Pomalidomide-containing pharmaceutical and method for producing the same

Abstract

To provide a pomalidomide-containing pharmaceutical with improved elution behavior.SOLUTION: According to one embodiment of the present invention, a method for producing pomalidomide-containing pharmaceutical includes a step of co-grinding pomalidomide and solid pharmaceutical excipients with a rotary grinder.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a pomalidomide-containing medicine and a method for producing the same. [Background technology]

[0002] Pomalidomide is a drug represented by the chemical name: 4-amino-2-[(3RS)-2,6-dioxopiperidin-3-yl]-2H-isoindole-1,3-dione. In Japan, it is used and sold as a therapeutic drug for relapsed or refractory multiple myeloma. In order to improve the pharmaceutical properties of pomalidomide, various forms of pomalidomide-containing drugs have been investigated (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special table number 2012-526855 Summary of the Invention [Problem to be solved by the invention]

[0004] The dissolution behavior of an active ingredient is one of the basic and important pharmaceutical properties. According to the findings of the present inventors, in the production of a pomalidomide-containing drug, the dissolution behavior differs depending on how pomalidomide and other ingredients are co-milled. By utilizing this knowledge, it may be possible to produce a pomalidomide-containing drug that exhibits more favorable pharmaceutical properties.

[0005] One aspect of the present invention aims to provide a pomalidomide-containing pharmaceutical having improved dissolution profile. [Means for solving the problem]

[0006] The present invention includes the following aspects. <1> A method for producing a pomalidomide-containing medicament, comprising the steps of: Co-grinding pomalidomide and a solid pharmaceutical excipient by a rotary mill; Manufacturing method. <2> The rotation speed of the rotary grinder is 4000 rpm or more. <1> The manufacturing method described in <3> The rotary grinder includes a stationary container and a rotor. <1> or <2> The manufacturing method described in <4> A method for producing a pomalidomide-containing medicament, comprising the steps of: co-grinding pomalidomide and a solid pharmaceutical excipient; The D90 of the co-milled pomalidomide and the solid pharmaceutical excipient is 300 μm or less. Manufacturing method. <5> The solid pharmaceutical excipient comprises one or more selected from the group consisting of an excipient and a disintegrant; The excipient includes D-mannitol, The disintegrant comprises partially pregelatinized starch. <1> ~ <4> 13. The method for producing a semiconductor device according to any one of the preceding claims. <6> A pomalidomide-containing drug comprising pomalidomide and a solid pharmaceutical excipient, The D90 of the pomalidomide and the solid pharmaceutical excipient is 300 μm or less; Pomalidomide-containing medicines. <7> A method for improving the dissolution profile of a pomalidomide-containing drug, comprising: Co-grinding pomalidomide and a solid pharmaceutical excipient by a rotary mill; method. <8> A method for improving the dissolution profile of a pomalidomide-containing drug, comprising: co-grinding pomalidomide and a solid pharmaceutical excipient; The D90 of the co-milled pomalidomide and the solid pharmaceutical excipient is 300 μm or less. method. Effect of the Invention

[0007] According to one aspect of the present invention, a pomalidomide-containing pharmaceutical agent having improved dissolution profile is provided. [Brief description of the drawings]

[0008] [Figure 1] 1 is a graph showing the dissolution profile of a pomalidomide-containing drug, mainly showing the results of Examples 1A to 1C. [Diagram 2] 1 is a graph showing the dissolution profile of a pomalidomide-containing drug, mainly showing the results of Example 2. [Diagram 3] 1 is a graph showing the dissolution profile of a pomalidomide-containing drug, mainly showing the results of Examples 3 and 4. [Figure 4] 1 is a graph showing the dissolution profile of a pomalidomide-containing drug, mainly showing the results of Example 5. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] An embodiment of the present invention will be described below. However, the present invention is not limited to each of the configurations described below. The present invention can be modified in various ways within the scope of the claims. The technical scope of the present invention also extends to embodiments or examples obtained by appropriately combining multiple technical means disclosed in this specification. In this case, multiple technical means may be disclosed across multiple embodiments or examples.

[0010] Unless otherwise specified in this specification, "A to B" expressing a numerical range means "A or more, and B or less."

[0011] 1. Method for producing pomalidomide-containing medicine A method for producing a pomalidomide-containing pharmaceutical according to one embodiment of the present invention includes a step of co-grinding pomalidomide and a solid pharmaceutical additive with a rotary mill. By co-grinding these components with a rotary mill, the dissolution behavior of the pomalidomide-containing pharmaceutical is improved (e.g., the rise of the dissolution curve becomes earlier). Without intending to be bound by theory, the inventors speculate that the reason for this phenomenon is as follows. That is, the pomalidomide drug substance is strongly aggregated, and a strong stress is applied by the rotary mill, so that the pomalidomide powder becomes uniformly dispersed in the co-ground pharmaceutical additive. This may contribute to the improvement of the dissolution behavior.

[0012] In this specification, the term "rotary mill" refers to a mill in which the milling process is carried out by the action of rotating members. In one embodiment, the rotating members of the rotary mill apply shear stress to the raw material, impact the raw material, cut the raw material, crush the raw material, agitate a plurality of raw materials, or perform any combination of these.

[0013] Examples of rotating members in a rotary mill include a container for storing raw materials and other rotating members. Examples of other rotating members include a rotor. Rotating blades are also called stirring blades, stirring vanes, mixing blades, screws, ribbons, cutters, choppers, impellers, knives, and the like. In one embodiment, the rotary mill includes a stationary container that does not rotate and a rotating rotor. Examples of such rotary mills include Wonder Blender WB-1 (Osaka Chemical Co., Ltd.), NMG (Nara Machinery Works, Ltd.), High Speed ​​Mixer (Earth Technica Co., Ltd.), Vertical Granulator (Powrex Corporation), New Speed ​​Kneader (Okada Seiko Co., Ltd.), Super Mixer (Kawata Co., Ltd.), Sanitary Crusher (Sansho Industry Co., Ltd.), and Henschel Mixer (ZEPPELIN).

[0014] The lower limit of the rotation speed of the rotary mill is preferably 4000 rpm or more, more preferably 8000 rpm or more, even more preferably 10000 rpm or more, and particularly preferably 12000 rpm or more. The upper limit of the rotation speed of the rotary mill may be, for example, 25000 rpm or less or 30000 rpm or less. In this specification, the rotation speed refers to the number of rotations around the rotation axis of the rotating member per minute. When there are two or more rotation axes in the rotation motion of the rotating member, the rotation speed is determined based on the rotation axis with the highest rotation speed. When there are multiple rotating members in the rotary mill, the rotation speed is determined based on the rotating member with the highest rotation speed.

[0015] The minimum stress that the rotary mill can apply to the co-ground material (e.g., pomalidomide, solid pharmaceutical excipients) is 20 N / mm 2 More than 40N / mm is preferable. 2 More preferably, 60N / mm 2 More preferably, the upper limit of the stress applied to the co-ground material by the rotary mill is 600 N / mm 2 Less than 400N / mm is preferable. 2 The following is more preferred:

[0016] In an embodiment in which the rotary grinder is equipped with a rotor, the lower limit of the rotation speed of the tip of the rotor is preferably 1.4 m / s or more, more preferably 5.0 m / s or more, and even more preferably 5.0 m / s. The upper limit of the rotation speed of the tip of the rotor is preferably 40 m / s or less, and more preferably 20 m / s or less.

[0017] The lower limit of the co-grinding time with a rotary grinder is preferably 10 seconds or more, more preferably 15 seconds or more, even more preferably 30 seconds or more, and particularly preferably 1 minute or more per 10 g of raw material. The upper limit of the co-grinding time may be, for example, 10 minutes or less or 5 minutes or less per 10 g of raw material.

[0018] As mentioned above, the inventors presume that the strong stress applied by the rotary mill may contribute to the improvement of the dissolution behavior. When such a strong stress is applied, the medicinal raw material becomes a finer powder. Therefore, one aspect of the present invention can also be described by the particle size of the powder.

[0019] That is, the method for producing a pomalidomide-containing pharmaceutical according to one embodiment of the present invention includes a step of co-grinding pomalidomide and a solid pharmaceutical additive. By co-grinding, the D90 of pomalidomide and the solid pharmaceutical additive becomes 300 μm or less. The upper limit of D90 is preferably 250 μm or less, more preferably 230 μm or less, and particularly preferably 200 μm or less. The lower limit of D90 may be, for example, 10 μm or more.

[0020] In this specification, D90 refers to the particle size when the cumulative frequency reaches 90% in the particle size distribution based on the number of particles. The particle size is measured using a MASTERSIZER 3000 (Malvern Panalytical). The measurement is performed by a wet method, and the dispersion medium is water.

[0021] In embodiments involving the step of co-grinding pomalidomide and a solid pharmaceutical excipient using a rotary mill, the D90 of the powder obtained by co-grinding may or may not satisfy the above conditions. In embodiments involving the step of co-grinding pomalidomide and a solid pharmaceutical excipient, the co-grinding may be performed using a rotary mill or by other means.

[0022] Examples of solid pharmaceutical additives include excipients, disintegrants, disintegration aids, binders, lubricants, flow agents, stabilizers, and stabilizers. In one embodiment, the solid pharmaceutical additive is one or more selected from the group consisting of excipients and disintegrants.

[0023] In one embodiment of the invention relating to the manufacturing method of the pomalidomide-containing pharmaceutical, the excipient contains D-mannitol. In one embodiment, the disintegrant contains partially pregelatinized starch. The excipient may contain an excipient other than D-mannitol. The disintegrant may contain a disintegrant other than partially pregelatinized starch. A part of the D-mannitol and / or partially pregelatinized starch contained in the pomalidomide-containing pharmaceutical may be co-milled by the rotary mill. A part of the D-mannitol and / or partially pregelatinized starch contained in the pomalidomide-containing pharmaceutical may be co-milled with pomalidomide.

[0024] Further examples of excipients and disintegrants are given in Section [2].

[0025] 2. Pomalidomide-containing medicines A pomalidomide-containing medicine according to one embodiment of the present invention includes pomalidomide and a solid pharmaceutical additive. The D90 of pomalidomide and the solid pharmaceutical additive is 300 μm or less. The upper limit of D90 is preferably 250 μm or less, more preferably 230 μm or less, and particularly preferably 200 μm or less. The lower limit of D90 may be, for example, 10 μm or more. In one embodiment, the solid pharmaceutical additive is one or more selected from the group consisting of an excipient and a disintegrant.

[0026] Examples of the excipient include D-mannitol, crystalline cellulose, anhydrous calcium hydrogen phosphate, D-sorbitol, lactose, sucrose, starch, low-substituted hydroxypropyl cellulose, dextrin, and synthetic aluminum silicate. In one embodiment, the excipient includes D-mannitol.

[0027] Examples of the disintegrant include potato starch, corn starch, partially pregelatinized starch, sodium starch glycolate, carmellose, carmellose sodium, carmellose calcium, low-substituted hydroxypropyl cellulose, and crospovidone. In one embodiment, the disintegrant comprises one or more members selected from the group consisting of partially pregelatinized starch and sodium starch glycolate.

[0028] The pomalidomide-containing pharmaceutical may contain other ingredients in addition to those mentioned above. Examples of the other ingredients include binders, lubricants, surfactants, foaming agents, acidulants, sweeteners, flavors, colorants, buffers, and light stabilizers.

[0029] Examples of binders include hypromellose, gum arabic, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, gum arabic, and pullulan.

[0030] Examples of lubricants include sodium stearyl fumarate, stearic acid, sodium stearate, talc, calcium stearate, hardened oil, sucrose fatty acid ester, magnesium stearate, and magnesium aluminometasilicate.

[0031] Examples of the surfactant include polysorbate 80, sodium lauryl sulfate, and polyoxyethylene hydrogenated castor oil.

[0032] An example of a foaming agent is baking soda.

[0033] Examples of acidulants include citric acid, tartaric acid, and malic acid.

[0034] Examples of sweeteners include sucralose, sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, and thaumatin.

[0035] Examples of flavors include lemon, lemon-lime, orange, and menthol.

[0036] Examples of coloring agents include ferric oxide, yellow ferric oxide, black ferric oxide, titanium oxide, Food Yellow No. 4, Food Yellow No. 5, Food Red No. 3, Food Red No. 102, and Food Blue No. 3.

[0037] Examples of buffering agents include citric acid, succinic acid, fumaric acid, tartaric acid, glutamic acid, glutamine, glycine, aspartic acid, alanine, arginine, phosphoric acid, boric acid or salts thereof. Further examples of buffering agents include magnesium oxide, zinc oxide, magnesium hydroxide.

[0038] The dosage form of the pomalidomide-containing medicine is not particularly limited. Examples of dosage forms include powder, granules, tablets, and capsules. Preferably, the pharmaceutical composition is a capsule.

[0039] 3. Method for improving the dissolution behavior of a drug containing pomalidomide A method for improving the dissolution profile of a pomalidomide-containing drug according to one aspect of the present invention includes a step of co-grinding pomalidomide and a solid pharmaceutical additive with a rotary grinder. A method for improving the dissolution profile of a pomalidomide-containing drug according to another aspect of the present invention includes a step of co-grinding pomalidomide and a solid pharmaceutical additive. Here, the D90 of the co-ground pomalidomide and the solid pharmaceutical additive is 300 μm or less. In one embodiment, the solid pharmaceutical additive is one or more selected from the group consisting of an excipient and a disintegrant. The description of these aspects is incorporated by reference in Section [1].

[0040] 4. Manufacturing and formulation examples [4.1. Manufacturing Example] (Production Example 1) 1. Premix pomalidomide, a portion of D-mannitol, and a portion of partially pregelatinized starch. 2. The resulting premix is ​​co-milled using a rotary mill. 3. The resulting co-ground product, the remainder of the D-mannitol, the remainder of the partially pregelatinized starch, and the low-substituted hydroxypropyl cellulose are mixed in a diffusion mixer. 4. Add sodium stearyl fumarate to the resulting mixture and mix with a diffusion mixer. 5. The resulting mixture is filled into capsules.

[0041] (Production Example 2) 1. Pomalidomide, the first portion of D-mannitol, and the first portion of partially pregelatinized starch are mixed in a sanitary crusher to obtain pomalidomide co-ground powder. 2. Mix the pomalidomide co-ground powder with the second portion of partially pregelatinized starch. 3. The mixed powder obtained in step 2 is sieved to obtain the sieved fraction. 4. Sift the third portion of the partially pregelatinized starch through the sieve used in step 3. This ensures that no pomalidomide co-ground powder is left behind in the sieve. 5. The second portion of D-mannitol, the fourth portion of partially pregelatinized starch, and low-substituted hydroxypropyl cellulose are added to the fractions obtained in steps 2 and 3 and mixed. 6. Add sodium stearyl fumarate to the mixed powder obtained in step 5 and mix. 7. The mixed powder obtained in step 6 is filled into capsules. 8. The capsules obtained in step 7 are packed in PTP packages.

[0042] [4.2. Prescription Examples] Capsules having the composition shown in Table 1 below are prepared. The obtained capsules are packaged in a primary package (PTP sheet) and a secondary package (aluminum pillow with zipper). The PTP sheet is composed of a PCTFE / PVC molded sheet and aluminum foil for PVC. [Table 1] EXAMPLES

[0043] [Examples 1A to 1C, Comparative Examples 1A to 1C] [Examples 1A to 1C] Pomalidomide and excipients were co-ground using a rotary grinder, and the dissolution behavior of the resulting drug was compared. The specific procedure was as follows. 1. 720 mg of pomalidomide and 18,900 mg of D-mannitol (excipient) were weighed out, which is equivalent to 180 capsules. 2. The entire amount of pomalidomide and D-mannitol was put into a rotary grinder (Wonder Blender WB-1, Osaka Chemical Co., Ltd.). This grinder is equipped with a container and a rotor (cutter). The sample is ground by rotating the rotor while the container is fixed. 3. The mixture was co-ground using a rotary grinder for 30 seconds (Example 1A), 1 minute (Example 1B), or 2 minutes (Example 1C). The rotation speed of the rotor blade was 18000 rpm. The rotation speed of the tip of the rotor blade was 10.2 m / s. 4. The obtained powder was scraped down into the container of the grinder and mixed. No adhesion was observed inside the grinder. 5. 109 mg of powder (one capsule) was weighed out and used as a sample for the dissolution test. 6. The dissolution test was carried out in accordance with the 18th Edition of the Japanese Pharmacopoeia. The specific test conditions were: Test method: paddle method, paddle rotation speed: 50 rpm, pH of the solvent: 6.8.

[0044] [Comparative Examples 1A to 1C] Samples for dissolution testing were prepared in the same manner as in Example 1A, except that pomalidomide and excipients were co-milled in a rotary mill. Comparative Example 1A: A sample for dissolution testing was prepared without co-milling pomalidomide and excipients. Comparative Example 1B: Pomalidomide and excipients were ground in a mortar to prepare a sample for dissolution test. Comparative Example 1C: Pomalidomide and excipients were triturated and sieved to prepare a sample for dissolution testing.

[0045] [result] The results are shown in Figure 1. As can be seen from the figure, the rise in the dissolution curve was significantly accelerated by co-grinding pomalidomide and excipients using a rotary mill. In addition, the longer the co-grinding time using the rotary mill, the more accelerated the rise in the dissolution curve tended to be.

[0046] [Example 2, Comparative Examples 2A to 2B] [Example 2] We prepared a pharmaceutical product in a form similar to the actual product, and compared the dissolution behavior caused by different co-grinding methods. The specific procedure is as follows. 1. 1800 mg of pomalidomide was premixed with 16200 mg of D-mannitol (excipient). 2. The premix was co-ground using a rotary grinder (Wonder Blender WB-1, Osaka Chemical Co., Ltd.). The co-grounding time was 2 minutes. The rotation speed of the rotor was 18,000 rpm. The rotation speed of the tip of the rotor was 10.2 m / s. 3. 9,816 mg of the obtained co-ground product, 15,951 mg of D-mannitol (excipient), and 32,981.8 mg of partially pregelatinized starch (disintegrant) were mixed in a polyethylene bag. 4. To 58748.8 mg of the resulting mixture, 147.2 mg of sodium stearyl fumarate (lubricant) was added and further mixed in a diffusion mixer. 5. The resulting mixture was filled into capsules to obtain capsules. 6. The dissolution test was carried out in accordance with the 18th Edition of the Japanese Pharmacopoeia. The specific test conditions were: Test method: paddle method, paddle rotation speed: 50 rpm, pH of the solvent: 6.8.

[0047] [Comparative Examples 2A~2B] Capsules for dissolution testing were prepared in the same manner as in Example 2, except that pomalidomide and excipients were co-milled in a rotary mill. Comparative Example 2A: Pomalidomide and excipients were ground in a mortar to prepare capsules for dissolution testing. Comparative Example 2B: Pomalidomide and excipients were triturated and sieved to prepare capsules for dissolution testing.

[0048] [result] The results are shown in Figure 2. Compared to Examples 1A to 1C, the rise in the dissolution curve was delayed due to the amount of capsules filled in. However, compared to Comparative Examples 2A to 2B, the rise in the dissolution curve was significantly earlier due to the co-grinding of pomalidomide and excipients using a rotary grinder.

[0049] [Examples 3 and 4] [Example 3] The effect of co-grinding pomalidomide and a disintegrant on the dissolution behavior was examined. The specific procedure was as follows. 1. 1800 mg of pomalidomide was premixed with 16200 mg of partially pregelatinized starch (disintegrant). 2. The premix was co-ground using a rotary grinder (Wonder Blender WB-1, Osaka Chemical Co., Ltd.). The co-grounding time was 2 minutes. The rotation speed of the rotor was 18,000 rpm. The rotation speed of the tip of the rotor was 10.2 m / s. 3. 9,816 mg of the obtained co-ground product, 24,147.4 mg of partially pregelatinized starch (disintegrant), and 24,785.4 mg of D-mannitol (excipient) were mixed in a polyethylene bag. 4. To 58748.8 mg of the resulting mixture, 147.2 mg of sodium stearyl fumarate (lubricant) was added and further mixed in a diffusion mixer. 5. The resulting mixture was filled into capsules to obtain capsules. 6. The dissolution test was carried out in accordance with the 18th Edition of the Japanese Pharmacopoeia. The specific test conditions were: Test method: paddle method, paddle rotation speed: 50 rpm, pH of the solvent: 6.8.

[0050] [Example 4] The effect of co-grinding pomalidomide, excipients, and disintegrants on the dissolution behavior was examined. The specific procedure was as follows. 1. 11,400 mg of pomalidomide was premixed with 51,300 mg of D-mannitol (excipient) and 51,300 mg of partially pregelatinized starch (disintegrant). 2. The premix was co-ground using a rotary grinder (Wonder Blender WB-1, Osaka Chemical Co., Ltd.). The co-grounding time was 30 seconds. The rotation speed of the rotor was 18,000 rpm. The rotation speed of the tip of the rotor was 10.2 m / s. 3. 114000 mg of the resulting co-milled product was mixed with 280440 mg of partially pregelatinized starch (disintegrant) and 287850 mg of D-mannitol (excipient) in a diffusion mixer bag. 4. To 682290 mg of the resulting mixture, 1710 mg of Sodium Stearyl Fumarate (lubricant) was added and further mixed in a diffusion mixer. 5. The resulting mixture was filled into capsules to obtain capsules. 6. The dissolution test was carried out in accordance with the 18th Edition of the Japanese Pharmacopoeia. The specific test conditions were: Test method: paddle method, paddle rotation speed: 50 rpm, pH of the solvent: 6.8.

[0051] [result] The results are shown in Figure 3. For comparison, the dissolution curves of the capsules examined in Example 2 and Comparative Examples 2A and 2B are also shown. As can be seen from the figure, the rise of the dissolution curve was significantly accelerated by co-grinding pomalidomide and a disintegrant using a rotary grinder. As can be seen from the figure, the rise of the dissolution curve was significantly accelerated by co-grinding pomalidomide, an excipient, and a disintegrant using a rotary grinder. Example 5 The effect of co-grinding pomalidomide, excipients, and disintegrants on the dissolution behavior was examined. The specific procedure is as follows. The composition of the resulting formulation was changed from that in Example 4 (for example, low-substituted hydroxypropylcellulose was added as a disintegrant). 1. 11,400 mg of pomalidomide was premixed with 51,300 mg of D-mannitol (excipient) and 51,300 mg of partially pregelatinized starch (disintegrant). 2. The premix was co-ground using a rotary grinder (Wonder Blender WB-1, Osaka Chemical Co., Ltd.). The co-grounding time was 30 seconds. The rotation speed of the rotor was 18,000 rpm. The rotation speed of the tip of the rotor was 10.2 m / s. 3. 114,000 mg of the obtained co-ground product was mixed with 139,935 mg of partially pregelatinized starch (disintegrant), 60,420 mg of low-substituted hydroxypropyl cellulose (disintegrant), and 140,505 mg of D-mannitol (excipient) in a diffusion mixer. 4. To 454860 mg of the resulting mixture, 1140 mg of Sodium Stearyl Fumarate (lubricant) was added and further mixed in a diffusion mixer. 5. The resulting mixture was filled into capsules to obtain capsules. 6. The dissolution test was carried out in accordance with the 18th Edition of the Japanese Pharmacopoeia. The specific test conditions were: Test method: paddle method, paddle rotation speed: 50 rpm, pH of the solvent: 6.8.

[0052] [result] The results are shown in Figure 4. For comparison, the dissolution curves of the capsules examined in Examples 2 and 3 and Comparative Examples 2A and 2B are also shown. As can be seen from the figure, the rise of the dissolution curve was significantly accelerated even in the pomalidomide formulation having the composition according to Example 5, by co-grinding pomalidomide, excipients, and disintegrants using a rotary grinder. [Industrial Applicability]

[0053] The present invention can be used to produce a medicine containing pomalidomide.

Claims

1. A method for producing a pomalidomide-containing medicament, comprising the steps of: Co-grinding pomalidomide and a solid pharmaceutical excipient by a rotary mill; Manufacturing method.

2. The rotation speed of the rotary grinder is 4000 rpm or more. The method of claim 1 .

3. The rotary grinder includes a stationary container and a rotor. The method of claim 1 .

4. A method for producing a pomalidomide-containing medicament, comprising the steps of: co-grinding pomalidomide and a solid pharmaceutical excipient; The D90 of the co-milled pomalidomide and the solid pharmaceutical excipient is 300 μm or less; Manufacturing method.

5. The solid pharmaceutical additive comprises one or more selected from the group consisting of an excipient and a disintegrant; The excipient comprises D-mannitol, The disintegrant comprises partially pregelatinized starch. The method according to any one of claims 1 to 4.

6. A pomalidomide-containing drug comprising pomalidomide and a solid pharmaceutical excipient, The D90 of the pomalidomide and the solid pharmaceutical excipient is 300 μm or less; Pomalidomide-containing medicines.

7. A method for improving the dissolution profile of a pomalidomide-containing drug, comprising: Co-grinding pomalidomide and a solid pharmaceutical excipient by a rotary mill; method.

8. A method for improving the dissolution profile of a pomalidomide-containing drug, comprising: co-grinding pomalidomide and a solid pharmaceutical excipient; The D90 of the co-milled pomalidomide and the solid pharmaceutical excipient is 300 μm or less; method.

Images