KR100307251B1 - Dispersible Formulation with Acyclovir Tablet and Its process - Google Patents

Abstract

PURPOSE: An acyclovir diffusion pill composition and its producing method are provided, therefore the composition can be easily dissolved in a mouth without water. CONSTITUTION: The acyclovir diffusion pill composition contains 50 to 60 wt.% of acyclovir, 0.5 to 10 wt.% of dissolving agent, diffusing agent consisting of 10 to 20 wt.% of organic acid and 10 to 20 wt.% of carbonate, 0.1 to 5 wt.% of sweetener, 5 to 20 wt.% of diluent, flavoring agent, 1 to 20 wt.% of powder binding agent and 0.2 to 2.5 wt.% of brightener. The method for producing the acyclovir dispersion pill composition comprises the steps of: dissolving 50 to 60 wt.% of acyclovir and 0.1 to 5 wt.% of sweetener in a light alkali solution; adding 5 to 20 wt.% of diluent and 10 to 20 wt.% of carbonate into the mixture; and granulating and drying the mixture; mixing the dried mixture with 10 to 20 wt.% of organic acid, 1 to 20 wt.% of powder binding agent, 0.2 to 2.5 wt.% of brightener, 0.5 to 10 wt.% of dissolving agent and flavoring agent and preparing the diffusion pill using the mixture.

Description

Acyclovir diffusion tablet composition and method for preparing the same {Dispersible Formulation with Acyclovir Tablet and Its process}

The present invention relates to a composition of Acyclovir diffusion tablets and a method for preparing the same, and more particularly, to quickly disintegrate tablets and make them easy to take, so that they can be easily disintegrated without water in the oral cavity and can be easily administered and provide high pharmacological activity. It relates to a composition of acyclovir diffusion tablet for the preparation and a method of manufacturing the same.

In general, if a drug is absorbed from the digestive tract and exhibits high pharmacological activity in vivo, it must be rapidly dissolved in the digestive tract. The rate of dissolution of the drug determines the rate of absorption of the digestive tract and influences drug concentration in the blood. Differently depending on

In particular, solid preparations, such as tablets and capsules, the faster the rate of disintegration in the digestive tract, the faster the rate of dissolution and a greater effect on absorption.

Acyclovir is a compound with the following structural formula. It is an antiviral agent used for the treatment of herpes simplex, shingles, chickenpox and herpes simplex. Soluble in hydrochloric acid, sodium hydroxide solution or ammonia solution, hardly soluble in most organic solvents, LD ₅₀ in rats is a relatively stable drug orally above 10,000 (mg / kg).

The US Pharmacopoeia contains capsules, injections, oral suspensions, and tablets, and is currently marketed in various countries around the world.

Commercially available tablets, however, take a long time to disintegrate and elute, and are used as micronized powder due to the poor solubility of acyclovir. In order to improve this, the present invention was invented acyclovir diffusion tablet, has the advantage that can be taken by dissolving in the mouth without water, or dissolved in a glass of water in advance.

1 is a result of the elution accumulation ratio comparison experiment.

Compositions and preparation methods of oral acyclovir diffusion tablets of the present invention are as follows. The composition of the present invention comprises 50 to 60% by weight of the main component acyclovir, 0.5 to 10% by weight of disintegrant, 10 to 20% by weight of organic acid and 10 to 20% by weight of carbonate, 0.1 to 5% by weight of sweetener, 5 to 5% of excipient It consists of 20% by weight, flavoring agent, powder binder 1-20% by weight and lubricant 0.2-2.5% by weight, and the manufacturing method is the remaining composition after dissolving the main ingredient raw material in a dilute mineral acid solution or dilute alkaline solution It can be prepared simply by mixing with ingredients directly and tabletting. A mixture of 50 to 60% by weight of acyclovir with 0.1 to 5% by weight of sweetener in a dilute mineral acid solution is mixed with 5 to 20% by weight of excipient and 10 to 20% by weight of organic acid. And granulated and dried, and then mixed with 10-20 wt% of carbonate, 1-20 wt% of powder binder, 0.2-2.5 wt% of lubricant, 0.5-10 wt% of disintegrant, and flavoring agent. Or dilute 50 to 60% by weight of acyclovir It is dissolved together with 0.1 to 5% by weight of sweetener in a Kali solution, placed in a mixture of 5 to 20% by weight of excipient and 10 to 20% by weight of carbonate, granulated and dried, and then 10 to 20% by weight of organic acid and 1 to 20 powder binder. It is a method of preparing oral acyclovir-containing diffusion tablets by mixing, mixing, and mixing the weight percent, the lubricant 0.2-2.5 weight percent, the disintegrant 0.5-10 weight percent, and the flavoring agent. In more detail, about 50 to 60% by weight of the active ingredient acyclovir is selected from dilute photoacid solution or dilute alkaline solution, preferably 10% hydrochloric acid or sulfuric acid solution, 10% caustic soda, potassium hydroxide or ammonium hydroxide solution. One excipient selected from D-sorbitol, xylitol, white sugar, glucose, fructose, mannitol, and lactose by dissolving with about 0.1 to 5% by weight of one sweetener selected from aspartame or stevioside as a sweetener in the solution of the species. 5-20 wt% and about 10-20 wt% of one organic acid selected from citric acid, tartaric acid, stearic acid, ascorbic acid, adipic acid, malic acid or sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium carbonate, potassium carbonate or potassium bicarbonate It is placed in a mixture of about 10 to 20% by weight of the selected one carbonate, granulated and dried, and then about 10 to 20% by weight of electric carbonate or electric About 10 to 20% by weight of organic acid and one powder selected from microcrystalline cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, Elsemer (TM), Adsolider or sodium carboxymethyl cellulose 1 to 20% by weight binder, 0.2 to 2.5% by weight of one type of lubricant selected from magnesium stearate, talc, stearic acid and light silicon dioxide, traces of micron powder flavors, crospovidone, dry corn starch, sodium starch glyconate, L-HPC, cross-linked sodium carboxymethyl cellulose (Cross Linked Sodium Carboxyl Methyl Cellulose) is selected from the mixture of 0.5 to 10% by weight of one disintegrant selected from the mixture and then prepared by direct compression.

In the present invention, the order of mixing the organic acid and the carbonate as the diffusion agent is to mix the organic acid when using the mineral acid solution to make granular form, and then to put the carbonate into the tablet, and to mix the carbonate when using the alkaline solution to form the granular organic acid. Put it in tablets.

Acyclovir may be present in the composition of the present invention may contain from about 35 to about 90% by weight, but in particular a concentration in the range of 50 to 60% by weight is more preferred, less than 25% by weight of the tablet is too large and more than 95% by weight of the excipient The amount is too small to form a tablet.

If the amount of sweetener is insufficient, the taste is not good at the time of taking it, and if too much, the sweetness is felt and the tablet becomes large. If the amount of organic acid is less than the range, the diffusion rate is slow, and if too much, the taste is sour. In addition, more stearic acid as a lubricant may further delay the diffusion and disintegration, and less than the lubricant effect. In addition, if the carbonate, such as sodium bicarbonate is less than the range, the diffusion rate is slow, too much if the diffusion rate is fast, but the irritation is felt in the oral cavity. If the disintegrant such as crospovidone is less than the range, the diffusion is slowed, and if too much, it is easily disintegrated by the convention and the size of the tablet becomes large.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, this does not limit the scope of the present invention.

(Example 1)

A pharmaceutical composition having the following composition was prepared by the following method.

ingredient Content (% by weight) Acyclovir 52.6 Microcrystalline cellulose 10.0 D-sorbitol 9.1 Crospovidone 3.2 Colloidal silicon dioxide 0.5 10% hydrochloric acid 0.5 Magnesium Stearate 0.2 Aspartame 3.4 Citric acid 10.1 Sodium bicarbonate 10.3 Strawberry Micron Quantity system 100

1) Preparation of Acyclovir Granules

Acyclovir is dissolved with aspartame in 10% hydrochloric acid solution, put into a mixture of D-sorbitol and citric acid, granulated with 18 mesh sieve, dried for 30 minutes at 50 ° C. in a fluidized bed dryer, and granulated with 25 mesh sieve.

2) Preparation and Tableting of Mixtures

Microcrystalline cellulose, crospovidone, colloidal silicon dioxide, sodium bicarbonate, strawberry micron, and the like are mixed with magnesium stearate and mixed in the above formulation. Tableting with a rotary tableting machine

(Example 2)

A pharmaceutical composition having the following composition was prepared by the following method.

ingredient Content (% by weight) Acyclovir 52.6 Microcrystalline cellulose 10.0 Xylitol 8.2 Crospovidone 4.0 Talc 0.7 Stearic acid 0.2 Stevioside 3.0 Malic acid 10.2 Sodium carbonate 10.5 10% caustic soda 0.3 Orange Micron Powder Flavor Quantity system 100

Preparation: Acyclovir was dissolved with stevioside in sodium carbonate and 10% caustic soda solution, put into a mixture of xylitol and microcrystalline cellulose, granulated with 18 mesh sieve, dried in a fluidized bed drier for 30 minutes at 50 ° C., and then granulated with 25 mesh sieve. Mix with crospovidone, talc, stearic acid, malic acid and orange micron and tablet directly with a rotary tablet press.

(Comparative Example)

A product having the following composition was used.

ingredient Content (% by weight) Acyclovir 38.5 Microcrystalline cellulose 41.3 Lactose 13.7 Povidone 3.0 Purified water Quantity Magnesium stearate 2.3 Sodium Starch Glyconate 1.2 system 100

Preparation: Acyclovir, lactose and microcrystalline cellulose were mixed and granulated separately using a solution of povidone dissolved in purified water. Then mix. Tableting with a rotary tableting machine

Experimental Example 1

Disintegration comparison experiment.

According to the disintegration test method of the Korean Pharmacopoeia, the disintegration comparison experiments were performed for Examples 1 and 2 and Comparative Examples. In other words, put the auxiliary plate using purified water at 37 ± 2 ℃ as a test solution, take 6 tablets each time in a tester that reciprocates for 29 ~ 32 for 1 minute, put them in a glass tube, and move them up and down for a certain time. It was.

Disintegration result. division Example 1 Example 2 Comparative example Remarks Disintegration time (min) 1.5 1.0 28

Experimental Example 2

Dissolution Accumulation Rate Comparison Experiment

Using the dissolution test method of USP 23, the elution accumulation was compared between Examples 1 and 2 and Comparative Examples. Rotate the paddle at 100 rpm while maintaining the pH of the artificial gastric fluid in a 900 mL solution for up to 2 hours, and then maintain the pH of the artificial intestine solution at 37 ± 0.2 ℃. Was analyzed, and the experimental results are shown in Table 2 (see FIG. 1).

Dissolution Accumulation Rate Comparison Results Minutes Elution accumulation rate (%) Example 1 Example 2 Comparative example 30 43.1 69.0 6.2 60 89.2 96.9 12.4 90 99.4 100.0 16.6 120 100.0 100.0 23.7 180 100.0 100.0 29.9 240 100.0 100.0 39.7 360 100.0 100.0 53.3

According to the present invention, a novel diffusion tablet containing acyclovir, which is an antiviral agent, can be prepared. The disintegration is quicker than conventional tablets, is convenient to take, and quickly disintegrates without water even in the oral cavity. There is an advantage in that it can be expected and higher pharmacological activity.

Claims (9)

50 to 60 weight percent acyclovir, 0.5 to 10 weight percent disintegrant, 10 to 20 weight percent organic acid and 10 to 20 weight percent carbonate, 0.1 to 5 weight percent sweetener, 5 to 20 weight percent excipient, flavoring agent, An oral acyclovir-containing diffusion tablet composition comprising 1 to 20% by weight of powder binder and 0.2 to 2.5% by weight of lubricant. The composition of claim 1, wherein the disintegrant includes a composition selected from crospovidone, dried corn starch, sodium starch glyconate, L-HPC or crosslinked sodium carboxymethyl cellulose (Cross Linked Sodium Carboxyl Methyl Cellulose). . The organic acid as a diffusing agent according to claim 1, wherein the organic acid contains one selected from citric acid, tartaric acid, stearic acid, ascorbic acid, adipic acid, malic acid. Or potassium bicarbonate. The composition of claim 1, wherein the sweetener contains one selected from aspartame or stevioside. The composition of claim 1, wherein the excipient contains one selected from D-sorbitol, xylitol, white sugar, glucose, fructose, mannitol, or lactose. The method of claim 1, wherein the powder binder is microcrystalline cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, Elsemer (trademark), ad solider (Adsolider) or carboxymethyl cellulose sodium A composition containing a binder of the. The composition according to claim 1, wherein the lubricant contains one selected from magnesium stearate, talc, stearic acid, and hard silicon dioxide. 50 to 60% by weight of acyclovir was dissolved in a dilute photoacid solution together with 0.1 to 5% by weight of sweetener and placed in a mixture of 5 to 20% by weight of excipient and 10 to 20% by weight of organic acid, followed by granulation and drying. 20% by weight, 1 to 20% by weight of powder binder, 0.2 to 2.5% by weight of lubricant, 0.5 to 10% by weight of disintegrant, and a flavoring agent are mixed and mixed to prepare a oral acyclovir-containing diffusion tablet. 50 to 60% by weight of acyclovir was dissolved in dilute alkaline solution together with 0.1 to 5% by weight of sweetener and placed in a mixture of 5 to 20% by weight of excipient and 10 to 20% by weight of carbonate, followed by granulation and drying. A method for preparing an oral acyclovir-containing diffusion tablet prepared by mixing, mixing, and flavoring by weight, 1 to 20% by weight of a powder binder, 0.2 to 2.5% by weight of a lubricant, 0.5 to 10% by weight of a disintegrant, and a flavoring agent.