KR102512866B1 - Solubility Enhanced Oral Formulation of Aprepitant - Google Patents

Abstract

It relates to an oral composition with improved water solubility and bioavailability, including a solid dispersion containing a poorly water-soluble drug, aprepitant, and a gastric polymer, and a method for preparing the same.

Description

Oral composition with increased solubility of aprepitant {Solubility Enhanced Oral Formulation of Aprepitant}

The present invention relates to an oral composition having improved water solubility and bioavailability obtained by forming a solid dispersion of a poorly water-soluble drug, Aprepitant, together with a solubilizing polymer, and a preparation method thereof.

Aprepitant is an anti-emetic (trade name: Emend ^® capsules (MSD Korea)) introduced in Korea in 2007 after receiving FDA approval in March 2003. It is a Substance P NK-1 receptor antagonist that antagonizes the action of Substance P. It is selective for the NK-1 receptor and has little activity on the 5-HT3 receptor and dopamine receptor Cisplatin It is known that the additional administration of aprepitant increases the effects of 5HT3 antagonists and dexamethasone for acute and delayed vomiting when chemotherapy drugs that cause severe vomiting, including chemotherapy, are administered.

To prevent acute vomiting, take 125mg in combination with a corticosteroid and 5-HT3 antagonist 1 hour before chemotherapy, and to prevent delayed-type vomiting, take 80mg daily in combination with corticosteroid for 2 days from the day after chemotherapy. take once in

When administered orally, the bioavailability is 60-80%, and absorption is not affected by food, so it can be taken regardless of meals. It is extensively metabolized and eliminated in the liver, and less than 5% of the unchanged form is excreted in the urine. Aprepitant is both a substrate and an inducer of CYP450 and an inducer of CYP2C9, so it can reduce the effects of drugs metabolized by these enzymes. Side effects include asthenia, fatigue, anorexia, constipation, and diarrhea.

Emend ^® capsule is a representative formulation applied with Nanocrystal ^TM technology that improves bioavailability by improving dissolution rate and solubility through nanoization of drug particles using a wet mill method.

However, since this type of technology may require special equipment, long manufacturing time, and high production cost, a technology capable of achieving the same effect by improving solubility in a more improved manner is required.

A first object of the present invention is to provide a solid dispersion containing aprepitant, a poorly water-soluble drug, and a gastric-soluble polymer.

A second object of the present invention is to provide an oral composition with improved water solubility and bioavailability by forming a solid dispersion of aprepitant, a poorly water-soluble drug, together with a gastric-soluble polymer.

A third object of the present invention is to provide a method for preparing an oral composition with improved water solubility and bioavailability by forming a solid dispersion of aprepitant, a poorly water-soluble drug, together with a gastric-soluble polymer.

One aspect of the present invention relates to a solid dispersion obtained by dissolving or dispersing aprepitant in a solvent together with a gastric soluble polymer and then removing the solvent.

In one embodiment, the solid dispersion includes a solid dispersion obtained by spray drying.

In one embodiment, the solid dispersion does not contain an inert core material.

In one embodiment, the solid dispersion includes a solid dispersion obtained by coating the aprepitant and gastric-soluble polymer in a single layer on an inert core material.

In one embodiment, the gastric polymer is a polymethacrylate copolymer.

In one embodiment, the gastric polymer is a cationic polymer having dimethylaminoethyl methacrylate as a polymethacrylate copolymer.

In one embodiment, the gastric polymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate).

In one embodiment, the gastric polymer has a weight average molecular weight of 3,000 to 200,000 g/mole.

In one embodiment, the solid dispersion includes 0.1 to 10 parts by weight of a gastric polymer based on 1 part by weight of aprepitant.

In one embodiment, the solid dispersion further includes D-α-tocopheryl polyethylene glycol succinate.

In one embodiment, the solid dispersion further includes 0.001 to 1 part by weight of D-α-tocopheryl polyethylene glycol succinate based on 1 part by weight of aprepitant.

In one embodiment, the solid dispersion further includes a hydrophilic polymer.

In one embodiment, the solid dispersion further includes 0.1 to 10 parts by weight of a hydrophilic polymer based on 1 part by weight of aprepitant.

In one embodiment, the solid dispersion does not contain a hydrophilic polymer.

Another aspect of the present invention is to prepare a solution or dispersion by dissolving or dispersing aprepitant in a solvent together with a gastric polymer; And it relates to a method for producing a solid dispersion comprising the step of spray drying the solution or dispersion.

Another aspect of the present invention is to prepare a coating solution by dissolving or dispersing aprepitant in a solvent together with a gastric polymer; and coating the coating solution as a single layer on an inert core material.

Another aspect of the present invention relates to an oral composition comprising the solid dispersion and one or more pharmaceutically acceptable additives.

Another aspect of the present invention relates to a method for preparing an oral composition comprising mixing the solid dispersion with one or more pharmaceutically acceptable additives.

According to the present invention, the oral composition in which aprepitant is formed as a solid dispersion together with a gastric-soluble polymer shows high bioavailability because water solubility and bioavailability are improved, and it is not affected by diet, so it can be taken regardless of food, so it is suitable for patients. It can be a useful agent for

Definition of Terms

Unless explicitly stated otherwise, several terms used throughout this specification may be defined as follows.

Throughout this specification, unless otherwise specified, "include" or "include" refers to including a certain component (or component) without particular limitation, and excludes the addition of other components (or components). not be interpreted as

"Aprepitant" includes aprepitant free base, isomers thereof, or mixtures thereof, pharmaceutically acceptable salts and prodrugs of aprepitant. In each case, it may be to form different hydrates or different crystal forms.

finding a solution

Various methods have been used to improve water solubility and bioavailability of poorly water-soluble drugs. Methods such as modification of the drug itself, such as salt, crystal form, or prodrug production, micro or nanoemulsion, preparation of solid dispersion, micronization or nanoization through particle size reduction of the drug, micelle formation, etc. have been mainly used. However, each poorly water-soluble drug has different characteristics such as solubility, pH, pKa, melting point, molecular weight, functional group, three-dimensional structure, crystallinity, permeability, absorption site, dissolution rate, and effective drug capacity. It cannot be commonly applied to drugs, and it is necessary to find a way that fits a specific drug through a lot of effort. In addition, other than the modification of the drug itself, it is one of the very important things to find essential substances or substance combinations to improve the water solubility and bioavailability of poorly water-soluble drugs. In addition, it is also very important to select a technology method that can be produced in a more efficient and economical way.

After much effort to evaluate the effect of various substances on the water solubility of aprepitant, the inventors of the present invention developed a solid dispersion excellent in improving the water solubility and bioavailability of aprepitant and an oral composition using the same. I found out.

details

One aspect of the present invention provides a solid dispersion obtained by dissolving or dispersing aprepitant in a solvent together with a gastric soluble polymer and then removing the solvent.

In one embodiment, the solid dispersion may be obtained by spray drying.

In one embodiment, the solid dispersion may not include an inert core material.

In another embodiment, the solid dispersion may be obtained by coating the aprepitant and gastric polymer in a single layer on an inert core material. If the solid dispersion has a single coating layer on an inert core, the aprepitant and gastric polymer may be included in the coating layer.

Solid dispersions that do not contain an inert core or have a single coating layer on an inert core are economical in terms of manufacturing cost, more easily controlled for dissolution, and have a more stable dissolution profile than multi-layer coated solid dispersions.

The gastric polymer may be, for example, a polymethacrylate copolymer, and more specifically, a cationic polymer with dimethyl-aminoethyl methacrylate as a polymethacrylate copolymer ), and more specifically, it may be poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate). The poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) may form a polymer in which each monomer has a molar ratio of 1:2:1.

As a specific example, the gastric polymer may be Eudragit® E PO (Evonik, Germany) or Eudragit® E 100 (Evonik, Germany). Eudragit ® E polymer is usually used as a coating material to encapsulate sensitive drugs or to shield the taste and smell of drugs when it is necessary to protect drugs from moisture or when patients' compliance with medications is poor, thereby alleviating patients' reluctance to take them, It is used for the purpose of providing a soft and shiny surface so that the medicine can be easily swallowed, but in the present invention, it is used as a gastric polymer to improve the water solubility and bioavailability of aprepitant.

The gastric polymer may have a weight average molecular weight of 3,000 to 200,000, or 5,000 to 150,000, or 10,000 to 100,000, or 20,000 to 80,000, or 37,000 to 57,000 g/mole. If the weight average molecular weight of the gastric polymer is less than 3,000 g/mole, there is a concern that the water solubility improvement effect may be low, and if the weight average molecular weight exceeds 200,000 g/mole, disintegration may be delayed.

In one embodiment, the stomach-soluble polymer is present in an amount of 0.1 parts by weight or more, 0.2 parts by weight or more, 0.3 parts by weight or more, 0.4 parts by weight or more, 0.5 parts by weight or more, or 0.6 parts by weight or more based on 1 part by weight of aprepitant. In addition, it may be included in the solid dispersion in an amount of 10 parts by weight or less, 5 parts by weight or less, 3 parts by weight or less, 2 parts by weight or less, or 1.5 parts by weight or less, for example, 0.1 to 10 parts by weight, 0.2 to 10 parts by weight. It may be included in the solid dispersion in an amount of 5 parts by weight, 0.3 to 3 parts by weight, 0.4 to 2 parts by weight, or 0.6 to 1.5 parts by weight. If the content of the gastric soluble polymer is less than the aforementioned lower limit range, the degree of improvement in water solubility and bioavailability of aprepitant may be insignificant and the effect may be reduced. Tablets) may become large, causing discomfort when the patient takes them.

The state of the stomach-soluble polymer is not particularly limited, but may be granular or powdery.

In one embodiment, the solid dispersion may further include D-α-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS). In this case, an excellent effect in improving the solubility and dissolution rate of aprepitant can be obtained.

The TPGS may be included in the solid dispersion in an amount of, for example, 0.001 to 1 part by weight, or 0.001 to 0.2 part by weight, or 0.005 to 0.1 part by weight based on 1 part by weight of aprepitant. If the content of TPGS is less than the aforementioned lower limit range, the degree of improvement in water solubility and bioavailability of aprepitant may be insignificant and the effect may be reduced. In addition, it may cause difficulties during film formation and storage.

The inert core material may be a particle comprising or consisting of microcrystalline cellulose, sucrose, lactose, starch, or a combination thereof. Alternatively, the inert core material may be a particle comprising or consisting of microcrystalline cellulose, sucrose, or a combination thereof.

The shape of the inert core material may be various, for example, spherical or close to spherical, but is not limited thereto. In terms of circularity, the circularity may be 0.2 or more, or 0.4 or more, or 0.5 or more, or 0.7 or more. The average diameter of the inert core material may be 20 to 2000 μm, or 50 to 1500 μm, or 100 to 1200 μm, or 200 to 800 μm.

In one embodiment, the solid dispersion may further include a hydrophilic polymer.

The hydrophilic polymer is, for example, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (eg Soluplus ^® ), hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), poly Vinyl acetate (PVA), carboxymethylcellulose (sodium salt and calcium salt), ethylcellulose, methylcellulose, hydroxyethylcellulose, ethylhydroxyethylcellulose, hydroxypropylcellulose (HPC), L-HPC (low-substituted HPC), polyvinyl alcohol, polymers of acrylic acid and its salts, vinylpyrrolidone-vinylacetate copolymers (eg Kollidon ^® VA64, BASF), Polycoat IR, gelatin, It may be at least one selected from the group consisting of guar gum, partially hydrolyzed starch, alginates, xanthans, and mixtures thereof, but is not limited thereto. Alternatively, the hydrophilic polymer may be a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (eg Soluplus ^® ), hydroxypropylmethylcellulose (HPMC), or a mixture thereof.

When the solid dispersion further includes a hydrophilic polymer, the hydrophilic polymer may be included in an amount of 0.1 to 10 parts by weight, 0.1 to 5 parts by weight, or 0.1 to 3 parts by weight based on 1 part by weight of aprepitant.

In another embodiment, the solid dispersion may not include a hydrophilic polymer, for example, HPMC. When the solid dispersion containing aprepitant includes a gastric polymer such as Eudragit E instead of a hydrophilic polymer such as HPMC, the dissolution rate is significantly improved, and the coating uniformity and completeness can be improved. A solid dispersion including a coating layer containing a hydrophilic polymer such as HPMC is highly likely to cause swelling and sticking, which may cause dissolution delay. However, since swelling and sticking do not occur when gastric polymers such as Eudragit E are used, a stable dissolution profile can be exhibited, and long-term storage stability and stability to external environments are high. In addition, since the viscosity of the coating solution is low and the solubility is high during production, the production speed is fast.

In one embodiment, the solid dispersion may further include a surfactant.

The surfactant may be, for example, an anionic surfactant. Anionic surfactants include sodium dodecyl sulfate, sodium lauryl sulfate, sodium N-lauroyl sarcosylate, N-long chain acyl glutamate, sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester, polyoxyethylene and It may be a copolymer of polyoxypropylene or a combination thereof, or it may be sodium dodecylsulfate.

The surfactant is, for example, 0.0001 to 1 part by weight, or 0.0005 to 0.5 part by weight, or 0.001 to 0.1 part by weight, or 0.001 to 0.01 part by weight, or 0.001 to 0.005 part by weight based on 1 part by weight of aprepitant. can be used in quantity.

The solvent used in the solution for preparing the solid dispersion may be a water-miscible organic solvent, water, or a mixture thereof. A water-miscible organic solvent, for example, one selected from the group consisting of alcohol, acetone, tetrahydrofuran, acetic acid, acetonitrile, dioxane, and combinations thereof may be used, but is not limited thereto. The water-miscible organic solvent may be, for example, a lower alcohol having 1 to 5 carbon atoms, acetone or a mixture thereof, or ethanol, acetone or a mixture thereof, or ethanol.

In the case of a solid dispersion prepared by a coating method, the thickness of the coating layer may be measured by a method such as a scanning electron microscope (SEM) after cutting a cross section of the coated particle. At this time, it is possible to check the average thickness by measuring 5 or more and averaging them. When observing the cross section of the coating layer for the coated particles, the average thickness of the coating layer is 10 μm or more and 500 μm or less, or 20 μm or more and 400 μm or less, or 50 μm or more and 300 μm or less, or 80 μm or more and 200 μm or less. can When the average thickness of the coating layer is smaller than the above-mentioned range, the content of the drug in the particles is lowered, requiring a large amount of inert core, which may increase the dosage form. The desired goal cannot be achieved due to delays, excessive processing time, etc.

In the process of coating as described above, various biologically inactive ingredients may be additionally used for additional purposes such as coating efficiency, drug stability, appearance, color, protection, maintenance, binding, performance improvement, and manufacturing process improvement. .

If the solid dispersion has a single-layer coating layer on an inert core, components other than the inert core such as aprepitant, gastric polymer, optionally hydrophilic polymer, and optionally TPGS may be included in the coating layer.

Another aspect of the present invention is to prepare a solution or dispersion by dissolving or dispersing aprepitant in a solvent together with a gastric polymer; And it provides a method for producing a solid dispersion comprising the step of spray drying the solution or dispersion.

Another aspect of the present invention is to prepare a coating solution by dissolving or dispersing aprepitant in a solvent together with a gastric polymer; And it provides a method for producing a solid dispersion comprising the step of coating the coating solution in a single layer on the inert core material.

In the spray drying step, spray drying may be performed using a spray dryer, a fluidized bed dryer, or other dryers.

The coating may be performed using a fluidized bed coater. In one embodiment, the coating may be performed using a bottom spray coating method, a tangential spray coating method, or a top spray coating method. Alternatively, the coating step may be a bottom spray coating method or a tangential spray coating method. The coating may further include drying after coating.

The coating step can be manufactured regardless of the size and batch size of the coating equipment, and can be smoothly manufactured in a mini-glatt (Glatt, Germany), which is a small unit on a lab scale, or in a large equipment of the GPCG series including GPCG 1. can do. It can also be manufactured in Soild Lab 2 (Bosch, Germany) of the tangential spray method.

Another aspect of the present invention provides an oral composition with improved water solubility and bioavailability, comprising the solid dispersion and one or more pharmaceutically acceptable additives.

Another aspect of the present invention provides a method for preparing an oral composition having improved water solubility and bioavailability, comprising mixing the solid dispersion with one or more pharmaceutically acceptable additives.

The oral composition may be in the form of a solid oral preparation in the form of, for example, tablets, capsules, granules, or powders, particularly tablets or capsules.

The one or more pharmaceutically acceptable additives are, for example, plasticizers, lubricants, colorants, flavoring agents, surfactants, stabilizers, antioxidants, foaming agents, antifoaming agents, desiccants (eg, paraffin, wax), etc. It may be one or more selected from the group consisting of For example, the plasticizer is 100% by weight or less (eg, 0.1 to 100% by weight), or 50% by weight or less (eg, 0.1 to 50% by weight), or 30% by weight or less based on the dry weight of the total polymer used in the coating layer. (eg, 0.1 to 30% by weight).

For example, the plasticizer is triethyl citrate, dibutyl phthalate, diethyl phthalate, dibutyl sebacate, diethyl sebacate, tributyl citrate, acetyl triethyl citrate, acetyl triethyl citrate, propylene glycol, triacetin , It may be at least one selected from the group consisting of polyethylene glycol, cetyl alcohol, stearyl alcohol, and cetostearyl alcohol, but is not limited thereto.

The lubricant may be included in an amount of 100 wt% or less (eg, 0.1 to 100 wt%) or 50 wt% or less based on the dry weight of the coating layer or oral composition.

Specifically, the lubricant is, for example, magnesium stearate, fumaric acid, stearic acid, calcium stearate, sodium stearyl fumarate, polyethylene glycol, starch (wheat, rice, corn or potato starch), talc, highly dispersed (colloidal) type) may be at least one selected from the group consisting of silica, magnesium oxide, magnesium carbonate, glyceryl behenate, glyceryl monostearate, silicon dioxide, calcium silicate, magnesium silicate, and mixtures thereof, but is limited thereto It is not.

In the tablet or capsule, various additives may be additionally mixed in order to improve the physical properties, manufacturability, compressibility, appearance, taste, and drug stability of the tablet or capsule. Such additional additives include, for example, solubilizers, sweeteners, corrigents, pigments, wetting agents, fillers, buffers, sweeteners, adsorbents, corrigents, binders, suspending agents, curing agents, brighteners, flavoring agents, pigments, coating agents, wetting agents , Wetting agent, filler, cooling agent, chewing agent, antistatic agent, dragee, isotonic agent, softener, emulsifier, adhesive, thickener, pH adjuster, excipient, dispersant, disintegrant, waterproofing agent, preservative, preservative, solubilizing agent, solvent , fluidizing agents, etc., but are not limited thereto, and any pharmaceutically acceptable ones may be used.

Hereinafter, examples are presented to aid understanding of the present invention. However, the following examples are only intended to illustrate the present invention, and do not limit the present invention in any way.

[Example]

Examples 1 to 3: Preparation of spray-dried solid dispersion

A first solution and a second solution were prepared with the ingredients in Table 1 below, and the first solution and the second solution were mixed. The mixture was sprayed using a bottom spray coating method in a fluid bed dryer (Mini-Glatt, Glatt, Germany) to obtain a spray-dried solid dispersion.

[Table 1]

Examples 4 to 6: Preparation of coated solid dispersion

A mixture of the first solution and the second solution in Table 2 was prepared and used to prepare Examples 4, 5, and 6, respectively. 10 g of the microcrystalline cellulose spherical core was placed in a fluid bed coater (Mini-Glatt, Glatt, Germany), and a mixture of the prepared first and second solutions was sprayed and coated on the core using a bottom spray coating method. After coating, it was dried for 5 minutes using residual heat and, if necessary, additionally dried in an oven at 40 ° C.

[Table 2]

Example 7: Preparation of capsules

After sieving Aerosil 0.25% (w/w%) (Aerosil 200, hydrophilic Fumed silica, silicon dioxide, Evonik) through a 250-600 μm sieve to break the agglomerates, mix them with the fine particles prepared in Examples 1 to 6, No. 1 The capsules of Examples 7 to 12 were prepared by filling the capsules with 125 mg of aprepitant. An oral composition with improved bioavailability for the capsule was finally obtained.

<Test Example 1: Dissolution test>

Using 900mL of pH 1.2 buffer solution, test by rotating 100 times per minute at 37±0.5℃ according to Pharmacopoeia Dissolution Test Method 2 (paddle method). After collecting the eluate 30 minutes after the start of elution, it was filtered with a syringe filter, and the elution rate was confirmed under the following conditions using HPLC, and the results are shown in Table 3 below.

Column: Zorbax Eclipse XDB-C8 (4.6 × 150 mm, 5 μm) or equivalent

Mobile phase: Phosphoric acid diluent/acetonitrile = 50/50 (Phosphoric acid diluent: a solution obtained by diluting 1 mL of phosphoric acid with purified water to make 1 L)

Flow rate: 1.5 mL/min

Detector: UV absorbance photometer (measurement wavelength: 220 nm)

Injection volume: 10 μL

[Table 3]

<Test Example 2: Pharmacokinetic test in beagle dogs>

For the sample obtained in Example 11, beagle dogs (males) weighing around 7.5 to 9.0 kg (7 to 8 months old) were supplied from BEIJING MARSHALL BIOTECHNOLOGY as experimental animals, and 8 test subjects were randomly distributed per group, and the samples were left in the finished form. It was administered orally (p.o.).

Each drug was administered once (125 mg/head), and blood samples for analysis were treated with heparin immediately before drug administration and at 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours after drug administration, respectively. Blood was collected from the left lateral cingulate vein with a syringe and centrifuged (12,000 rpm) to separate plasma. The separated plasma was stored in -70°C deep freezer (Sanyo, Japan) until the time of analysis. The concentration of the drug in plasma was analyzed by LC/MS/MS (HPLC; HP1100 series, US, MS; Quattro Ultima-Pt, UK) after pretreatment.

The results of analyzing the obtained parameters are shown in Table 4 below, and the AUC _{0-48 hr} of the sample of Example 11 compared to Emend ^® was 95.6%, confirming that it was bioequivalent.

[Table 4]

Claims (18)

As a solid dispersion containing aprepitant,
It is obtained by dissolving or dispersing aprepitant in a solvent together with a gastric soluble polymer and D-α-tocopheryl polyethylene glycol succinate and then removing the solvent,
The gastric polymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate),
Based on 1 part by weight of aprepitant, 0.5 to 1 part by weight of the gastric polymer and 0.001 to 1 part by weight of the D-α-tocopheryl polyethylene glycol succinate,
solid dispersion. The solid dispersion according to claim 1, which is obtained by spray drying. The solid dispersion according to claim 1, which does not contain an inert core material. The solid dispersion according to claim 1, which is obtained by coating the aprepitant and the gastric-soluble polymer in a single layer on an inert core material comprising or consisting of microcrystalline cellulose, sucrose, or a combination thereof. The solid dispersion according to claim 1, wherein the gastric polymer has a weight average molecular weight of 3,000 to 200,000 g/mole. The solid dispersion according to claim 1, further comprising a hydrophilic polymer of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, hydroxypropylmethylcellulose (HPMC), or a mixture thereof. The solid dispersion according to claim 6, further comprising 0.1 to 10 parts by weight of the hydrophilic polymer based on 1 part by weight of aprepitant. The solid dispersion according to claim 1, which does not contain a hydrophilic polymer. As a method for producing a solid dispersion,
preparing a solution or dispersion by dissolving or dispersing aprepitant in a solvent together with a gastric soluble polymer and D-α-tocopheryl polyethylene glycol succinate; and spray drying the solution or dispersion,
The gastric polymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate),
The prepared solid dispersion contains 0.5 to 1 part by weight of the gastric polymer and 0.001 to 1 part by weight of the D-α-tocopheryl polyethylene glycol succinate, based on 1 part by weight of aprepitant.
A method for preparing a solid dispersion. As a method for producing a solid dispersion,
preparing a solution or dispersion by dissolving or dispersing aprepitant in a solvent together with a gastric soluble polymer and D-α-tocopheryl polyethylene glycol succinate; and
Including; coating the solution or dispersion in a single layer on an inert core material,
The gastric polymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate),
The prepared solid dispersion contains 0.5 to 1 part by weight of the gastric polymer and 0.001 to 1 part by weight of the D-α-tocopheryl polyethylene glycol succinate, based on 1 part by weight of aprepitant.
A method for preparing a solid dispersion. An oral composition comprising the solid dispersion of any one of claims 1 to 8 and one or more pharmaceutically acceptable additives. Claims 1 to 8, comprising the step of mixing the solid dispersion of any one of claims and one or more pharmaceutically acceptable additives, a method for preparing an oral composition. delete delete delete delete delete delete