CN108815121A - A kind of Dimethylcurcumin solid dispersions and the preparation method and application thereof - Google Patents
A kind of Dimethylcurcumin solid dispersions and the preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a kind of Dimethylcurcumin solid dispersions and the preparation method and application thereof, are related to field of pharmaceutical preparations.It is made of Dimethylcurcumin and water soluble carrier material, wherein water soluble carrier material includes PEG4000, PEG 6000, polyvinylpyrrolidone (PVP K30), PLURONICS F87, prepares Dimethylcurcumin solid dispersions using fusion method or solvent method.Solid dispersions are made in insoluble drug Dimethylcurcumin by the present invention, improve dissolution rate, dispersion degree, solubility and the bioavilability of drug, which can be further prepared into the solid pharmaceutical preparations such as tablet, capsule.Preparation process of the present invention is simple, it is cheap, be easy to industrialization.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of Dimethylcurcumin solid dispersions and preparation method thereof
With application.
Background technique
Dimethylcurcumin (dimethoxycurcumin, ASC-J9) chemical name：5-hydroxy-1,7-bis(3,4-
Dimethoxyphenyl) -1,4,6-heptatrien-3-one molecular formula：C23H24O6, molecular weight：396, structure such as following formula institute
Show
It is a kind of compound by obtaining to curcumin structural modification, in the relevant disease of androgen receptor, than
Curcumin shows higher pharmacological activity.
Dimethylcurcumin is that one kind of Rochester University of U.S. chawnshang Chang professor laboratory invention is new
Type androgen receptor (Androgen Receptor, AR) drug, degradable androgen receptor and its androgen receptor co-activation because
Effect between sub (ARA55 or ARA70) inhibits androgen receptor body function, for treating androgen-receptor related diseases, including male
Property alopecia, prostate cancer, liver cancer, bladder cancer, spinal cord and oblongata muscular atrophy.
Carver, B.S et al. are the study found that with the various anti-heros of androgen ablation therapy (ADT) used at present
Hormone, Dimethylcurcumin can also constantly inhibit prostate cancer in the castration resistance stage, and in the treatment in other stages
Effect is better than existing medical procedure, and in an experiment, to the side effect very little of the sexual function of test mouse, this shows this medicine
Object may be a better choice to treat prostate cancer and androgen-receptor related diseases.
Solid dispersions, which are meant, divides drug uniformly in the form of particle, crystallite, molecular state etc. by solid dispersion technology
It is dispersed in solid carrier materials.Applying solid dispersion technology can improve the solubility property of insoluble drug, improve dissolution rate,
The dissolution rate for accelerating drug can promote the absorption of drug, improve bioavilability.
Solid dispersions are a kind of preparation intermediates, can be further by adding auxiliary material appropriate and suitable preparation process
The dosage forms such as tablet, capsule are made.
The country there is no the report in relation to Dimethylcurcumin solid dispersions at present.Dimethylcurcumin poorly water-soluble, leads
Cause takes orally rate of release, and metabolism is rapid slowly, in vivo, bioavilability is low, is restricted so that its formulation development utilizes.
Summary of the invention
In order to solve the problem above-mentioned, the present invention provides a kind of Dimethylcurcumin solid dispersions and preparation method thereof
And application.
In order to achieve the above object, the present invention provides the following technical solutions：
A kind of Dimethylcurcumin solid of the present invention is seperated, is made of Dimethylcurcumin and water soluble carrier material,
Dimethylcurcumin and water soluble carrier material mass ratio are 1:2~10,
Wherein the water soluble carrier material be Macrogol 4000 (PEG4000), Macrogol 6000 (PEG6000),
One of polyvinylpyrrolidone, PLURONICS F87.
Further, the polyvinylpyrrolidone is PVP K30 (PVP K30).
A kind of preparation method of above-mentioned solid dispersions, carries out as steps described below：
1) Dimethylcurcumin and water soluble carrier material are proportionally weighed.
2) Dimethylcurcumin solid dispersions are prepared using fusion method.
Wherein, when preparing Dimethylcurcumin solid dispersions using fusion method, the water soluble carrier material is
One of PEG4000, PEG6000, PLURONICS F87；
The fusion method operation is as follows：In proportion 1:2~1:10 weigh Dimethylcurcumin and water-solubility carrier material respectively
Dimethylcurcumin is added in batches, fusant is poured onto glass for material, water soluble carrier material heating stirring to molten condition
Container upper berth straticulation, cooling rapidly, dry, crushing are sieved to get Dimethylcurcumin solid dispersions.
A kind of preparation method of above-mentioned solid dispersions, or carry out as steps described below：
1) Dimethylcurcumin and water soluble carrier material are proportionally weighed.
2) Dimethylcurcumin solid dispersions are prepared using solvent method.
When preparing Dimethylcurcumin solid dispersions using solvent method, the water-soluble material is polyvinylpyrrolidone
(PVP K30), the organic solvent are ethyl alcohol, methanol, acetone, methylene chloride, ethyl acetate, preferred alcohol.
The solvent method is as follows：In proportion 1:2~1:10 weigh Dimethylcurcumin and water soluble carrier material, use
Organic solvent dissolution, ultrasound is to as clear as crystal, and decompression rotary evaporation removal solvent, drying, crushing, sieving are to get dimethyl ginger
Flavine solid dispersions.
The present invention also provides the oral solid formulation that solid dispersions and auxiliary material are prepared by mixing into, the auxiliary material is selected
It is filler, lubricant, disintegrating agent, one or several kinds of in adhesive.
Further, the oral solid formulation preferred tablet, capsule.
Compared with prior art, the features of the present invention and beneficial effect are：
1) Dimethylcurcumin solid dispersions provided by the invention can make Dimethylcurcumin keep high degree of dispersion shape
State is present in carrier with crystallite state, unformed shape, colloidal dispersions state or molecule dispersed, is conducive to Dimethylcurcumin
Effectively dissolution improves bioavilability to promote the absorption of drug.Suitable auxiliary material is added by solid dispersions to be prepared into
Tablet, capsule equally have the characteristics that dissolution rate is high, bioavilability is high.
2) Dimethylcurcumin solid dispersions preparation process provided by the invention is simple, cheap favorable reproducibility, fits
Close industrialized production.
Detailed description of the invention
The In Vitro Dissolution curve of Fig. 1 embodiment 1~-4.
The In Vitro Dissolution curve of Fig. 2 embodiment 5~8.
The In Vitro Dissolution curve of Fig. 3 embodiment 9~12.
The In Vitro Dissolution curve of Fig. 4 embodiment 13~16.
Fig. 5 Dimethylcurcumin bulk pharmaceutical chemicals, PVP K30, physical mixture, Dimethylcurcumin solid dispersions FT-
IR analysis of spectra；Wherein, a in Fig. 5:Dimethylcurcumin b:PVP K30c:Dimethylcurcumin-PVP K30 physical mixed
d:Dimethylcurcumin-PVP K30 solid dispersions.
Fig. 6 Dimethylcurcumin bulk pharmaceutical chemicals, PVP K30, physical mixture, Dimethylcurcumin solid dispersions XRD
Scan spectrogram；In Fig. 6, a:Dimethylcurcumin b:PVP K30c:Dimethylcurcumin-PVP K30 physical mixed d:Diformazan
Base curcumin-PVP K30 solid dispersions.
Fig. 7 Dimethylcurcumin bulk pharmaceutical chemicals, physical mixture, Dimethylcurcumin solid dispersions SEM scan spectrogram；
In Fig. 7, A:Dimethylcurcumin B:Dimethylcurcumin-PVP K30 physical mixed C：Dimethylcurcumin-PVP K30 solid
Dispersion.
Specific embodiment
Illustrate technical solution of the present invention in order to clearer, in the following with reference to the drawings and specific embodiments to the present invention do into
One step detailed description.
To the dissolution rate reference Chinese Pharmacopoeia of Dimethylcurcumin solid dispersions and its tablet, capsule in present example
The paddle method of version in 2015：Dissolution medium is 0.5%SDS aqueous solution, and temperature (37 ± 0.5) DEG C, revolving speed 100r/min accurately weighs
Physical mixture and various fraction solid dispersions sample 5m in 900ml stripping rotor, in 5,10,20,40,60,90,120min
L crosses 0.45 μm of miillpore filter, while supplementing the dissolution medium of equality of temperature same volume, using dissolution medium as blank control, in 420nm
Place's measurement its absorbance value A, calculates the accumulation dissolution rate of each period, draws dissolution curve.
Embodiment 1
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PEG4000, will using fusion method
2g PEG4000 is in 60~80 DEG C of heating water baths to melting, and under conditions of being stirred continuously, 1g Dimethylcurcumin adds in batches
Enter, continue to stir 30min, fusant is poured onto glass container upper berth straticulation, is cooled down rapidly, sets and dried in drier for 24 hours,
Crush, sieve with 100 mesh sieve to get Dimethylcurcumin/PEG4000 solid dispersions, In Vitro Dissolution the experimental results showed that：5min is molten
Out-degree is that 51.07%, 2h dissolution rate is 71.15%, it is seen that can be effective using the solid dispersions that PEG4000 is prepared as carrier
Improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 2
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PEG4000, will using fusion method
10g PEG4000 is in 60~80 DEG C of heating water baths to melting, and under conditions of being stirred continuously, 1g Dimethylcurcumin adds in batches
Enter, continue to stir 30min, fusant is poured onto glass container upper berth straticulation, is cooled down rapidly, sets and dried in drier for 24 hours,
Crush, sieve with 100 mesh sieve to get Dimethylcurcumin/PEG4000 solid dispersions, In Vitro Dissolution the experimental results showed that：5min is molten
Out-degree is that 50.08%, 2h dissolution rate is 73.51%, it is seen that can be effective using the solid dispersions that PEG4000 is prepared as carrier
Improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 3
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PEG4000, will using fusion method
4g PEG4000 is in 60~80 DEG C of heating water baths to melting, and under conditions of being stirred continuously, 1g Dimethylcurcumin adds in batches
Enter, continue to stir 30min, fusant is poured onto glass container upper berth straticulation, is cooled down rapidly, sets and dried in drier for 24 hours,
Crush, sieve with 100 mesh sieve to get Dimethylcurcumin/PEG4000 solid dispersions, In Vitro Dissolution the experimental results showed that：5min is molten
Out-degree is that 51.07%, 2h dissolution rate is 71.15%, it is seen that can be effective using the solid dispersions that PEG4000 is prepared as carrier
Improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 4
A kind of physical mixed of Dimethylcurcumin, Dimethylcurcumin and PEG4000 are sieved with 100 mesh sieve respectively, mixing
Uniformly to get Dimethylcurcumin/PEG4000 physical mixture, In Vitro Dissolution the experimental results showed that：5min dissolution rate is
6.86%, 2h dissolution rate are 37.31%.Specifically, embodiment 4 is the comparison example of embodiment 1,2,3.
Embodiment 5
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PEG6000, will using fusion method
2g PEG6000 is in 60~80 DEG C of heating water baths to melting, and under conditions of being stirred continuously, 1g Dimethylcurcumin adds in batches
Enter, continue to stir 30min, fusant is poured onto glass container upper berth straticulation, is cooled down rapidly, sets and dried in drier for 24 hours,
Crush, sieve with 100 mesh sieve to get Dimethylcurcumin/PEG6000 solid dispersions, In Vitro Dissolution the experimental results showed that：5min is molten
Out-degree is that 49.95%, 2h dissolution rate is 68.41%, it is seen that can be effective using the solid dispersions that PEG6000 is prepared as carrier
Improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 6
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PEG6000, will using fusion method
10g PEG6000 is in 60~80 DEG C of heating water baths to melting, and under conditions of being stirred continuously, 1g Dimethylcurcumin adds in batches
Enter, continue to stir 30min, fusant is poured onto glass container upper berth straticulation, is cooled down rapidly, sets and dried in drier for 24 hours,
Crush, sieve with 100 mesh sieve to get Dimethylcurcumin/PEG6000 solid dispersions, In Vitro Dissolution the experimental results showed that：5min is molten
Out-degree is that 71.16%, 2h dissolution rate is 80.6%, it is seen that can be effective using the solid dispersions that PEG6000 is prepared as carrier
Improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 7
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PEG6000, will using fusion method
6g PEG6000 is in 60~80 DEG C of heating water baths to melting, and under conditions of being stirred continuously, 1g Dimethylcurcumin adds in batches
Enter, continue to stir 30min, fusant is poured onto glass container upper berth straticulation, is cooled down rapidly, sets and dried in drier for 24 hours,
Crush, sieve with 100 mesh sieve to get Dimethylcurcumin/PEG6000 solid dispersions, In Vitro Dissolution the experimental results showed that：5min is molten
Out-degree is that 54.63%, 2h dissolution rate is 76.05%, it is seen that can be effective using the solid dispersions that PEG6000 is prepared as carrier
Improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 8
A kind of physical mixed of Dimethylcurcumin, Dimethylcurcumin and PEG6000 are sieved with 100 mesh sieve respectively, mixing
Uniformly to get Dimethylcurcumin/PEG6000 physical mixture, In Vitro Dissolution the experimental results showed that：5min dissolution rate is
10.29%, 2h dissolution rate are 38.09%.Specifically, embodiment 8 is the comparison example of embodiment 5,6,7.
Embodiment 9
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PLURONICS F87, using melting
Method, by 2g PLURONICS F87 in 60~80 DEG C of heating water baths to melting, under conditions of being stirred continuously, 1g Dimethylcurcumin
It is added in batches, continues to stir 30min, fusant is poured onto glass container upper berth straticulation, it is cooling rapidly, it sets in drier
It is dry to crush for 24 hours, it sieves with 100 mesh sieve to get Dimethylcurcumin/PLURONICS F87 solid dispersions, In Vitro Dissolution experiment knot
Fruit shows：5min dissolution rate is that 42.03%, 2h dissolution rate is 65.85%, it is seen that is consolidated using PLURONICS F87 as prepared by carrier
Body dispersion can effectively improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 10
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PLURONICS F87, using melting
Method, by 10g PLURONICS F87 in 60~80 DEG C of heating water baths to melting, under conditions of being stirred continuously, 1g Dimethylcurcumin
It is added in batches, continues to stir 30min, fusant is poured onto glass container upper berth straticulation, it is cooling rapidly, it sets in drier
It is dry to crush for 24 hours, it sieves with 100 mesh sieve to get Dimethylcurcumin/PLURONICS F87 solid dispersions, In Vitro Dissolution experiment knot
Fruit shows：5min dissolution rate is that 70.59%, 2h dissolution rate is 83.26%, it is seen that is consolidated using PLURONICS F87 as prepared by carrier
Body dispersion can effectively improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 11
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PLURONICS F87, using melting
Method, by 8g PLURONICS F87 in 60~80 DEG C of heating water baths to melting, under conditions of being stirred continuously, 1g Dimethylcurcumin
It is added in batches, continues to stir 30min, fusant is poured onto glass container upper berth straticulation, it is cooling rapidly, it sets in drier
It is dry to crush for 24 hours, it sieves with 100 mesh sieve to get Dimethylcurcumin/PLURONICS F87 solid dispersions, In Vitro Dissolution experiment knot
Fruit shows：5min dissolution rate is that 71.64%, 2h dissolution rate is 76.2%, it is seen that the solid prepared using PLURONICS F87 as carrier
Dispersion can effectively improve the dissolved corrosion of Dimethylcurcumin.
Embodiment 12
A kind of physical mixed of Dimethylcurcumin, Dimethylcurcumin and PLURONICS F87 are sieved with 100 mesh sieve respectively,
Be uniformly mixed to get Dimethylcurcumin/PLURONICS F87 physical mixture, In Vitro Dissolution the experimental results showed that：5min dissolution
It is 50.53% that degree, which is 30.9%, 2h dissolution rate,.Specifically, embodiment 12 is that the comparison of embodiment 9,10,11 is real
Example.
Embodiment 13
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PVP K30, will using solvent method
1g Dimethylcurcumin and 2g PVP K30 are dissolved with dehydrated alcohol, ultrasound to as clear as crystal, decompression rotation after magnetic agitation 1h
Evaporative removal solvent, products obtained therefrom set in vacuum oven it is dry for 24 hours, crush, sieve with 100 mesh sieve, i.e., Dimethylcurcumin/
PVP K30 solid dispersions, In Vitro Dissolution the experimental results showed that：5min dissolution rate is that 60.84%, 2h dissolution rate is 77.13%,
It can be seen that can effectively improve the dissolved corrosion of Dimethylcurcumin using PVP K30 as solid dispersions prepared by carrier.
Embodiment 14
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PVP K30, will using solvent method
1g Dimethylcurcumin and 10g PVP K30 are dissolved with dehydrated alcohol, ultrasound to as clear as crystal, decompression rotation after magnetic agitation 1h
Evaporative removal solvent, products obtained therefrom set in vacuum oven it is dry for 24 hours, crush, sieve with 100 mesh sieve, i.e., Dimethylcurcumin/
PVP K30 solid dispersions, In Vitro Dissolution the experimental results showed that：5min dissolution rate is that 83.15%, 2h dissolution rate is 85.81%,
It can be seen that can effectively improve the dissolved corrosion of Dimethylcurcumin using PVP K30 as solid dispersions prepared by carrier.
Embodiment 15
A kind of Dimethylcurcumin solid dispersions, are made of Dimethylcurcumin and PVP K30, will using solvent method
1g Dimethylcurcumin and 4g PVP K30 are dissolved with dehydrated alcohol, ultrasound to as clear as crystal, decompression rotation after magnetic agitation 1h
Evaporative removal solvent, products obtained therefrom set in vacuum oven it is dry for 24 hours, crush, sieve with 100 mesh sieve, i.e., Dimethylcurcumin/
PVP K30 solid dispersions, In Vitro Dissolution the experimental results showed that：5min dissolution rate is that 61.93%, 2h dissolution rate is 74.95%,
It can be seen that can effectively improve the dissolved corrosion of Dimethylcurcumin using PVP K30 as solid dispersions prepared by carrier.
Embodiment 16
A kind of physical mixed of Dimethylcurcumin, Dimethylcurcumin and PVP K30 are sieved with 100 mesh sieve respectively, mixing
Uniformly to get Dimethylcurcumin/PVP K30 physical mixture, In Vitro Dissolution the experimental results showed that：5min dissolution rate is
10.53%, 2h dissolution rate are 21.41%.Specifically, embodiment 16 is the comparison example of embodiment 13,14,15.
Embodiment 17
A kind of Dimethylcurcumin solid dispersions prepare Dimethylcurcumin piece and Dimethylcurcumin capsule, and formula is such as
Under：
Note：Every/capsule 5mg containing Dimethylcurcumin
Preparation method：Dimethylcurcumin solid dispersions, lactose, microcrystalline cellulose, Sodium Hydroxymethyl Stalcs are mixed equal
It is even, suitable 5% povidone aqueous solution is added, sieves with 100 mesh sieve, in 50~70 DEG C of dryings, magnesium stearate is added, is uniformly mixed,
It is pressed into piece or is packed into capsule, carry out In Vitro Dissolution experiment.
The dissolution in vitro experimental result of 1 embodiment 17 of table, 18 Dimethylcurcumin tablets/capsules of embodiment at 2 hours：
| Tablet | Capsule | |
| Embodiment 17 | 81.56% | 85.43% |
| Embodiment 18 | 40.41% | 50.59% |
As shown in Table 1, the dissolution rate of the tablet of Dimethylcurcumin solid dispersions preparation either capsule is obvious high
In the tablet of Dimethylcurcumin bulk pharmaceutical chemicals preparation or the dissolution rate of capsule, and the dissolution rate of capsule is greater than the dissolution of tablet
Degree.
Embodiment 18
A kind of Dimethylcurcumin bulk pharmaceutical chemicals prepare Dimethylcurcumin piece and Dimethylcurcumin capsule, are formulated as follows：
| Supplementary material | Effect | Tablet | Capsule |
| Dimethylcurcumin | Main ingredient | 5g | 5g |
| PVP K30 | Water-solubility carrier | 50g | 50g |
| Lactose | Filler | 45g | 45g |
| Microcrystalline cellulose | Filler | 80g | 80g |
| Sodium Hydroxymethyl Stalcs | Disintegrating agent | 5g | 5g |
| Magnesium stearate | Lubricant | 1g | 1g |
| Povidone | Adhesive | 4g | 4g |
| It is made | 1000 | 1000 |
Note：Every/capsule 5mg containing Dimethylcurcumin
Preparation method：Dimethylcurcumin, PVP K30, lactose, microcrystalline cellulose, Sodium Hydroxymethyl Stalcs are uniformly mixed,
Suitable 5% povidone aqueous solution is added, sieves with 100 mesh sieve, in 50~70 DEG C of dryings, magnesium stearate is added, is uniformly mixed, is pressed into
Piece is packed into capsule, carries out In Vitro Dissolution experiment, specifically, embodiment 18 is the comparison example of embodiment 17.
Embodiment 19
A kind of Dimethylcurcumin solid dispersions prepare Dimethylcurcumin piece and Dimethylcurcumin capsule, and formula is such as
Under：
Note：Every/capsule 10mg containing Dimethylcurcumin
Preparation method：Dimethylcurcumin solid dispersions, lactose, microcrystalline cellulose, Sodium Hydroxymethyl Stalcs are mixed equal
It is even, suitable 5% povidone aqueous solution is added, sieves with 100 mesh sieve, in 50~70 DEG C of dryings, magnesium stearate is added, is uniformly mixed,
It is pressed into piece or is packed into capsule, carry out In Vitro Dissolution experiment.
The dissolution in vitro experimental result of 2 embodiment 19 of table, 20 Dimethylcurcumin tablets/capsules of embodiment at 2 hours：
| Tablet | Capsule | |
| Embodiment 19 | 80.68% | 84.23% |
| Embodiment 20 | 39.47% | 49.99% |
As shown in Table 2, the dissolution rate of the tablet of Dimethylcurcumin solid dispersions preparation either capsule is obvious high
In the tablet of Dimethylcurcumin bulk pharmaceutical chemicals preparation or the dissolution rate of capsule, and the dissolution rate of capsule is greater than the dissolution of tablet
Degree.
Embodiment 20
A kind of Dimethylcurcumin bulk pharmaceutical chemicals prepare Dimethylcurcumin piece and Dimethylcurcumin capsule, are formulated as follows：
| Supplementary material | Effect | Tablet | Capsule |
| Dimethylcurcumin | Main ingredient | 10g | 10g |
| PVP K30 | Filler | 40g | 40g |
| Lactose | Filler | 55g | 55g |
| Microcrystalline cellulose | Filler | 75g | 75g |
| Sodium Hydroxymethyl Stalcs | Disintegrating agent | 5g | 5g |
| Magnesium stearate | Lubricant | 1g | 1g |
| Povidone | Adhesive | 4g | 4g |
| It is made | 1000 | 1000 |
Note：Every/capsule 10mg containing Dimethylcurcumin
Preparation method：Dimethylcurcumin, PVP K30, lactose, microcrystalline cellulose, Sodium Hydroxymethyl Stalcs are uniformly mixed,
Suitable 5% povidone aqueous solution is added, sieves with 100 mesh sieve, in 50~70 DEG C of dryings, magnesium stearate is added, is uniformly mixed, is pressed into
Piece is packed into capsule, carries out In Vitro Dissolution experiment, specifically, embodiment 12 is the comparison example of embodiment 11.
Embodiment 21
A kind of Dimethylcurcumin solid dispersions prepare Dimethylcurcumin piece and Dimethylcurcumin capsule, and formula is such as
Under：
Note：Every/capsule 20mg containing Dimethylcurcumin
Preparation method：Dimethylcurcumin solid dispersions, lactose, microcrystalline cellulose, Sodium Hydroxymethyl Stalcs are mixed equal
It is even, suitable 5% povidone aqueous solution is added, sieves with 100 mesh sieve, in 50~70 DEG C of dryings, magnesium stearate is added, is uniformly mixed,
It is pressed into piece or is packed into capsule, carry out In Vitro Dissolution experiment.
The dissolution in vitro experimental result of 3 embodiment 21 of table, 22 Dimethylcurcumin tablets/capsules of embodiment at 2 hours：
| Tablet | Capsule | |
| Embodiment 21 | 80.12% | 82.91% |
| Embodiment 22 | 38.32% | 49.01% |
As shown in Table 3, the dissolution rate of the tablet of Dimethylcurcumin solid dispersions preparation either capsule is obvious high
In the tablet of Dimethylcurcumin bulk pharmaceutical chemicals preparation or the dissolution rate of capsule, and the dissolution rate of capsule is greater than the dissolution of tablet
Degree.
Embodiment 22
A kind of Dimethylcurcumin bulk pharmaceutical chemicals prepare Dimethylcurcumin piece and Dimethylcurcumin capsule, are formulated as follows：
| Supplementary material | Effect | Tablet | Capsule |
| Dimethylcurcumin | Main ingredient | 20g | 20g |
| PVP K30 | Filler | 40g | 40g |
| Lactose | Filler | 50g | 50g |
| Microcrystalline cellulose | Filler | 70g | 70g |
| Sodium Hydroxymethyl Stalcs | Disintegrating agent | 5g | 5g |
| Magnesium stearate | Lubricant | 1g | 1g |
| Povidone | Adhesive | 4g | 4g |
| It is made | 1000 | 1000 |
Note：Every/capsule 20mg containing Dimethylcurcumin
Preparation method：Dimethylcurcumin, PVP K30, lactose, microcrystalline cellulose, Sodium Hydroxymethyl Stalcs are uniformly mixed,
Suitable 5% povidone aqueous solution is added, sieves with 100 mesh sieve, in 50~70 DEG C of dryings, magnesium stearate is added, is uniformly mixed, is pressed into
Piece is packed into capsule, carries out In Vitro Dissolution experiment.Specifically, embodiment 14 is the comparison example of embodiment 13.
Solid dispersions Fourier Transform Infrared Spectroscopy (Fig. 2) that the embodiment of the present invention 14 is prepared, X-ray powder spread out
Penetrate (Fig. 6), Dimethylcurcumin bulk pharmaceutical chemicals exist electron-microscope scanning (Fig. 7) as the result is shown with crystal form, with PVP K30 preparation
Solid dispersion drug is dispersed in carrier material with amorphous or molecular state.
Claims (7)
1. a kind of Dimethylcurcumin solid is seperated, it is characterised in that it is by Dimethylcurcumin and water soluble carrier material group
At,
Wherein Dimethylcurcumin and water soluble carrier material mass ratio are 1:2~10,
Wherein the water soluble carrier material is Macrogol 4000 (PEG4000), Macrogol 6000 (PEG6000), poly- second
One of alkene pyrrolidone, PLURONICS F87.
2. a kind of Dimethylcurcumin solid according to claim 1 is seperated, it is characterised in that the polyvinylpyrrolidine
Ketone is PVP K30 (PVP K30).
3. a kind of preparation method of Dimethylcurcumin solid fission of any of claims 1 or 2, it is characterised in that according to following
Step carries out：
1) Dimethylcurcumin and water soluble carrier material are proportionally weighed；
2) Dimethylcurcumin solid dispersions are prepared using fusion method；
Wherein, when preparing Dimethylcurcumin solid dispersions using fusion method, the water soluble carrier material be PEG4000,
One of PEG6000, PLURONICS F87.
4. a kind of preparation method of Dimethylcurcumin solid fission according to claim 3, it is characterised in that described molten
It is as follows to melt method operation：In proportion 1:2~1:10 weigh Dimethylcurcumin and water soluble carrier material, water-solubility carrier material respectively
Expect that heating stirring to molten condition, Dimethylcurcumin is added in batches, fusant is poured onto glass container upper berth straticulation,
Cooling rapidly, dry, crushing is sieved to get Dimethylcurcumin solid dispersions.
5. a kind of preparation method of Dimethylcurcumin solid fission of any of claims 1 or 2, it is characterised in that or according to
Following step carries out：
1) Dimethylcurcumin and water soluble carrier material are proportionally weighed；
2) Dimethylcurcumin solid dispersions are prepared using solvent method；
When preparing Dimethylcurcumin solid dispersions using solvent method, the water-soluble material is polyvinylpyrrolidone (PVP
K30), the organic solvent is ethyl alcohol, methanol, acetone, methylene chloride, ethyl acetate.
6. a kind of preparation method of Dimethylcurcumin solid fission according to claim 5, it is characterised in that described molten
The operation of agent method is as follows：In proportion 1:2~1:10 weigh Dimethylcurcumin and water soluble carrier material, are dissolved with organic solvent,
Ultrasound is to as clear as crystal, and decompression rotary evaporation removal solvent, drying, crushing, sieving are to get the dispersion of Dimethylcurcumin solid
Body.
7. a kind of preparation method of Dimethylcurcumin solid fission according to claim 5, it is characterised in that You Jirong
Agent is ethyl alcohol.
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| CN113332433A (en) * | 2021-05-11 | 2021-09-03 | 浙江工业大学 | Drug solubilization system and application thereof in solubilization of insoluble drugs |
| CN115998687A (en) * | 2022-11-04 | 2023-04-25 | 温州医科大学 | Solid dispersion of curcumin derivative and preparation and application thereof |
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