CN101716162B - Aminophylline slow-release capsules and preparation method thereof - Google Patents

Abstract

The invention discloses aminophylline slow-release capsules, which comprise the following components in percentage by weight: 45 to 60 percent of aminophylline, 10 to 20 percent of adhesive, 0.3 to 2 percent of flow aid, 18 to 25 percent of coating material and 7 to 13 percent of porogenic agent. The invention also discloses a preparation method for the aminophylline slow-release capsules. The aminophylline slow-release capsules of the invention greatly improve the defects that the oral aminophylline formulation has poor mouthfeel, poor compliance and low bioavailability. In the method, the aminophylline is prepared into tablets; the aminophylline tablets are prepared into slow-release tablets by adopting a fluidized bed coating method; and then the slow-release tablets are filled into capsules so as to prepare the aminophylline slow-release capsules. The preparation method has simple operation and good repeatability, is easy to implement mass production, and achieves the aim of exerting the therapeutic effect better by optimizing the proportion of the coating material and the porogenic agent to control the slow release of the aminophylline in vivo.

Description

A kind of aminophylline slow releasing capsule and preparation method thereof

Technical field

The invention belongs to medical technical field, be specifically related to a kind of aminophylline slow releasing capsule and preparation method thereof.

Background technology

The aminophylline bronchial smooth muscle that can relax alleviates the hyperemia and the edema of bronchial mucosa, is at present unique have bronchiectasis and suppressing panting calming medicine that alleviates the airway inflammation double effect.Aminophylline is widely used in bronchial asthma and chronic obstructive respiratory tract disease with its definite curative effect and cheap price.Common Truphylline needs oral three times every day, medication influence sleep at night, and also aminophylline treatment blood drug level scope is narrow; The blood drug level scope is 10～20ug/mL; Its bioavailability is relevant with elimination speed in vivo, and individual variation is bigger, and is subject to influence of various factors such as physiology, pathology, drug combination; It is improper that dosage is grasped; Be prone to make curative effect not show or produce and poison, blood drug level is prone to " peak valley " phenomenon after the frequent drug administration, causes headache, feels sick, vomiting, dizzy, insomnia, anticardium pain, generates heat, palpitates quickly, knots and side effect such as allergy.And as suppressing panting calming medicine, the aminophylline suction that can not atomize, route of administration is main with oral and intravenously administrable, reason is bigger in its zest, the few at present usefulness of intramuscular injection and rectally.

A kind of Aminophylline dropping pill and preparation technology thereof with antiasthmatic effect disclosed in patent (publication number CN1813755A); The quick release of this dosage form; Easy to carry, preparation process is simple, but owing to the reason of dosage form; Need repeatedly volume to take, just can keep certain blood drug level to reach therapeutic purposes.A kind of Aminophylline oral solution and preparation method thereof is disclosed in patent (publication number CN101361742A); This solution good mouthfeel, steady quality, but by conventional morning, noon and afternoon 3 administrations; Concentration differs bigger round the clock; Night, blood drug level will drop to below the effect level, made curative effect not good enough, had certain limitation.The blood level that granule and pilule also are difficult to remain on interior curative effect concentration is released in slow (control) of some aminophyllines of being sold on the market simultaneously.

Summary of the invention

Technical problem to be solved by this invention provides a kind of aminophylline slow releasing capsule, and is poor to improve oral absorption, the defective that bioavailability is low.

The technical problem that the present invention also will solve provides the method for preparing of above-mentioned aminophylline slow releasing capsule.

Following for solving the problems of the technologies described above the technical scheme that the present invention adopts:

A kind of aminophylline slow releasing capsule, it comprises following components in weight percentage: aminophylline 45～60%, adhesive 10～20%, fluidizer 0.3～2%, coating material 18～25%, porogen 7～13%.

Through regulating the consumption proportion of adhesive, fluidizer, porogen and coating material in the prescription; Carry out the dissolution rate in vitro test and confirm that above composition can effectively delay aminophylline at the intravital release of people, absorption, distribution, metabolism and discharge process, but the blood drug level long period remains within the valid density scope.As write out a prescription proportioning not in above scope, can not guarantee the rate of releasing drug in the unit interval, and blood concentration fluctuation is bigger.

Above-mentioned aminophylline slow releasing capsule preferably includes following components in weight percentage: aminophylline 50～55%, adhesive 13～16%, fluidizer 0.5～1%, coating material 20～25%, porogen 7～10%.

Wherein, described adhesive is the mixture of any one or two or more arbitrary proportions in hydroxypropyl emthylcellulose, pregelatinized Starch, carbopol, dextrin, microcrystalline Cellulose, Icing Sugar and the sodium carboxymethyl cellulose.Described adhesive is preferably hydroxypropyl emthylcellulose or sodium carboxymethyl cellulose.

Wherein, described fluidizer is the mixture of any one or two or more arbitrary proportions in magnesium stearate, micropowder silica gel and the Pulvis Talci.Described fluidizer is preferably magnesium stearate or micropowder silica gel.

Wherein, described coating material is the mixture of any one or two or more arbitrary proportions in ethyl cellulose, Eudragit RL100, Eudragit RS 100 and the Opadry.Described coating material is preferably ethyl cellulose.

Wherein, described porogen is the mixture of any one or two or more arbitrary proportions in PEG1540, Eudragit L or the polysorbate 20.Described porogen is preferably PEG1540 and polysorbate 20.

The method for preparing of above-mentioned aminophylline slow releasing capsule comprises the steps:

(1) take by weighing the aminophylline and the adhesive of formula ratio, add the wetting agent mix homogeneously and process soft material, 20 mesh sieves are granulated, 50～60 ℃ of oven dry;

(2) the dried granule that step (1) is obtained adds the fluidizer of formula ratio, and mixing also is pressed into diameter 1～3mm medicated core sheet;

(3) take by weighing the coating material of formula ratio, add the porogen and the dissolution with solvents of formula ratio;

(4) the medicated core sheet to step (2) gained carries out fluidized coating with the coating solution that step (3) makes, and makes coated pellets;

(5) coated pellets of step (4) gained is carried out the drying plasticizing and promptly get aminophylline slow release microplate, filling capsule can get the aminophylline slow releasing capsule.

In the step (1), described wetting agent is the mixture of any one or two kinds of arbitrary proportions in water and the ethanol, and the addition of wetting agent is 8～12%, preferred 10% of aminophylline and an adhesive gross weight.

In the step (3), described solvent is the mixture of any one or two kinds of arbitrary proportions in isopropyl alcohol and the acetone, and the addition of solvent is 3～7%, preferred 5% of coating material and a porogen gross weight.

In the step (4), described fluidized coating, its condition is: 40～50 ℃ of EATs, intake 1.5～2.5g/min, hydrojet speed 1.0～4.0g/min.

In the step (5), described dry plasticizing, its condition is: put the interior plasticizing of 40～50 ℃ of baking ovens 6～12 hours.

Beneficial effect: it is poor that aminophylline slow releasing capsule of the present invention has been improved Aminophylline oral dosage form mouthfeel greatly, poor compliance, the deficiency that bioavailability is low.Aminophylline is processed small pieces; Adopt fluidized bed coating that the aminophylline small pieces are processed the slow release small pieces, and filling capsule, make the aminophylline slow releasing capsule; Simple to operate, favorable reproducibility; Be easy to realize mass production, and control slowly release in the aminophylline body, reach the purpose of better performance curative effect through the proportioning of optimizing coating material and porogen.

The specific embodiment

According to following embodiment, can understand the present invention better.Yet, those skilled in the art will readily understand that the described concrete material proportion of embodiment, process conditions and result thereof only are used to explain the present invention, and the present invention that should also can not limit in claims to be described in detail.

Experimental facilities and raw material sources that following examples adopted are following:

Aminophylline: Yangzhou Zhongbao Pharmaceutical Co., Ltd.;

Fluidized-bed coating machine: Changzhou good granulation drying equipment company limited;

All the other reagent materials are conventional commercially available prod.

Embodiment 1:

A kind of aminophylline slow releasing capsule comprises following components in weight percentage:

Aminophylline 50%,

Sodium carboxymethyl cellulose 18%,

Magnesium stearate 0.5%,

Ethyl cellulose 20%,

Polyethylene Glycol (PEG1540) 11.5%.

Production method is following:

(1) take by weighing aminophylline and sodium carboxymethyl cellulose, the water mix homogeneously that adds its gross weight 10% (w/w) is processed soft material, and 20 mesh sieves are granulated, 60 ℃ of oven dry;

(2) be pressed into diameter 2mm medicated core sheet behind the adding magnesium stearate mixing;

(3) take by weighing ethyl cellulose and Polyethylene Glycol, the acetone solution that adds its gross weight 5% (w/w) is as coating solution;

(4) utilize step (3) gained coating solution to carry out fluidized bed coating to step (2) gained aminophylline medicated core sheet, 50 ℃ of EATs, intake 2g/min, hydrojet speed 3.0g/min makes coated pellets;

(5) step (4) gained coated pellets is placed in 45 ℃ of baking ovens plasticizing filling capsule after 12 hours, make the aminophylline slow releasing capsule.

Embodiment 2:

A kind of aminophylline slow releasing capsule comprises following components in weight percentage:

Aminophylline 48%,

Hydroxypropyl emthylcellulose 17%,

Pulvis Talci 0.5%,

Eudragit?RS?100 25％，

Polysorbate 20 9.5%.

Production method is following:

(1) take by weighing aminophylline and hydroxypropyl emthylcellulose, the water mix homogeneously that adds its gross weight 10% (w/w) is processed soft material, and 20 mesh sieves are granulated, 60 ℃ of oven dry;

(2) be pressed into diameter 2mm medicated core sheet behind the adding Pulvis Talci mixing;

(3) take by weighing Eudragit RS 100 and polysorbate 20, the isopropyl alcohol dissolving that adds its gross weight 5% (w/w) is as coating solution;

(4) utilize step (3) gained coating solution to carry out fluidized bed coating to step (2) gained aminophylline medicated core sheet, 50 ℃ of EATs, intake 2g/min, hydrojet speed 3.0g/min makes coated pellets;

(5) step (4) gained coated tablet is placed in 45 ℃ of baking ovens plasticizing filling capsule after 12 hours, make the aminophylline slow releasing capsule.

Embodiment 3:

A kind of aminophylline slow releasing capsule comprises following components in weight percentage:

Aminophylline 55%,

Carbopol 15%,

Micropowder silica gel 0.8%,

Eudragit?RL100 21.2％，

Polysorbate 20 8%.

Production method is following:

(1) take by weighing aminophylline and carbopol, the water mix homogeneously that adds its gross weight 10% (w/w) is processed soft material, and 20 mesh sieves are granulated, 60 ℃ of oven dry;

(2) be pressed into diameter 2mm medicated core sheet behind the adding micropowder silica gel mixing;

(3) take by weighing Eudragit RL100 and polysorbate 20, the isopropyl alcohol dissolving that adds its gross weight 5% (w/w) is as coating solution;

(4) utilize step (3) gained coating solution to carry out fluidized bed coating to step (2) gained aminophylline medicated core sheet, 45 ℃ of EATs, intake 2.5g/min, hydrojet speed 2.0g/min makes coated pellets;

(5) step (4) gained coated pellets is placed in 50 ℃ of baking ovens plasticizing filling capsule after 10 hours, make the aminophylline slow releasing capsule.

Embodiment 4: in vivo test.

Using body weight is 5 of 12～15kg Canis familiaris L.s; Fasting 24h before the administration; Feed each 1 of the slow releasing preparation that embodiment 1,2,3 makes respectively with 100ml water; 1 of the capsule of 1 of commercially available aminophylline slow releasing tablet and the fill of aminophylline powder, regularly (1～24h) from the jugular vein blood sampling, measures blood drug level with fluorescent immune method.Pharmacokinetic parameter is following:

Comparison sheet medium power mathematic(al) parameter can be found out: preparation A, B, C and E absorb in vivo all about 100%; Relatively there is not significant difference between its AUC; Four groups of extent of drug absorption are suitable; The degree of absorption of preparation A, B, C is higher than preparation D, and onset is faster, and their treatment concentration persistent period are longer simultaneously.In a word, the prepared preparation of embodiment not only has slow releasing function but also have the high characteristics of bioavailability in vivo.

Claims (9)

1. aminophylline slow releasing capsule is characterized in that its capsule 's content is made up of following components in weight percentage: aminophylline 45～60%, adhesive 10～20%, fluidizer 0.3～2%, coating material 18～25%, porogen 7～13%.

2. aminophylline slow releasing capsule according to claim 1 is characterized in that described adhesive is the mixture of any one or two or more arbitrary proportions in hydroxypropyl emthylcellulose, pregelatinized Starch, carbopol, dextrin, microcrystalline Cellulose, Icing Sugar and the sodium carboxymethyl cellulose.

3. aminophylline slow releasing capsule according to claim 1 is characterized in that described fluidizer is the mixture of any one or two or more arbitrary proportions in magnesium stearate, micropowder silica gel and the Pulvis Talci.

4. aminophylline slow releasing capsule according to claim 1 is characterized in that described coating material is the mixture of any one or two or more arbitrary proportions among ethyl cellulose, acrylic resin RL 100 and the acrylic resin RS 100.

5. the method for preparing of the described aminophylline slow releasing capsule of claim 1 is characterized in that this method comprises the steps:

(1) take by weighing the aminophylline and the adhesive of formula ratio, add the wetting agent mix homogeneously and process soft material, 20 mesh sieves are granulated, 50～60 ℃ of oven dry;

(2) the dried granule that step (1) is obtained adds the fluidizer of formula ratio, and mixing also is pressed into diameter 1～3mm medicated core sheet;

(3) take by weighing the coating material of formula ratio, add the porogen and the dissolution with solvents of formula ratio;

(4) the medicated core sheet to step (2) gained carries out fluidized coating with the coating solution that step (3) makes, and makes coated pellets;

(5) coated pellets of step (4) gained is carried out the drying plasticizing and promptly get aminophylline slow release microplate, filling capsule can get the aminophylline slow releasing capsule.

6. the method for preparing of aminophylline slow releasing capsule according to claim 5; It is characterized in that in the step (1); Described wetting agent is the mixture of any one or two kinds of arbitrary proportions in water and the ethanol, and the addition of wetting agent is 8～12% of aminophylline and an adhesive gross weight.

7. the method for preparing of aminophylline slow releasing capsule according to claim 5; It is characterized in that in the step (3); Described solvent is the mixture of any one or two kinds of arbitrary proportions in isopropyl alcohol and the acetone, and the addition of solvent is 3～7% of coating material and a porogen gross weight.

8. the method for preparing of aminophylline slow releasing capsule according to claim 5 is characterized in that in the step (4), described fluidized coating, and its condition is: 40～50 ℃ of EATs, intake 1.5～2.5g/min, hydrojet speed 1.0～4.0g/min.

9. the method for preparing of aminophylline slow releasing capsule according to claim 5 is characterized in that in the step (5), described dry plasticizing, and its condition is: put the interior plasticizing of 40～50 ℃ of baking ovens 6～12 hours.