Application of slow-release film coating premix in preparation of methylphenidate hydrochloride tablet

Abstract

The invention provides an application of a sustained-release film coating premix in preparation of methylphenidate hydrochloride tablets. The provided slow-release film coating premix is prepared from the following components in parts by weight: 35-55 parts of a film forming material, 18-32 parts of a plasticizer, 14-22 parts of a coloring agent, 1-4 parts of a dispersing agent, 5-15 parts of an anti-sticking agent and 40-60 parts of a solvent, and the film forming material is prepared from hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30; the plasticizer comprises polyethylene glycol 6000 and propylene glycol; the solvent is water. The sustained-release film-coated premix is used for preparing the methylphenidate hydrochloride sustained-release tablet, the release speed of the medicine can be controlled, and the stability, safety and effectiveness of the medicine are improved.

Description

Technical Field

[0001] The invention relates to the field of pharmaceutical preparations, and in particular to application of a sustained-release film coating premix in the preparation of methylphenidate hydrochloride tablets. Background Art

[0002] Sustained-release preparations refer to preparations that can continuously release drugs for a long time after administration to achieve long-term effects. Sustained-release preparations refer to preparations that release oral drugs slowly and at a non-constant rate as required in a specified solvent, and the number of daily doses is at least reduced by one compared to corresponding ordinary preparations, or the interval between doses is extended.

[0003] Methylphenidate hydrochloride tablets are a drug for treating ADHD. The drug is a central nervous system stimulant that blocks the reuptake of norepinephrine and dopamine by presynaptic neurons and increases the release of these monoamine substances into the extraneuronal space. However, methylphenidate hydrochloride tablets have many side effects. Methylphenidate hydrochloride sustained-release tablets can reduce the efficiency of administration, improve bioavailability, and reduce side effects.

[0004] Further improvements are needed regarding methylphenidate hydrochloride sustained-release tablets. Summary of the invention

[0005] The present invention aims to solve one of the technical problems in the related art at least to a certain extent. The present invention provides a sustained-release film coating premix, which can be used in methylphenidate hydrochloride tablets to prepare methylphenidate hydrochloride sustained-release tablets.

[0006] In a first aspect of the present invention, there is provided a use of a sustained-release film coating premix in the preparation of methylphenidate hydrochloride tablets, wherein the sustained-release film coating premix comprises, in parts by weight:

[0007] 35 to 55 parts of a film-forming material, wherein the film-forming material comprises hypromellose, polyvinyl alcohol and povidone K30;

[0008] 18 to 32 parts of a plasticizer, wherein the plasticizer comprises polyethylene glycol 6000 and propylene glycol;

[0009] 14 to 22 parts of colorant,

[0010] 1 to 4 parts of dispersant,

[0011] 5 to 15 parts of anti-adhesive agent,

[0012] 40 to 60 parts of a solvent, wherein the solvent is water.

[0013] According to an embodiment of the present invention, the above-mentioned use may further include the following technical features:

[0014] In some embodiments of the present invention, the sustained-release film coating premix comprises:

[0015] 40 to 50 parts of film-forming material,

[0016] 20-30 parts of plasticizer,

[0017] 16-20 parts of colorant,

[0018] 2-3 parts of dispersant,

[0019] 8 to 12 parts of anti-adhesive agent,

[0020] 45 to 55 parts of solvent.

[0021] In some embodiments of the present invention, the mass ratio of the hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30 is (12-15): (4-6): (3-5).

[0022] In some embodiments of the present invention, the mass ratio of polyethylene glycol 6000 to propylene glycol is (3-5):1.

[0023] In some embodiments of the present invention, the dispersant is selected from at least one of dextrin, phospholipids, sorbitan monopalmitate or Tween 80;

[0024] In some embodiments of the present invention, the anti-sticking agent is selected from at least one of talc and magnesium stearate.

[0025] In some embodiments of the present invention, the colorant is selected from at least one of titanium dioxide, lemon yellow aluminum lake, chrysoprase aluminum lake, and carmine aluminum lake.

[0026] The second aspect of the present invention provides a methylphenidate hydrochloride sustained-release tablet, comprising: 88 to 92 parts by weight of a methylphenidate hydrochloride core and 8 to 12 parts by weight of a sustained-release film coating premix, wherein the sustained-release film coating premix forms a coating on the surface of the methylphenidate hydrochloride core;

[0027] The sustained-release film coating premix comprises, by weight:

[0028] 35 to 55 parts of a film-forming material, wherein the film-forming material comprises hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30;

[0029] 18 to 32 parts of a plasticizer, wherein the plasticizer comprises polyethylene glycol 6000 and propylene glycol;

[0030] 14 to 22 parts of colorant,

[0031] 1 to 4 parts of dispersant,

[0032] 5 to 15 parts of anti-adhesive agent,

[0033] 40 to 60 parts of a solvent, wherein the solvent is water.

[0034] According to an embodiment of the present invention, the above-mentioned methylphenidate hydrochloride sustained-release tablet may further include the following technical features:

[0035] In some embodiments of the present invention, the dispersant is phospholipid and the anti-adherent is talc;

[0036] The colorants include titanium dioxide, lemon yellow aluminum lake and sunset yellow aluminum lake.

[0037] In some embodiments of the present invention, the mass ratio of the hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30 is (12-15): (4-6): (3-5).

[0038] In some embodiments of the present invention, the mass ratio of polyethylene glycol 6000 to propylene glycol is (3-5): 1

[0039] The beneficial effects achieved by the present invention are at least:

[0040] The sustained-release film coating premix provided by the present invention is a composition formed by mixing the film-forming materials of hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30 and raw materials such as plasticizers, anti-adherents, dispersants, and colorants in a specific proportion, which not only gives the coated tablet core a good sustained-release effect, but also makes the tablet surface have a good glossiness, and makes the entire tablet have good moisture resistance and crack resistance. The plasticizer used contains polyethylene glycol 6000 and propylene glycol, wherein propylene glycol is not only a plasticizer, but also makes the film formed by it elastic, tough or has good flexibility and is not easy to break. Moreover, the addition of propylene glycol can reduce the amount of film coating premix during coating, thereby reducing production costs. The time for propylene glycol to diffuse into the internal particles of the film-forming material is about 30 minutes, which greatly shortens the time for preparing the coating solution in the early stage of coating, and improves production efficiency. The sustained-release film coating premix provided can control the drug release rate, reduce the adverse reactions caused by taking a large amount of drugs, thereby ensuring the stability, safety and effectiveness of the drug. DETAILED DESCRIPTION

[0041] Embodiments of the present invention are described in detail below. The embodiments are exemplary and intended to be used to explain the present invention, but should not be construed as limiting the present invention.

[0042] The present invention provides a sustained-release film coating premix for use in methylphenidate hydrochloride tablets. According to a specific embodiment, the sustained-release film coating premix comprises, by weight, 35 to 55 parts of a film-forming material, 18 to 32 parts of a plasticizer, 14 to 22 parts of a colorant, 1 to 4 parts of a dispersant, 5 to 15 parts of an anti-adherent, and 40 to 60 parts of a solvent, wherein the film-forming material comprises hydroxypropyl methylcellulose, polyvinyl alcohol, and povidone K30; the plasticizer comprises polyethylene glycol 6000 and propylene glycol; and the solvent is water.

[0043] The provided sustained-release film coating premix is ​​compounded with film-forming materials, plasticizers, colorants, dispersants, anti-adherents and solvents in a specific mass ratio, and is used to prepare methylphenidate hydrochloride sustained-release tablets, showing good film-forming properties and adhesion. When used as a coating, it can achieve the control of drug release rate after drug coating. In addition, the provided sustained-release film coating premix is ​​used as a coating for methylphenidate hydrochloride tablets, which improves the elasticity, flexibility and density of the coating film and the adhesion between the coating film and the tablet core, thereby reducing the incidence of cracking of the coating film, improving the moisture resistance of the coating film, making the coating film more protective of the tablet core, and ensuring the stability, safety and effectiveness of the drug; and having a better tablet gloss.

[0044] According to a specific embodiment, the sustained-release film coating premix comprises, by weight, 40 to 50 parts of film-forming material, 20 to 30 parts of plasticizer, 16 to 20 parts of colorant, 2 to 3 parts of dispersant, 8 to 12 parts of anti-sticking agent, and 45 to 55 parts of solvent.

[0045] According to a preferred embodiment, the sustained-release film coating premix comprises, by weight, 45 parts of film-forming material, 25 parts of plasticizer, 18 parts of colorant, 2 parts of dispersant, 10 parts of anti-sticking agent, and 50 parts of solvent.

[0046] The film-forming material mentioned includes a compound of hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30. According to a specific embodiment, the mass ratio of hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30 is (12-15): (4-6): (3-5). According to a preferred embodiment, the mass ratio of hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30 is (13-14): 5: 4.

[0047] The plasticizers used include polyethylene glycol 6000 and propylene glycol. Compared with other plasticizers, such as triethyl citrate, glycerol, etc., the compounding of propylene glycol and polyethylene glycol 6000 can not only make the prepared sustained-release tablets more resilient and elastic, but also effectively reduce the amount of film coating premix, and effectively improve production efficiency. According to a preferred embodiment, the mass ratio of polyethylene glycol 6000 to propylene glycol is (3-5):1.

[0048] According to a specific embodiment, the colorant is selected from one or more mixtures of titanium dioxide, lemon yellow aluminum lake, sunset yellow aluminum lake, carmine aluminum lake; the dispersant mentioned includes but is not limited to a mixture of one or more of dextrin, phospholipids, sorbitan monopalmitate or Tween 80; the anti-adherent is selected from at least one of talc and magnesium stearate. According to a preferred embodiment, the dispersant is phospholipids, the anti-adherent is talc, and the colorant includes titanium dioxide, lemon yellow aluminum lake and sunset yellow aluminum lake.

[0049] The technical scheme of the present invention is explained below through specific examples. It should be noted that these examples are only used to facilitate the understanding of those skilled in the art and should not be regarded as limiting the scope of protection of the present invention. The reagents used in the examples can all be obtained commercially. For example, the hydroxypropyl methylcellulose used is model 2910, with a viscosity of 0.005-0.075pa.s. The average particle size of talcum powder is 4-5um, whiteness 94, particle size 50m, and sieve residue 0.1%. The viscosity of the polyethylene glycol 6000 is 5.5-9.0mm 2 / s, pH value is 6. The relative density of Tween 80 is 1.1, and the pH value is 6-8.

[0050] Example 1

[0051] The auxiliary material components of the sustained-release film coating premix provided in Example 1 are shown in Table 1 below.

[0052] Example 2

[0053] The auxiliary material components of the sustained-release film coating premix provided in Example 2 are shown in Table 1 below.

[0054] Example 3

[0055] The auxiliary material components of the sustained-release film coating premix provided in Example 3 are shown in Table 1 below.

[0056] Comparative Example 1

[0057] The auxiliary material components of the sustained-release film coating premix provided in Comparative Example 1 are shown in Table 1 below.

[0058] Comparative Example 2

[0059] The auxiliary ingredients of the sustained-release film coating premix provided in Comparative Example 2 are shown in Table 1 below.

[0060] Comparative Example 3

[0061] The auxiliary material components of the sustained-release film coating premix provided in Comparative Example 3 are shown in Table 1 below.

[0062] Comparative Example 4

[0063] The auxiliary material components of the sustained-release film coating premix provided in Comparative Example 4 are shown in Table 1 below.

[0064] Table 1 Raw materials used in different embodiments and comparative examples

[0065]

[0066] The sustained-release film coating premixes of different embodiments and comparative examples were coated on methylphenidate hydrochloride chips (methylphenidate hydrochloride chips were 6 parts by weight, and the sustained-release film coating premixes were 94 parts by weight) according to the following method:

[0067] (1) Pour the weighed solid excipients in the sustained-release film coating premix into a mixer with a stirring blade, start the stirring blade of the mixer, mix and stir at room temperature for 1 hour, then gradually and slowly add deionized water, mix and stir for another 30 minutes, then slowly add other liquid coating materials into the mixer, mix and stir for 1 hour, wherein the speed of the stirring blade is 2700 rpm;

[0068] (2) After drying the mixture at 35-45°C for 5 hours, take a sample for inspection to check the moisture content ≤8%. If the product is qualified, proceed to the next step. If the moisture content is >8%, continue drying.

[0069] (3) Grind the mixture dried in step (2) for 7 hours, pass it through a 200-mesh sieve, and mix it for another 60 minutes to obtain a finished product of a sustained-release film coating premix.

[0070] (4) Take a small amount of the above finished product for coating test. If it is qualified, weigh the tablet core and put it into the coating pot. The amount of tablet core to be put in is determined according to the size of the coating pot, generally two-thirds of the capacity of the coating pot. Start the coating pot, set the air inlet temperature to 70 degrees, preheat the tablet bed to 45 degrees, and set the pot body speed to 15 revolutions per minute. Start the exhaust air volume to 2000 cubic meters per hour, turn on the air compressor to a pressure of 10 kg, start the atomization pressure, adjust the fan pressure, start the peristaltic pump, and adjust the coating liquid flow rate to 150 g per minute. After coating, take a sample tablet to check the appearance quality of the coating film to see whether it is smooth, flat, and free of defects.

[0071] Disintegration and dissolution experiments were carried out on the prepared methylphenidate hydrochloride sustained-release tablets and methylphenidate hydrochloride chips using simulated gastric fluid and simulated intestinal fluid, respectively.

[0072] The simulated gastric fluid is prepared by taking 3.84 ml of hydrochloric acid, adding 800 ml of water and 10 g of pepsin, shaking well and then diluting with water to 10000 ml to obtain the simulated gastric fluid;

[0073] The simulated intestinal fluid is prepared by taking 6.8 g of potassium dihydrogen phosphate, adding 500 ml of water, and adjusting the pH value to 6.8 with 0.1 mol / L sodium hydroxide solution to obtain a mixed solution; then taking 10 g of pancreatic enzyme, dissolving it in water, adding the pancreatic enzyme solution to the mixed solution, and diluting it to 1000 ml with water to obtain simulated intestinal fluid.

[0074] Table 2 Drug disintegration of different examples and comparative examples

[0075]

[0076] Table 3 The appearance of the methylphenidate hydrochloride sustained-release tablets prepared in different embodiments and comparative examples was investigated, and the results are shown in Table 3 below.

[0077] The appearance of the drugs in different embodiments and comparative examples in Table 3 is as follows:

[0078]

[0079]

[0080] It was found during the research process that: taking Example 1 to Example 3 as an example, the excellent methylphenidate hydrochloride sustained-release tablets prepared all have good sustained-release properties, especially the best performance in Example 1. Compared with Example 1, Comparative Example 1 does not use polyethylene glycol 6000 and propylene glycol, but uses triethyl citrate and glycerol. It is found that the plasticity is relatively weak, and when coating, more coating premixes are required to achieve a more ideal coating effect. Compared with Example 1, Comparative Example 2 does not add povidone K30, and by compounding hydroxypropyl methylcellulose and polyvinyl alcohol, the dosage of the two is increased at the same time. It is found that the prepared methylphenidate hydrochloride sustained-release tablets have slightly weaker adhesion and film-forming properties. Compared with Example 1, the ratio of each component in the film-forming material in Comparative Example 3 is adjusted, and it is found that the prepared methylphenidate hydrochloride sustained-release tablets have slightly weaker sustained-release properties. Compared with Comparative Example 1, Comparative Example 4 uses triethyl citrate and propylene glycol as plasticizers, but the sustained-release performance of the methylphenidate hydrochloride sustained-release tablets prepared therefrom is also slightly weaker.

[0081] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. Use of a sustained-release film coating premix in the preparation of methylphenidate hydrochloride tablets, characterized in that: The sustained-release film coating premix comprises, by weight: 35 to 55 parts of a film-forming material, wherein the film-forming material comprises hypromellose, polyvinyl alcohol and povidone K30; 18 to 32 parts of a plasticizer, wherein the plasticizer comprises polyethylene glycol 6000 and propylene glycol; 14-22 parts of colorant; 1 to 4 parts of dispersant; 5 to 15 parts of anti-adhesive agent; and 40 to 60 parts of a solvent, wherein the solvent is water.

2. The use according to claim 1, characterized in that The sustained-release film coating premix comprises: 40 to 50 parts of film-forming material, 20-30 parts of plasticizer, 16-20 parts of colorant, 2-3 parts of dispersant, 8 to 12 parts of anti-adhesive agent, and 45 to 55 parts of solvent.

3. The use according to claim 1, characterized in that The mass ratio of the hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30 is (12-15): (4-6): (3-5).

4. The use according to claim 1, characterized in that The mass ratio of polyethylene glycol 6000 to propylene glycol is (3-5):

1.

5. The use according to claim 1, characterized in that: The dispersant is selected from at least one of dextrin, phospholipid, sorbitan monopalmitate or Tween 80; The anti-sticking agent is selected from at least one of talc and magnesium stearate. The colorant is selected from at least one of titanium dioxide, lemon yellow aluminum lake, sunset yellow aluminum lake, and carmine aluminum lake.

6. A methylphenidate hydrochloride sustained-release tablet, characterized in that: include: 92-94 parts by weight of methylphenidate hydrochloride chips and 6-8 parts by weight of a sustained-release film coating premix, wherein the sustained-release film coating premix forms a coating on the surface of the methylphenidate hydrochloride chips; The sustained-release film coating premix comprises, by weight: 35 to 55 parts of a film-forming material, wherein the film-forming material comprises hypromellose, polyvinyl alcohol and povidone K30; 18 to 32 parts of a plasticizer, wherein the plasticizer comprises polyethylene glycol 6000 and propylene glycol; 14 to 22 parts of colorant, 1 to 4 parts of dispersant, 5 to 15 parts of anti-adhesive agent, 40 to 60 parts of a solvent, wherein the solvent is water.

7. The methylphenidate hydrochloride sustained-release tablet according to claim 6, characterized in that The dispersant is lecithin, and the anti-adhesive agent is talc; The colorants include titanium dioxide, lemon yellow aluminum lake and sunset yellow aluminum lake.

8. The methylphenidate hydrochloride sustained-release tablet according to claim 6, characterized in that The mass ratio of the hydroxypropyl methylcellulose, polyvinyl alcohol and povidone K30 is (12-15): (4-6): (3-5).

9. The methylphenidate hydrochloride sustained-release tablet according to claim 6, characterized in that The mass ratio of polyethylene glycol 6000 to propylene glycol is (3-5):1.

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