CN107028890A - A kind of characteristics of indomethacin solid dispersion - Google Patents
A kind of characteristics of indomethacin solid dispersion Download PDFInfo
- Publication number
- CN107028890A CN107028890A CN201710262850.2A CN201710262850A CN107028890A CN 107028890 A CN107028890 A CN 107028890A CN 201710262850 A CN201710262850 A CN 201710262850A CN 107028890 A CN107028890 A CN 107028890A
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- Prior art keywords
- indomethacin
- solid dispersion
- water
- carrier material
- solvent
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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
- A61K9/14—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
- A61K9/146—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 macromolecular compounds
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
Abstract
The present invention discloses a kind of characteristics of indomethacin solid dispersion, belongs to technical field of medicine, is made up of following preparation methods：Water-soluble carrier material is added in solvent, is stirred to dissolve, is then added Indomethacin, it is stirred to dissolve, rotary evaporation eliminates organic solvent after stirring at low speed 1h, residue is dried under reduced pressure 12~24h in an oven, ground after drying in mortar, cross 80 mesh sieves, produce characteristics of indomethacin solid dispersion.The present invention can effectively improve the solubility and dissolution rate of Indomethacin, so as to effectively improve the bioavilability of Indomethacin.
Description
Technical field
The present invention relates to technical field of medicine, more particularly to a kind of characteristics of indomethacin solid dispersion.
Background technology
Indomethacin chemistry is entitled：2- methyl isophthalic acids-(4- chlorobenzene formacyls) -5- methoxyl group -1H- indole-3-acetic acids, molecule
Formula is C19H16ClNO4, molecular weight is 357.79, structural formula such as following formula：
Indomethacin is white or slightly yellow crystalline powder, and fusing point is 158~162 DEG C, is dissolved in acetone, is slightly soluble in second
Alcohol, chloroform, ether, are practically insoluble in water, tasteless, almost odorless.
Indomethacin has anti-inflammatory, antipyretic and analgesic activity, and its mechanism of action is subtracts by the suppression to Cycloxygenase
The synthesis of few prostaglandin, prevents the formation of inflammatory tissue pain nerve impulsion, suppresses inflammatory reaction, including suppress leucocyte
Release of chemotaxis and lysosomal enzyme etc..It is due to that it acts on hypothalamus heat-regulating centers as antipyretic effect, causes outer
All blood vessel dilatation and perspiration, increase radiating, and this central antipyretic effect may also be synthesized with the prostaglandin in hypothalamus
It is suppressed relevant.The acute toxicity tests：Rat oral LD50For 12mg/kg；Its mouse oral LD5For 50mg/kg.
Indoles U.S. Yin is practically insoluble in water, is insoluble drug, insoluble drug (poorly water-soluble
Drug) solubility is small in water, and medicine is difficult to be absorbed by organisms, and internal release rate is very fast, and peak valley easily occurs in blood concentration
Phenomenon, oral formulations bioavilability is low, and is difficult to the variation of formulation.The absorption rate of insoluble drug generally depends on
In dissolution rate, dissolution rate is improved with the raising of decentralization.
The content of the invention
The invention provides a kind of characteristics of indomethacin solid dispersion, existing Indomethacin preparation dissolution rate is solved relatively low
Problem.
In order to solve the above technical problems, the technical scheme is that：
A kind of characteristics of indomethacin solid dispersion, is made up of following preparation methods：Water-soluble carrier material adds solvent
In, it is stirred to dissolve, then adds Indomethacin, be stirred to dissolve, rotary evaporation eliminates organic solvent after stirring at low speed 1h, remains
Excess is dried under reduced pressure 12~24h in an oven, is ground after drying in mortar, crosses 80 mesh sieves, produces Indomethacin solid and disperses
Body.
Wherein it is preferred to, the water soluble carrier material is PVP K30, polyethylene glycol, PVPP
Any one of polyethylene glycol oxide carboxymethyl cellulose.
Wherein it is preferred to, the solvent is that volume ratio is 2：1 second alcohol and water, volume ratio are 2:1 first alcohol and water or body
Product is than being 2:1 acetone and water.
Wherein it is preferred to, the temperature control being dried under reduced pressure is at 45~55 DEG C.
Wherein it is preferred to, the usage ratio of the water soluble carrier material and the solvent is 1g：5~7ml.
Wherein it is preferred to, the weight ratio of the water soluble carrier material and the Indomethacin is 2~3:1.
Beneficial effect of the present invention：
The present invention can effectively improve the solubility and dissolution rate of Indomethacin, beautiful so as to effectively improve indoles
Pungent bioavilability.
In Vitro Dissolution, which is tested, to be shown, solid dispersions prepared by the present invention, compared with the Indomethacin with crystalline state, in 0.1M
In hydrochloric acid solution, pH 4.5, pH 6.0 and pH 7.4 microcosmic salt buffer solution, the water solubility of Indomethacin is improved, and has
Higher dissolution rate.
Brief description of the drawings
In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing
There is the accompanying drawing used required in technology description to be briefly described, it should be apparent that, drawings in the following description are only this
Some embodiments of invention, for those of ordinary skill in the art, without having to pay creative labor, may be used also
To obtain other accompanying drawings according to these accompanying drawings.
Fig. 1 is the stripping curve figure of the embodiment of the present invention 1；
Fig. 2 is the stripping curve figure of the embodiment of the present invention 2；
Fig. 3 is the stripping curve figure of the embodiment of the present invention 3；
Fig. 4 is the stripping curve figure of the embodiment of the present invention 4；
Fig. 5 is the stripping curve figure of the embodiment of the present invention 5.
Embodiment
Below in conjunction with the specific embodiment of the invention, the technical scheme to the present invention carries out clear, complete description, institute
The example of description is only the section Example of the present invention, rather than whole embodiments.Based on the embodiment in the present invention, sheet
Field those of ordinary skill, the every other embodiment obtained under the premise of creative work is not made, belongs to this hair
Bright protection domain.
Embodiment 1
The present embodiment provides a kind of characteristics of indomethacin solid dispersion, is made up of following preparation methods：Water-soluble carrier
Material is added in solvent, is stirred to dissolve, is then added Indomethacin, be stirred to dissolve, rotary evaporation is removed after stirring at low speed 1h
Most organic solvent, residue is dried under reduced pressure 18h for 45~55 DEG C in an oven, is ground after drying in mortar, crosses 80 mesh sieves, produces
Characteristics of indomethacin solid dispersion.
Wherein, the water soluble carrier material is PVP K30.
Wherein, the solvent is that volume ratio is 2：1 second alcohol and water.
Wherein, the usage ratio of the water soluble carrier material and the solvent is 1g：6ml.
Wherein, the weight ratio of the water soluble carrier material and the Indomethacin is 2.5:1.
The sample and bulk drug for taking the above method to prepare, are placed in wide-mouth bottle, and the microcosmic salt for adding 200m L pH 7.4 delays
Fliud flushing is as dissolution medium, rolling of being shaken in 37 DEG C of shaking tables, in different time points sampling, through filtering with microporous membrane, surveys its absorbance,
The solubility of comparative sample.Stripping curve figure is as shown in Figure 1.
It can be seen from Fig. 1 stripping curve compared with bulk drug, the dissolution rate and dissolution rate of solid dispersions have
It is obvious to improve.
Embodiment 2
The present embodiment provides a kind of characteristics of indomethacin solid dispersion, is made up of following preparation methods：Water-soluble carrier
Material is added in solvent, is stirred to dissolve, is then added Indomethacin, be stirred to dissolve, rotary evaporation is removed after stirring at low speed 1h
Most organic solvent, residue is dried under reduced pressure 12h for 45~55 DEG C in an oven, is ground after drying in mortar, crosses 80 mesh sieves, produces
Characteristics of indomethacin solid dispersion.
Wherein, the water soluble carrier material is polyethylene glycol.
Wherein, the solvent is that volume ratio is 2:1 first alcohol and water.
Wherein, the usage ratio of the water soluble carrier material and the solvent is 1g：5ml.
Wherein, the weight ratio of the water soluble carrier material and the Indomethacin is 3:1.
The sample and bulk drug for taking the above method to prepare, are placed in wide-mouth bottle, and the microcosmic salt for adding 200m L pH 7.4 delays
Fliud flushing is as dissolution medium, rolling of being shaken in 37 DEG C of shaking tables, in different time points sampling, through filtering with microporous membrane, surveys its absorbance,
The solubility of comparative sample.Stripping curve figure is as shown in Figure 2.
It can be seen from Fig. 2 stripping curve compared with bulk drug, the dissolution rate and dissolution rate of solid dispersions have
It is obvious to improve.
Embodiment 3
The present embodiment provides a kind of characteristics of indomethacin solid dispersion, is made up of following preparation methods：Water-soluble carrier
Material is added in solvent, is stirred to dissolve, is then added Indomethacin, be stirred to dissolve, rotary evaporation is removed after stirring at low speed 1h
Most organic solvent, residue is dried under reduced pressure 24h for 45~55 DEG C in an oven, is ground after drying in mortar, crosses 80 mesh sieves, produces
Characteristics of indomethacin solid dispersion.
Wherein, the water soluble carrier material is PVPP.
Wherein, the solvent is that volume ratio is that volume ratio is 2:1 acetone and water.
Wherein, the usage ratio of the water soluble carrier material and the solvent is 1g：7ml.
Wherein, the weight ratio of the water soluble carrier material and the Indomethacin is 2:1.
The sample and bulk drug for taking the above method to prepare, are placed in wide-mouth bottle, and the microcosmic salt for adding 200m L pH 7.4 delays
Fliud flushing is as dissolution medium, rolling of being shaken in 37 DEG C of shaking tables, in different time points sampling, through filtering with microporous membrane, surveys its absorbance,
The solubility of comparative sample.Stripping curve figure is as shown in Figure 3.
It can be seen from Fig. 3 stripping curve compared with bulk drug, the dissolution rate and dissolution rate of solid dispersions have
It is obvious to improve.
Embodiment 4
The present embodiment provides a kind of characteristics of indomethacin solid dispersion, is made up of following preparation methods：Water-soluble carrier
Material is added in solvent, is stirred to dissolve, is then added Indomethacin, be stirred to dissolve, rotary evaporation is removed after stirring at low speed 1h
Most organic solvent, residue is dried under reduced pressure 16h for 45~55 DEG C in an oven, is ground after drying in mortar, crosses 80 mesh sieves, produces
Characteristics of indomethacin solid dispersion.
Wherein, the water soluble carrier material is polyethylene glycol oxide.
Wherein, the solvent is that volume ratio is 2：1 second alcohol and water.
Wherein, the usage ratio of the water soluble carrier material and the solvent is 1g：6ml.
Wherein, the weight ratio of the water soluble carrier material and the Indomethacin is 2.6:1.
The sample and bulk drug for taking the above method to prepare, are placed in wide-mouth bottle, and the microcosmic salt for adding 200m L pH 7.4 delays
Fliud flushing is as dissolution medium, rolling of being shaken in 37 DEG C of shaking tables, in different time points sampling, through filtering with microporous membrane, surveys its absorbance,
The solubility of comparative sample.Stripping curve figure is as shown in Figure 4.
It can be seen from Fig. 4 stripping curve compared with bulk drug, the dissolution rate and dissolution rate of solid dispersions have
It is obvious to improve.
Embodiment 5
The present embodiment provides a kind of characteristics of indomethacin solid dispersion, is made up of following preparation methods：Water-soluble carrier
Material is added in solvent, is stirred to dissolve, is then added Indomethacin, be stirred to dissolve, rotary evaporation is removed after stirring at low speed 1h
Most organic solvent, residue is dried under reduced pressure 20h for 45~55 DEG C in an oven, is ground after drying in mortar, crosses 80 mesh sieves, produces
Characteristics of indomethacin solid dispersion.
Wherein, the water soluble carrier material is carboxymethyl cellulose.
Wherein, the solvent is that volume ratio is 2:1 acetone and water.
Wherein, the usage ratio of the water soluble carrier material and the solvent is 1g：7ml.
Wherein, the weight ratio of the water soluble carrier material and the Indomethacin is 2：1.
The sample and bulk drug for taking the above method to prepare, are placed in wide-mouth bottle, and the microcosmic salt for adding 200m L pH 7.4 delays
Fliud flushing is as dissolution medium, rolling of being shaken in 37 DEG C of shaking tables, in different time points sampling, through filtering with microporous membrane, surveys its absorbance,
The solubility of comparative sample.Stripping curve figure is as shown in Figure 5.
It can be seen from Fig. 5 stripping curve compared with bulk drug, the dissolution rate and dissolution rate of solid dispersions have
It is obvious to improve.
Solid dispersions made from above-described embodiment equally also delay in 0.1N hydrochloric acid solutions, pH 4.5, the phosphate of pH 6.0
Make Dissolution Rate Testing in fliud flushing, as a result show, solid dispersions produced by the present invention are compared with bulk drug, dissolution rate and dissolution
Degree is also what is significantly improved.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
God is with principle, and any modification, equivalent substitution and improvements made etc. should be included in the scope of the protection.
Claims (6)
1. a kind of characteristics of indomethacin solid dispersion, it is characterised in that be made up of following preparation methods：Water-soluble carrier material
Add in solvent, be stirred to dissolve, then add Indomethacin, be stirred to dissolve, rotary evaporation has been eliminated after stirring at low speed 1h
Machine solvent, residue is dried under reduced pressure 12~24h in an oven, is ground after drying in mortar, crosses 80 mesh sieves, produces Indomethacin
Solid dispersions.
2. a kind of characteristics of indomethacin solid dispersion according to claim 1, it is characterised in that：The water soluble carrier material
For any one of PVP K30, polyethylene glycol, PVPP, polyethylene glycol oxide, carboxymethyl cellulose.
3. a kind of characteristics of indomethacin solid dispersion according to claim 1, it is characterised in that：The solvent is that volume ratio is
2：1 second alcohol and water, volume ratio are 2:1 first alcohol and water or volume ratio is 2:1 acetone and water.
4. a kind of characteristics of indomethacin solid dispersion according to claim 1, it is characterised in that：The temperature being dried under reduced pressure
Control is at 45~55 DEG C.
5. a kind of characteristics of indomethacin solid dispersion according to claim 1, it is characterised in that：The water soluble carrier material
Usage ratio with the solvent is 1g：5~7ml.
6. a kind of characteristics of indomethacin solid dispersion according to claim 1, it is characterised in that：The water soluble carrier material
Weight ratio with the Indomethacin is 2~3:1.
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| CN201710262850.2A CN107028890A (en) | 2017-04-20 | 2017-04-20 | A kind of characteristics of indomethacin solid dispersion |
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| CN201710262850.2A CN107028890A (en) | 2017-04-20 | 2017-04-20 | A kind of characteristics of indomethacin solid dispersion |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111658615A (en) * | 2020-07-31 | 2020-09-15 | 青岛科技大学 | Indometacin nano particle and preparation method thereof |
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| CN101732233A (en) * | 2009-11-19 | 2010-06-16 | 浙江工业大学 | Method for preparing solid dispersion |
| WO2010133611A1 (en) * | 2009-05-18 | 2010-11-25 | Royal College Of Surgeons In Ireland | Solid drug dispersions |
| CN106138006A (en) * | 2015-03-26 | 2016-11-23 | 天津药物研究院有限公司 | A kind of capsule containing characteristics of indomethacin solid dispersion and preparation method thereof |
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2017
- 2017-04-20 CN CN201710262850.2A patent/CN107028890A/en active Pending
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| WO2010133611A1 (en) * | 2009-05-18 | 2010-11-25 | Royal College Of Surgeons In Ireland | Solid drug dispersions |
| CN101732233A (en) * | 2009-11-19 | 2010-06-16 | 浙江工业大学 | Method for preparing solid dispersion |
| CN106138006A (en) * | 2015-03-26 | 2016-11-23 | 天津药物研究院有限公司 | A kind of capsule containing characteristics of indomethacin solid dispersion and preparation method thereof |
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| CN111658615A (en) * | 2020-07-31 | 2020-09-15 | 青岛科技大学 | Indometacin nano particle and preparation method thereof |
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Application publication date: 20170811 |