CN115444832A - Pharmaceutical composition containing omeprazole magnesium and preparation thereof - Google Patents

Pharmaceutical composition containing omeprazole magnesium and preparation thereof Download PDF

Info

Publication number
CN115444832A
CN115444832A CN202110641214.7A CN202110641214A CN115444832A CN 115444832 A CN115444832 A CN 115444832A CN 202110641214 A CN202110641214 A CN 202110641214A CN 115444832 A CN115444832 A CN 115444832A
Authority
CN
China
Prior art keywords
omeprazole
magnesium
pharmaceutical composition
sodium bicarbonate
disintegrant
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202110641214.7A
Other languages
Chinese (zh)
Inventor
徐天帅
牟立燕
于乐
王孝方
韩翠娟
马小涛
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhien Biotechnology Co ltd
Changchun Lanjiang Pharmaceutical Technology Co ltd
Original Assignee
Zhien Biotechnology Co ltd
Changchun Lanjiang Pharmaceutical Technology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhien Biotechnology Co ltd, Changchun Lanjiang Pharmaceutical Technology Co ltd filed Critical Zhien Biotechnology Co ltd
Priority to CN202110641214.7A priority Critical patent/CN115444832A/en
Publication of CN115444832A publication Critical patent/CN115444832A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nutrition Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Inorganic Chemistry (AREA)

Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to a pharmaceutical composition containing omeprazole magnesium and a preparation thereof, wherein the pharmaceutical composition contains omeprazole magnesium, sodium bicarbonate, a disintegrating agent and a lubricating agent; in the pharmaceutical composition, the filling agent is not used, and only the disintegrant sodium carboxymethyl starch is used; the disintegrant in the pharmaceutical composition is not simply replaced, but is obtained by creative test screening such as compatibility test and the like, and the preparation formula of the invention is adopted, particularly, the disintegrant of sodium carboxymethyl starch, omeprazole magnesium/sodium bicarbonate compound preparation has small change of related substances, good stability and dissolution rate meeting the requirement of quality standard.

Description

Pharmaceutical composition containing omeprazole magnesium and preparation thereof
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a pharmaceutical composition containing omeprazole magnesium and a preparation thereof.
Background
Omeprazole magnesium is an antacid over-the-counter drug. The molecular formula is C 17 H 19 MgN 3 O 3 S; the product is H + ，K + -ATPase proton pump inhibitors, which, after absorption through the small intestine, concentrate on the stomach wall via the blood circulation, thereby inhibiting gastric acid. Clinically, the omeprazole magnesium enteric-coated tablet is used for treating duodenal ulcer, gastric ulcer and reflux esophagitis: treating duodenal ulcer infected with helicobacter pylori in combination with antibiotic; treating peptic ulcer and gastroduodenal erosion associated with non-steroidal anti-inflammatory drugs; preventing peptic ulcer, gastroduodenal erosion or dyspepsia symptoms caused by non-steroidal anti-inflammatory drugs; also for the long-term treatment of chronic recurrent peptic ulcers and reflux esophagitis; for symptomatic treatment of heartburn and reflux in gastro-esophageal reflux disease; symptomatic treatment of ulcer-like symptoms and acid-related dyspepsia; can be used for treating Zollinger-Ellison syndrome.
In 6 months 2004, the united states first approved a normal-release formulation of omeprazole sodium bicarbonate, namely, a compound omeprazole oral dry suspension (omeprazole/sodium bicarbonate), in which sodium bicarbonate replaces an enteric coating to play a role in preventing omeprazole from degrading when encountering acid before being absorbed, and the omeprazole oral dry suspension is suitable for short-term treatment of active duodenal ulcer and gastroesophageal reflux disease and maintenance treatment of healed erosive esophagitis. On the same year 12 months, 40mg/1.68g of the compound omeprazole 12525of the specification is taken for clinical approval in the united states, and the indications for the short-term treatment of benign gastric ulcer and the risk of upper gastrointestinal hemorrhage of critically ill patients are increased.
Chinese patent CN102727516B discloses a compound omeprazole capsule and a preparation method thereof, wherein the omeprazole raw material passes through 180 meshes, the granularity of sodium bicarbonate is 80-150 meshes, the dosage of magnesium stearate in each unit preparation is 6-10 mg, and the dosage of croscarmellose sodium is 6-18 mg.
Chinese patent CN103006691A discloses an omeprazole sodium bicarbonate compound capsule, which is prepared by uniformly mixing omeprazole gastric-soluble pellets, sodium bicarbonate, a disintegrating agent and a lubricating agent and filling the mixture into a capsule, wherein the sodium bicarbonate is rapidly released in a hydrochloric acid solution, and the omeprazole is rapidly released after the sodium bicarbonate is completely released.
Chinese patent CN 101816641B discloses a method for preparing omeprazole-containing quick-release capsules, each unit preparation is composed of 20mg omeprazole, 1100mg sodium bicarbonate and a proper amount of pharmaceutical excipients (solubilizer is sodium dodecyl sulfate, adhesive is 5% povidone, disintegrant is croscarmellose sodium, lubricant is magnesium stearate), and capsules are filled by adopting a granulation production process. The preparation has many adjuvants and production processes.
The stability of the omeprazole/sodium bicarbonate compound preparation is not considered in the patents, so that the development of the omeprazole/sodium bicarbonate preparation with simple process and good preparation stability has important significance.
Disclosure of Invention
For the above reasons, the applicant has studied, through several inventive tests, a new pharmaceutical composition containing magnesium omeprazole in which the filler is not used, but only the disintegrant sodium carboxymethyl starch; the disintegrant in the pharmaceutical composition is not simply replaced, but is obtained by creative test screening such as compatibility test and the like, and the preparation formula of the invention is adopted, particularly, the disintegrant carboxymethyl starch sodium and the omeprazole magnesium/sodium bicarbonate compound preparation have small change of related substances, good stability and dissolution meeting the requirement of quality standard.
The invention is realized by the following technical scheme.
A pharmaceutical composition containing magnesium omeprazole comprises magnesium omeprazole, sodium bicarbonate, a disintegrating agent and a lubricant.
The pharmaceutical composition containing omeprazole magnesium comprises, by weight, 10-11 parts of omeprazole magnesium, 1000-1600 parts of sodium bicarbonate, 10-25 parts of a disintegrating agent and 2-10 parts of a lubricating agent.
The pharmaceutical composition containing omeprazole magnesium comprises, by weight, 10-11 parts of omeprazole magnesium, 1000-1600 parts of sodium bicarbonate, 10-25 parts of a disintegrating agent and 2-10 parts of a lubricating agent.
The pharmaceutical composition containing omeprazole magnesium, wherein the disintegrant comprises carboxymethyl starch sodium.
The pharmaceutical composition containing omeprazole magnesium, wherein the lubricant comprises magnesium stearate, talcum powder and silica gel micropowder.
The pharmaceutical composition containing omeprazole magnesium is prepared into capsules.
The pharmaceutical composition containing omeprazole magnesium, wherein the preparation method of the capsule comprises the following steps:
(1) Sieving omeprazole magnesium, sodium bicarbonate, disintegrating agent and lubricant with a 80-mesh sieve;
(2) Premixing omeprazole magnesium, sodium bicarbonate and a disintegrating agent;
(3) Adding a lubricant into the step (2) for total mixing treatment;
(4) And (4) preparing the mixture prepared in the step (3) into capsules.
The invention has the following beneficial technical effects:
1. the pharmaceutical composition of the invention does not use the common auxiliary material filler, only uses the disintegrating agent and the lubricant, meets the requirements of quality standards on dissolution rate, reduces the dosage of the auxiliary material, is beneficial to reducing cost and has higher safety.
2. The disintegrant of the present invention was obtained by screening test studies, rather than the simple substitution of the same, and it was shown by studies on formulation stability, particularly compatibility, that the use of sodium starch glycolate as a disintegrant in omeprazole magnesium/sodium bicarbonate formulations,
3. the invention has simple process, and can well meet the requirement of dissolution without preparing the raw materials into nano raw materials.
Detailed Description
In order to make the technical means, the original characteristics, the achieved purposes and the effects of the invention easily understood, the invention is further explained with the following embodiments, but the following embodiments are only the preferred embodiments of the invention, and not all embodiments. Based on the embodiments in the implementation, other embodiments obtained by those skilled in the art without any creative efforts belong to the protection scope of the present invention.
The experimental procedures in the following examples were carried out in a conventional manner unless otherwise specified, and materials, reagents and the like used in the following examples were commercially available unless otherwise specified.
1. Screening test for auxiliary Material
[ EXAMINATION ] the related substances are measured by high performance liquid chromatography (China pharmacopoeia 2020 edition of general rules of the four departments 0512), and are protected from light for fresh preparation.
The test solution is prepared by collecting appropriate amount of the content (about 20mg of omeprazole) in a 100ml measuring flask, adding 27ml of acetonitrile, shaking, diluting with phosphate buffer (pH 7.6) to scale, shaking, and filtering.
The control solution was prepared by precisely measuring an appropriate amount of the test solution and diluting the solution with phosphate buffer (pH 7.6) -acetonitrile (73).
System applicability a mixed solution containing about 0.02mg of omeprazole and impurity D as a control in each 1ml was prepared by dissolving and diluting the omeprazole and the impurity D in a phosphate buffer (ph 7.6) -acetonitrile (73).
Octadecylsilane chemically bonded silica is used as a filler under chromatographic conditions; acetonitrile-phosphate buffer (pH 7.6) (1.4 g/L of disodium hydrogen phosphate dodecahydrate solution adjusted to pH7.6 with phosphoric acid) (25; the detection wavelength is 302nm; the flow rate was 1.0ml per minute; the temperature of the chromatographic column is 30 ℃; the injection volume was 20. Mu.l.
The system applicability requires that in a system applicability solution chromatogram, the separation degree between an omeprazole peak and an impurity D peak is more than 2.0, and the theoretical plate number is not less than 2000 calculated according to omeprazole.
The determination method comprises precisely measuring 20 μ l of each of the test solution and the control solution, respectively injecting into a liquid chromatograph, and recording the chromatogram until the retention time of the main component is 5 times.
If an impurity peak exists in the chromatogram of the limit test solution, the peak area of the impurity D is not more than 5 times (0.5%) of the peak area of the reference substance, the peak area of the impurity E is not more than 2 times (0.2%) of the peak area of the reference substance, the peak area of other single impurities is not more than 2 times (0.2%) of the peak area of the reference substance, and the peak area of each impurity is not more than 20 times (2.0%) of the peak area of the reference substance.
[ CONTENT DETERMINATION ] the magnesium content of omeprazole is determined by high performance liquid chromatography (China pharmacopoeia 2020 edition of the general rules of the four kingdoms 0512).
Taking 10 test sample solutions, pouring the contents into 100ml (10 mg specification) or 200ml (20 mg specification) measuring bottles respectively, washing capsule shells with 5ml (10 mg specification) or 10ml (20 mg specification) of methanol, merging the washing liquor into the measuring bottles, adding 5ml (10 mg specification) or 10ml (20 mg specification) of methanol, shaking for 1 minute, adding 80ml (10 mg specification) or 130ml (20 mg specification) of methanol-0.05 mol/L sodium hydroxide solution (20).
The control solution is prepared by taking an omeprazole magnesium control (about equivalent to 20mg of omeprazole), precisely weighing, placing in a 200ml measuring flask, adding 20ml of methanol, shaking for 1 minute, adding 130ml of methanol-0.05 mol/L sodium hydroxide solution (20) and carrying out ultrasonic treatment for 5 minutes to dissolve, diluting to a scale with the methanol-0.05 mol/L sodium hydroxide solution (20).
The chromatographic condition uses octyl silane bonded silica gel as a filling agent; phosphate buffer (ph 7.6) -acetonitrile (65) as a mobile phase; the detection wavelength is 302nm; the temperature of the chromatographic column is 30 ℃; the flow rate was 1.0ml per minute; the injection volume was 20. Mu.l.
The applicability of the system requires that the theoretical plate number is not less than 2000 calculated according to omeprazole peak.
The determination method comprises precisely measuring the solution of the test sample and the solution of the reference substance, respectively injecting into a liquid chromatograph, recording chromatogram, calculating the content of each granule by peak area according to external standard method, and calculating the average content of 10 granules.
Taking 20 granules of the product, precisely weighing, calculating average loading amount, taking the content, uniformly mixing, grinding, precisely weighing an appropriate amount (about equal to 1g of sodium bicarbonate), adding 50ml of water, shaking to dissolve the sodium bicarbonate, measuring by a potentiometric titration method, and titrating by hydrochloric acid titration solution (0.5 mol/L). Each 1ml of hydrochloric acid titration solution (0.5 mol/L) corresponds to 42.00mg of NaHCO3.
Mixing the raw materials and the auxiliary materials according to the proportion of 1; if the test result of the sample is not up to the expected purpose after being exposed for 30 days, other sample tests are carried out.
Prescription information
The raw materials and auxiliary materials are weighed and mixed according to different proportions, and the detailed composition is shown in the table below.
Table 1 raw and auxiliary material compatibility each sample composition
Figure BDA0003107134760000041
Figure BDA0003107134760000051
And (3) data statistics: counting the characters and weight gain and loss ratios before and after sample lofting: and (3) lofting by adopting a weighing bottle, recording the weight of the sample before and after lofting, calculating the weight gain and loss ratio of the sample, providing data support for detecting the content, and judging the compatibility condition of the raw materials and the auxiliary materials through character investigation.
TABLE 2 compatibility of the raw and auxiliary materials results (preparation)
Figure BDA0003107134760000052
Figure BDA0003107134760000061
TABLE 3 compatibility results of raw and auxiliary materials (formulations)
Figure BDA0003107134760000062
TABLE 4 compatibility of the raw and auxiliary materials results (analysis)
Figure BDA0003107134760000063
Figure BDA0003107134760000071
To summarize: through the analysis of the compatibility result of the raw materials and the auxiliary materials, the disintegrant croscarmellose sodium is incompatible with the raw materials, and the compatibility result of other auxiliary materials and the raw materials is better. The reference preparation has the advantages that the impurity growth is faster under high-humidity conditions and high-temperature conditions, and the self-made sample is more stable under the high-temperature conditions. In the next experiment, the types of the disintegrating agents need to be changed, and compatibility investigation work of the raw materials and different disintegrating agents is independently carried out.
The next test idea is as follows: 1. the types of the disintegrating agents are changed, the temporary disintegrating agents are crospovidone, carboxymethyl starch sodium and low-substituted hydroxypropyl cellulose, and the temporary disintegrating agents are mixed with the raw materials to carry out compatibility investigation. The experimental idea of the disintegrating agent species investigation test is as follows: when the compatibility of the raw materials and the auxiliary materials is investigated in the early stage, the cross-linked sodium carboxymethyl cellulose serving as the disintegrant is incompatible with the raw materials, and the compatibility results of other auxiliary materials and the raw materials are better. Therefore, the disintegrating agent is replaced and the proper disintegrating agent is screened out.
Prescription information: the raw materials and auxiliary materials are weighed and mixed according to different proportions, and the detailed composition is shown in the following table.
TABLE 5 compatibility of raw and auxiliary materials the compositions of the various samples
Figure BDA0003107134760000072
Figure BDA0003107134760000081
And (3) data statistics: and (3) counting the characters and weight gain and loss ratios before and after sample lofting, adopting a weighing bottle to loft, recording the weights of the samples before and after lofting, calculating the weight gain and loss ratios of the samples, providing data support for detecting the content, and judging the compatibility condition of the raw materials and the auxiliary materials through character investigation.
TABLE 6 statistics of weight gain and loss results of disintegrant species investigation traits
Figure BDA0003107134760000082
Figure BDA0003107134760000091
Figure BDA0003107134760000101
Figure BDA0003107134760000111
Figure BDA0003107134760000121
And (3) knotting: according to the experimental result, the API-containing sample changes from white-like powder to yellow-like powder after being placed at the high temperature of 60 ℃ in character, and the color of the blank auxiliary material group is unchanged; under the high-humidity open condition, the caking phenomenon is generated;
crospovidone (stacck), crospovidone (ashland), sodium starch glycolate and API 1:1 the mixed samples gained significant weight, exceeding 5%, and the weight gain was not much different between 15 days and 30 days per sample, which may be related to the upper limit of the absorption of moisture by the disintegrant. The weight gain of the individual samples was not significant under high humidity closed conditions. Under the conditions of high temperature and illumination, each sample has weight loss of different degrees.
The conclusion of the compatibility test of the raw materials and the auxiliary materials is as follows: a raw material and auxiliary material compatibility test is carried out according to the basic technical guidance principle of chemical pharmaceutical preparation research, the formula proportion of the raw materials and the auxiliary materials is analyzed according to the empirical dosage of the auxiliary materials, a proper amount of the raw materials and the auxiliary materials are taken and uniformly mixed according to a certain proportion, the mixture is placed for 30 days under the conditions of high temperature (60 ℃), acceleration (75 percent and 40 ℃), samples are taken for 0 day and 30 days respectively, the mixture is placed for 10 days under the condition of illumination (5000 lx), samples are taken for 0 day and 10 days respectively, and the changes of characters, contents, related substances and moisture absorption weight gain are inspected. The specific test results are shown in the following table.
TABLE 7 test results of the compatibility of omeprazole magnesium with auxiliary materials
Figure BDA0003107134760000122
Figure BDA0003107134760000131
From the above results, it can be seen that the omeprazole magnesium crude drug has a slightly poor stability at high temperature, and the total impurities at 60 ℃ are increased as compared to 0 day at room temperature. The omeprazole magnesium and all auxiliary materials have relatively good compatibility, and the total impurities are equivalent to those of the omeprazole magnesium under the conditions of high temperature and acceleration at room temperature. The omeprazole magnesium enteric-coated tablet has the advantages that the impurity growth is fast under high temperature and accelerated conditions, the growth amount is large, and a self-made sample is stable under the accelerated conditions.
2. Experimental report for investigating dosage of sodium carboxymethyl starch as disintegrant
Investigating the use level of the disintegrant sodium carboxymethyl starch:
the experimental thought is that the early stage disintegrating agent species investigation experimental result shows that the compatibility of the carboxymethyl starch sodium and the raw auxiliary materials in the omeprazole magnesium sodium bicarbonate capsule is good, so that the disintegrating agent is preliminarily determined to be the carboxymethyl starch sodium. The experiment examines the influence of the dosage (0%, 1%, 2%, 3%, 4%, 5%) of the sodium carboxymethyl starch serving as a disintegrant on the dissolution curve of a product with the specification of 20mg of an omeprazole magnesium sodium bicarbonate capsule. Meanwhile, whether the medicine powder is uniformly mixed in the technical process is determined by inspecting the content uniformity condition.
Prescription information, namely preparing a prescription according to different added amounts of the disintegrating agent, keeping the used materials of other auxiliary materials unchanged, ensuring that the added amounts of the disintegrating agent are different by changing the weight of the content of the whole capsule, and measuring the dissolution curve of the capsule.
TABLE 8 different disintegrant prescription compositions
Figure BDA0003107134760000132
Data statistics loading investigation results in the capsule filling process, the loading difference of the capsules is in a qualified range.
TABLE 9 filling amount for different prescriptions
Figure BDA0003107134760000133
Dissolution condition survey data statistics
According to the previous experimental results, the dissolution medium was first used at pH7.4, basket method 50rpm. Dissolution data are given in the table below.
TABLE 10 comparison of dissolution curves for different recipes
Figure BDA0003107134760000134
Figure BDA0003107134760000141
And (3) knotting: through the examination of dissolution curves of different disintegrating agent carboxymethyl starch sodium formulas, the dissolution amount of 5min is gradually increased along with the increase of the addition amount of the disintegrating agent, and when the addition amount of the disintegrating agent is 1-3%, the dissolution amount in the previous period is not obviously influenced. The maximum amount of F10 eluted at 15min was over 85%, and the target formula F3 was close to 85%. The dissolution amount of the F5 and the F6 in the early stage is higher, but the dissolution platform in the later stage is low, which may be the influence of low loading.
The F2 value of other prescriptions is greater than 50 calculated based on the target prescription F3, and the range of variation of + -1% and + -2% of the disintegrant dosage based on the target prescription is similar to the target prescription.
Comparison of 1.3.3F5, F6 dissolution curves
The dissolution conditions were such that the medium used was pH7.4 and basket method 50rpm, and the results were as follows:
TABLE 11 comparison of the dissolution curves for F5 and F6
Figure BDA0003107134760000142
Examination of other dissolution conditions
TABLE 12F2 100rpm Condition comparison
Figure BDA0003107134760000143
And (3) knotting: the number of elution revolutions was examined by F2 and the results were shown. The dissolution speed of 100rpm is higher than that of 50 revolutions, the dissolution amount at the early stage is higher, and the dissolution platform liquid at the later stage is higher. The amount of elution was greater than 85% at 30min at 50 revolutions and close to 85% at 10min at 100 revolutions.
TABLE 13 content uniformity
Figure BDA0003107134760000144
Figure BDA0003107134760000151
And (4) summarizing: the A +2.2S values of the F1-F6 are less than 15, the content uniformity requirement is met, and the powder can be completely and uniformly mixed by adding sodium bicarbonate in an equivalent incremental manner and a sieving process.
And (3) data analysis and summarization: the early-stage dissolution amount is gradually increased along with the increase of the consumption of the disintegrant sodium carboxymethyl starch, and the variation ranges of +/-1% and +/-2% of the consumption of the disintegrant on the basis of the target formula are similar to the target formula.
The content uniformity results show that the mixture can be completely mixed by adding sodium bicarbonate in an equal amount in an increasing way and sieving the mixture for 5 times in other raw and auxiliary materials.
Preparation examples
Example 1
10g of omeprazole magnesium, 1000g of sodium bicarbonate, 10g of disintegrating agent carboxymethyl starch sodium and 2g of lubricating agent magnesium stearate.
(1) Sieving omeprazole magnesium, sodium bicarbonate, disintegrating agent and lubricant with a 80-mesh sieve;
(2) Premixing omeprazole magnesium, sodium bicarbonate and a disintegrating agent;
(3) Adding a lubricant into the step (2) for total mixing treatment;
(4) And (4) preparing the mixture prepared in the step (3) into capsules.
Example 2
11g of omeprazole magnesium, 1600g of sodium bicarbonate, 25g of disintegrant carboxymethyl starch sodium and 10g of lubricant magnesium stearate.
(1) Sieving omeprazole magnesium, sodium bicarbonate, disintegrating agent and lubricant with a 80-mesh sieve;
(2) Premixing omeprazole magnesium, sodium bicarbonate and a disintegrating agent;
(3) Adding a lubricant into the step (2) for total mixing treatment;
(4) And (4) preparing the mixture prepared in the step (3) into capsules.
Example 3
10.3g of omeprazole magnesium, 1100g of sodium bicarbonate, 10.3g of disintegrant sodium carboxymethyl starch and 6g of lubricant magnesium stearate.
(1) Sieving omeprazole magnesium, sodium bicarbonate, disintegrating agent and lubricant with a 80-mesh sieve;
(2) Premixing omeprazole magnesium, sodium bicarbonate and a disintegrating agent;
(3) Adding a lubricant into the step (2) for total mixing treatment;
(4) And (4) preparing the mixture prepared in the step (3) into capsules.
It should be understood that the above examples are only for clearly illustrating the present invention and are not intended to limit the embodiments of the present invention. It is intended that the present invention be understood and implemented by those skilled in the art, and not limited to the scope of the present invention. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.

Claims (7)

1. A pharmaceutical composition containing omeprazole magnesium, which is characterized by containing omeprazole magnesium, sodium bicarbonate, a disintegrating agent and a lubricating agent.
2. The pharmaceutical composition comprising magnesium omeprazole according to claim 1, wherein the magnesium omeprazole is 10 to 11 parts by weight, the sodium bicarbonate is 1000 to 1600 parts by weight, the disintegrating agent is 10 to 25 parts by weight, and the lubricant is 2 to 10 parts by weight.
3. The pharmaceutical composition comprising magnesium omeprazole according to claim 1, wherein 10.3 parts by weight of magnesium omeprazole, 1100 parts by weight of sodium bicarbonate, 10-25 parts by weight of disintegrant, and 6 parts by weight of lubricant.
4. A pharmaceutical composition containing magnesium omeprazole according to any of claims 1 to 3 wherein the disintegrant comprises sodium starch glycolate.
5. A pharmaceutical composition containing magnesium omeprazole according to any of claims 1 to 3 wherein the lubricant comprises magnesium stearate, talc, aerosil.
6. A pharmaceutical composition comprising magnesium omeprazole according to any of claims 1 to 3 which is formulated as a capsule.
7. The pharmaceutical composition containing magnesium omeprazole according to claim 6, wherein the capsule preparation method comprises:
(1) Sieving omeprazole magnesium, sodium bicarbonate, disintegrating agent and lubricant with a 80-mesh sieve;
(2) Premixing omeprazole magnesium, sodium bicarbonate and a disintegrating agent;
(3) Adding a lubricant into the step (2) for total mixing treatment;
(4) And (4) preparing the mixture prepared in the step (3) into capsules.
CN202110641214.7A 2021-06-09 2021-06-09 Pharmaceutical composition containing omeprazole magnesium and preparation thereof Pending CN115444832A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110641214.7A CN115444832A (en) 2021-06-09 2021-06-09 Pharmaceutical composition containing omeprazole magnesium and preparation thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110641214.7A CN115444832A (en) 2021-06-09 2021-06-09 Pharmaceutical composition containing omeprazole magnesium and preparation thereof

Publications (1)

Publication Number Publication Date
CN115444832A true CN115444832A (en) 2022-12-09

Family

ID=84294993

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110641214.7A Pending CN115444832A (en) 2021-06-09 2021-06-09 Pharmaceutical composition containing omeprazole magnesium and preparation thereof

Country Status (1)

Country Link
CN (1) CN115444832A (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101002769A (en) * 2007-01-12 2007-07-25 广东华南药业有限公司 Compound preparation of omeprazol
CN101455629A (en) * 2008-11-17 2009-06-17 马晶 Oral solid preparation containing omeprazole
CN101816641A (en) * 2010-03-11 2010-09-01 沈阳亿灵医药科技有限公司 Omeprazole quick-release solid preparation and preparation method thereof
CN102793682A (en) * 2012-08-20 2012-11-28 安徽华佗国药股份有限公司 Rapid-release compound omeprazole tablet and preparation method thereof
CN112022829A (en) * 2019-06-04 2020-12-04 厦门恩成制药有限公司 Method for preparing esomeprazole magnesium sodium bicarbonate capsule

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101002769A (en) * 2007-01-12 2007-07-25 广东华南药业有限公司 Compound preparation of omeprazol
CN101455629A (en) * 2008-11-17 2009-06-17 马晶 Oral solid preparation containing omeprazole
CN101816641A (en) * 2010-03-11 2010-09-01 沈阳亿灵医药科技有限公司 Omeprazole quick-release solid preparation and preparation method thereof
CN102793682A (en) * 2012-08-20 2012-11-28 安徽华佗国药股份有限公司 Rapid-release compound omeprazole tablet and preparation method thereof
CN112022829A (en) * 2019-06-04 2020-12-04 厦门恩成制药有限公司 Method for preparing esomeprazole magnesium sodium bicarbonate capsule

Similar Documents

Publication Publication Date Title
CN103340892B (en) Compound omeprazole capsule and preparation method thereof and detection method
CN105560249B (en) A kind of pharmaceutical composition containing mosapride citrate
CN101596165A (en) Enteric coated mini-pill of pantoprazole sodium
CN105287424B (en) Sofosbuvir tablet and preparation method thereof
CN101273973B (en) Pharmaceutical combination containing Mosapride citrate
CN109662950B (en) Pharmaceutical composition containing dapoxetine hydrochloride
Gonjari et al. Evaluation of in vitro dissolution profile comparison methods of sustained release tramadol hydrochloride liquisolid compact formulations with marketed sustained release tablets
CN104523746B (en) A kind of esomeprazole magnesium sodium bicarbonate composition
CN103202816A (en) Pantoprazole sodium freeze-dried powder injection
CN115444832A (en) Pharmaceutical composition containing omeprazole magnesium and preparation thereof
CN112022829A (en) Method for preparing esomeprazole magnesium sodium bicarbonate capsule
Rukari et al. Formulation and evaluation of esomeprazole delayed release tablets
CN101829044A (en) Tamibarotene solid preparation and preparation method thereof
Kadam et al. Formulation and evaluation of colon targeted enteric coated tablets of loperamide
CN103385863B (en) Sodium azulene sulfonate sustained-release preparation
CN105796528A (en) Amoxicillin and dicloxacillin sodium compound medicine composition
CN105372372A (en) Detection method of febuxostat tablet
Neharika et al. Design, development and in-vitro evaluation of pinaverium colon targeted tablets
CN105125539A (en) Pioglitazone metformin tablet and preparation method thereof
CN111281875A (en) Composition containing mosapride citrate and preparation method thereof
CN112494459B (en) Medicinal preparation and application thereof
CN115487151B (en) Compound omeprazole dry suspension and preparation method thereof
CN112587491B (en) Famciclovir tablet composition
CN107998091A (en) A kind of montelukast sodium tablet and preparation method thereof
CN116236451B (en) Acarbose tablet, preparation method and application

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination