CN109288808A - A kind of vegetable cellulose capsule with high dissolution rate - Google Patents
A kind of vegetable cellulose capsule with high dissolution rate Download PDFInfo
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- CN109288808A CN109288808A CN201811346534.4A CN201811346534A CN109288808A CN 109288808 A CN109288808 A CN 109288808A CN 201811346534 A CN201811346534 A CN 201811346534A CN 109288808 A CN109288808 A CN 109288808A
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- Prior art keywords
- capsule
- plant fiber
- dissolution rate
- fiber cellulose
- cellulose capsule
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- 239000002775 capsule Substances 0.000 title claims abstract description 76
- 238000004090 dissolution Methods 0.000 title claims abstract description 31
- 229920002678 cellulose Polymers 0.000 title claims description 17
- 239000001913 cellulose Substances 0.000 title claims description 17
- 235000013311 vegetables Nutrition 0.000 title 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 25
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 25
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 20
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 20
- 239000000661 sodium alginate Substances 0.000 claims abstract description 20
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 20
- 239000000835 fiber Substances 0.000 claims abstract description 15
- 230000002496 gastric effect Effects 0.000 claims abstract description 14
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 14
- 229960003943 hypromellose Drugs 0.000 claims abstract description 13
- 239000012530 fluid Substances 0.000 claims abstract description 12
- 239000003230 hygroscopic agent Substances 0.000 claims abstract description 10
- 239000004094 surface-active agent Substances 0.000 claims abstract description 9
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims description 16
- 235000010333 potassium nitrate Nutrition 0.000 claims description 8
- 239000004323 potassium nitrate Substances 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 4
- 239000001736 Calcium glycerylphosphate Substances 0.000 claims description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 3
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 claims description 3
- UHHRFSOMMCWGSO-UHFFFAOYSA-L calcium glycerophosphate Chemical compound [Ca+2].OCC(CO)OP([O-])([O-])=O UHHRFSOMMCWGSO-UHFFFAOYSA-L 0.000 claims description 3
- 229940095618 calcium glycerophosphate Drugs 0.000 claims description 3
- 235000019299 calcium glycerylphosphate Nutrition 0.000 claims description 3
- -1 polyoxyethylene oleic acid Polymers 0.000 claims description 3
- 229950008882 polysorbate Drugs 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 229940069328 povidone Drugs 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- RZYKUPXRYIOEME-UHFFFAOYSA-N CCCCCCCCCCCC[S] Chemical group CCCCCCCCCCCC[S] RZYKUPXRYIOEME-UHFFFAOYSA-N 0.000 claims 1
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical group CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 241000196324 Embryophyta Species 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 229920000159 gelatin Polymers 0.000 description 7
- 235000019322 gelatine Nutrition 0.000 description 7
- 239000003292 glue Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000003349 gelling agent Substances 0.000 description 5
- 239000001828 Gelatine Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 3
- 229920002148 Gellan gum Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000000216 gellan gum Substances 0.000 description 3
- 235000010492 gellan gum Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000007598 dipping method Methods 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- AEMOLEFTQBMNLQ-AZLKCVHYSA-N (2r,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-AZLKCVHYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-SYJWYVCOSA-N (2s,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-SYJWYVCOSA-N 0.000 description 1
- UJPKMTDFFUTLGM-UHFFFAOYSA-N 1-aminoethanol Chemical compound CC(N)O UJPKMTDFFUTLGM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000512259 Ascophyllum nodosum Species 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 241000985630 Lota lota Species 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000199919 Phaeophyceae Species 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 241000195474 Sargassum Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008104 plant cellulose Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- A61K9/4816—Wall or shell material
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of plant fiber capsules that dissolution rate is high, include following components: 100 parts by weight of hypromellose；15~30 parts by weight of sodium alginate；0.1~1 parts by weight of surfactant；2.5~6 parts by weight of hygroscopic agent.The capsule of invention has the characteristics that rapidly-soluble in simulated gastric fluid gastric solubility drug suitable for slightly solubility.
Description
Technical field
The present invention relates to Medical Packing Materials fields, and in particular to a kind of plant fiber cellulose capsule.
Background technique
Hypromellose (HPMC) plant capsule is the Capsules made of plant cellulose material, meets whole day
So demand of positioning and capsule preparations solution.HPMC plant capsule is a kind of exquisite, preservative free all natural dosage form,
It remains the advantages of Capsules of all standards: conveniently taking, effective taste masking and smell, content is transparent visible
Deng, while more having the unexistent intension of traditional gelatine capsule.
The raw material as used by gelatine capsule are animal product, its molecular structure is very active, it is easy to by
The intrusion of moisture in air, makes content dampness conglomeration, and capsule becomes soft and deformed；Simultaneously again vulnerable to external influence, make water
Divide transfer, capsule, which is hardened, to become fragile, and forms harsh storage requirement；Secondly, remaining lysine, neighbouring lysine residue in gelatin
Oxidation generates aldehyde group, reacts production pyridine ring through Aldehyde-ammonia Condensation and crosslinked action occurs, therefore have in placement process and collapse
Delay phenomenon is solved, to influence effective dissolution rate of content.And the main raw material(s) of plant capsule is hypromellose,
Because of its molecular structure stabilized, in addition the advantages such as water content is low, exactly compensate for deficiency existing for gelatine capsule:
1. molecular structure stabilized, no cross-linking reaction not will lead to disintegration delay；
2. disintegration mode is that entirety dissolves simultaneously, more preferably in the softgel shell for being used as quick releasing formulation；
3. water content is low, it will not become fragile or bonding phenomenon, product weight are easy to control, be more suitable for Chinese medical extract
Filling；
4. small to content Electrostatic Absorption, fragment incidence is low, is conducive to the filling of drug；
5. plant capsule is inert material, interact with content small, is suitble to filling oxygen sensitivity content；
6. plant capsule hardly friability in low-humidity environment, high temperatures are good, and condition of storage requires low, product
Quality is easy to control；
But cellulose capsule has the shortcomings that disintegration time is long, individual difference is big.With the HPMC capsule of certain capsule manufacture quotient
For commercial product, in the disintegration time in simulated gastric fluid mostly between 15-30min, and the individual difference between more capsules
It is obvious, the phenomenon that will appear 45min once in a while；And gelatine capsule generally bursts apart in 1.5-4min, the overwhelming majority in 2-3min,
Disintegration time is than more uniform.
Problem above Producing reason may be to need since the preparation process of HPMC plant hollow capsule makees solvent with water
Add gelling agent, such as gellan gum, because natural plant gum itself is without congealing point, it is necessary to add gelling agent to complete consolidating for glue into HPMC
Change, but the presence of gelling agent can extend the disintegration time of capsule, the potassium ion in dissolving medium can be with the gellan gum hair in capsule
It is raw to be coupled, reduce the solubility and uniformity of HPMC capsule.
Disintegration time is too long to be likely to result in not being able to satisfy the quickly disintegrated demand of some drugs requirement.
Summary of the invention
The present invention provides a kind of plant fiber cellulose capsule and preparation method thereof that dissolution rate is high, it can solve the prior art
The problem that existing capsule dissolution rate in simulated gastric fluid is low, dissolution rate is low.
The technical solution of the present invention is to provide a kind of plant fiber cellulose capsules that dissolution rate is high, include following components:
Hypromellose (HPMC) is a kind of semi-synthetic, inactive polymer, belongs to nonionic cellulose
A kind in compound ether is the main component for preparing capsule in technical solution of the present invention.
Sodium alginate is the by-product after extracting iodine and mannitol in the kelp or sargassum of brown algae, molecule by
Beta-D-mannuronic acid (β-D-mannuronic, M) and α-L- guluronic acid (α-L-guluronic, G) press (1 → 4) key company
It connects, is a kind of natural polysaccharide, stability, dissolubility, viscosity and safety needed for there is pharmaceutical preparation auxiliary material, for white
Or pale yellow powder, almost odorless, tasteless, is dissolved in water into viscous liquid, then viscosity reduces when being heated to 80 DEG C or more.Seaweed
Sour sodium can quickly form gel under conditions of extremely mild.In technical solution of the present invention, by the way that sodium alginate is added,
Sodium alginate is easily converted to insoluble alginic acid, and phenomenon of burst release occurs in gastric juice, to improve dissolution rate.In capsule
Hypromellose be 100 parts by weight meters, if sodium alginate be more than 30 parts by weight, the solution viscosity of sodium alginate and HPMC
It is excessive, it is unfavorable for capsule preparation, and will cause the reduction of dissolution rate；If sodium alginate is less than 15 parts by weight, sodium alginate is in people
Phenomenon of burst release is unobvious in work gastric juice.
Sodium alginate content in HPMC capsule can measure by the following method:
Capsule about 1g after weighing 105 DEG C of dry 6h is dissolved with 100ml distilled water, and adds 1:1 hydrochloric acid about 4ml, makes pH ≈
2, after filtering off precipitating, is dissolved with 0.1moL/L NaOH solution 100ml, make pH ≈ 10, adding 95% ethyl alcohol 200mL makes sea
Mosanom precipitating, after 200 mesh screens, extracting after filter residue 105 DEG C, drying to constant weight.Contained with the weight percent of filter residue and capsule
Measure the content as sodium alginate.
Surfactant, which refers to, is added the substance that significant change occurs for the interface state that can make solution system on a small quantity.It can be with
It enumerates: dodecyl sodium sulfate, lauryl sodium sulfate, polyoxyethylene oleic acid ester, povidone, polysorbate etc..In this hair
In bright technical solution, by the way that surfactant is added, improving hypromellose capsule, capsule is fragile during the preparation process
Broken problem.By the hypromellose in capsule be 100 parts by weight in terms of, if surfactant be more than 1 parts by weight, or less than
0.1 parts by weight all can not effectively improve the breakable problem of capsule in preparation process.
Hygroscopic agent refers to any substance that moisture can be absorbed from environment.Sodium chloride, three second of glycerol can be enumerated
Ester, calcium glycerophosphate etc..In technical solution of the present invention, by the way that hygroscopic agent is added, make capsule can be very in simulated gastric fluid
Quickly water suction, to improve the dissolution rate and dissolution rate of capsule.With the hypromellose in capsule for 100 parts by weight
Meter can have an impact to the surface state of capsule if hygroscopic agent is more than 15 parts by weight, the reduction of capsule transparency, rough surface；If
Hygroscopic agent is less than 2.5 parts by weight, does not have the apparent effect for improving dissolution rate.
In the inventive solutions, preferably have following technical characteristic: the weight percent of hypromellose contains
The aqueous solution that amount is 2%, viscosity is 5-30mPas at 20 DEG C.The HPMC of solution viscosity within this range has good
Water solubility, transparency are high, gelling performance is good, mobile performance is strong, has surface-active.
In the inventive solutions, from the angle for improving dissolution rate and dissolution rate, preferably there is following skill
Art feature: the aqueous solution that the weight percentage of sodium alginate is 1%, viscosity is 200-800mPas at 20 DEG C.
In the inventive solutions, also with following technical characteristic: the potassium nitrate dissolution of 5min in simulated gastric fluid
Degree is 50% or more, and the potassium nitrate dissolution rate of 10min is 80% or more in simulated gastric fluid, and the 15min in simulated gastric fluid
Potassium nitrate dissolution rate is 95% or more.
In the inventive solutions, also have following technical characteristic: friability is 50 this product tests, damaged glue
Capsule is less than 5.
Capsule of the invention can be prepared with well known method, such as be prepared in accordance with the following methods:
Step 1: surfactant, hygroscopic agent, alkaline matter being dissolved into solution with deionized water at room temperature；
Step 2: after the solution of step 1 is heated to 80-100 DEG C, sodium alginate and hypromellose is added, prepares
The solution for being about 25% at concentration expressed in percentage by weight；
Step 3: the solution of step 2 being continued into heating 2-4 hours, obtains the glue of viscosity about 200000mPas；
Step 4: being carried out after dipping in glue with capsule die, in 40 DEG C of dry 2h；
Step 5: again through demoulding, cutting, fitting, inspection and packaging to get arrive the higher plant fiber cellulose capsule of dissolution rate.
The present invention has the advantage that capsule of the invention does not add the gelling agents such as gellan gum compared with prior art, thus
Influence there is no gelling agent to dissolution rate；Sodium alginate is easily converted into insoluble alginic acid in simulated gastric fluid, in stomach
Phenomenon of burst release occurs in liquid, to improve dissolution rate；The addition of surfactant improves the tough of hypromellose capsule
Property, solve the problems, such as that capsule is breakable during the preparation process；Hygroscopic agent can be improved the absorption speed of capsule, to improve capsule
Dissolution rate；In addition, the aqueous solution of sodium alginate viscosity with higher also adds by adding sodium alginate and prepares glue
The viscosity of liquid is conducive to prepare capsule.
Capsule of the invention has the characteristics that rapidly-soluble in simulated gastric fluid gastric solubility drug suitable for slightly solubility.
Specific embodiment
The present invention is further illustrated below by the mode of embodiment, does not therefore limit the present invention to the embodiment
Among range.The techniques implemented on the basis of the foregoing are all within the scope of the present invention.For being familiar with this field
For personnel, other modifications may be easily implemented, therefore without departing substantially from general general defined by claim and equivalency range
Under thought, the present invention is not limited to specific details.
Raw material used, reagent in following embodiment and comparative examples is as follows:
[hydroxypropyl methylcellulose]
South Korea's Lotte Company produces, AN6 type, the aqueous solution that weight percentage is 2%, and viscosity is 6mPa at 20 DEG C
s。
[sodium alginate]
Shanghai Aladdin Chemical Co., Ltd. produces, and the aqueous solution that weight percentage is 1%, viscosity is at 20 DEG C
600mPa·s。
[surfactant]
A1: polysorbate, the upper smooth Science and Technology Co., Ltd. of Haitai produce, purity AR
A2: lauryl sodium sulfate, Shanghai Mike woods biochemical technology Co., Ltd produce, purity AR；
A3: dodecyl sodium sulfate, Shanghai Mike woods biochemical technology Co., Ltd produce, purity AR；
A4: polyoxyethylene oleic acid ester, Mo Bei (Shanghai) Biotechnology Co., Ltd produce；
A5: povidone, Shanghai Jiang Ge Chemical Co., Ltd. produce, purity 98%；
[hygroscopic agent]
B1: sodium chloride, the upper smooth Science and Technology Co., Ltd. of Haitai produce, purity AR；
B2: triethylglycerides, Shanghai Aladdin biochemical technology limited liability company produce, purity AR；
B3: calcium glycerophosphate, Shanghai Jiang Ge Chemical Co., Ltd. produce, purity AR.
Test item and its measuring method of the present invention are as follows, unless otherwise instructed, each test all at 25 DEG C into
Row.
1, it friability: is surveyed by the test method of version " Chinese Pharmacopoeia " four gelatin hollow capsule friabilities in 2015
Examination.
2, dissolution rate: content is 800mg potassium nitrate, and dissolution medium is 800mL 0.1moL/L HCl, using Rotating shaker,
Revolving speed 100r/min, 37 DEG C of temperature.10ml dissolution medium is taken to dilute 5 times respectively in 5min, 10min, 15min, at 236nm
Test absorbance A；Setting reference: taking 800mg potassium nitrate to be dissolved in 800mL 0.1moL/L HCl, and 10ml is taken to dilute 5 times,
Absorbance A is tested under 236nm0；Dissolution rate=A/A0。
3, elasticity: by version " Chinese Pharmacopoeia " four gelatin hollow capsule elasticity test method tests in 2015.
4, water content: the weight difference using at 105 DEG C before and after dry 2h is as water content, and before dry, sample is in 25 DEG C, 50%
It is stored 2 days under RH.
Embodiment 1~12 and comparative example 1~3:
Using each raw material and its proportion shown in table 1,0# Capsules are prepared by following steps.
Step 1: surfactant, hygroscopic agent, alkaline matter being dissolved into solution with deionized water at room temperature；
Step 2: after the solution of step 1 is heated to 80-100 DEG C, sodium alginate and hypromellose is added, prepares
The solution for being about 25% at concentration expressed in percentage by weight；
Step 3: the solution of step 2 being continued into heating 2-4 hours, obtains the glue of viscosity about 200000mPas；
Step 4: being carried out after dipping in glue with capsule die, in 40 DEG C of dry 2h；
Step 5: again through demoulding, cutting, fitting, inspection and packaging to get arrive the higher plant fiber cellulose capsule of dissolution rate.
1 formula table of table
The capsule of embodiment and comparative example is subjected to performance measurement according to detection method provided by the invention, measurement result is such as
Shown in table 2.The water content of each capsule is all 8% ± 1%.
2 the performance test results of table
Therefrom it can be seen that, the water content of the capsule of each embodiment and comparative example does not have substantial differences.Each embodiment
The elasticity and friability of capsule meet the standard of Chinese Pharmacopoeia (2015 editions), have practicability；And there is preferable dissolution rate.
Comparative example 1 only contains HPMC, and friability is higher, and dissolution rate when 5min is only 39%；Sodium alginate content in comparative example 2
Excessive, capsule preparation is difficult, and uniformity is poor, it is high to cause friability, and dissolution rate is lower；Sodium alginate content in comparative example 3
It is lower, it is unobvious to the raising effect of dissolution rate.
Claims (8)
1. a kind of plant fiber cellulose capsule, which is characterized in that include following components:
2. plant fiber cellulose capsule according to claim 1, which is characterized in that the weight of the hypromellose
The aqueous solution that percentage composition is 2%, viscosity is 5-30mPas at 20 DEG C.
3. plant fiber cellulose capsule according to claim 1, which is characterized in that the weight percent of the sodium alginate contains
The aqueous solution that amount is 1%, viscosity is 200-800mPas at 20 DEG C.
4. plant fiber cellulose capsule according to claim 1, which is characterized in that the surfactant is dodecyl sulphur
One of sour sodium, lauryl sodium sulfate, polyoxyethylene oleic acid ester, povidone or polysorbate are a variety of.
5. plant fiber cellulose capsule according to claim 1, which is characterized in that the hygroscopic agent is sodium chloride, glycerol
One of triethyl or calcium glycerophosphate are a variety of.
6. plant fiber cellulose capsule according to claim 1, which is characterized in that the potassium nitrate of 5min is molten in simulated gastric fluid
Out-degree is 50% or more, and the potassium nitrate dissolution rate of 10min is 80% or more in simulated gastric fluid, and the 15min in simulated gastric fluid
Potassium nitrate dissolution rate be 95% or more.
7. plant fiber cellulose capsule according to claim 1, which is characterized in that friability is damaged in 50 capsules of test
Number is no more than 5.
8. a kind of capsule, which is characterized in that contain the described in any item plant fiber cellulose capsules of claim 1~7.
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| CN1741819A (en) * | 2002-10-23 | 2006-03-01 | 韩美药品株式会社 | Sustained-release compositions for oral administration of drugs |
| CN101317831A (en) * | 2008-07-10 | 2008-12-10 | 青岛益青药用胶囊有限公司 | Cellulose, plant polyoses capsule and preparation thereof |
| CN102885799A (en) * | 2012-10-31 | 2013-01-23 | 江苏省庆缘康生物科技有限公司 | Preparation method of gelatine-free double-layer hollow capsule |
| CN103656655A (en) * | 2013-12-11 | 2014-03-26 | 江苏力凡胶囊有限公司 | Empty capsule and preparation method thereof |
| CN104042589A (en) * | 2014-06-20 | 2014-09-17 | 刘杰 | Capsule without animal proteins and preparation method thereof |
| CN105878209A (en) * | 2016-05-13 | 2016-08-24 | 西宁鑫沃化工有限公司 | Plant protein empty capsule and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1741819A (en) * | 2002-10-23 | 2006-03-01 | 韩美药品株式会社 | Sustained-release compositions for oral administration of drugs |
| CN101317831A (en) * | 2008-07-10 | 2008-12-10 | 青岛益青药用胶囊有限公司 | Cellulose, plant polyoses capsule and preparation thereof |
| CN102885799A (en) * | 2012-10-31 | 2013-01-23 | 江苏省庆缘康生物科技有限公司 | Preparation method of gelatine-free double-layer hollow capsule |
| CN103656655A (en) * | 2013-12-11 | 2014-03-26 | 江苏力凡胶囊有限公司 | Empty capsule and preparation method thereof |
| CN104042589A (en) * | 2014-06-20 | 2014-09-17 | 刘杰 | Capsule without animal proteins and preparation method thereof |
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