Montelukast sodium chewable tablet, preparation method and determination method of dissolution rate

Abstract

The invention relates to the field of medicinal preparations and particularly relates to a montelukast sodium chewable tablet, apreparation method and a determination method of a dissolution rate. Raw materials of the montelukast sodium chewable tablet comprise montelukast sodium, mannitol, microcrystalline cellulose, hydroxy propyl cellulose, crosslinking sodium carboxymethylcellulose, aspartame, ferric oxide, magnesium stearate and cherry essence. The hydroxy propyl cellulose is prepared into a solution with a mass percentage content being 6-8% through water being a solvent and a disintegrating agent is prepared through a wet process of an internal addition method. The montelukast sodium chewable tablet is significantly increased in disintegrating speed and in-vitro dissolution rate. By means of a dissolution curve detection method, quality differences among products in each batch can be effectively distinguished. Differences between products in each batch can be reduced better and a quality risk of the products can be controlled in a controllable range.

Description

technical field

[0001] The invention relates to the field of medicine, in particular to a montelukast sodium chewable tablet, a preparation method and a dissolution method thereof. Background technique

[0002] Montelukast is a new generation of non-steroidal anti-inflammatory drugs, which is a selective leukotriene receptor antagonist. This product has high affinity and selectivity to CysLT1 receptor (cysteine ​​leukotriene receptor 1), blocks the inflammatory effect of leukotriene and controls asthma attacks without any receptor agonistic activity. The clinical efficacy and safety of childhood asthma have been confirmed.

[0003] Montelukast sodium is the sodium salt form of montelukast, which has poor stability, is unstable to strong acid and light, is easy to decompose, and is easy to oxidize when encountering oxidizing agents. Montelukast sodium is currently one of the best-selling asthma medicines in the world. It has been on the market in many countries and regions ...

Examples

Embodiment 1- Embodiment 3

[0049] In embodiment 1-embodiment 3, montelukast sodium chewable tablet comprises raw material as follows:

[0050] Example 1 Example 2 Example 3 Montelukast Sodium 3g Montelukast Sodium 2g Montelukast Sodium 1g Mannitol 128g Mannitol 75.25g Mannitol 42.6g Microcrystalline cellulose 22g Microcrystalline Cellulose 14.75 Microcrystalline cellulose 7.5g Hydroxypropyl cellulose 2.33g Hydroxypropyl cellulose 1.5g Hydroxypropyl cellulose 0.8g Croscarmellose Sodium 9g Croscarmellose Sodium 6g Croscarmellose Sodium 3g Aspartame 0.3g Aspartame 0.2g Aspartame 0.1g Red iron oxide 0.9g Red iron oxide 0.9g Red iron oxide 0.3g Magnesium stearate 0.6g Magnesium stearate 0.6g Magnesium stearate 0.2g Cherry essence 0.45g Cherry essence 0.45g Cherry essence 0.15g

Embodiment 1

[0051] The preparation method of embodiment 1 montelukast sodium chewable tablet comprises the following steps:

[0052] (1) Under the condition of avoiding light, pass the montelukast sodium bulk drug, magnesium stearate, and red iron oxide through a 100-mesh sieve; mannitol, microcrystalline cellulose, croscarmellose sodium, and Spartame and cherry essence are passed through an 80-mesh sieve;

[0053] (2) Weigh hydroxypropyl cellulose and add purified water, stir until completely dissolved, and prepare 8% hydroxypropyl cellulose binder aqueous solution;

[0054] (3) Sifted montelukast sodium, mannitol, microcrystalline cellulose, and partially cross-linked carmellose sodium (by mass ratio, accounting for 60% of all cross-linked carmellose sodium) 1. Mix the red iron oxide evenly in the wet granulation equipment, add the 8% hydroxypropyl cellulose aqueous solution prepared in step (2), wet granulate, and granulate with a 30-mesh sieve;

[0055] (4) Put the wet granules prep...

experiment example 1

[0060] This experimental example is a study on the dissolution profile of the montelukast sodium chewable tablets prepared in Example 1-Example 3 according to the dissolution testing method of the present invention.

[0061] The dissolution testing method of embodiment 1, comprises the following steps:

[0062] (1) According to Chinese Pharmacopoeia 2010 edition two appendices XC dissolution method second method, take one piece of chewable tablet (5mg / tablet) with 0.4% (mass volume ratio) sodium lauryl sulfate phosphate buffer solution (pH= 6.8) 900ml is the dissolution medium, and the rotating speed is 50 revolutions per minute. Take 10ml of samples at the 5th, 10th, 15th, 20th, and 30th minutes respectively, filter, and take the subsequent filtrate as the test solution. Dissolution medium with fresh temperature; take another 15mg of montelukast dicyclohexylamine salt, add methanol to dissolve and dilute to 50ml, shake well, take 2ml of the above solution, add 0.5% sodium lau...

technical field

[0001] The invention relates to the field of medicine, in particular to a montelukast sodium chewable tablet, a preparation method and a dissolution method thereof. Background technique

[0002] Montelukast is a new generation of non-steroidal anti-inflammatory drugs, which is a selective leukotriene receptor antagonist. This product has high affinity and selectivity to CysLT1 receptor (cysteine ​​leukotriene receptor 1), blocks the inflammatory effect of leukotriene and controls asthma attacks without any receptor agonistic activity. The clinical efficacy and safety of childhood asthma have been confirmed.

[0003] Montelukast sodium is the sodium salt form of montelukast, which has poor stability, is unstable to strong acid and light, is easy to decompose, and is easy to oxidize when encountering oxidizing agents. Montelukast sodium is currently one of the best-selling asthma medicines in the world. It has been on the market in many countries and regions ...

Examples

Embodiment 1- Embodiment 3

[0049] In embodiment 1-embodiment 3, montelukast sodium chewable tablet comprises raw material as follows:

[0050] Example 1 Example 2 Example 3 Montelukast Sodium 3g Montelukast Sodium 2g Montelukast Sodium 1g Mannitol 128g Mannitol 75.25g Mannitol 42.6g Microcrystalline cellulose 22g Microcrystalline Cellulose 14.75 Microcrystalline cellulose 7.5g Hydroxypropyl cellulose 2.33g Hydroxypropyl cellulose 1.5g Hydroxypropyl cellulose 0.8g Croscarmellose Sodium 9g Croscarmellose Sodium 6g Croscarmellose Sodium 3g Aspartame 0.3g Aspartame 0.2g Aspartame 0.1g Red iron oxide 0.9g Red iron oxide 0.9g Red iron oxide 0.3g Magnesium stearate 0.6g Magnesium stearate 0.6g Magnesium stearate 0.2g Cherry essence 0.45g Cherry essence 0.45g Cherry essence 0.15g

Embodiment 1

[0051] The preparation method of embodiment 1 montelukast sodium chewable tablet comprises the following steps:

[0052] (1) Under the condition of avoiding light, pass the montelukast sodium bulk drug, magnesium stearate, and red iron oxide through a 100-mesh sieve; mannitol, microcrystalline cellulose, croscarmellose sodium, and Spartame and cherry essence are passed through an 80-mesh sieve;

[0053] (2) Weigh hydroxypropyl cellulose and add purified water, stir until completely dissolved, and prepare 8% hydroxypropyl cellulose binder aqueous solution;

[0054] (3) Sifted montelukast sodium, mannitol, microcrystalline cellulose, and partially cross-linked carmellose sodium (by mass ratio, accounting for 60% of all cross-linked carmellose sodium) 1. Mix the red iron oxide evenly in the wet granulation equipment, add the 8% hydroxypropyl cellulose aqueous solution prepared in step (2), wet granulate, and granulate with a 30-mesh sieve;

[0055] (4) Put the wet granules prep...

experiment example 1

[0060] This experimental example is a study on the dissolution profile of the montelukast sodium chewable tablets prepared in Example 1-Example 3 according to the dissolution testing method of the present invention.

[0061] The dissolution testing method of embodiment 1, comprises the following steps:

[0062] (1) According to Chinese Pharmacopoeia 2010 edition two appendices XC dissolution method second method, take one piece of chewable tablet (5mg / tablet) with 0.4% (mass volume ratio) sodium lauryl sulfate phosphate buffer solution (pH= 6.8) 900ml is the dissolution medium, and the rotating speed is 50 revolutions per minute. Take 10ml of samples at the 5th, 10th, 15th, 20th, and 30th minutes respectively, filter, and take the subsequent filtrate as the test solution. Dissolution medium with fresh temperature; take another 15mg of montelukast dicyclohexylamine salt, add methanol to dissolve and dilute to 50ml, shake well, take 2ml of the above solution, add 0.5% sodium lau...

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