CN104415340A - Solid drug preparation and preparing method thereof - Google Patents
Solid drug preparation and preparing method thereof Download PDFInfo
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- CN104415340A CN104415340A CN201310376999.5A CN201310376999A CN104415340A CN 104415340 A CN104415340 A CN 104415340A CN 201310376999 A CN201310376999 A CN 201310376999A CN 104415340 A CN104415340 A CN 104415340A
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- insoluble drug
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Abstract
The invention relates to a solid drug preparation and a preparing method thereof; a combined carrier is adopted and contains a water-soluble polymer and an inorganic porous material, and an insoluble drug and the water-soluble polymer form a complex attached to the surface of the inorganic porous material; the weight ratio of the water-soluble polymer to the insoluble drug is 3-20:1; the weight ratio of the inorganic porous material to the insoluble drug is 4-10:1. The solid preparation has the advantages of simple preparation process, significantly improves the dissolution rate of the insoluble drug, has stable properties, and has no organic solvent residue.
Description
Technical field
The present invention relates to a kind of solid pharmaceutical preparation and preparation method thereof, belong to medicine, field of health care products.
Background technology
At design solid pharmaceutical preparation, particularly during oral formulations, bioavailability investigates the important one side of medicine effect.Permitted the bioavailability of multifactor impact oral administration.These factors comprise the dissolution of medicine in water, the drug absorption in whole digestive tract, and dose intensity and head cross elimination effect.Dissolution wherein in medicine water is the deciding factor in exploitation medicine.But, for poorly soluble in water of many chemical substances of medicine and only few dosage shift in blood and absorb, therefore their bioavailability is very low.
Solid dispersion technology has been widely used in and has improved insoluble drug dissolution, and many insoluble drugs drop into practice as solid dispersion medicine.Solid dispersion is defined as " being dispersed in solid inert carrier by one or more active component by fusion method, solvent method or solvent-fusion method ".
In solid dispersion system, have certain dissolubility due to carrier to medicine, medicine is often dispersed in carrier material with amorphous.
At first, first generation solid dispersion system uses carrier crystal.Pass through some carrier molecules in replacement lattice at this system Chinese medicine molecule or be inserted in carrier molecule centre when not affecting lattice structure thus be merged in support crystal lattice.After this amorphous carrier developed, it can make medicine with amorphous better dispersion.Amorphous substance is in higher energy state, therefore, has higher dissolubility and dissolution rate compared with crystal, and then can improve the bioavailability of medicine.
Solid dispersion system although it is so greatly can improve the dissolution of medicine, but still there is some problems, and one of them problem is exactly the stability of gained solid dispersion, because in processing or storing process, the amorphous state of medicine may recrystallization.Used carrier is generally hydrophilic carrier, easy moisture absorption, easily causes being separated, medicine crystal growth or be converted into more stable crystalline state.All these all can cause dissolution to reduce and rate of dissolution declines, thus reduce bioavailability.
Therefore, how being designed by solid carrier, both improved insoluble drug dissolution, also can keep the stability of solid preparation simultaneously, is that current medical researches and develops the difficult problem faced.The present invention, by solid dispersions technique, uses joint vector, improves the dissolution of insoluble drug and have good stability in prepared solid preparation storing process.
Summary of the invention
The object of the invention is by solid dispersions technique, improve the dissolution of insoluble drug, improve its bioavailability, prepare the solid preparation had good stability in storing process.
Concrete invention is as follows: a kind of solid pharmaceutical preparation, it is characterized in that: adopt joint vector, this joint vector comprises water-soluble polymer and inorganic porous material, and described insoluble drug and water-soluble polymer form complex and be attached on the surface of inorganic porous material; The weight ratio of water-soluble polymer and insoluble drug is 3-20:1; The weight ratio of inorganic porous material and insoluble drug is 4-10:1.
On the basis of such scheme, the optimum ratio amount of described various component is: the weight ratio of polyvinylpyrrolidone and described insoluble drug is 3-20:1; The weight ratio of hydroxypropyl emthylcellulose and described insoluble drug is 6-15:1; The weight ratio of described organic solvent and insoluble drug is 10-20:1.
A kind of joint vector solid preparation method, carries out: insoluble drug and described water-soluble polymer dissolves obtain solution in organic solvent as follows, by this solution and inorganic porous material mix and blend, then drying, pulverizes and obtain described solid preparation.
Solid preparation preparation technology of the present invention is simple, significantly improves the dissolution of insoluble drug, stable in properties, and organic solvent-free remains, and therefore can be suitable for most of insoluble drug.
Infer and have hydrogen bond to exist between the water-soluble polymer in insoluble drug and these solid preparations, insoluble drug and water-soluble polymer form complex and are attached on the surface of inorganic porous material, porous mass water absorption is strong, the dissolving of water-soluble substances promotes the dissolving of insoluble drug, and but joint vector has medicine brilliant effect, makes medicine keep amorphous state.
In addition, the solid preparation prepared by the present invention, is uniformly dispersed, and does not stick to internal tank, can be directly loaded in hard capsule or in statu quo tabletting.
Accompanying drawing explanation
Fig. 1 is dissolution results figure;
Fig. 2 is unbodied verification test result figure.
Detailed description of the invention
Example 1
Below, state the present invention in detail by embodiment and testing example, but the invention is not restricted to these.
(1) 1g resveratrol is joined in 20g dehydrated alcohol, fully dissolve;
(2) 5g polyvinylpyrrolidone (PVPK29/32) is joined gradually in the resveratrol ethanol solution that step (1) dissolved, be stirred to dissolving;
(3) 5g differential silica gel is joined in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) pulverized by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 2
(1) 1g resveratrol is joined in 20g dehydrated alcohol, fully dissolve;
(2) 3g polyvinylpyrrolidone (PVPK29/32) is joined gradually in the resveratrol ethanol solution that step (1) dissolved, be stirred to dissolving;
(3) 4g differential silica gel is joined in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) pulverized by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 3
(1) 1g resveratrol is joined in 15g dehydrated alcohol, fully dissolve;
(2) 4g hydroxypropyl emthylcellulose is joined gradually in the resveratrol ethanol solution that step (1) dissolved, be stirred to dissolving;
(3) 4g differential silica gel is joined in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 4
(1) 1g resveratrol is joined in 20g dehydrated alcohol, fully dissolve;
(2) 5g hydroxypropyl emthylcellulose is joined gradually in the resveratrol ethanol solution that step (1) dissolved, be stirred to dissolving;
(3) 4g differential silica gel is joined in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 5
(1) 1g griseofulvin is joined in 15g dichloromethane, fully dissolve;
(2) 3g hydroxypropyl emthylcellulose (TC-5EW) is joined gradually in the griseofulvin dichloromethane solution that step (1) dissolved, be stirred to dissolving;
(3) by 4g differential silica gel, join in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 6
(1) 1g griseofulvin is joined in 20g dichloromethane, fully dissolve;
(2) 3g Polyethylene Glycol (PEG6000) is joined gradually in the griseofulvin dichloromethane solution that step (1) dissolved, be stirred to dissolving;
(3) by 4g differential silica gel, join in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) pulverized by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 7
(1) 1g ibuprofen is joined in 10g isopropyl alcohol, fully dissolve;
(2) 5g copolyvidone is joined gradually in the ibuprofen aqueous isopropanol that step (1) dissolved, be stirred to dissolving;
(3) 4g magnesium silicate is joined in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 8
(1) 1g ibuprofen is joined in 10g isopropyl alcohol, fully dissolve;
(2) 4g poloxamer (F68) is joined gradually in the ibuprofen aqueous isopropanol that step (1) dissolved, be stirred to dissolving;
(3) 4g calcium silicates is joined in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) pulverized by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 9
(1) 1g curcumin is joined in 10g dehydrated alcohol, fully dissolve;
(2) 4g poloxamer (F68) is joined gradually in the curcumin ethanol solution that step (1) dissolved, be stirred to dissolving;
(3) 4g aluminosilicate magnesium is joined in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) pulverized by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 10
(1) 1g Quercetin is joined in 20g ethyl acetate, fully dissolve;
(2) 4g poloxamer (F68) is joined gradually in the Quercetin ethyl acetate solution that step (1) dissolved, be stirred to dissolving;
(3) 4g aluminosilicate magnesium is joined in the mixed solution of step (2), stir;
(4) mixture of vacuum drying step (3);
(5) pulverized by conventional method, use 80 object sieves to carry out progressive operation, make particle size <180 μm.
Embodiment 11
Dissolution test
Measure according to the Pharmacopoeia of the People's Republic of China one (2010 editions) annex XC " dissolution method " second method " paddle method " in accordance with the law.Result display in FIG.As shown in Figure 1, example 1 solid preparation of the present invention dissolves 90% in 15min, and control compound (raw material medicine body) even if can not dissolve completely in 60min.Consider that the food of entrance is about 15min to 30min and arrives small intestinal, will to dissolve completely when thing of the present invention arrives small intestinal and will extremely effectively by intestinal absorption.Low dose of administration in addition, because it has fabulous dissolution, dosage can be reduced, even if also can play due drug effect.This can prevent undegradable medicine to be transferred to caused toxic and side effects in liver.
Embodiment 12
Acceleration study
Treating excess syndrome example 1-3 solid preparation is about 200mg and is placed in five tool plug glass weighing botle (m through precise weighing
0, precise weighing (m
2).Shake up after capping plug, medicated powder be uniformly distributed in bottom weighing botle go plug to be placed in wet (RH75%), the environment of heat (40 DEG C); Respectively at 0, each time point of 30d, 60d, 90d jumps a queue and weighs each tool plug vial quality (m in each humidity environment
3), draw wet rate according to following formulae discovery: draw wet rate=(m
3-m
2)/(m
2-m
1) × 100%; Observe 0, the physical behavior of 30d, 60d, 90d, hygroscopicity and dissolution change.90d the results are shown in subordinate list 1.As can be seen from subordinate list 1, the example utilizing this technology to prepare 1-3 three kinds of solid preparations 3 months stable in properties under acceleration conditions, solid preparation still with amorphous existence, the numerical value drawing wet rate of body weight gain is very little, there is not significant change in accumulation dissolution, shows that solid preparation prepared by the inventive method has good stability yet.
Subordinate list 1
| Sample | Existence | Draw wet rate (%) | Accumulation dissolution (%) |
| Embodiment 1 | Amorphous | 0.48 | 85.78 |
| Embodiment 2 | Amorphous | 0.39 | 83.14 |
| Embodiment 3 | Amorphous | 0.45 | 86.25 |
Embodiment 13
Unbodied confirmation
Be amorphous state to observe the solid preparation obtained in embodiment 1,0d and temperature 40 DEG C after the production, under the acceleration environment of humidity 75%, measures the existence of 60d, 90d by powder x mono-ray diffraction method.Result display in fig. 2.Obviously find out from Fig. 2, preparation of the present invention still can keep good amorphous state in 3 months under the condition of Acceleration study, therefore has good stability.
Solid preparation preparation technology of the present invention is simple, significantly improves the dissolution of insoluble drug, stable in properties, and organic solvent-free remains, and therefore can be suitable for most of insoluble drug.
Claims (8)
1. a solid pharmaceutical preparation, is characterized in that: adopt joint vector, this joint vector comprises water-soluble polymer and inorganic porous material, and described insoluble drug and water-soluble polymer form complex and be attached on the surface of inorganic porous material; The weight ratio of water-soluble polymer and insoluble drug is 3-20:1; The weight ratio of inorganic porous material and insoluble drug is 4-10:1.
2. solid pharmaceutical preparation according to claim 1, is characterized in that:
Described water-soluble polymer is hydroxypropyl emthylcellulose, polyvinylpyrrolidone, poloxamer, copolyvidone, Polyethylene Glycol, wherein one or two or more kinds mixture;
Described inorganic porous material is magnesium silicate, calcium silicates, aluminosilicate magnesium, micropowder silica gel, wherein one or two or more kinds mixture.
3. solid pharmaceutical preparation according to claim 1, is characterized in that:
Insoluble drug comprises the one in Biopharmaceutics Classification system (BCS) in II class and IV class medicine.
4. solid pharmaceutical preparation according to claim 3, insoluble drug comprises:
Ibuprofen, simvastatin, hymecromone, resveratrol, curcumin, Quercetin, furosemide, ritonavir, Saquinavir, paclitaxel, vitamin E, carbamazepine or griseofulvin.
5. a preparation method for the arbitrary described solid pharmaceutical preparation of claim 1-4, is characterized in that:
(1) insoluble drug and water-soluble polymer are jointly dissolved in organic solvent in required ratio and obtain solution;
(2) by (1) gained solution and inorganic porous material mix and blend, dry, pulverize and obtain described solid preparation.
6. preparation method according to claim 4, is characterized in that: described organic solvent is dehydrated alcohol, isopropyl alcohol, dichloromethane, methanol, propanol or ethyl acetate.
7. preparation method according to claim 4, is characterized in that:
(1) the water-soluble polymer of described formation joint vector is sheet crystal or impalpable structure;
(2) described insoluble drug forms amorphous state in water-soluble polymer;
(3) the weight ratio of described organic solvent and described insoluble drug is 10-20:1.
8. preparation method according to claim 4, is characterized in that: described water-soluble polymer preferably polyethylene ketopyrrolidine or hydroxypropyl emthylcellulose, and the weight ratio of polyvinylpyrrolidone and described insoluble drug is 3-20:1; The weight ratio of hydroxypropyl emthylcellulose and described insoluble drug is 6-15:1.
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| CN201310376999.5A CN104415340A (en) | 2013-08-23 | 2013-08-23 | Solid drug preparation and preparing method thereof |
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| CN201310376999.5A CN104415340A (en) | 2013-08-23 | 2013-08-23 | Solid drug preparation and preparing method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106620711A (en) * | 2015-11-03 | 2017-05-10 | 中国科学院大连化学物理研究所 | Resveratrol-containing composition and preparation method thereof |
| CN106983734A (en) * | 2017-06-01 | 2017-07-28 | 海南妙音春制药有限公司 | A kind of ibuprofen sustained release capsules and preparation method thereof |
| CN107184565A (en) * | 2017-06-01 | 2017-09-22 | 海南妙音春制药有限公司 | A kind of preparation method of ibuprofen sustained release capsules |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101048180A (en) * | 2004-10-25 | 2007-10-03 | 日本烟草产业株式会社 | Solid formulation with improved solubility and stability, and method for producing said formulation |
| CN101444494A (en) * | 2008-12-31 | 2009-06-03 | 江苏大学 | Efficient long-acting sustained-release preparation of slightly soluble medicine and preparation method thereof |
| CN102657598A (en) * | 2012-05-09 | 2012-09-12 | 上海交通大学 | Porous inorganic material based oral preparation of secondary-dispersion insoluble drug and preparation method thereof |
-
2013
- 2013-08-23 CN CN201310376999.5A patent/CN104415340A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101048180A (en) * | 2004-10-25 | 2007-10-03 | 日本烟草产业株式会社 | Solid formulation with improved solubility and stability, and method for producing said formulation |
| CN101444494A (en) * | 2008-12-31 | 2009-06-03 | 江苏大学 | Efficient long-acting sustained-release preparation of slightly soluble medicine and preparation method thereof |
| CN102657598A (en) * | 2012-05-09 | 2012-09-12 | 上海交通大学 | Porous inorganic material based oral preparation of secondary-dispersion insoluble drug and preparation method thereof |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106620711A (en) * | 2015-11-03 | 2017-05-10 | 中国科学院大连化学物理研究所 | Resveratrol-containing composition and preparation method thereof |
| CN106620711B (en) * | 2015-11-03 | 2019-06-25 | 中国科学院大连化学物理研究所 | A kind of composition and preparation method thereof containing resveratrol |
| CN106983734A (en) * | 2017-06-01 | 2017-07-28 | 海南妙音春制药有限公司 | A kind of ibuprofen sustained release capsules and preparation method thereof |
| CN107184565A (en) * | 2017-06-01 | 2017-09-22 | 海南妙音春制药有限公司 | A kind of preparation method of ibuprofen sustained release capsules |
| CN107184565B (en) * | 2017-06-01 | 2018-04-03 | 海南妙音春制药有限公司 | A kind of preparation method of ibuprofen sustained release capsules |
| CN106983734B (en) * | 2017-06-01 | 2018-09-14 | 海南妙音春制药有限公司 | A kind of ibuprofen sustained release capsules and preparation method thereof |
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