CN105982860A - Gualfenesin water-free deglutible odor masking granule - Google Patents

Abstract

The invention provides a guaifenesin anhydrous swallow taste-masking granule, which is formed by mixing guaifenesin-coated pellets and flavoring materials, and the guaifenesin-coated pellets are composed of pills Made by encapsulating a specific taste-masking layer and a specific smoothing layer. The guaifenesin anhydrous swallowing taste-masking granules of the present invention on the one hand cover up the bitterness and peculiar smell of the medicine, on the other hand, surprisingly, the patient can swallow it without drinking water, effectively improving medication compliance It improves the applicable population of patients, especially for children, and the test results also prove that although the granules of the present invention are packaged through a taste-masking layer and a smooth layer, the main drug guaifenesin releases rapidly in the body and Absorption, after oral administration to the gastrointestinal system, it can quickly release the drug, and the taste-masking layer and smooth layer of the package will not affect the release and absorption of the drug.

Description

Guaifenesin Anhydrous Swallow Taste-Masking Granules

technical field

The present invention relates to a guaifenesin pharmaceutical preparation, in particular, it provides a guaifenesin anhydrous swallow taste-masking granule, the patient takes the granule without water to assist smooth swallowing, and adopts anhydrous swallowing method Taking medicine belongs to the field of pharmaceutical preparations.

Background technique

Guaifenesin is 3-(2-methoxyphenoxy)propane-1,2-diol, white or off-white crystalline powder, slightly soluble in water and soluble in ethanol.

After oral administration, it stimulates the gastric mucosa, reflexively increases bronchial secretion, and dilutes sputum. It also has antiseptic and antiseptic effects. This product also has antitussive, antispasmodic, and anticonvulsant effects. It is used for chronic bronchitis with phlegm cough, lung abscess, bronchiectasis, and secondary asthma. Often used in combination with other antitussive and antiasthmatic drugs. It is used when mucus is difficult to cough up.

The main adverse reactions of the drug are nausea, dizziness, drowsiness and allergies. This product has the effect of stimulating and dilating vascular smooth muscle, so it is contraindicated in patients with pulmonary hemorrhage, acute gastroenteritis and nephritis.

The guaifenesin pharmaceutical preparations in the prior art are mainly syrups, granules and tablets. On the one hand, there are bitter and peculiar smells after taking the medicine, which affects the compliance of the medicine after taking the medicine. On the other hand, the existing oral solid preparations of guaifenesin When taking medicine, all need to drink water and carry out pharynx, for some patients who drink water inconvenience, limit the application of medicine.

At present, in the prior art of oral solid preparations, especially granules, there is no study or report on anhydrous swallowing or anhydrous swallowing of granules. Research and development of oral solid preparations for swallowing without water, especially oral granules for swallowing without water, not only expands the applicable patient population, but also greatly facilitates patients to take medicine, etc., which has important invention significance.

Contents of the invention

The purpose of the present invention is to provide a new guaifenesin pharmaceutical preparation, specifically, to provide a guaifenesin anhydrous swallow taste-masking granule, which not only effectively eliminates or masks the bitter taste and peculiar smell of the drug itself, but also makes the Surprisingly, the patient does not need to drink water to swallow the granules after oral administration, and can swallow the medicine without water.

Technical scheme of the present invention is as follows:

The invention provides a guaifenesin anhydrous swallow taste-masking granule, which is formed by mixing guaifenesin-coated pellets and flavoring materials, and is characterized in that the guaifenesin-coated pellets are made of The drug-loaded pills are made by encapsulating a taste-masking layer and a smooth layer in sequence, wherein: the taste-masking layer is composed of Eudragit E model series and optional plasticizers and/or anti-sticking agents, and the The Eudragit E model series is Eudragit E100 or Eudragit E PO, and the plasticizer and/or anti-sticking agent is selected from the group consisting of acetyl tributyl citrate, acetyl diethyl citrate, diethyl citrate Ethyl Ester, Triethyl Citrate, Oleic Acid, Dibutyl Sebacate, Glycerin, Propylene Glycol, Tween-80, Macrogol, Talc, Glyceryl Monostearate, Magnesium Stearate, Titanium Dioxide, One or more than one of calcium carbonate and magnesium oxide; the smooth layer is composed of Eudragit E model series, sodium bicarbonate, Carbomer 971PNF and other auxiliary materials optionally, wherein the Eudra The Qi E model series is Eudragit E100 or Eudragit E PO, and the other excipients are selected from glyceryl monostearate, magnesium stearate, stearic acid, titanium dioxide, talcum powder, calcium carbonate, and magnesium oxide One or more than one.

Preferably, the above-mentioned guaifenesin anhydrous swallow taste-masking granules, wherein the taste-masking layer is composed of Eudragit E100, talcum powder, triethyl citrate and magnesium stearate.

Preferably, the above-mentioned guaifenesin anhydrous swallow taste-masking granules, wherein the smooth layer is composed of Eudragit E100, sodium bicarbonate, carbomer 971PNF, talc and stearic acid.

The above-mentioned guaifenesin anhydrous swallowing taste-masking granules of the present invention, wherein the drug-loaded pills are composed of guaifenesin and optional fillers or binders, preferably the fillers or binders The mixture is selected from one or one of microcrystalline cellulose, lactose, starch, pregelatinized starch, dextrin, glucose, mannitol, povidone, hypromellose, hypromellose, and carbomer above.

Preferably, the above-mentioned guaifenesin anhydrous swallow taste-masking granules, wherein the taste-masking layer is 1.0%-33.6% by weight of the guaifenesin-coated pellets, more preferably 5.0%- 23.6%.

Preferably, the above-mentioned guaifenesin anhydrous swallowing taste-masking granules, wherein the smooth layer is 0.5%-40.7% by weight of the guaifenesin-coated pellets, more preferably 3.7%- 35.7%.

The above-mentioned guaifenesin anhydrous swallowing taste-masking granules of the present invention, wherein the flavoring material is composed of sorbitol and optional auxiliary materials, and the auxiliary materials are selected from smoothing agents, essences, and sweeteners Or glidant, preferably the auxiliary material is selected from sodium carboxymethylcellulose, hypromellose, hypromellose, carbomer, xanthan gum, fruit essence, fresh milk essence, aspartame, One or more of sucralose, cyclamate, acesulfame potassium, magnesium stearate or talc.

Preferably, the above-mentioned guaifenesin anhydrous swallowing taste-masking granules, wherein calculated in parts by weight, the anhydrous guaifenesin swallowing taste-masking granules are coated with 0.5-10 parts of guaifenesin The pellets are mixed with 0.5-10 parts of flavoring materials.

The guaifenesin anhydrous swallowing taste-masking granules of the present invention, wherein the content of guaifenesin is 0.5%-31.8%, more preferably 2.0%-21.8%.

As a specific embodiment of the present invention, the above-mentioned guaifenesin anhydrous swallow taste-masking granules, wherein the unit preparation contains the following components:

Pills: Guaifenesin 100mg, Microcrystalline Cellulose 10596.15mg, Povidone K 258.0mg;

Taste-masking layer: Eudragit E100 12.10mg, talc 22.10mg, triethyl citrate 1.0mg, magnesium stearate 1.4mg;

Smooth layer: Eudragit E100 9.0mg, carbomer 971PNF 7.2mg, sodium bicarbonate 7.2mg, talcum powder 3.7mg, stearic acid 501.8mg;

Flavoring materials: sorbitol 549mg, sodium carboxymethylcellulose 10.0mg, orange flavor 10.0mg, strawberry flavor 8.0mg, aspartame 2.0mg, magnesium stearate 3.0mg.

The above-mentioned Eudragit E100 of the present invention refers to aminoalkyl methacrylate copolymer E type (butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate (1:2 :1) copolymer), is colorless transparent or light yellow granule, has weak ammonia odor, and the commercial source is Evonik Degussa.

The above-mentioned carbomer 971PNF of the present invention refers to a high-molecular polymer of acrylic acid bonded with allyl sucrose or pentaerythritol allyl ether, a white loose powder; slightly sour, hygroscopic, and the commercial source is Lubrizol.

The above-mentioned stearic acid 50 of the present invention refers to the solid fatty acid that this strain obtains from animal and vegetable oils and fats, the main components are stearic acid (C18H36O2) and palmitic acid (C16H32O2), and this product is white or off-white Creamy powder or crystalline hard lump, the cross-section has fine needle-like crystals with slight luster; it has a slight odor similar to oil, and is tasteless. This product is soluble in chloroform or ether, soluble in ethanol, almost insoluble in water. Commodity source is BASF.

The above-mentioned povidone K25 of the present invention is a nonionic polymer compound, which refers to polyvinylpyrrolidone, a linear homopolymer synthesized by 1-vinyl-2-pyrrolidone, and the commercial source is ISP.

The above-mentioned microcrystalline cellulose 105 of the present invention refers to a uniform polymer formed by connecting D-glucopyranose groups with 1,4-β-glycosidic bonds. This product is widely used in oral medicines It is a relatively non-toxic and non-irritating substance in preparations and foods. This product is not absorbed after oral administration and has almost no potential toxicity. The source of the product is Taiwan Mingtai.

The guaifenesin anhydrous swallowing taste-masking granules of the present invention adopts the preparation form of drug-loaded granules or pellets prepared from the main drug and specific auxiliary materials, and then uses specific polymer materials to sequentially perform taste-masking film coating. Coating and coating with a smooth layer, the obtained coating pellets are mixed with a part of specific flavoring materials, and the prepared guaifenesin anhydrous swallowing taste-masking granules cover the bitter taste and peculiar smell of the medicine on the one hand, and on the other hand On the one hand, it is unexpected that the patient can swallow without drinking water, and there is no bad taste and bitter taste in the process of taking, which effectively improves the compliance of medication; it improves the applicable population of patients, especially for children. And the test results also prove that although the granules of the present invention are packaged with a taste-masking layer and a smooth layer, the main drug guaifenesin is rapidly released and absorbed in the body, and can be rapidly released after oral administration to the gastrointestinal system. The taste-masking and smoothing layers do not affect drug release and absorption.

Description of drawings

Figure 1: Release rate of guaifenesin anhydrous swallowed taste-masking granules in 0.01mol/L HCl vehicle in Example 1

Figure 2: Test for the influence of the weight increase of the taste-masking layer on the release rate

Figure 3: Test for the influence of the weight gain of the smooth layer on the release rate

detailed description

The following examples are for explaining or illustrating the technical solutions of the present invention, which do not limit the protection scope of this patent.

Example 1: Guaifenesin Anhydrous Swallowing Taste-Masking Granules

The composition of the guaifenesin anhydrous swallow taste-masking granule unit preparation is as follows:

Composition list:

making process:

The drug-loaded pills are prepared by extrusion and spheronization. The drug-loaded pills are respectively covered with a taste-masking layer and a smooth layer. Each layer is packaged in a fluidized bed, and the coated pellets are mixed with flavoring materials to make a semi-finished product. Concrete preparation process is as follows:

1. Preparation of loaded pills:

The drug-loaded pellets are prepared by extrusion and spheronization.

1.1 Preparation of the adhesive: the prescription amount of povidone K25 was prepared into an aqueous solution with a concentration of 15% (w/w) for later use.

1.2 Preparation of soft materials: Put the prescribed amount of microcrystalline cellulose 105 and guaifenesin into the wet granulator, turn on the granulator and stir evenly, and add the bonding agent by pouring while the material is stirring. After the addition is completed, when the granulator is running, add an appropriate amount of purified water and continue stirring for a certain period of time to obtain a soft material.

1.3 Extrusion of soft materials: use 0.5mm extrusion screen to extrude the materials to obtain extrudates of suitable length.

1.4 Shot blasting: When the shot blasting machine is running, add extrudates, and the speed of the shot blasting machine follows the principle of slow first and then fast to throw the pellets, and run for a certain period of time to obtain the required pellets.

1.5 Drying: The fluidized bed is used to dry the pellets, the temperature of the material is controlled at 40°C, the water content of the pellets is controlled at 2-4%, and the pellets between 35 and 50 meshes are collected.

2. Packing of taste-masking layer

2.1 Preparation of taste-masking layer solution:

Mix an appropriate amount of ethanol and water to prepare an alcohol-water solvent, take 50% of the above solvent to dissolve Eudragit E100, and the remaining 50% of the solvent to disperse the rest of the prescription, and finally add the dispersion to the Eudragit solution in a stirring state , and stirred for 20 min to form the final solution.

2.2 Packing of taste-masking layer:

The coating of the taste-masking layer is carried out in a fluidized bed, and the coating process controls the material temperature at 30±5°C.

3. Packing of smooth layer:

3.1 Preparation of smooth layer solution:

Dissolve Eudragit E100 in 50% ethanol, add other components in the prescription to the remaining 50% ethanol to form a colloidal suspension, add the colloidal suspension to the Eudragit E100 solution in a stirring state, and finally use a uniform Homogenize with a pulper for 45 minutes to form the final solution.

3.2 Packaging of smooth layer:

The coating of the taste-masking layer is carried out in a fluidized bed, and the temperature of the material is controlled at 30±5°C during the coating process according to the properties of the material.

4. Mixing of flavoring materials:

The coated pellets prepared above are mixed with the flavoring material to obtain the anhydrous swallowing taste-masking guaifenesin granules.

Preparation effect evaluation: dissolution rate, mouthfeel, anhydrous swallowing effect. The results are shown in the table below.

The degree of release in water in table 1 is as follows

In order to simulate the drug release rate of the drug in the oral cavity, the release rate in water will be tested to evaluate the taste-masking effect of the drug in the oral cavity. The results show that the release rate of the drug in water is 2.7% in 5 minutes, and there is almost no drug release. Volunteers in good health tested the drug and found that the drug did not taste bitter or peculiar in the oral cavity for 5 minutes, and all reported a cool and light feeling in the oral cavity after taking the drug, which shows that the effect of masking the bad taste of the drug has been achieved.

Swallowing effect without water: the blank coated pellets were mixed to make the final preparation. After oral administration by volunteers, 90% of the volunteers could swallow smoothly within 1 minute under the condition of swallowing without water. 10% of the volunteers finished swallowing the drug within 1.5 minutes. Since the coated pellets formed a smooth layer after contacting saliva, and the sorbitol in the flavoring material helped the secretion of saliva, a certain smooth effect was achieved. The effect meets the drug quality requirements.

Table 2 Release in 0.01mol/L HCl

The results showed that the drug was released rapidly in acid, meeting the requirement of rapid onset of effect after oral administration.

Example 2: Guaifenesin Anhydrous Swallowing Taste-Masked Granules

1. Prescription composition and preparation process parameters of drug-loaded pills:

2. The preparation and packaging process of the taste-masking layer solution

3. The preparation and packaging process of the smooth layer solution

4. Experiments on the influence of weight gain of each layer on release rate:

(1) Test of influence of taste-masking layer weight increase on release rate: the results are shown in Table 3-4 and Figure 2

1.1 Release in water: See Table 3 for the results.

Table 3 Release degree in water

The results show that the sample with a weight gain of 7.3% in the taste-masking layer, the release rate in water exceeds the limit requirement due to the thin coating film, and the other samples with weight gain meet the limit requirement.

1.2 Release in acid: See Table 4 and Figure 2 for the results.

Table 4 Release in acid

Analysis of the results: The taste-masking layer has no effect on the release rate within the investigated range.

(2) Investigation test on the influence of smooth layer weight gain on release rate: the results are as follows in Table 5 and Figure 3

1.3 Release rate of smooth layer pellets in acid: see Table 5 and Figure 3 for the results.

Table 5 Effect of weight gain of smooth layer on release rate

The results showed that within the range investigated, the increase in the weight of the smooth layer had no significant effect on the release rate in acid.

Claims (10)

1. a guaifenesin is anhydrous swallows taste masked particle, mixed by guaifenesin coated micropill and taste masking material, it is characterized in that described guaifenesin coated micropill is sequentially passed through by medicine carrying ball to pack taste mask layer and smooth layer and make, wherein: described taste mask layer is made up of especially strange E range of models and plasticizer and/or the antiplastering aid being optionally present, described especially strange E range of models is especially strange E100 or especially strange E PO, described plasticizer and/or antiplastering aid are selected from tributyl 2-acetylcitrate, acetyl tributyl citrate diethylester, citric acid diethylester, triethyl citrate, oleic acid, dibutyl sebacate, glycerol, propylene glycol, tween 80, Polyethylene Glycol, Pulvis Talci, glyceryl monostearate, magnesium stearate, titanium dioxide, calcium carbonate, in magnesium oxide one or more；Described smooth layer is by especially strange E range of models, sodium bicarbonate, Carbomer971 PNF forms with being optionally present other adjuvants, wherein said especially strange E range of models is especially strange E100 or especially strange E PO, and other described adjuvants are selected from glyceryl monostearate, magnesium stearate, stearic acid, titanium dioxide, Pulvis Talci, calcium carbonate, magnesium oxide one or more.

The anhydrous taste masked particle of swallowing of guaifenesin the most according to claim 1, wherein said taste mask layer is made up of especially strange E100, Pulvis Talci, triethyl citrate and magnesium stearate.

3., according to the anhydrous taste masked particle of swallowing of the guaifenesin described in claim 1-2, wherein said smooth layer is made up of especially strange E100, sodium bicarbonate, Carbomer971 PNF, Pulvis Talci and stearic acid.

4. swallow taste masked particle according to the guaifenesin described in claim 1-3 is anhydrous, wherein said medicine carrying ball is made up of guaifenesin and filler or the binding agent being optionally present, and preferably described filler or binding agent are selected from microcrystalline Cellulose, lactose, starch, pregelatinized Starch, dextrin, glucose, mannitol, polyvidone , hypromellose, hydroxypropylcellulose, in carbomer one or more.

5., according to the anhydrous taste masked particle of swallowing of the guaifenesin described in claim 1-4, wherein said taste mask layer is the 1.0%～33.6% of guaifenesin coated micropill percentage by weight, more preferably 5.0%～23.6%.

6., according to the anhydrous taste masked particle of swallowing of the guaifenesin described in claim 1-5, wherein said smooth layer is the 0.5%～40.7% of guaifenesin coated micropill percentage by weight, more preferably 3.7%～35.7%.

7. swallow taste masked particle according to the guaifenesin described in claim 1-6 is anhydrous, wherein said taste masking material is made up of sorbitol and the adjuvant being optionally present, described adjuvant selected from smooth dose, essence, sweeting agent or fluidizer, preferably described adjuvant is sweet selected from sodium carboxymethyl cellulose, hypromellose, hydroxypropylcellulose, carbomer, xanthan gum, fruit essence, fresh milk essence, aspa, in sucralose, cyclamate, acesulfame-K, magnesium stearate or Pulvis Talci one or more.

8. swallowing taste masked particle according to the guaifenesin described in claim 1-7 is anhydrous, calculate the most by weight, the anhydrous taste masked particle of swallowing of described guaifenesin is mixed by 0.5～10 part of guaifenesin coated micropill and 0.5～10 part of taste masking material.

9. swallowing taste masked particle according to the guaifenesin described in claim 1-8 is anhydrous, wherein guaifenesin content is 0.5%～31.8%, more preferably 2.0%～21.8%.

10. swallow taste masked particle according to the guaifenesin described in claim 1-9 is anhydrous, wherein in unit formulation, containing following component:

(1) medicine carrying ball: guaifenesin 100mg, microcrystalline Cellulose 105 96.15mg, 30 POVIDONE K 30 BP/USP 25 8.0mg；

(2) taste mask layer: especially strange E100 12.10mg, Pulvis Talci 22.10mg, triethyl citrate 1.0mg, magnesium stearate 1.4mg；

(3) smooth layer: especially strange E100 9.0mg, Carbomer971 PNF 7.2mg, sodium bicarbonate 7.2mg, Pulvis Talci 3.7mg, stearic acid 50 1.8mg；

(4) taste masking material: sorbitol 549mg, sodium carboxymethyl cellulose 10.0mg, Fructus Citri tangerinae essence 10.0mg, strawberry essence 8.0mg, Aspartane 2.0mg, magnesium stearate 3.0mg.