CN105030694A - Ranitidine hydrochloride composition dry suspension for treating gastric ulcer - Google Patents
Ranitidine hydrochloride composition dry suspension for treating gastric ulcer Download PDFInfo
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- CN105030694A CN105030694A CN201510467703.XA CN201510467703A CN105030694A CN 105030694 A CN105030694 A CN 105030694A CN 201510467703 A CN201510467703 A CN 201510467703A CN 105030694 A CN105030694 A CN 105030694A
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- ranitidine hydrochloride
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Abstract
The invention discloses a ranitidine hydrochloride composition dry suspension for treating gastric ulcer, and belongs to the technical field of medicine. A composition is composed of ranitidine hydrochloride, sucrose, sodium carboxymethylcellulose, sodium alginate, pectin, polyethylene glycol and stevioside; the ranitidine hydrochloride is a new crystal form compound, is measured with a Cu-Ka ray to obtain an X-ray powder diffraction pattern and is different from ranitidine hydrochloride reported by the prior art, wherein the X-ray powder diffraction pattern is as shown in figure 1. Experiments find that the dry suspension prepared with the ranitidine hydrochloride-new crystal form compound solves the problem that the ranitidine hydrochloride is extremely prone to being deliquesced, moisture is prone to being absorbed, color is prone to being changed, and the stability is poor, the components are simple, adverse reactions are greatly prevented from occurring, and the stability, medicine effects and bioavailability of the dry suspension are improved.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine hydrochloric acid ranitidine compositions dry suspension for the treatment of gastric ulcer.
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 hour, 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 minute blood concentration peaking 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 pharmaceutical adjunct 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 the impurity etc. in the incompatibility of the toxic and side effects of adjuvant itself, adjuvant and principal agent, adjuvant 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 preparation, improve bioavailability and the stability of ranitidine hydrochloride preparation, for ensureing that the safety of clinical application has positive effect.
The present invention develops a kind of ranitidine hydrochloride noval chemical compound, dry suspension 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 dry suspension, 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 dry suspension for the treatment of gastric ulcer.
In order to complete object of the present invention, the technical scheme of employing is:
Treat a medicine hydrochloric acid ranitidine compositions dry suspension for gastric ulcer, described compositions is made up of ranitidine hydrochloride, sucrose, sodium carboxymethyl cellulose, sodium alginate, pectin, Polyethylene Glycol, stevioside; 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 sucrose of 7.3-7.5 weight portion, the sodium carboxymethyl cellulose of 0.6-0.8 weight portion, the sodium alginate of 0.25-0.35 weight portion, the pectin of 0.15-0.25 weight portion, the Polyethylene Glycol of 0.1-0.2 weight portion, the stevioside of 0.08-0.12 weight portion.
Preferably, with parts by weight, described compositions is made up of the ranitidine hydrochloride of 1.5 weight portions, the sucrose of 7.4 weight portions, the sodium carboxymethyl cellulose of 0.7 weight portion, the sodium alginate of 0.3 weight portion, the pectin of 0.2 weight portion, the Polyethylene Glycol of 0.15 weight portion, the stevioside of 0.1 weight portion.
The preparation method of described compositions comprises the following steps:
(1) supplementary material process: ranitidine hydrochloride was pulverized 100 mesh sieves with pulverizer;
(2) weigh: weigh each supplementary material according to technology preparation amount;
(3) always mix: whole supplementary materials of recipe quantity are joined in three-dimensional mixer, mixing velocity 12r/min, open mixer and mix 60 minutes;
(4) pack: granule is joined particles packing machine intermediate package, control content uniformity and meet inner quality standard.
The preparation method of the ranitidine hydrochloride crystal in the present composition comprises the following steps:
Get ranitidine hydrochloride crude drug, the volume adding 30 DEG C is that in the mixed solvent A of the water of ranitidine hydrochloride weight 8 times, ethanol, N-methylacetamide, water, ethanol, N-methylacetamide volume ratio are 4:1:1, obtain solution; Then in the horizontal direction of the liquid level of gained solution, apply the stationary magnetic field that magnetic field intensity is 1.0T, and under the condition of this stationary magnetic field, in solution, drip the acetone that volume is ranitidine hydrochloride weight 8 times; After being added dropwise to complete, be cooled to-10 DEG C, leave standstill 2 hours, filter, washing, vacuum drying, obtains described 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, dry suspension 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 dry suspension, 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
Get ranitidine hydrochloride crude drug, the volume adding 30 DEG C is that in the mixed solvent A of the water of ranitidine hydrochloride weight 8 times, ethanol, N-methylacetamide, water, ethanol, N-methylacetamide volume ratio are 4:1:1, obtain solution; Then in the horizontal direction of the liquid level of gained solution, apply the stationary magnetic field that magnetic field intensity is 1.0T, and under the condition of this stationary magnetic field, in solution, drip the acetone that volume is ranitidine hydrochloride weight 8 times; After being added dropwise to complete, be cooled to-10 DEG C, leave standstill 2 hours, filter, washing, vacuum drying, obtains described 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 dry suspension:
Prescription: with parts by weight as table 1
Table 1 ranitidine hydrochloride composition prescription
Preparation method:
(1) supplementary material process: ranitidine hydrochloride was pulverized 100 mesh sieves with pulverizer;
(2) weigh: weigh each supplementary material according to technology preparation amount;
(3) always mix: whole supplementary materials of recipe quantity are joined in three-dimensional mixer, mixing velocity 12r/min, open mixer and mix 60 minutes;
(4) pack: granule is joined particles packing machine intermediate package, control content uniformity and meet inner quality standard.
embodiment 3:the preparation of ranitidine hydrochloride dry suspension:
Prescription: with parts by weight as table 2
Table 2 ranitidine hydrochloride composition prescription
Preparation method:
(1) supplementary material process: ranitidine hydrochloride was pulverized 100 mesh sieves with pulverizer;
(2) weigh: weigh each supplementary material according to technology preparation amount;
(3) always mix: whole supplementary materials of recipe quantity are joined in three-dimensional mixer, mixing velocity 12r/min, open mixer and mix 60 minutes;
(4) pack: granule is joined particles packing machine intermediate package, control content uniformity and meet inner quality standard.
embodiment 4:the preparation of ranitidine hydrochloride dry suspension:
Prescription: with parts by weight as table 3
Table 3 ranitidine hydrochloride composition prescription
Preparation method:
(1) supplementary material process: ranitidine hydrochloride was pulverized 100 mesh sieves with pulverizer;
(2) weigh: weigh each supplementary material according to technology preparation amount;
(3) always mix: whole supplementary materials of recipe quantity are joined in three-dimensional mixer, mixing velocity 12r/min, open mixer and mix 60 minutes;
(4) pack: granule is joined particles packing machine intermediate package, control content uniformity and meet inner quality standard.
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: GlaxoWellcomeManufacturingPteLtd);
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 hygroscopicity testing 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 dry suspension that Example 2-4 is obtained, under high temperature 40 DEG C, relative humidity 75% ± 5% condition 6 months, carry out accelerated test investigation, result was as table 5:
Table 5 accelerated test investigates result
From above result, accelerated test is after 6 months, and the sample related substance of embodiment of the present invention 2-4 significant change does not occur, and the good stability of the ranitidine hydrochloride dry suspension that the present invention obtains is described.
test example 3:bioavailability study
This experimental example has investigated the bioavailability of ranitidine hydrochloride dry suspension 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: before taking medicine and after taking medicine, 0.5,1,1.5,2,3,4,5,6,8,10,12h each moment gathered venous blood 3mL respectively, and detect according to above-mentioned literature method, testing result is as table 6, table 7:
Table 6 commercially available ranitidine hydrochloride sheet pharmacokinetic studies data
Table 7 ranitidine hydrochloride dry suspension of the present invention pharmacokinetic studies data
From upper table result, the blood drug level of ranitidine hydrochloride dry suspension of the present invention is significantly higher than the blood drug level of ranitidine hydrochloride tablet, shows that ranitidine hydrochloride dry suspension of the present invention bioavailability is in vivo significantly improved.
Claims (5)
1. treat a medicine hydrochloric acid ranitidine compositions dry suspension for gastric ulcer, it is characterized in that: described compositions is made up of ranitidine hydrochloride, sucrose, sodium carboxymethyl cellulose, sodium alginate, pectin, Polyethylene Glycol, stevioside; 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 dry suspension for the treatment of gastric ulcer according to claim 1, it is characterized in that: described compositions, with parts by weight, is made up of the ranitidine hydrochloride of 1.5 weight portions, the sucrose of 7.3-7.5 weight portion, the sodium carboxymethyl cellulose of 0.6-0.8 weight portion, the sodium alginate of 0.25-0.35 weight portion, the pectin of 0.15-0.25 weight portion, the Polyethylene Glycol of 0.1-0.2 weight portion, the stevioside of 0.08-0.12 weight portion.
3. the medicine hydrochloric acid ranitidine compositions dry suspension for the treatment of gastric ulcer according to claim 2, it is characterized in that: described compositions, with parts by weight, is made up of the ranitidine hydrochloride of 1.5 weight portions, the sucrose of 7.4 weight portions, the sodium carboxymethyl cellulose of 0.7 weight portion, the sodium alginate of 0.3 weight portion, the pectin of 0.2 weight portion, the Polyethylene Glycol of 0.15 weight portion, the stevioside of 0.1 weight portion.
4., according to the medicine hydrochloric acid ranitidine compositions dry suspension of the arbitrary described treatment gastric ulcer 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 was pulverized 100 mesh sieves with pulverizer;
(2) weigh: weigh each supplementary material according to technology preparation amount;
(3) always mix: whole supplementary materials of recipe quantity are joined in three-dimensional mixer, mixing velocity 12r/min, open mixer and mix 60 minutes;
(4) pack: granule is joined particles packing machine intermediate package, control content uniformity and meet inner quality standard.
5. the medicine hydrochloric acid ranitidine compositions dry suspension for the treatment of gastric ulcer according to claim 1, it is characterized in that, in described compositions, ranitidine hydrochloride crystal preparation method comprises the following steps:
Get ranitidine hydrochloride crude drug, the volume adding 30 DEG C is that in the mixed solvent A of the water of ranitidine hydrochloride weight 8 times, ethanol, N-methylacetamide, water, ethanol, N-methylacetamide volume ratio are 4:1:1, obtain solution; Then in the horizontal direction of the liquid level of gained solution, apply the stationary magnetic field that magnetic field intensity is 1.0T, and under the condition of this stationary magnetic field, in solution, drip the acetone that volume is ranitidine hydrochloride weight 8 times; After being added dropwise to complete, be cooled to-10 DEG C, leave standstill 2 hours, filter, washing, vacuum drying, obtains described ranitidine hydrochloride crystal.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510467703.XA CN105030694A (en) | 2015-08-04 | 2015-08-04 | Ranitidine hydrochloride composition dry suspension for treating gastric ulcer |
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| CN201510467703.XA CN105030694A (en) | 2015-08-04 | 2015-08-04 | Ranitidine hydrochloride composition dry suspension for treating gastric ulcer |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115252884A (en) * | 2022-07-11 | 2022-11-01 | 湖北工业大学 | Powder composition and application thereof in preparation of pet wound powder dressing |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4521431A (en) * | 1980-10-01 | 1985-06-04 | Glaxo Group Limited | Aminoalkyl furan derivative |
| CN1092648A (en) * | 1992-10-16 | 1994-09-28 | 格拉克索公司 | Ranitidine compositions |
| WO2000061118A1 (en) * | 1999-04-12 | 2000-10-19 | Pharmexcel Srl | Anhydrous tablet of ranitidine hydrochloride with double-layer coating and its composition |
| CN1724526A (en) * | 2005-07-11 | 2006-01-25 | 石药集团中诺药业（石家庄）有限公司 | Synthesis method of ranitidine alkali and its hydrochloride |
-
2015
- 2015-08-04 CN CN201510467703.XA patent/CN105030694A/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 |
| CN1092648A (en) * | 1992-10-16 | 1994-09-28 | 格拉克索公司 | Ranitidine compositions |
| WO2000061118A1 (en) * | 1999-04-12 | 2000-10-19 | Pharmexcel Srl | Anhydrous tablet of ranitidine hydrochloride with double-layer coating and its composition |
| CN1724526A (en) * | 2005-07-11 | 2006-01-25 | 石药集团中诺药业（石家庄）有限公司 | Synthesis method of ranitidine alkali and its hydrochloride |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115252884A (en) * | 2022-07-11 | 2022-11-01 | 湖北工业大学 | Powder composition and application thereof in preparation of pet wound powder dressing |
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Application publication date: 20151111 |