CN115487151B - Compound omeprazole dry suspension and preparation method thereof - Google Patents
Compound omeprazole dry suspension and preparation method thereof Download PDFInfo
- Publication number
- CN115487151B CN115487151B CN202211135155.7A CN202211135155A CN115487151B CN 115487151 B CN115487151 B CN 115487151B CN 202211135155 A CN202211135155 A CN 202211135155A CN 115487151 B CN115487151 B CN 115487151B
- Authority
- CN
- China
- Prior art keywords
- omeprazole
- dry suspension
- xylitol
- compound
- sucrose
- 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.)
- Active
Links
- 229960000381 omeprazole Drugs 0.000 title claims abstract description 63
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 239000000725 suspension Substances 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 150000001875 compounds Chemical class 0.000 title claims abstract description 31
- 239000002245 particle Substances 0.000 claims abstract description 33
- 239000000463 material Substances 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000000945 filler Substances 0.000 claims abstract description 5
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 4
- 239000000375 suspending agent Substances 0.000 claims abstract description 4
- 239000003765 sweetening agent Substances 0.000 claims abstract description 4
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 239000006172 buffering agent Substances 0.000 claims abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 36
- 229930006000 Sucrose Natural products 0.000 claims description 29
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 29
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 29
- 229960004793 sucrose Drugs 0.000 claims description 29
- 239000000811 xylitol Substances 0.000 claims description 29
- 235000010447 xylitol Nutrition 0.000 claims description 29
- 229960002675 xylitol Drugs 0.000 claims description 29
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 29
- 239000005720 sucrose Substances 0.000 claims description 27
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 26
- 238000002156 mixing Methods 0.000 claims description 25
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 18
- 239000000686 essence Substances 0.000 claims description 11
- 239000004376 Sucralose Substances 0.000 claims description 10
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 10
- 235000019408 sucralose Nutrition 0.000 claims description 10
- 239000000230 xanthan gum Substances 0.000 claims description 10
- 229920001285 xanthan gum Polymers 0.000 claims description 10
- 229940082509 xanthan gum Drugs 0.000 claims description 10
- 235000010493 xanthan gum Nutrition 0.000 claims description 10
- 238000007873 sieving Methods 0.000 claims description 6
- 235000006040 Prunus persica var persica Nutrition 0.000 claims description 5
- 125000000185 sucrose group Chemical group 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical group [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000000872 buffer Substances 0.000 claims description 2
- 240000006413 Prunus persica var. persica Species 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 abstract description 10
- 239000002994 raw material Substances 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 6
- 238000011160 research Methods 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 47
- 239000000047 product Substances 0.000 description 17
- 239000011812 mixed powder Substances 0.000 description 5
- 244000144730 Amygdalus persica Species 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241000124033 Salix Species 0.000 description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 208000000718 duodenal ulcer Diseases 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- 235000012907 honey Nutrition 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229940013618 stevioside Drugs 0.000 description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 2
- 235000019202 steviosides Nutrition 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010063655 Erosive oesophagitis Diseases 0.000 description 1
- 235000016623 Fragaria vesca Nutrition 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 1
- XINCECQTMHSORG-UHFFFAOYSA-N Isoamyl isovalerate Chemical compound CC(C)CCOC(=O)CC(C)C XINCECQTMHSORG-UHFFFAOYSA-N 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 201000008629 Zollinger-Ellison syndrome Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- -1 compound omeprazole sodium bicarbonate Chemical class 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- FPLYNRPOIZEADP-UHFFFAOYSA-N octylsilane Chemical group CCCCCCCC[SiH3] FPLYNRPOIZEADP-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic 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
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a compound omeprazole dry suspension and a preparation method thereof, relating to the field of pharmaceutical compositions. Is prepared by omeprazole and pharmaceutic adjuvant; the medicinal auxiliary materials are selected from one or more of filling agent, sweetening agent, suspending agent, buffering agent and aromatic, and through a large amount of researches in the implementation process, the particle size and the proportion of the auxiliary materials are controlled, so that the adsorption effect of the raw materials can be reduced, the fluidity can be improved, the content uniformity of the product can be ensured, and the fluidity, the content and the content uniformity of the obtained dry suspension can meet the requirements and are superior to the preparations on the market.
Description
Technical Field
The application relates to the field of pharmaceutical compositions, in particular to a compound omeprazole dry suspension and a preparation method thereof.
Background
Omeprazole, the first marketed Proton Pump Inhibitor (PPI), was successfully developed by astomers, sweden, first marketed in switzerland in 1988 and entered the us market in 1989 for the treatment of duodenal ulcers, gastric ulcers, reflux esophagitis and Zollinger-Ellison syndrome, under the trade name "loxeke". The variety is popular in the world and is one of the largest medicines in the US. The traditional Chinese medicine composition is approved to be marketed in 1992 in China, has been widely applied to clinic for more than 20 years, is safe and effective, has few adverse reactions, and has been fully accepted by the public.
Because the primary omeprazole is unstable to acid and can be quickly degraded by gastric acid, most of the preparations sold on the market are enteric preparations, including enteric capsules, enteric tablets, enteric pellets and the like. The omeprazole sodium bicarbonate dry suspension is used for maintaining and treating duodenal ulcer, gastric ulcer, gastroesophageal reflux disease (GERD) and erosive esophagitis, is used in the market abroad for many years, and has definite curative effect and guaranteed safety.
The sodium bicarbonate in the compound omeprazole sodium bicarbonate preparation has the direct effect of neutralizing gastric acid, can prevent omeprazole from being degraded by gastric acid, fully exerts the effect of resisting peptic ulcer of omeprazole, has quick and lasting effect, treats both symptoms and root causes, and can reduce the cost of the original preparation.
Through the analysis result of the preparations on the market, the preparations on the market are all direct mixing technology, and the technology is simple and controllable, but through the technology analysis of the preparations on the market and a large amount of researches, the technology of directly mixing and then filling the products has the problems of serious adsorption of raw material medicines, low content and poor particle flowability.
The inventor conducts repeated research on a compound omeprazole dry suspension disclosed by Chinese patent CN102641286A and a preparation method thereof, the preparation method in the invention mainly controls the particle size of omeprazole within a certain range, so that the preparation can be quickly dissolved and absorbed in vivo, and the research on the adsorption phenomenon, particle fluidity and mixing uniformity in the production process of raw materials of the preparation is not conducted.
Chinese patent CN106798750B discloses a preparation method of compound omeprazole dry suspension, the preparation method comprises a wet granulation process, a drying process, a total mixing process and a separation process, and finally, the dissolution rate, the acid resistance and the maximum impurities of the finally produced compound omeprazole dry suspension are far higher than the national standard, so that the defective rate is greatly reduced, the product quality is improved, and the product curative effect is improved.
Chinese patent CN111388425a discloses a compound omeprazole dry suspension and a preparation method thereof, the preparation method is a wet granulation process, wherein the micronized omeprazole has large sieving loss, the whole process flow is complex, the time consumption is long, and the material and labor cost of the compound omeprazole dry suspension are increased integrally.
However, in the prior art, the adsorption of the compound omeprazole dry suspension to equipment in the production process and the flowability of the product are not concerned, so that the compound omeprazole dry suspension with low adsorbability, good flowability and high mixing uniformity and the preparation method thereof need to be developed.
Disclosure of Invention
Based on the problems in the prior art, the application aims to provide the compound omeprazole dry suspension with low adsorptivity, good fluidity and high mixing uniformity and the preparation method thereof.
In order to achieve the purpose, the following technical scheme is adopted in the application:
a compound omeprazole dry suspension is prepared from omeprazole and medicinal adjuvants.
The pharmaceutical auxiliary materials are selected from one or more of filling agent, sweetening agent, suspending agent, buffering agent and aromatic;
wherein:
the particle size D90 of the omeprazole is less than or equal to 10 mu m; preferably 10 μm.
The filler is sucrose and xylitol, and the particle size D90 of the sucrose is 150-250 μm; the grain size D90 of the xylitol is 100-150 μm.
In some preferred embodiments, the mass ratio of xylitol to sucrose is 1.5 to 3:1; preferably 1.6 to 1.8.
The buffer is sodium bicarbonate, and the particle size D90 of the sodium bicarbonate is 100-200 mu m;
the sweetener is one or two of sucrose, xylitol and sucralose; the flavoring agent is selected from one or more of, but not limited to, juicy peach essence, apple essence and strawberry essence.
The suspending agent is xanthan gum.
As a preferred embodiment, the compound omeprazole dry suspension is prepared by combining 0.68 parts of omeprazole with the D90 of 10 microns, 28.62 parts of sodium bicarbonate with the D90 of 150 microns, 25.55 parts of cane sugar with the D90 of 200 microns, 42.59 parts of xylitol with the D90 of 125 microns, 0.34 parts of xanthan gum, 1.36 parts of sucralose and 0.85 parts of juicy peach essence.
The application also provides a preparation method of the compound omeprazole dry suspension, which comprises the following steps:
(1) Sieving omeprazole and xylitol in the amount of the prescription together to obtain a material A;
(2) And (2) mixing the material A obtained in the step (1) with xanthan gum, sucralose, essence, sucrose and sodium bicarbonate to obtain the compound omeprazole dry suspension.
Compared with the prior art, the beneficial effect of this application lies in:
(1) The particle size of the xylitol is controlled to be 100-150 mu m, the particle size of the sucrose is controlled to be 150-250 mu m, and the mass ratio of the xylitol to the sucrose is controlled to be 1.5-3:1, so that the adsorption effect of the raw materials can be effectively reduced, and the main reason is presumed to be that the raw materials are adsorbed on the surfaces of the auxiliary materials by controlling the particle sizes and the proportion of the two auxiliary materials, so that the adsorption of the raw materials in the production process is reduced;
(2) The particle size of the sodium bicarbonate is controlled to be 100-200 mu m, so that the obtained product has better fluidity, and the content uniformity of the product is ensured;
(3) The compound omeprazole dry suspension provided by the invention reduces raw material adsorption, improves the fluidity of the product, reduces the cost, enables the product to be produced in a large scale and reduces the problem of reduced clinical effectiveness caused by uneven content.
Detailed Description
The present invention will be described in further detail with reference to the following experiments and specific embodiments. It should not be understood that the scope of the above-described subject matter of the present invention is limited to the following examples, and any technique realized based on the present disclosure falls within the scope of the present invention.
The raw and auxiliary materials used by the invention are as follows:
example 1 Compound omeprazole dry suspension and preparation method thereof
The formula is as follows:
| name of material | mg/bag | In proportion% |
| Omeprazole (D90 is 10 μm) | 40 | 0.68 |
| Sodium bicarbonate (D90 150 μm) | 1680 | 28.62 |
| Sucrose (D90 is 200 μm) | 1500 | 25.55 |
| Xylitol (D90 is 125 μm) | 2500 | 42.59 |
| Xanthan gum | 20 | 0.34 |
| Sucralose | 80 | 1.36 |
| Honey peach flavor essence | 50 | 0.85 |
| Total of | 5870 | 100 |
| Loading capacity | 5870 | / |
The preparation method comprises the following steps:
(1) Sieving omeprazole in a prescription amount and xylitol in a prescription amount together by a 40-mesh sieve to obtain a material A;
(2) Mixing the material A in the step (1) with xanthan gum, sucralose and essence according to the prescription amount for 15 minutes to obtain a material B;
(3) And (3) mixing the material B obtained in the step (2) with the sucrose and the sodium bicarbonate according to the prescription amount for 15 minutes to obtain the compound omeprazole dry suspension.
Example 2 Compound omeprazole dry suspension and preparation method thereof
The formula is as follows:
the preparation method comprises the following steps:
(1) Sieving omeprazole in a prescription amount and xylitol in a prescription amount together by a 40-mesh sieve to obtain a material A;
(2) Mixing the material A in the step (1) with xanthan gum, sucralose and essence according to the prescription amount for 15 minutes to obtain a material B;
(3) And (3) mixing the material B in the step (2) with the sucrose and the sodium bicarbonate in the prescription amount for 15 minutes to obtain the compound omeprazole dry suspension.
Example 3 Compound omeprazole dry suspension and preparation method thereof
The formula is as follows:
| name of material | mg/bag | In proportion% |
| Omeprazole (D90 is 10 μm) | 40 | 0.68 |
| Sodium bicarbonate (D90 is 200 μm) | 1680 | 28.62 |
| Sucrose (D90 is 150 μm) | 1000 | 17.04 |
| Xylitol (D90 is 250 μm) | 3000 | 51.11 |
| Xanthan gum | 20 | 0.34 |
| Sucralose | 80 | 1.36 |
| Honey peach flavor essence | 50 | 0.85 |
| Total of | 5870 | 100 |
| Loading capacity | 5870 | / |
The preparation method comprises the following steps:
(1) Sieving omeprazole with xylitol with the prescription amount together by a 40-mesh sieve to obtain a material A;
(2) Mixing the material A in the step (1) with xanthan gum, sucralose and essence according to the prescription amount for 15 minutes to obtain a material B;
(3) And (3) mixing the material B in the step (2) with the sucrose and the sodium bicarbonate in the prescription amount for 15 minutes to obtain the compound omeprazole dry suspension.
Comparative example 1
The difference from example 1 is only that the xylitol has a particle size D90 of 170 μm and the content of the components is the same as that of example 1.
Comparative example 2
The difference from example 1 is only that the xylitol has a particle size D90 of 80 μm and the content of the components is the same as that of example 1.
Comparative example 3
The only difference from example 1 is that the sucrose particle size D90 was 260. Mu.m, and the content of the components was the same as that of example 1.
Comparative example 4
The only difference from example 1 is that the sucrose particle size D90 was 145. Mu.m, and the content of the components was the same as that of example 1.
Comparative example 5
The difference from example 1 is only that the xylitol is used in 3200 parts, the sucrose is used in 800 parts, the ratio is 4:1, and the component content and the particle size are the same as example 1.
Comparative example 6
The difference from the example 1 is only that the dosage of the xylitol is 2333 parts, the dosage of the sucrose is 1667 parts, the proportion is 1.4.
Comparative example 7
The only difference from example 1 is that the sodium bicarbonate particle size D90 is 80 μm, and the component content is the same as in example 1.
Comparative example 8
The only difference from example 1 is that the sodium bicarbonate particle size D90 is 220 μm, and the component content is the same as in example 1.
Comparative example 9
The only difference from example 1 is that the omeprazole has a particle size D90 of 12 μm and the contents of its components are the same as those of example 1.
Comparative example 10
The only difference from example 1 is that sucrose is replaced by stevioside, which has a particle size D90 of about 180 μm and the same component content as in example 1.
Comparative example 11
The only difference from example 1 is that xylitol was replaced with mannitol having a particle size D90 of about 130 μm and having the same content of components as in example 1.
And (3) product quality detection:
1. the dry suspension content detection method comprises the following steps: referring to the Chinese pharmacopoeia 2020 edition, high performance liquid chromatography; wavelength: 305nm; a chromatographic column: octyl silane bonded silica gel chromatography column.
2. The method for detecting the mixing uniformity of the omeprazole of the dry suspension comprises the following steps: measuring the content of each point, calculating the mixing uniformity, and evaluating the RSD by the RSD to be less than or equal to 5.0 percent and basically meeting the requirement;
3. the method for detecting the content uniformity of the omeprazole in the dry suspension comprises the following steps: measuring the content of each point, wherein the content range is 95-105 percent and basically meets the requirement; calculating the content uniformity, evaluating by RSD to be less than or equal to 5.0 percent, and basically meeting the requirement;
4. the angle of repose of the dry suspension is mainly used for evaluating the fluidity, and the determination method comprises the following steps: the powder is slowly added from the upper part of the funnel, and the inclination angle of a conical accumulation body formed on the horizontal plane by the material leaked from the bottom of the funnel is the angle of repose. The judged limit is that the fluidity is satisfactory when the angle of repose is less than 30 degrees, and poor when the angle of repose is less than 30 degrees.
Respectively sampling 11 point positions of the intermediate products obtained in the examples 1-3 and the comparative examples 1-11 in a mixing barrel after total mixing, determining the content of omeprazole, and calculating the content and the content uniformity, which are detailed in table 1;
TABLE 1 data of the total powder content and the mixing uniformity in examples 1-3 and comparative examples 1-11
| Examples of the invention | Theoretical content | Measured content (%) | RSD(％) |
| Example 1 | 0.68 | 0.68 | 0.42 |
| Example 2 | 0.68 | 0.68 | 1.12 |
| Example 3 | 0.68 | 0.68 | 0.65 |
| Comparative example 1 | 0.68 | 0.59 | 4.27 |
| Comparative example 2 | 0.68 | 0.55 | 4.42 |
| Comparative example 3 | 0.68 | 0.58 | 8.42 |
| Comparative example 4 | 0.68 | 0.62 | 5.46 |
| Comparative example 5 | 0.68 | 0.56 | 4.42 |
| Comparative example 6 | 0.68 | 0.59 | 4.26 |
| Comparative example 7 | 0.68 | 0.66 | 8.14 |
| Comparative example 8 | 0.68 | 0.65 | 6.55 |
| Comparative example 9 | 0.68 | 0.61 | 4.64 |
| Comparative example 10 | 0.68 | 0.51 | 7.42 |
| Comparative example 11 | 0.68 | 0.54 | 8.18 |
The finished products obtained after filling the real reference preparation (batch number: CBFZZ, manufacturer: salix) and examples 1-3 and comparative examples 1-11 were tested for the content uniformity of omeprazole in unit dose of 6 parts and the content of omeprazole was calculated, and the final results are shown in Table 2;
TABLE 2 results of data on content and content uniformity of finished products of examples 1-3 and comparative examples 1-11
The angles of repose were determined by measuring the angles of repose of examples 1 to 3 and comparative examples 1 to 11 and a reference preparation (lot: CBFZZ, manufacturer: salix), and the results are shown in Table 3.
TABLE 3 results of angle of repose test data for reference formulations and products of examples 1-3 and comparative examples 1-11
| Examples of the invention | Angle of repose (°) |
| Reference formulation | 35.74 |
| Example 1 | 22.42 |
| Example 2 | 25.44 |
| Example 3 | 20.67 |
| Comparative example 1 | 18.64 |
| Comparative example 2 | 36.17 |
| Comparative example 3 | 17.55 |
| Comparative example 4 | 34.27 |
| Comparative example 5 | 35.48 |
| Comparative example 6 | 18.95 |
| Comparative example 7 | 35.49 |
| Comparative example 8 | 19.17 |
| Comparative example 9 | 25.40 |
| Comparative example 10 | 45.26 |
| Comparative example 11 | 40.43 |
As is clear from the results of the measurements in tables 1 to 3:
(1) The content proportion and the particle size range of each raw and auxiliary material in the examples 1-3 are all within the protection range of the application, and the content, the content uniformity of the total mixed powder, the powder flowability and the content uniformity of the finished product of the dry suspension can meet the requirements;
(2) Comparative examples 1-2 change the particle size D90 of xylitol to 170 μm or 80 μm, which is not in the protection range of the application, the content is lower, and the raw materials have certain adsorption; comparative examples 3-4, changing the grain diameter D90 of sucrose to 260 μm or 145 μm, which is not within the protection scope of the present application, and the RSD measured by mixing uniformity is more than 5%, which indicates that the mixing uniformity is poor due to the adsorption of the raw material, thereby proving that the grain diameter of xylitol is controlled to be 100-150 μm, the grain diameter of sucrose is 150-250 μm, and the mixing uniformity and the content uniformity can meet the requirements;
(3) The comparative examples 5 to 6 change the weight ratio of the xylitol to the sucrose out of the protection range of the application, the content of the total mixed powder and the content of the finished product are lower, which shows that the adsorption exists, thereby proving that the mixing uniformity and the content uniformity can meet the requirements only when the weight ratio of the xylitol to the sucrose is controlled to be 1.5 to 3:1;
(4) In comparative examples 7 to 8, the particle size D90 of sodium bicarbonate was changed to 80 μm or 220 μm, which is outside the scope of the present application, the mixing uniformity RSD of the total mixed powder was large, and the larger angle of repose indicated that the fluidity was poor, thus proving that controlling the particle size of sodium bicarbonate to be in the range of 100 to 200 μm was satisfactory.
(5) Comparative example 9, the particle size D90 of omeprazole was changed to 12 μm, which is not within the scope of the present application, and the content of the finished product is low, indicating that large particle size omeprazole has a great risk for content uniformity. Therefore, the omeprazole particle size D90 is controlled to be less than or equal to 10 mu m, and the requirements can be met.
(6) Comparative example 10, after sucrose was replaced with stevioside, the content was low, the content uniformity of the total mixed powder and the content uniformity of the finished product were both high, the fluidity was poor, and the requirements were not met;
(7) Comparative example 11, after replacing xylitol with mannitol, the absolute content of the mixing uniformity is lower, the content uniformity of the mixed powder and the content uniformity of the finished product are both higher, the fluidity is poorer, and the requirements are not met.
And (4) conclusion:
the results of the above examples and comparative examples were combined to show that the invention within the scope of the present invention is satisfactory and the invention not within the scope of the present invention does not meet the intended requirements.
Although the present invention has been described in detail with reference to examples, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the scope of the present invention as set forth in the claims below.
Claims (6)
1. The compound omeprazole dry suspension is characterized in that: is prepared by combining omeprazole and pharmaceutic adjuvant; the pharmaceutic adjuvant is selected from one or more of a filling agent, a sweetening agent, a suspending agent, a buffering agent and an aromatic;
the particle size D90 of the omeprazole is less than or equal to 10 mu m;
the filler is sucrose and xylitol, and the particle size D90 of the sucrose is 150-250 μm; the grain diameter D90 of the xylitol is 100-150 mu m;
the mass ratio of the xylitol to the sucrose is 1.5-3:1;
the buffer is sodium bicarbonate, and the particle size D90 of the sodium bicarbonate is 100-200 mu m.
2. The compound omeprazole dry suspension according to claim 1, which is characterized in that: the particle size D90 of the omeprazole is 10 mu m.
3. The compound omeprazole dry suspension according to claim 1, which is characterized in that: the grain diameter D90 of the sucrose is 200 mu m; the grain diameter D90 of the xylitol is 125 mu m.
4. The compound omeprazole dry suspension according to claim 1, which is characterized in that: the particle diameter D90 of the sodium bicarbonate is 150 μm.
5. The dry suspension of compound omeprazole according to any of claims 1-4, characterized in that: the compound omeprazole dry suspension is prepared by combining 0.68 part of omeprazole with the D90 of 10 mu m, 28.62 parts of sodium bicarbonate with the D90 of 150 mu m, 25.55 parts of cane sugar with the D90 of 200 mu m, 42.59 parts of xylitol with the D90 of 125 mu m, 0.34 part of xanthan gum, 1.36 parts of sucralose and 0.85 part of juicy peach essence.
6. The preparation method of the compound omeprazole dry suspension according to claim 5, which is characterized in that: the method comprises the following steps:
(1) Sieving omeprazole and xylitol in the amount of the prescription together to obtain a material A;
(2) And (2) mixing the material A obtained in the step (1) with xanthan gum, sucralose, essence, sucrose and sodium bicarbonate to obtain the compound omeprazole dry suspension.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211135155.7A CN115487151B (en) | 2022-09-19 | 2022-09-19 | Compound omeprazole dry suspension and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211135155.7A CN115487151B (en) | 2022-09-19 | 2022-09-19 | Compound omeprazole dry suspension and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115487151A CN115487151A (en) | 2022-12-20 |
| CN115487151B true CN115487151B (en) | 2023-04-07 |
Family
ID=84469984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211135155.7A Active CN115487151B (en) | 2022-09-19 | 2022-09-19 | Compound omeprazole dry suspension and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115487151B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102641286A (en) * | 2012-03-12 | 2012-08-22 | 南京海纳医药科技有限公司 | Compound omeprazole dry suspension and preparation method thereof |
| CN103054896A (en) * | 2012-12-29 | 2013-04-24 | 北京阜康仁生物制药科技有限公司 | Compound dry suspension preparation containing omeprazole and sodium bicarbonate |
| CN106798750B (en) * | 2017-03-23 | 2019-08-20 | 济宁华能制药厂有限公司 | A kind of preparation method of compound omeprazole dry suspension |
| CN111388425B (en) * | 2020-04-22 | 2020-12-08 | 一力制药(罗定)有限公司 | Omeprazole dry suspension and preparation method thereof |
-
2022
- 2022-09-19 CN CN202211135155.7A patent/CN115487151B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN115487151A (en) | 2022-12-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2005945B1 (en) | Oseltamivir phosphate granule and preparation method thereof | |
| CN101389323B (en) | Pharmaceutical composition comprising oseltamivir phosphate | |
| CN108938626B (en) | Carbazochrome sodium sulfonate pharmaceutical composition with good stability and high safety as well as preparation method and application thereof | |
| CN102499923B (en) | Drug combination, as well as preparation method and application of same | |
| CN109662950B (en) | Pharmaceutical composition containing dapoxetine hydrochloride | |
| CN115487151B (en) | Compound omeprazole dry suspension and preparation method thereof | |
| CN105193841A (en) | Compound reserpine medicine composition for treating hypertension and preparation method of compound reserpine medicine composition | |
| CN109908104B (en) | Amoxicillin capsule and preparation method thereof | |
| CN102772395A (en) | Sustained release preparation containing ambroxol hydrochloride and clenbuterol hydrochloride, and preparation method thereof | |
| CN104856970B (en) | A kind of vildagliptin tablet for treating type II diabetes | |
| CN112717137B (en) | Medicinal composition containing oseltamivir phosphate and preparation method thereof | |
| CN113116827B (en) | Oseltamivir phosphate granules and preparation method thereof | |
| CN112386578B (en) | Montelukast sodium chewable tablet and preparation method thereof | |
| CN113504325A (en) | Detection method of changyanning preparation | |
| CN105902564A (en) | Pharmaceutical composition for treating hypertension and preparation method thereof | |
| CN113504326A (en) | Detection method of changyanning preparation | |
| KR101748796B1 (en) | Inhalation capsule with enhanced delivery rate of active ingredients | |
| CN112843001B (en) | Amlodipine preparation and preparation method thereof | |
| EP1547584B1 (en) | Particulate product comprising pantethine | |
| CN113648284B (en) | Tablet containing Sacubitril valsartan sodium and preparation method thereof | |
| EP3799861A1 (en) | Pediatric suspension formulation | |
| CN112546023A (en) | Calcitriol enteric-coated granule | |
| CN113384556A (en) | Gel-forming oral solid preparation for treating hyperacidity and preparation method thereof | |
| CN102764235B (en) | Strontium ranelate dry suspension and preparation method thereof | |
| CN117679370A (en) | Solid dispersion and preparation method and application thereof |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |