a patient in any suitable manner, the route of administration of the composition of the present invention being oral or parenteral as long as it can reach the target tissue. Administration can be via a variety of routes. Preferably oral administration. Enteric coated tablets according to the invention can be prepared in a variety of formulations depending on the mode of administration desired.
  • Administration can be effected prophylactically or therapeutically.
  • the frequency of administration of the enteric coated tablet of the present invention is not particularly limited, but may be administered once daily or divided into several doses.
  • the subject to which the enteric coated tablet according to the invention is to be administered may mean any animal, including humans.
  • the animal may be a mammal such as, but not limited to, a human, a cow, a horse, a sheep, a pig, a goat, a camel, a antelope, a dog, a cat, and the like, which require treatment of similar symptoms.
  • the present invention comprises the steps of (a) preparing a mixture by mixing fenofibric acid or a pharmaceutically acceptable salt, disintegrant, and alkalizing agent thereof; (b) tableting the mixture of step (a) by direct method; And (c) coating the resultant of step (b) with an enteric coating agent, a method for producing a pharmaceutical enteric coated tablet comprising fenofibric acid or a pharmaceutically acceptable salt thereof.
  • Step (a) is a step of preparing a mixture by mixing fenofibric acid or a pharmaceutically acceptable salt, disintegrant, and alkalizing agent thereof.
  • the type and content of the fenofibric acid, the pharmaceutically acceptable salt, the disintegrant, and the alkalizing agent are the same as described above.
  • the disintegrant may be included in an amount of 0.075 to 0.3 parts by weight based on 1 part by weight of the total enteric coated tablet.
  • the alkalizing agent may be included in an amount of 0.5 to 2 parts by weight, specifically 0.75 to 1.5 parts by weight, based on 1 part by weight of fenofibric acid or a pharmaceutically acceptable salt thereof.
  • Step (b) is a step of tableting the mixture of step (a) by direct method.
  • the mixture of (a) may further include, but is not limited to, excipients for lubricants, lubricants, binders for direct movements.
  • step (b) and step (c) a step of primary coating the result of (b) with Opadry II may be further included.
  • Step (c) is a step of coating the resultant of step (b), or a material which is moisture-coated with Opadry II with an enteric coating.
  • the pharmaceutical enteric coated tablet prepared by the above method may include 100 to 120 mg of fenofibric acid or a pharmaceutically acceptable salt thereof per unit enteric coated tablet.
  • Enteric-coated tablets according to the present invention minimize the loss of drugs in the stomach and release the drug in the small intestine, which is an alkaline condition, thus providing high bioavailability even with a small amount of drug.
  • the dissolution of the drug is started in alkaline conditions, it is possible to reduce the production cost by using a much smaller amount of excipient than the prior art. This can reduce the final dosage form, increasing patient convenience.
  • Figure 2 shows the dissolution rate of Preparation Examples 2, 3 according to an embodiment of the present invention.
  • Figure 3 shows the dissolution rate of Preparation Examples 4, 5, 6 according to an embodiment of the present invention.
  • Figure 4 shows the dissolution rate of Preparation Example 8 according to an embodiment of the present invention.
  • the tablets of Preparation Example 1 were subjected to the dissolution test by applying the USP No. 2 method (paddle method, rotational speed of the paddle: 75 rpm).
  • the dissolution test method was designed in consideration of the retention time in the stomach, and after performing the test for 2 hours in 750ml (pH 1.2) of 0.1N HCl (observation: 60 minutes, 120 minutes), tribasic sodium phosphate The test was performed for 6 hours at pH 6.8 with the addition of 250 ml.
  • the dissolution rate was calculated by the following formula.
  • Preparation Example 2 (30), Preparation Example 2 (40), Preparation Example 3 (30), and Enteric Tablet of Preparation Example 3 (40) were prepared. Specifically, in Preparation Example 1, the amount of the lubricant was added, and the binder was changed for direct use.
  • Dissolution test was carried out in the same manner as in Example 1-2 for the tablets of Preparation Examples 2 and 3.
  • Example 1-1 In the same manner as in Example 1-1, the components shown in Table 3 were mixed, lubricated, and compressed to the corresponding weights, followed by primary coating with Opadry Orange and purified water. Thereafter, enteric coating of 30 mg thickness was prepared in the same manner to prepare enteric tablets of Preparation Examples 4 to 6. Specifically, in Preparation Examples 2 and 3, the amount of disintegrant, excipient (soluplus) was added, and the primary coating was added.
  • Example 3-1 In the same manner as in Example 3-1, the components shown in Table 4 were mixed, lubricated, and compressed to the corresponding weights, followed by primary coating and enteric coating to prepare enteric tablets of Preparation Examples 7 and 8. Fenofibric acid was used by grinding into 25 mesh.
  • Example 3-1 In the same manner as in Example 3-1, the components shown in Table 5 were mixed, lubricated, and compressed to the corresponding weights, followed by primary coating and enteric coating to prepare enteric tablets of Preparation Examples 7 and 8. Fenofibric acid was used by grinding into 25 mesh.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un comprimé à enrobage entérique comprenant de l'acide fénofibrique ou un sel pharmaceutiquement acceptable de celui-ci et son procédé de fabrication. La présente invention peut réduire au minimum la perte d'un médicament et augmenter la solubilité du médicament, maximisant ainsi la biodisponibilité avec même une petite quantité du médicament.
PCT/KR2019/004601 2018-04-24 2019-04-16 Comprimé à enrobage entérique comprenant de l'acide fénofibrique ou un sel pharmaceutiquement acceptable de celui-ci WO2019208967A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PH12020551635A PH12020551635A1 (en) 2018-04-24 2020-10-01 Enteric coated tablet comprising fenofibric acid or pharmaceutically acceptable salt thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2018-0047078 2018-04-24
KR1020180047078A KR102081095B1 (ko) 2018-04-24 2018-04-24 페노피브릭산 또는 이의 약학적으로 허용 가능한 염을 포함하는 장용성 코팅 정제

Publications (1)

Publication Number Publication Date
WO2019208967A1 true WO2019208967A1 (fr) 2019-10-31

Family

ID=68295511

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2019/004601 WO2019208967A1 (fr) 2018-04-24 2019-04-16 Comprimé à enrobage entérique comprenant de l'acide fénofibrique ou un sel pharmaceutiquement acceptable de celui-ci

Country Status (3)

Country Link
KR (1) KR102081095B1 (fr)
PH (1) PH12020551635A1 (fr)
WO (1) WO2019208967A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112603899A (zh) * 2020-12-23 2021-04-06 南京友杰医药科技有限公司 瑞巴派特肠溶片及其制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20080004600A (ko) * 2005-04-13 2008-01-09 라이프사이클 파마 에이/에스 피브레이트를 포함하는 정제
US20080152714A1 (en) * 2005-04-08 2008-06-26 Yi Gao Pharmaceutical Formulations
KR20110114073A (ko) * 2010-04-12 2011-10-19 한미홀딩스 주식회사 페노피브린산 및 알칼리화제를 포함하는 경구용 약학 조성물
KR20120057664A (ko) * 2002-05-24 2012-06-05 풔니어 래버러토리 아일랜드 리미티드 나노입자 피브레이트 제제
KR20180024505A (ko) * 2016-08-30 2018-03-08 대원제약주식회사 개선된 생체이용률을 갖는 페노피브릭산 제제

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120057664A (ko) * 2002-05-24 2012-06-05 풔니어 래버러토리 아일랜드 리미티드 나노입자 피브레이트 제제
US20080152714A1 (en) * 2005-04-08 2008-06-26 Yi Gao Pharmaceutical Formulations
KR20080004600A (ko) * 2005-04-13 2008-01-09 라이프사이클 파마 에이/에스 피브레이트를 포함하는 정제
KR20110114073A (ko) * 2010-04-12 2011-10-19 한미홀딩스 주식회사 페노피브린산 및 알칼리화제를 포함하는 경구용 약학 조성물
KR20180024505A (ko) * 2016-08-30 2018-03-08 대원제약주식회사 개선된 생체이용률을 갖는 페노피브릭산 제제

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112603899A (zh) * 2020-12-23 2021-04-06 南京友杰医药科技有限公司 瑞巴派特肠溶片及其制备方法

Also Published As

Publication number Publication date
PH12020551635A1 (en) 2021-07-26
KR20190123411A (ko) 2019-11-01
KR102081095B1 (ko) 2020-02-25

Similar Documents

Publication Publication Date Title
WO2013147462A1 (fr) Composition pharmaceutique comprenant de l'olmésartan médoxomil et de la rosuvastatine ou son sel
WO2013162114A1 (fr) Préparation à libération contrôlée utilisant un système d'administration de médicaments gastrorétentifs
WO2018070671A1 (fr) Composition de comprimé oral de lénalidomide
US20070160664A1 (en) Pharmaceutical compositions comprising of proton pump inhibitor and prokinetic agent
WO2011152652A2 (fr) Préparation d'acéclofénac à libération lente présentant un effet clinique pharmacologique optimal lorsqu'elle est administrée une fois par jour
WO2018021772A1 (fr) Formulation ayant des caractéristiques améliorées de libération de médicament en fonction du ph, contenant de l'ésoméprazole ou un sel pharmaceutiquement acceptable de celui-ci
WO2019108021A2 (fr) Composition pharmaceutique comprenant du tofacitinib
WO2019208967A1 (fr) Comprimé à enrobage entérique comprenant de l'acide fénofibrique ou un sel pharmaceutiquement acceptable de celui-ci
WO2020242132A1 (fr) Comprimé gastrorésistant contenant du fumarate de diméthyle
US20110086102A1 (en) Delayed release compositions
WO2016013795A1 (fr) Preparation a liberation prolongee
WO2017150803A1 (fr) Préparation contenant de l'ésoméprazole
WO2012077968A2 (fr) Formulation complexe contenant de l'hydrochlorure de lercanidipine et du valsartan et son procédé de préparation
WO2016024844A1 (fr) Préparation pour voie orale associant un ester d'acide gras omega-3 et un médicament à base de statine
WO2021145676A1 (fr) Comprimé comprenant de l'atorvastatine et de l'ézétimibe
AU2016231883B2 (en) Pharmaceutical compositions of dimethyl fumarate
KR102216579B1 (ko) 페노피브릭산 또는 이의 약학적으로 허용 가능한 염을 포함하는 장용성 코팅 정제
WO2016122226A2 (fr) Composition pharmaceutique pour le traitement de maladies gastro-intestinales
WO2021112548A1 (fr) Composition pharmaceutique
WO2019199133A1 (fr) Composition de comprimé enrobé à administration par voie orale à base de lénalidomide
WO2019212214A1 (fr) Préparation pharmaceutique
WO2013169082A1 (fr) Préparation orale à libération contrôlée de bosentan
WO2019245150A1 (fr) Composition pharmaceutique comprenant du cilostazol et un médicament à base de statine
WO2013187700A1 (fr) Formulation pharmaceutique combinée comprenant de la métformine et un inhibiteur de la hmg-coa réductase
WO2006111853A2 (fr) Formes posologiques solides stables d'un medicament labile en milieu acide

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19793396

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19793396

Country of ref document: EP

Kind code of ref document: A1