CN112843012B - Lamotrigine-containing preparation composition and preparation method thereof - Google Patents

Abstract

The invention relates to a lamotrigine-containing formulation composition comprising a tablet core and an outer coating; the outer coating contains 0.1-15% of colorant by mass percent. According to the invention, the coloring agent with a specific proportion is added into the outer coating, so that the drug release curve can be regulated, the in-vitro release curve of the preparation composition is ensured to be similar to that of a commercially available product under the condition that no perforation is needed and no pore-forming agent is needed, the in-vivo bioequivalence of a human body is ensured, the requirement of drug replacement in clinical treatment is met, and the production cost is greatly reduced.

Description

Lamotrigine-containing preparation composition and preparation method thereof

Technical Field

The invention relates to the field of pharmaceutical preparations, in particular to a preparation composition containing lamotrigine.

Background

Lamotrigine (Lamotrigine ), originally discovered and developed by the gram company (GlaxoSmithKline, GSK), a product sold to more than 90 countries worldwide. Lamotrigine has a chemical name of 3, 5-diamino-6- (2, 3-dichlorophenyl l) -1,2, 4-triazine, a molecular weight of 256.09, and a molecular formula:

lamotrigine is very slightly soluble in methylene chloride (< 0.1mg/mL,25 ℃), ethyl acetate (< 0.1mg/mL,25 ℃) and water (0.17 mg/mL,25 ℃) and slightly soluble in methanol (11.1 mg/mL,25 ℃) ethanol (1.1 mg/mL,25 ℃) and 0.1M HCl (4.1 mg/mL,25 ℃).

Lamotrigine is used as an oral sodium channel blocker and a benzotriazine antiepileptic, and is suitable for the adjuvant treatment of adult and children patients with partial epileptic seizure, lennox-Gastaut syndrome systemic epileptic seizure and primary generalized tonic-clonic seizure (PGCT) epileptic seizure. For adults who are receiving single enzyme induced anti-epileptic drug therapy for partial epileptic seizures, it is also suitable for conversion to monotherapy. Lamotrigine is also used to maintain treatment of bipolar I disorder to delay the time for an emotional episode in an adult treated with standard therapy. In japan, this drug is also considered as a single drug treatment for the typical absence of childhood.

The drug was introduced in 1995, month 3, in the united states as an adjuvant epileptic therapy, and in 1997, month 9, in the european union. It was approved and released in the united kingdom in month 1 of 2001. Month 6 of 2003, the FDA approved lamotrigine for long-term maintenance therapy in adults with bipolar I disorder. Month 1 of 2004, the drug was approved by the FDA for use as a monotherapy for the treatment of partial seizures when patients 16 years old and older were transformed from valproate. In month 9 of 2006, the FDA approved lamotrigine for the adjuvant treatment of PGCT seizures in patients 2 years old and older. The drug is introduced in japan for 12 months in 2008 and is used for the adjuvant treatment of epilepsy. The drug was approved and introduced in japan for bipolar disorder 7 months 2011. Lamotrigine was approved in japan for single drug treatment of partial seizures and tonic-clonic seizures in month 8 of 2014. In 2015, 9 months, japan approved the use of this drug as a single drug treatment for the typical absence of children.

While the mechanism of action of lamotrigine is not known, it is believed that the antiepileptic effect of drugs is due to inhibition of voltage-sensitive sodium channels, leading to stabilization of neuronal membranes, which in turn regulate the release of excitatory amino acids (e.g., glutamate and aspartate) by presynaptic transmitters. The GSK commercial lamotrigine sustained release tablet is marketed abroad, and adopts a Diffcore drug release technology according to the characteristics and the drug properties of epilepsy treatment, and the basic procedures are that a framework type tablet core is prepared, enteric coating is carried out, and holes accounting for 10-60% of the surface area of the tablet are punched on a coating film (shown in figure 1). The skeleton type tablet core controls the slow release of the medicine, and the enteric-coated film can effectively avoid adverse reaction caused by rapid release of lamotrigine in gastric juice. After enteric coating, the drug is hardly released in the stomach, so that after perforation of the coating film, a small amount of drug is released in a controlled manner through the hole to achieve a rapid onset of action. However, the Diffcore technology has high equipment requirement, expensive laser drilling equipment, unpopular domestic drilling technology, high production threshold and high production cost, and is difficult for patients to obtain the product at a low price.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a lamotrigine-containing preparation composition with low production cost, good drug effect and excellent release performance.

The invention creatively discovers that the coloring agent with a specific proportion is added into the outer coating, so that the drug release curve can be regulated, the in-vitro release curve of the preparation composition is ensured to be similar to that of a GSK (GSK) commercial product under the condition that no perforation is needed and no pore-forming agent is needed to be added, the biological equivalence in the human body is realized, the requirement of drug replacement in clinical treatment is met, and the production cost is greatly reduced.

Specifically, the lamotrigine-containing preparation composition provided by the invention comprises a tablet core and an outer coating; the outer coating contains 0.1-15% of colorant by mass percent.

In one embodiment of the present invention, the colorant comprises 0.1 to 1% by mass of the outer coating.

In one embodiment of the present invention, the colorant comprises 1 to 5% by mass of the outer coating.

In one embodiment of the present invention, the colorant comprises 5 to 9% by mass of the outer coating.

In one embodiment of the present invention, the colorant comprises 9 to 15% by mass of the outer coating.

The colorant selected in the invention can be one or more selected from dye, lake and pigment. Preferably, the colorant is a mixture of one or more of titanium dioxide, iron oxide, aluminum lakes.

In one embodiment of the invention, the colorants include titanium dioxide, iron oxide, and aluminum lakes. Preferably, the mass ratio of the titanium dioxide to the ferric oxide to the aluminum lake is (34-37): (8-10): 1. wherein, the ferric oxide can be formed by mixing yellow ferric oxide and red ferric oxide, and the preferable mass ratio of the yellow ferric oxide to the red ferric oxide is (6-10): 1, and mixing.

The preparation composition provided by the invention also contains enteric materials in the outer coating. The enteric material may be used in an amount of 60 to 90%, preferably 70 to 80% of the mass of the outer coating. The enteric material may be selected from one or more of the following: acrylic resin, cellulose Acetate Phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP) or hydroxypropyl methylcellulose succinate (HPMAS).

In one embodiment of the present invention, the enteric material is acrylic resin. In one embodiment of the present invention, the outer coating contains 60 to 90% of the mass of the outer coating, preferably 70 to 80% of the mass of the outer coating.

Common acrylic resins include a variety of polymers polymerized from acrylic acid, methacrylic acid and derivatives thereof in varying proportions. The present invention preferably employs an acrylic resin polymerized from methacrylic acid and ethyl acrylate in a 1:1 ratio, such as Uttky L30D-55.

The outer coating of the preparation composition provided by the invention can also contain a plasticizer. The plasticizer may be used in an amount of 5 to 10% by mass of the outer coating. The plasticizer may be selected from one or more of the following: triethyl citrate (TEC), polyethylene glycol (PEG), glycerol, triacetin or castor oil.

In one embodiment of the present invention, the plasticizer is triethyl citrate. In one embodiment of the invention, the outer coating contains triethyl citrate which accounts for 5-10% of the mass of the outer coating.

The external coating of the preparation composition provided by the invention can also contain an anti-adhesion agent. The anti-sticking agent may be used in an amount of 3 to 5% by mass of the outer coating.

In one embodiment of the invention, the anti-sticking agent is selected from mono-and diglycerides (i.e., a mixture of glyceryl monostearate and glyceryl distearate). In one embodiment of the present invention, the outer coating contains 3 to 5% by mass of mono-and di-glycerides (i.e., a mixture of glyceryl monostearate and glyceryl distearate) of the outer coating.

The outer coating of the preparation composition provided by the invention can also contain a surfactant. The surfactant may be used in an amount of 1 to 5% by mass of the outer coating.

In one embodiment of the invention, the surfactant is polysorbate 80. In one embodiment of the invention, the outer coating contains polysorbate 80 in an amount of 1-5% by weight of the outer coating.

As a specific embodiment of the present invention, the outer coating of the formulation composition contains the following components in parts by weight: 100-140 parts of Eudragit L30D-55, 5-20 parts of triethyl citrate, 2-10 parts of mono-and diglycerides, 1-8 parts of polysorbate, and 0.5-20 parts of colorant; the colorant is formed by mixing titanium dioxide, yellow ferric oxide, red ferric oxide and blue No. 2 aluminum lake. Preferably, the colorant is 0.5 to 2 parts, 2 to 7 parts, 7 to 15 parts, or 15 to 20 parts by weight.

The invention optimizes the percentage of the outer coating to the total mass of the preparation composition, can make the substances in the outer coating of the tablet for regulating the release rate act synergistically with various components in the tablet core, and controls the disintegration rate of the whole preparation composition, thereby ensuring that the lamotrigine is released at the optimal rate.

In one embodiment of the invention, the outer coating comprises 1 to 10%, preferably 2 to 5%, more preferably 3.4 to 4.0% of the total mass of the formulation composition. Specifically, the outer coating may comprise 3.4 to 3.5%,3.5 to 3.6%,3.6 to 3.7%,3.7 to 3.8%, or 3.9 to 4.0% of the total mass of the formulation composition.

In the preparation composition provided by the invention, the efficacy component lamotrigine is contained in the tablet core.

In one embodiment of the invention, the tablet core contains lamotrigine accounting for 40-50% of the mass of the tablet core. In one embodiment of the present invention, the tablet core contains lamotrigine in an amount of 50% or more by mass of the tablet core.

The sustained-release matrix material in the tablet core of the preparation composition provided by the invention is hydroxypropyl methylcellulose (HPMC). In one embodiment of the present invention, the tablet core contains 10 to 35% hydroxypropyl methylcellulose, preferably 13 to 20% hydroxypropyl methylcellulose by mass of the tablet core.

In the production, the hydroxypropyl methylcellulose with specific viscosity can be selected or the hydroxypropyl methylcellulose with different viscosities can be mixed for use so as to meet the actual requirements of the preparation. In one embodiment of the present invention, the disintegrating agent is formed by mixing hydroxypropyl methylcellulose with different viscosities, specifically, hydroxypropyl methylcellulose with a viscosity of 4000mPas (HPMC K4M) and hydroxypropyl methylcellulose with a viscosity of 100mPas (HPMC K100), preferably, HPMC K4M and HPMC K100 in a mass ratio of 1: (0.8-1.2) and mixing.

The tablet core of the preparation composition provided by the invention can be added with a filler. The addition amount of the filler can account for 30-40% of the mass of the tablet core. The filler may be selected from one or more of the following: calcium carbonate, anhydrous dibasic calcium phosphate, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, calcium sulfate, powdered cellulose, silicified microcrystalline cellulose, cellulose acetate, compressible sugar, dextran, dextrin, dextrose, fructose, clavulanate, lactose (lactose monohydrate or lactose anhydrous), magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, microcrystalline cellulose, polydextrose, simethicone, sodium alginate, sodium chloride, sorbitol, starch, pregelatinized starch, sucrose, trehalose or xylitol.

In one embodiment of the invention, the filler is lactose monohydrate. In one embodiment of the invention, the tablet core contains lactose monohydrate in an amount of 30-40%, preferably 32-36% by mass of the tablet core.

Lubricants may be added to the tablet cores of the formulation compositions provided by the present invention. The addition amount of the lubricant can be 0.1-2% of the mass of the tablet core. The lubricant may be selected from one or more of the following: calcium stearate, glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, magnesium lauryl sulfate, magnesium stearate, medium chain triglycerides, poloxamers, polyethylene glycols, sodium benzoate, sodium chloride, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, sucrose stearate or zinc stearate.

In one embodiment of the present invention, the lubricant is magnesium stearate. In one embodiment of the present invention, the tablet core contains magnesium stearate in an amount of 0.1 to 2% by mass, preferably 0.8 to 1.2% by mass, based on the tablet core.

As a specific embodiment of the present invention, the tablet core of the formulation composition contains the following components in parts by weight: 40-60 parts of lamotrigine, 10-20 parts of hydroxypropyl methylcellulose, 30-40 parts of lactose monohydrate and 0.1-2 parts of magnesium stearate; the hydroxypropyl methylcellulose is prepared by mixing hydroxypropyl methylcellulose with the viscosity of 4000mPas and hydroxypropyl methylcellulose with the viscosity of 100 mPas.

The invention also provides a preparation method of the preparation composition.

Specifically, the preparation method comprises the following steps:

(1) Fully mixing tablet core raw materials including lamotrigine, granulating by a wet method, and tabletting to obtain tablet cores;

(2) Fully mixing the outer coating raw materials including the coloring agent with purified water to obtain coating liquid;

(3) And uniformly spraying the coating liquid on the surface of the tablet core.

The specific operations in the above steps, such as wet granulation in step (1), mixing in step (2), spraying in step (3), etc., can be accomplished by conventional means known in the art using equipment conventional in the art, and the present invention is not particularly limited.

The invention adopts common production equipment, adds a colorant with a specific proportion into the outer coating through prescription innovation, reduces the production threshold and the production cost of the lamotrigine sustained-release tablet, ensures that the developed product is bioequivalent with the commercial original ground product in human body, meets the requirement of medicament replacement in clinical treatment, and can lead patients to acquire the product with lower price as soon as possible.

Drawings

FIG. 1 is a schematic diagram of perforation of a commercially available GSK product;

FIG. 2 is a graph of human bioequivalence plasma concentration prior to meals (A is the product provided in example 1, B is the commercially available raw product of GSK);

FIG. 3 is a graph of human bioequivalence plasma concentration after meal (A is the product provided in example 1, and B is the commercially available raw product of GSK).

Detailed Description

The following examples are illustrative of the invention and are not intended to limit the scope of the invention.

Example 1

The embodiment provides a lamotrigine-containing sustained release tablet, wherein the proportion of the colorant accounts for 7.08% of the weight of the dry material of the outer coating; the raw materials of the composition are as follows:

remarks: the solids content of the aqueous Uttky L30D-55 dispersion was 30% (w/w).

The embodiment further provides a preparation method of the sustained-release tablet, which specifically comprises the following steps:

(1) Preparing a tablet core:

1) Weighing lamotrigine, hydroxypropyl methylcellulose, purified water and magnesium stearate according to the above table batch amounts;

2) Lamotrigine and hydroxypropyl methylcellulose are sequentially screened by a 20-mesh screen, then are placed in a 4L high-speed shearing wet granulator, and are mixed for 10min after the stirring paddle is started at 300 rpm;

3) The rotation speed of the stirring paddle is set to 300rpm, the rotation speed of the cutting knife is set to 1500rpm, a proper amount of purified water is pumped into the wet granulator, and the liquid adding time is 2-6 min; setting the rotating speed of a stirring paddle to 300rpm after the liquid adding is finished, setting the rotating speed of a cutting knife to 2500rpm, granulating for 3-8 min, and holding the wet particles to form clusters without touching or scattering;

4) Wet granules are put into a fluidized bed for drying after being wet granulated by using a screen with the size of 8mm, the air inlet temperature is 50-70 ℃, the drying is carried out until the Loss On Drying (LOD) is less than or equal to 4.0%, and dry granules are dried and granulated by using a screen with the size of 2 mm;

5) Putting the dry particles into a 6L mixing barrel, sieving the magnesium stearate in the step 1) by a 20-mesh sieve, adding the magnesium stearate, mixing for 5min, and rotating at 20rpm;

6) Tabletting, wherein the hardness is not less than 120N, and the friability is less than 0.5%;

(2) Preparing a coating liquid:

solution a: weighing about 20% of purified water for later use;

solution B: stirring the Eudragit L30D-55 solution, slowly adding the solution A, and diluting to obtain a solution B;

solution C: adding titanium dioxide, yellow iron oxide and red iron oxide, and blue aluminum lake No. 2 to about 40% of the batch of purified water, and stirring for 10 minutes;

solution D: placing about 40% of purified water in a container, heating to 70-80deg.C, adding mono-and diglycerides, adding polysorbate 80 and triethyl citrate after it melts, and stirring for 10min;

solution E: stirring the solution C, pouring the solution D, and continuously stirring for 10 minutes; homogenizing for 20 min with a high-shear homogenizer, and continuously stirring with a stirrer until the temperature of the emulsion is reduced to below 30deg.C;

solution F: stirring the solution B, pouring the solution E, adjusting the rotating speed to keep proper vortex, and continuously stirring for 30 minutes; the prepared coating solution is filtered by a nylon screen with 100 meshes.

Coating liquid is filtered through a 100-mesh nylon screen, and the integrity of the screen is checked before and after filtration;

(3) Uniformly spraying coating liquid on the surface of the tablet core:

a: adding the plain tablets into a coating pan, and turning on a hot air switch to heat the tablet bed before spraying. Slowly rotating the coating pan during the heating of the tablet bed;

b: before spraying the liquid, the distance between the spray gun and the slice bed is regulated to be about 20 cm-30 cm. After liquid spraying is started, the angle and atomization effect of the spray gun are adjusted, the liquid spraying amount of the spray gun is ensured to be consistent, and meanwhile, the spray liquid level can cover as many flakes as possible and the flakes are not overlapped with each other;

c: the rotating speed of the pan is 2-6 rpm, the temperature of the slice bed is 25-35 ℃, the air inlet temperature is not more than 70 ℃, the air inlet quantity is 60-100 m < 3 >/h, the air exhaust pressure difference is-20 pa, and the liquid spraying speed is gradually regulated to the maximum acceptable range according to the appearance of the slice surface;

the coating pan should run at a low speed as much as possible to reduce the abrasion of the surface of the coating pan within 10-30 minutes from the start of coating on the premise of ensuring the stable sheet bed; the liquid amount is properly increased to ensure that a film is formed rapidly to protect one side;

in the spraying process, the spraying condition of the spray gun and whether the spraying fan surface is normal or not are inspected at least once every 15 minutes, so that the spray gun is prevented from being blocked;

observing the appearance of the film during the spraying process, avoiding the phenomena of adhesion, uneven spraying, uneven color and the like;

(4) Tablet printing and packaging.

Example 2

The embodiment provides a lamotrigine-containing sustained release tablet, wherein the proportion of the colorant accounts for 3.04% of the weight of the dry material of the outer coating; the raw materials of the composition are as follows:

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the preparation method is the same as in example 1.

Example 3

The present example provides a lamotrigine-containing sustained release tablet wherein the proportion of the colorant is 0.43% by weight of the dry material of the outer coating; the raw materials of the composition are as follows:

the preparation method is the same as in example 1.

Example 4

The embodiment provides a lamotrigine-containing sustained release tablet, wherein the proportion of the colorant accounts for 12.25% of the weight of the dry material of the outer coating; the raw materials of the composition are as follows:

the preparation method is the same as in example 1.

Comparative example 1

The comparative example provides a lamotrigine-containing sustained release tablet, wherein the outer coating does not contain a colorant; the raw materials of the composition are as follows:

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the preparation method is the same as in example 1.

Comparative example 2

The embodiment provides a lamotrigine-containing sustained release tablet, wherein the proportion of the colorant accounts for 16.27% of the weight of the dry material of the outer coating; the raw materials of the composition are as follows:

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the preparation method is the same as in example 1.

Experimental example 1: in vitro Release test

The experimental examples evaluate and compare the in vitro release conditions of lamotrigine sustained release tablets and GSK commercial raw ground products provided in the examples and the comparative examples.

1. Dissolution conditions:

medium 1:0.01M hydrochloric acid; 700 ml;

medium 2: 7.8g trisodium phosphate and 22.5g sodium dodecyl sulfate were added to 1L of water; the pH of the solution is about 12;

volume of dissolution medium: 900mL;

the device comprises: paddle method, 50rpm, with settling basket;

temperature: 37.0+/-0.5 ℃;

sample amount: 5mL.

2. The measuring method comprises the following steps:

the test was performed with medium 1 for 2 hours. 200mL of medium 2 was added, preheated at 37℃and samples were taken 2 hours during 5 minutes of addition of medium 2, followed by sampling at 3/4/5/7/9/12/14/15/17/20 hours. Drug concentration was determined using HPLC at a wavelength of 310 nm. And calculating the similarity factor F2 (%) of the in vitro dissolution curve corresponding to each example and each comparative example and the in vitro dissolution curve of the commercially available raw product.

3. Measurement results: as shown in table 1.

Table 1: in vitro dissolution curve of lamotrigine sustained release tablet

As can be seen from the results in Table 1, the in vitro release profile of the enteric coating film of example 1 showed a high similarity to the commercial as-ground product at a colorant ratio of 7.08%, and a similarity factor F2 (%) of 78%.

As the proportion of colorant in the enteric coating film was reduced (example 2 to 3.04%, example 3 to 0.43%), the in vitro release profile and dissolution profile similarity of the commercially available as-ground product were reduced to 69% and 60%, respectively. When the proportion of the colorant in the enteric coating film was reduced to 0 (comparative example 1), the in vitro release rate was significantly slowed, and the dissolution profile F2 (%) was less than 55% as compared with the original product.

As the proportion of the colorant in the enteric coating film increased (example 4, 12.25%), the in vitro release profile decreased with respect to the similarity of the original product, and the similarity factor F2 (%) was 58%. When the proportion of colorant in the enteric coating film was increased to 16.27% (comparative example 2), the release rate was significantly faster, and the in vitro release profile was already dissimilar to that of the commercially available as-ground product, with an F2 (%) value of less than 50%.

Experimental example 2: bioequivalence test

The experimental example evaluates the human bioequivalence of lamotrigine sustained release tablets provided in example 1 and GSK commercial original ground products.

This experimental example used a two-cycle double crossover test protocol with 34 people enrolled healthy subjects before meals and 20 people enrolled healthy subjects after meals, with fasting and meal port tests performed at blood sampling points of 0, 3, 6, 9, 12, 15, 18, 20, 22, 24, 26, 29, 36, 48, 72, 96 and 120 hours, respectively.

The human bioequivalence results before meal are shown in figure 2 and table 2. In FIG. 2, A-Test represents the product provided in example 1, and B-Reference represents the commercially available raw product.

Table 2: human bioequivalence results before meal

The human bioequivalence results after meal are shown in FIG. 3 and Table 3. In FIG. 3, A-Test represents the product provided in example 1, and B-Reference represents the commercially available raw product.

Table 3: postprandial human bioequivalence results

From the above results, the lamotrigine-containing preparation composition provided by the invention is bioequivalent to the commercial raw product in human body, C _max 、AUC _0-t 、AUC _0-∞ The 90% confidence interval of the medicine is within the range of 80-125%, thereby meeting the requirement of medicine replacement in clinical treatment.

While the invention has been described in detail in the foregoing general description, embodiments and experiments, it will be apparent to those skilled in the art that modifications and improvements can be made thereto. Accordingly, such modifications or improvements may be made without departing from the spirit of the invention and are intended to be within the scope of the invention as claimed.

Claims (12)

1. A lamotrigine-containing formulation composition comprising a core and an outer coating; the tablet core contains lamotrigine accounting for 40-50% or more than 50% of the tablet core, hydroxypropyl methylcellulose accounting for 10-35% of the tablet core, filler accounting for 30-40% of the tablet core and lubricant accounting for 0.1-2% of the tablet core;

the outer coating comprises 60-90% of enteric coating material, 5-10% of plasticizer, 3-5% of anti-adhesion agent, 1-5% of surfactant and 5-9% of colorant, wherein the mass ratio of the colorant is titanium dioxide, ferric oxide and aluminum lake is (34-37): (8-10): 1.

2. The formulation composition according to claim 1, wherein the enteric material is selected from one or more of the following: acrylic resin, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate or hydroxypropyl methylcellulose succinate.

3. Formulation composition according to claim 1 or 2, characterized in that the plasticizer is selected from one or more of the following: triethyl citrate, polyethylene glycol, glycerol, triacetin or castor oil.

4. Formulation composition according to claim 1 or 2, characterized in that the anti-sticking agent is selected from glycerol monostearate, glycerol distearate or a mixture of both.

5. Formulation composition according to claim 1 or 2, characterized in that the surfactant is selected from polysorbate 80.

6. The formulation composition according to claim 1 or 2, wherein the outer coating comprises 1-10% of the total mass of the formulation composition.

7. The formulation composition according to claim 6, wherein the outer coating comprises 2-5% of the total mass of the formulation composition.

8. The formulation composition according to claim 7, wherein the outer coating comprises 3.4 to 4.0% of the total mass of the formulation composition.

9. Formulation composition according to claim 1 or 2, characterized in that the hydroxypropyl methylcellulose is mixed from hydroxypropyl methylcellulose with a viscosity of 4000mPas and hydroxypropyl methylcellulose with a viscosity of 100 mPas.

10. Formulation composition according to claim 1 or 2, characterized in that the filler is selected from one or more of the following: calcium carbonate, anhydrous dibasic calcium phosphate, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, calcium sulfate, powdered cellulose, silicified microcrystalline cellulose, cellulose acetate, dextran, dextrin, dextrose, fructose, clavitol, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, microcrystalline cellulose, polydextrose, simethicone, sodium alginate, sodium chloride, sorbitol, starch, pregelatinized starch, sucrose, trehalose or xylitol.

11. Formulation composition according to claim 1 or 2, characterized in that the lubricant is selected from one or more of the following: calcium stearate, glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, magnesium lauryl sulfate, magnesium stearate, medium chain triglycerides, poloxamers, polyethylene glycols, sodium benzoate, sodium chloride, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, sucrose stearate or zinc stearate.

12. The method for preparing the preparation composition as claimed in any one of claims 1 to 11, comprising the steps of:

(1) Fully mixing tablet core raw materials including lamotrigine, granulating by a wet method, and tabletting to obtain tablet cores;

(2) Fully mixing the outer coating raw materials including the coloring agent with purified water to obtain coating liquid;

(3) And uniformly spraying the coating liquid on the surface of the tablet core.

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