CN109288808A - A kind of plant fiber cellulose capsule that dissolution rate is high - Google Patents
A kind of plant fiber cellulose capsule that dissolution rate is high 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
- plant fiber
- capsule
- fiber cellulose
- dissolution rate
- cellulose capsule
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- 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
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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811346534.4A CN109288808A (en) | 2018-11-13 | 2018-11-13 | A kind of plant fiber cellulose capsule that dissolution rate is high |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811346534.4A CN109288808A (en) | 2018-11-13 | 2018-11-13 | A kind of plant fiber cellulose capsule that dissolution rate is high |
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| Publication Number | Publication Date |
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| CN109288808A true CN109288808A (en) | 2019-02-01 |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1741819A (en) * | 2002-10-23 | 2006-03-01 | 韩美药品株式会社 | Sustained release composition 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 |
-
2018
- 2018-11-13 CN CN201811346534.4A patent/CN109288808A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1741819A (en) * | 2002-10-23 | 2006-03-01 | 韩美药品株式会社 | Sustained release composition 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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Application publication date: 20190201 |
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