CN104971053A - Ranitidine hydrochloride composition tablet medicine for treating digestive system diseases - Google Patents
Ranitidine hydrochloride composition tablet medicine for treating digestive system diseases Download PDFInfo
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- CN104971053A CN104971053A CN201510471737.6A CN201510471737A CN104971053A CN 104971053 A CN104971053 A CN 104971053A CN 201510471737 A CN201510471737 A CN 201510471737A CN 104971053 A CN104971053 A CN 104971053A
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- ranitidine hydrochloride
- ranitidine
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Abstract
The invention relates to a ranitidine hydrochloride composition tablet medicine for treating digestive system diseases and belongs to the technical field of medicines. The ranitidine hydrochloride composition is composed of ranitidine hydrochloride, calcium hydrogen phosphate, pregelatinized starch, aluminium-magnesium silicate and aerosol, wherein ranitidine hydrochloride is a new crystal form compound, and an X-ray powder differentiation pattern obtained through Cu-Kalpha radioactive measurement is shown as a Figure 1, so that the ranitidine hydrochloride adopted in the ranitidine hydrochloride composition tablet medicine is different from the ranitidine hydrochloride reported in the prior art. Experiments show that the tablet prepared from the ranitidine hydrochloride new crystal form compound can be used for solving the problem that ranitidine hydrochloride is extremely easy to deliquesce, high in possibility of moisture adsorption and colour change and poor in stability, and the composition is simple, so that adverse reactions are greatly reduced, and the stability, pharmaceutical effect and biological availability of a tablet preparation are improved.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine hydrochloric acid ranitidine compositions tablet for the treatment of digestive system disease.
Background technology
Ranitidine is the same with cimetidine is the medicine of current most widely used treatment Peptic Ulcers.Developed by Britain Ge Lan element (glaxo) company.1976 by synthesis such as Britain's Prices (price), 1979 Bradshaw (bradshaw) illustrate its pharmacology, it is effective that bass tower (berstad) report in 1980 is used for duodenal ulcer, and listing in 1981 years, in the world more or less a hundred countries use.China was produced in 1985 by Shanghai No.6 Pharmaceutical Factory.
Ranitidine is an optionally bisfentidine, and the gastric acid secretion caused after effectively suppressing histamine, pentagastrin and food stimulus reduces the activity of gastric acid and gastric enzyme, but on the secretion of gastrin and gonadal hormone without impact.Act on stronger than cimetidine 5 ~ 8 times, high to the curative effect of gastric and duodenal ulcers, there is quick-acting and long-acting feature, the little and safety of side effect.After single oral 80mg 30 ~ 90 minutes, mean Cmax was 165ng/ml, effect lasts 12 hours.
Ranitidine absorbs fast, the impact of unable to take food thing and antacid.Oral administration biaavailability is about 50%, t1/2 and is about 2 ~ 2.7 hours, and comparatively cimetidine is slightly long.The gastric acid secretion that pentagastrin can be made to cause in oral latter 12 hours reduces 30%.Quiet note 1mg/kg, instantaneous blood concentration is 3000ng/ml, maintains more than 100ng/ml and can reach 4 hours; With 30 ~ 60 minutes blood concentration peakings after quiet of 0.5ng/kg speed per hour, be proportionate between peak concentration and dosage.Major part is with original shape from renal excretion, and renal clearance is per minute 7.2ml/kg.
Ranitidine hydrochloride is deliquescence very easily, causes instability after moisture absorption, darkens, and content declines, and drug effect declines.The pharmaceutical preparation of the ranitidine hydrochloride gone on the market has capsule, conventional tablet, injection, effervescent granule, chewable tablet, effervescent tablet, oral liquid, syrup etc., wherein ranitidine hydrochloride additive of tablet kind and quantity more, generally to use filler, lubricant, disintegrating agent, adhesive etc., and at least with 4 kinds of adjuvants.Increasing research shows that impurity in the incompatibility of the toxic and side effects of adjuvant itself, adjuvant and principal agent, adjuvant etc. all can have an impact to the safety of medicine,
Therefore, select suitable adjuvant and technique, reduce supplementary product kind and the consumption of ranitidine hydrochloride tablet, improve bioavailability and the stability of ranitidine hydrochloride tablet, for ensureing that the safety of clinical application has positive effect.
The present invention develops a kind of ranitidine hydrochloride noval chemical compound, tablet prepared by this ranitidine hydrochloride noval chemical compound not only solves the problem of ranitidine hydrochloride very easily deliquescence, moisture absorption, variable color, poor stability, and component is simple, greatly reduce the generation of untoward reaction, improve the stability of tablet formulation, drug effect and bioavailability.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of medicine hydrochloric acid ranitidine compositions tablet for the treatment of digestive system disease.
In order to complete object of the present invention, the technical scheme of employing is:
The present invention relates to a kind of medicine hydrochloric acid ranitidine compositions tablet for the treatment of digestive system disease, described compositions is made up of ranitidine hydrochloride, calcium hydrogen phosphate, pregelatinized Starch, aluminium-magnesium silicate, micropowder silica gel; Described ranitidine hydrochloride is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
Preferably, with parts by weight, described compositions is made up of the ranitidine hydrochloride of 1.5 weight portions, the calcium hydrogen phosphate of 1.5-2.5 weight portion, the pregelatinized Starch of 0.8-1.2 weight portion, the aluminium-magnesium silicate of 0.4-0.6 weight portion, the micropowder silica gel of 0.04-0.06 weight portion.
Preferably, with parts by weight, described compositions is made up of the ranitidine hydrochloride of 1.5 weight portions, the calcium hydrogen phosphate of 2 weight portions, the pregelatinized Starch of 1 weight portion, the aluminium-magnesium silicate of 0.5 weight portion, the micropowder silica gel of 0.05 weight portion.
The preparation method of described compositions comprises the following steps:
(1) supplementary material process: ranitidine hydrochloride is crossed 80 mesh sieves with vibration screen-dividing machine;
(2) weigh: weigh according to recipe quantity;
(3) mix: load weighted whole supplementary material is joined in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 45 minutes;
(4) tabletting: join in high speed tablet press by granule after mixing, Hardness Control 8-12kgF, tablet weight variation need meet inner quality standard;
(5) pack.
The preparation method of the ranitidine hydrochloride crystal in compositions comprises the following steps:
(1) ground by ranitidine hydrochloride crude product, cross 60 mesh sieves, then joining volume is in the deionized water of 8 times of ranitidine hydrochloride weight, and 130 revs/min are stirred 10 minutes;
Add the ethanol that volume is 5 times of ranitidine hydrochloride weight under (2) 110 revs/min of stirrings, be warming up to 35 DEG C simultaneously;
(3) after solution adds, leave standstill 2 hours, the volume dripping 0 DEG C under 165 revs/min of conditions stirred is 8 times of acetone of ranitidine hydrochloride weight, the mixed solution of ether, and the volume ratio of acetone, ether is at the uniform velocity dropwise in 3:1,2h;
(4) be cooled to-10 DEG C after being added dropwise to complete, continue to stir 2h under the stir speed (S.S.) of 100 revs/min, leave standstill 1h crystallize out, filter, washing, vacuum drying obtains ranitidine hydrochloride crystal.
Below technical scheme of the present invention is made further explanation:
The present invention is by the precise controlling to crystallization condition, and prepared a kind of ranitidine hydrochloride novel crystal forms unlike the prior art, the X-ray powder diffraction pattern of this ranitidine hydrochloride crystal unlike the prior art.Simultaneously due to the ins and outs of this crystal formation, find through test, tablet prepared by this ranitidine hydrochloride noval chemical compound not only solves the problem of ranitidine hydrochloride very easily deliquescence, moisture absorption, variable color, poor stability, and component is simple, greatly reduce the generation of untoward reaction, improve the stability of tablet formulation, drug effect and bioavailability.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the ranitidine hydrochloride crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
Detailed description of the invention
Below by specific embodiment, summary of the invention of the present invention is described in further detail, but does not therefore limit content of the present invention.
embodiment 1:the preparation of ranitidine hydrochloride crystal
(1) ground by ranitidine hydrochloride crude product, cross 60 mesh sieves, then joining volume is in the deionized water of 8 times of ranitidine hydrochloride weight, and 130 revs/min are stirred 10 minutes;
Add the ethanol that volume is 5 times of ranitidine hydrochloride weight under (2) 110 revs/min of stirrings, be warming up to 35 DEG C simultaneously;
(3) after solution adds, leave standstill 2 hours, the volume dripping 0 DEG C under 165 revs/min of conditions stirred is 8 times of acetone of ranitidine hydrochloride weight, the mixed solution of ether, and the volume ratio of acetone, ether is at the uniform velocity dropwise in 3:1,2h;
(4) be cooled to-10 DEG C after being added dropwise to complete, continue to stir 2h under the stir speed (S.S.) of 100 revs/min, leave standstill 1h crystallize out, filter, washing, vacuum drying obtains ranitidine hydrochloride crystal.
The X-ray powder diffraction pattern that the ranitidine hydrochloride crystal prepared uses the measurement of Cu-K alpha ray to obtain as shown in Figure 1.
embodiment 2:the preparation of ranitidine hydrochloride tablet:
Prescription: with parts by weight as table 1
Table 1 ranitidine hydrochloride composition prescription
Preparation method:
(1) supplementary material process: ranitidine hydrochloride is crossed 80 mesh sieves with vibration screen-dividing machine;
(2) weigh: weigh according to recipe quantity;
(3) mix: load weighted whole supplementary material is joined in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 45 minutes;
(4) tabletting: join in high speed tablet press by granule after mixing, Hardness Control 8-12kgF, tablet weight variation need meet inner quality standard;
(5) pack.
embodiment 3:the preparation of ranitidine hydrochloride tablet:
Prescription: with parts by weight as table 2
Table 2 ranitidine hydrochloride composition prescription
Preparation method:
(1) supplementary material process: ranitidine hydrochloride is crossed 80 mesh sieves with vibration screen-dividing machine;
(2) weigh: weigh according to recipe quantity;
(3) mix: load weighted whole supplementary material is joined in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 45 minutes;
(4) tabletting: join in high speed tablet press by granule after mixing, Hardness Control 8-12kgF, tablet weight variation need meet inner quality standard;
(5) pack.
embodiment 4:the preparation of ranitidine hydrochloride tablet:
Prescription: with parts by weight as table 3
Table 3 ranitidine hydrochloride composition prescription
Preparation method:
(1) supplementary material process: ranitidine hydrochloride is crossed 80 mesh sieves with vibration screen-dividing machine;
(2) weigh: weigh according to recipe quantity;
(3) mix: load weighted whole supplementary material is joined in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 45 minutes;
(4) tabletting: join in high speed tablet press by granule after mixing, Hardness Control 8-12kgF, tablet weight variation need meet inner quality standard;
(5) pack.
experimental example 1:moisture absorption comparative test
1. instrument and reagent
1.1 instrument
PL203 electronic balance, LRH-250-S constant temperature and humidity incubator, HH-400SD testing chamber for medicine stability;
1.2 reagent
Comparative example 1:: Singapore's imported raw material ranitidine hydrochloride (manufacturer: GlaxoWellcome Manufacturing Pte Ltd);
Comparative example 2: domestic raw material ranitidine hydrochloride (manufacturer: Changzhou Kangpu Pharmaceutical Co., Ltd.)
2 methods
Get the glass desicator (for ensureing that saline solution is saturated, excessive salt should be had bottom exsiccator to exist) that bottom fills salt supersaturated solution, the built-in weighing botle of exsiccator, places 48h to constant humidity in calorstat.Sample thief is about 2g, puts in weighing botle, accurately weighed, bottle cap is opened, puts into exsiccator top, put in 25 DEG C of constant temperature and humidity incubators or 20 DEG C of stability test casees by different temperatures requirement and preserve, operation repetitive 3 parts, weighs respectively at different time, calculates the hydroscopicity of different time.
Computing formula: hydroscopicity=(medicated powder weight after moisture absorption-moisture absorption prodrug grain weight amount)/moisture absorption prodrug grain weight amount × 100%.Result is as shown in table 4:
Table 4 fuchsin(e)test result
According to above-mentioned experiment, the hygroscopicity of ranitidine hydrochloride compound prepared by the present invention is variant compared with prior art, lower than prior art, points out the stability of this compound higher than prior art.
test example 2:stability test
The ranitidine hydrochloride tablet that Example 2-4 is obtained and listing preparation ranitidine hydrochloride tablet (Qingdao Huanghai Pharmaceutical Co., Ltd.), under high temperature 40 DEG C, relative humidity 75% ± 5% condition 6 months, carry out accelerated test investigation, result is as table 5:
Table 5 accelerated test investigates result
From above result, accelerated test is after 6 months, and the sample dissolution of embodiment of the present invention 2-4, content and related substance significant change do not occur, and the preparation dissolution that goes on the market declines larger, related substance raises obviously, and the good stability of the ranitidine hydrochloride tablet that the present invention obtains is described.
test example 3:bioavailability study
This experimental example has investigated the bioavailability of ranitidine hydrochloride tablet by pharmacokinetic.
Test method: reference literature " Pharmacokinetic of ranitidine hydrochloride chewable tablets and relative bioavailability " (Journal of Chinese Hospital Pharmacy the 24th volume the 8th phase 456-458 page in 2004) method measures.
Sampling: respectively before taking medicine and after taking medicine 0. 5,1,1. 5,2,3,4,5,6,8,10,12 h each moment gathered venous blood 3mL, and detect according to above-mentioned literature method, result is as table 6, table 7:
Table 6 commercially available ranitidine hydrochloride tablet pharmacokinetic studies data
Table 7 ranitidine hydrochloride tablet of the present invention pharmacokinetic studies data
From upper table result, the blood drug level of ranitidine hydrochloride tablet of the present invention is significantly higher than the blood drug level of ranitidine hydrochloride tablet, shows that ranitidine hydrochloride tablet of the present invention bioavailability is in vivo significantly improved.
Claims (5)
1. treat a medicine hydrochloric acid ranitidine compositions tablet for digestive system disease, it is characterized in that: described compositions is made up of ranitidine hydrochloride, calcium hydrogen phosphate, pregelatinized Starch, aluminium-magnesium silicate, micropowder silica gel; Described ranitidine hydrochloride is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
2. the medicine hydrochloric acid ranitidine compositions tablet for the treatment of digestive system disease according to claim 1, it is characterized in that: with parts by weight, be made up of the ranitidine hydrochloride of 1.5 weight portions, the calcium hydrogen phosphate of 1.5-2.5 weight portion, the pregelatinized Starch of 0.8-1.2 weight portion, the aluminium-magnesium silicate of 0.4-0.6 weight portion, the micropowder silica gel of 0.04-0.06 weight portion.
3. the medicine hydrochloric acid ranitidine compositions tablet for the treatment of digestive system disease according to claim 2, it is characterized in that: with parts by weight, be made up of the ranitidine hydrochloride of 1.5 weight portions, the calcium hydrogen phosphate of 2 weight portions, the pregelatinized Starch of 1 weight portion, the aluminium-magnesium silicate of 0.5 weight portion, the micropowder silica gel of 0.05 weight portion.
4., according to the medicine hydrochloric acid ranitidine compositions tablet of the arbitrary described treatment digestive system disease of claim 1-3, it is characterized in that, the preparation method of described compositions comprises the following steps:
(1) supplementary material process: ranitidine hydrochloride is crossed 80 mesh sieves with vibration screen-dividing machine;
(2) weigh: weigh according to recipe quantity;
(3) mix: load weighted whole supplementary material is joined in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 45 minutes;
(4) tabletting: join in high speed tablet press by granule after mixing, Hardness Control 8-12kgF, tablet weight variation meets inner quality standard;
(5) pack.
5. the medicine hydrochloric acid ranitidine compositions tablet for the treatment of digestive system disease according to claim 1, it is characterized in that, in described compositions, the crystal preparation method of ranitidine hydrochloride comprises the following steps:
(1) ground by ranitidine hydrochloride crude product, cross 60 mesh sieves, then joining volume is in the deionized water of 8 times of ranitidine hydrochloride weight, and 130 revs/min are stirred 10 minutes;
Add the ethanol that volume is 5 times of ranitidine hydrochloride weight under (2) 110 revs/min of stirrings, be warming up to 35 DEG C simultaneously;
(3) after solution adds, leave standstill 2 hours, the volume dripping 0 DEG C under 165 revs/min of conditions stirred is 8 times of acetone of ranitidine hydrochloride weight, the mixed solution of ether, and the volume ratio of acetone, ether is at the uniform velocity dropwise in 3:1,2h;
(4) be cooled to-10 DEG C after being added dropwise to complete, continue to stir 2h under the stir speed (S.S.) of 100 revs/min, leave standstill 1h crystallize out, filter, washing, vacuum drying obtains ranitidine hydrochloride crystal.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510471737.6A CN104971053A (en) | 2015-08-05 | 2015-08-05 | Ranitidine hydrochloride composition tablet medicine for treating digestive system diseases |
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| CN201510471737.6A CN104971053A (en) | 2015-08-05 | 2015-08-05 | Ranitidine hydrochloride composition tablet medicine for treating digestive system diseases |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107714687A (en) * | 2017-10-31 | 2018-02-23 | 武汉中钰钰民医药科技有限公司 | Ranitidine pharmaceutical composition and preparation method thereof |
| CN108670959A (en) * | 2018-06-30 | 2018-10-19 | 郑州明泽医药科技有限公司 | A kind of ranitidine hydrochloride capsules and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4521431A (en) * | 1980-10-01 | 1985-06-04 | Glaxo Group Limited | Aminoalkyl furan derivative |
| EP0694540A1 (en) * | 1994-06-24 | 1996-01-31 | Ranbaxy Laboratories Limited | Process for the manufacture of form 1 ranitidine hydrochloride |
| CN1621036A (en) * | 2003-11-28 | 2005-06-01 | 刘军 | Powder injection of hydrochloric acid ranitidine and its preparation method |
-
2015
- 2015-08-05 CN CN201510471737.6A patent/CN104971053A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4521431A (en) * | 1980-10-01 | 1985-06-04 | Glaxo Group Limited | Aminoalkyl furan derivative |
| NZ198522A (en) * | 1980-10-01 | 1985-07-12 | Glaxo Group Ltd | Form 2 ranitidine hydrochloride:the hydrochloric salt of n-(2-(((5-(dimethylamino)methyl)-2-furanyl)methyl)-thio)ethyl-n1-methyl-2-nitro-1,1-ethenediamine |
| EP0694540A1 (en) * | 1994-06-24 | 1996-01-31 | Ranbaxy Laboratories Limited | Process for the manufacture of form 1 ranitidine hydrochloride |
| CN1621036A (en) * | 2003-11-28 | 2005-06-01 | 刘军 | Powder injection of hydrochloric acid ranitidine and its preparation method |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107714687A (en) * | 2017-10-31 | 2018-02-23 | 武汉中钰钰民医药科技有限公司 | Ranitidine pharmaceutical composition and preparation method thereof |
| CN108670959A (en) * | 2018-06-30 | 2018-10-19 | 郑州明泽医药科技有限公司 | A kind of ranitidine hydrochloride capsules and preparation method thereof |
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Application publication date: 20151014 |