CN103040828A

CN103040828A - Compound diphenoxylate tablet and preparation method thereof

Info

Publication number: CN103040828A
Application number: CN2013100038714A
Authority: CN
Inventors: 王苏南; 汤金春
Original assignee: CHANGZHOU KANGPU PHARMACEUTICAL Co Ltd
Current assignee: CHANGZHOU KANGPU PHARMACEUTICAL Co Ltd
Priority date: 2013-01-07
Filing date: 2013-01-07
Publication date: 2013-04-17
Anticipated expiration: 2033-01-07
Also published as: CN103040828B

Abstract

The invention relates to a preparation prescription and a technology of a compound diphenoxylate tablet. Every ten thousand compound diphenoxylate tablets comprise the following raw and auxiliary materials: 25g of diphenoxylate hydrochloride, 0.25g of atropine sulphate, 152-168g of starch, 522.5-577.5g of lactose, 47.5-52.5g of calcium hydrogen phosphate, 76g-84g 40 percent (ml/ml) of ethanol and 6.65-7.35g of magnesium stearate. The compound diphenoxylate tablet has better dissolution rate and content homogeneity.

Description

R-1132 and preparation method thereof

Technical field

The present invention relates to R-1132 and preparation method thereof.

Background technology

Every hydrochloric diphenoxylate 2.5mg of R-1132, atropine sulfate 25 μ g are used for acute and chronic functional diarrhea and chronic enteritis.Diphenoxylate can directly act on intestinal smooth muscle, by suppressing the intestinal mucosa sensor, eliminate the wriggling reflection of local mucosa and weaken enterokinesia, the segmental that can increase intestinal is simultaneously shunk, make intestinal contents pass through to postpone, being conducive to the absorption of enteral moisture, showing stronger anti-diarrhea effect, is the functional diarrhea specific drug.But existing R-1132 dissolution difference is poor large, and ordinary tablet is also often larger less than 80%, A+1.8S, because principal agent atropine content is low, uniformity of dosage units is undesirable.

Summary of the invention

The present invention will solve the existing technical problem that the R-1132 dissolution is little, uniformity of dosage units is undesirable.

R-1132 provided by the invention write out a prescription per ten thousand Central Plains supplementary product kinds and consumption: diphenoxylate hydrochloride 25g, atropine sulfate 0.25g, starch 152-168g, lactose 522.5-577.5g, calcium hydrogen phosphate 47.5-52.5g, 40%(ml/ml) ethanol 76-84g, magnesium stearate 6.65-7.35g.

As preferred R-1132 of the present invention write out a prescription per ten thousand Central Plains supplementary product kinds and consumption: diphenoxylate hydrochloride 25g, atropine sulfate 0.25g, starch 160g, lactose 550g, calcium hydrogen phosphate 50g, 40%(ml/ml) ethanol 80g, magnesium stearate 7g.

The present invention also provides a kind of preparation method of R-1132, comprises the following steps:

1, supplementary material is pulverized, is sieved;

2, supplementary material weighing, mixing:

In prescription, measure few (≤total amount 5%) because of former medicine (diphenoxylate hydrochloride), adopt in operation the equivalent dilution method that progressively increases to carry out.Operate as follows: take by weighing first starch and former medicine mixed diluting with the diphenoxylate hydrochloride equal weight, sieve, the starch that takes by weighing again the mixture equal weight mixes with it, sieves, and obtains the principal agent material mixture of mix homogeneously; Take by weighing lactose, calcium hydrogen phosphate and remaining starch;

Take by weighing atropine sulfate, it is dissolved in 40% ethanol (ml/ml);

3, granulate: load weighted diphenoxylate hydrochloride, lactose, calcium hydrogen phosphate and remaining starch have been mixed in the principal agent material by material, in the input mixer-granulator, be dry mixed first 10～15 minutes, 40% ethanol (ml/ml) that is dissolved with atropine sulfate that the property adding prepares again, wet mixing 5～10 minutes, start at a high speed and granulate, the cutter rotating speed is controlled to be 10 ~ 12Hz and makes wet granular;

4, drying; The wet granular of making is added in the feed hopper of HighefficientFluidbeddrier by material, and inlet temperature is controlled at about 80 ℃, about 45 ℃ of leaving air temp controls.Be controlled to be 5～10 minutes drying time, granule to be dried is confirmed dry good (moisture control 3% ~ 5%).Stopped heating, cooling.Discharging when treating 37 ℃ of left and right sides of drop temperature.

5, granulate: the Fast granulate machine granulate of the granule after will drying, select the cylinder screen cloth, 16 ~ 18 orders.

6, total mixed: as the granule behind each material granulate is contained on the elevator is fed in the three-dimensional motion mixer, and drop into load weighted lubricant magnesium stearate and mix and mixed in 10～15 minutes;

7, tabletting;

8, packing.

The technique effect of R-1132 of the present invention is: have preferably dissolution and content uniformity.

The specific embodiment

Embodiment 1 R-1132 prescription

Table 1

The preparation of embodiment 2 R-1132s

1, supplementary material is pulverized, sieved: the pulverizing of supplementary material is finished by omnipotent high speed disintegrator; Sieve and use shaking screen.The requirements such as crude drug diphenoxylate hydrochloride and supplementary product starch, magnesium stearate, calcium hydrogen phosphate were sieved 80 mesh sieves with vortex oscillation; The lactose adjuvant requires with sieving 80 mesh sieves with vortex oscillation after the omnipotent high speed disintegrator pulverizing;

2, weighing: the supplementary product starch that takes by weighing first with the diphenoxylate hydrochloride equal weight is fed into mixed diluting in the container with former medicine, crosses 80 mesh sieves, and the starch that takes by weighing again the mixture equal weight mixes with it, crosses 80 mesh sieves, obtains the mixture of mix homogeneously;

Take by weighing again the adjuvant of other ormal weight: lactose, calcium hydrogen phosphate and remaining starch;

Minimum because of the atropine sulfate amount, be dissolved in 40% ethanol it for subsequent use;

3, granulate: load weighted every material supplementary material is dropped in the efficient wet granulator by material, build cover, start anchor type stirring paddle, be dry mixed first 10～15 minutes, again the dissolving for preparing of property adding 40% ethanol of atropine sulfate, wet mixing 5～10 minutes is started at a high speed and is granulated, the cutter rotating speed is controlled to be 10 ~ 12Hz, makes suitable wet granular;

4, drying: the wet granular of making is added in the feed hopper of HighefficientFluidbeddrier by material, and inlet temperature is controlled at about 80 ℃, about 45 ℃ of leaving air temp controls.Be controlled to be 5～10 minutes drying time, granule to be dried is confirmed dry good (moisture control is 3% ~ 5%).Stopped heating, cooling.Discharging when treating 37 ℃ of left and right sides of drop temperature;

5, granulate: the Fast granulate machine granulate of the granule after will drying, select cylinder (16 ~ 18 order);

6, total mixed: as the granule behind each material granulate is contained on the elevator is fed in the three-dimensional motion mixer, and drop into load weighted lubricant magnesium stearate and mixed 10～15 minutes;

7, tabletting;

8, packing.

Embodiment 3 is according to the item inspection of the R-1132 of the prescription of embodiment 1 and the preparation of embodiment 2 methods

Dissolution: dissolution medium: the aqueous acetic acid that contains 0.2mol/L; Operative installations 1, rotating speed 150rpm, 45 minutes time, detection method: mobile phase: acetonitrile: potassium dihydrogen phosphate (65:35), standard solution: compound concentration is the solution of the diphenoxylate hydrochloride standard substance of 250ug/ml, is settled to 500ml with dissolution medium, filter chromatographic system; The 210nm wavelength detecting, L11 packed column (3.9mm*30mm), flow velocity: 1.0ml/ minute, standard solution sample introduction, record chromatogram, tailing factor must not surpass 1.5, relative standard deviation must not cross 2.0%, with standard solution and product to be tested difference sample introduction, sample size 50ul, the record chromatogram, dissolution must not be lower than the 75%(of labelled amount with reference to American Pharmacopeia method 34 editions in 45 minutes).

Outward appearance, uniformity of dosage units: press 2010 editions checks of Chinese Pharmacopoeia

Table 2

Table 2 result shows that the present invention selects the adjuvant of specific proportioning can make the gained tablet obtain desirable outward appearance, dissolution and uniformity of dosage units.

Comparative Examples 1 is pressed table 3 and is changed the R-1132 prescription, prepares R-1132 according to embodiment 2 methods, carries out item inspection according to embodiment 3 methods

Table 3

Table 3 is the result show: contrast prescription 1 is compared with the prescription 2 in the table 1, adopts 42%(ml/ml) ethanol, the tablet hardness of extrusion bad (being about 15N), easy loose sheet, friability 1.8%.

Contrast 2 is compared with the prescription 2 in the table 1, adopts 38%(ml/ml) ethanol, the gained tablet hardness is excessive, and is bright and clean not, and dissolution descends, and average dissolution is 82%.

Contrast prescription 3 is compared with prescription 1, changes lactose into sucrose, and gained tablet not only outer light is bright and clean not, and the disintegrate difficulty, and dissolution only is 76%.

Hence one can see that, the present invention is directed to ethanol that per ten thousand diphenoxylate hydrochloride 25g, atropine sulfate 0.25g select certain concentration as binding agent and select starch, lactose, calcium hydrogen phosphate can obtain desirable slice, thin piece outward appearance, desirable dissolution and uniformity of dosage units as filler gained tablet.

Comparative Examples 2 is pressed the R-1132 prescription of table 1, prepares by the following method R-1132, carries out item inspection according to embodiment 3 methods

1, supplementary material is pulverized, is sieved; (with embodiment 2)

2, weighing: the supplementary product starch and diphenoxylate hydrochloride, the atropine sulfate that take by weighing first with diphenoxylate hydrochloride, atropine sulfate gross weight equal weight are fed into mixed diluting in the container, cross 80 mesh sieves, the starch that takes by weighing again the mixture equal weight mixes with it, cross 80 mesh sieves, obtain the mixture of mix homogeneously; Take by weighing again the adjuvant of other ormal weight: lactose, calcium hydrogen phosphate and remaining starch;

3, granulate: load weighted every material supplementary material is dropped in the efficient wet granulator by material, build cover, start anchor type stirring paddle, be dry mixed first 10～15 minutes, property adding 40% ethanol again, wet mixing 5～10 minutes is started at a high speed and is granulated, the cutter rotating speed is controlled to be 10 ~ 12Hz, makes suitable wet granular; 4 ~ 8(is with embodiment 2)

Namely this preparation technology compares the same diphenoxylate hydrochloride of adding mode of atropine sulfate with embodiment 2, but not adds after being dissolved in 40% ethanol.Gained tablet content homogeneity A+1.8S, such as table 4, data show, because atropine content in this prescription is low, every content adopts directly to add hybrid mode at 0.03mg, is difficult to mix homogeneously.

Table 4

Take above-mentioned foundation desirable embodiment of the present invention as enlightenment, by above-mentioned description, associated production personnel can in the scope that does not depart from this invention technological thought, carry out various change and modification fully.The technical scope of this invention is not limited to the content on the description, must determine its technical scope according to the claim scope.

Claims

1. R-1132, per ten thousand Central Plains supplementary product kinds and consumption in the prescription: diphenoxylate hydrochloride 25g, atropine sulfate 0.25g, starch 152-168g, lactose 522.5-577.5g, calcium hydrogen phosphate 47.5-52.5g, 40%(ml/ml) ethanol 76-84g, magnesium stearate 6.65-7.35g.

2. R-1132 claimed in claim 1, its feature with, write out a prescription per ten thousand Central Plains supplementary product kinds and consumption: diphenoxylate hydrochloride 25g, atropine sulfate 0.25g, starch 160g, lactose 550g, calcium hydrogen phosphate 50g, 40%(ml/ml) ethanol 80g, magnesium stearate 7g.

3. a preparation method for preparing claim 1 or 2 R-1132s comprises the following steps:

(1) supplementary material is pulverized, is sieved;

(2) supplementary material weighing, mixing:

Take by weighing first starch and former medicine mixed diluting with the diphenoxylate hydrochloride equal weight, sieve, take by weighing again mixture and equate

The starch of weight mixes with it, sieves, and obtains the principal agent material of mix homogeneously.

Take by weighing lactose, calcium hydrogen phosphate and remaining starch;

Take by weighing atropine sulfate, it is dissolved in 40% ethanol (ml/ml);

(3) granulate: load weighted lactose, calcium hydrogen phosphate and remaining starch are added mixed in the principal agent material, in the input mixer-granulator, be dry mixed first 10～15 minutes, 40% ethanol (ml/ml) that is dissolved with atropine sulfate that the property adding prepares again, wet mixing 5～10 minutes, start at a high speed and granulate, the cutter rotating speed is controlled to be 10 ~ 12Hz, makes wet granular;

(4) drying; The wet granular of making is added in the feed hopper of HighefficientFluidbeddrier by material, and inlet temperature is controlled at about 80 ℃, about 45 ℃ of leaving air temp controls.Be controlled to be 5～10 minutes drying time, granule to be dried is confirmed dry good (moisture control is 3% ~ 5%), stopped heating, cooling.Discharging when treating 37 ℃ of drop temperatures.

(5) granulate: the Fast granulate machine granulate of the granule after will drying, select the cylinder screen cloth, sieve number 16 ~ 18 orders.(6) always mix: the granule behind each material granulate is contained on the elevator drops in the three-dimensional motion mixer, and drop into load weighted lubricant magnesium stearate and mix mixing in 10～15 minutes;

(7) tabletting;

(8) packing.