CN107334737A - Tadalafei solid dispersion system and preparation method thereof - Google Patents
Tadalafei solid dispersion system and preparation method thereof Download PDFInfo
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- CN107334737A CN107334737A CN201710602004.0A CN201710602004A CN107334737A CN 107334737 A CN107334737 A CN 107334737A CN 201710602004 A CN201710602004 A CN 201710602004A CN 107334737 A CN107334737 A CN 107334737A
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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
- A61K9/145—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 compounds
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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Abstract
The present invention relates to pharmacy solid dispersion system field, and in particular to a kind of Tadalafei solid dispersion system and preparation method thereof.Tadalafei solid dispersion system is mainly made up of Tadalafei and pharmaceutical carrier.Wherein, in parts by weight, Tadalafei for 14 parts, pharmaceutical carrier is 69 parts.The Tadalafei solid dispersion system better stability of preparation, the crystallite stability of medicine is good, and drug bioavailability is also good.
Description
Technical field
The present invention relates to solid dispersion system pharmaceutical field, and in particular to a kind of Tadalafei solid dispersion system and its system
Preparation Method.
Background technology
Combinatorial chemistry and high flux screening are used in drug development process, filters out the pharmaceutically active of a large amount of poorly water-solubles
Compound.About 70% new drug candidates compound water soluble is poor in new drug development, and the bulk drug of about 40% oral preparation of quick releasing is
Insoluble drug.The water solubility of medicine is the key factor of its rate of dissolution.Low rate of dissolution is often led as caused by low solubility
The low bioavilability of oral administration medicine is caused, and the water-soluble compound less than 100 μ g/mL generally has what dissolving limited
Absorb.At present, the method for a variety of poorly water-solubles for overcoming drug candidate has been worked out in drug development research.But for
The effect for improving drug dissolution and raising bioavilability is bad.
The content of the invention
It is an object of the invention to provide a kind of Tadalafei solid dispersion system, better stability of preparation, the crystallite of medicine
Stability is good, and drug bioavailability is also good.
Another object of the present invention is to provide a kind of method for preparing Tadalafei solid dispersion system, this method technique
Route is simple, can be continuously produced.
The present invention is solved its technical problem and realized using following technical scheme：
The present invention proposes a kind of Tadalafei solid dispersion system, and it is mainly made up of Tadalafei and pharmaceutical carrier.
Wherein, in parts by weight, Tadalafei is 6-9 parts for 1-4 parts, pharmaceutical carrier.
The present invention also proposes a kind of method for preparing Tadalafei solid dispersion system, comprises the following steps：With parts by weight
Meter, the mixture of Tadalafei and pharmaceutical carrier is subjected to hot melt after 1-4 parts Tadalafei and 6-9 parts pharmaceutical carrier are mixed and squeezed
Go out.
The beneficial effect of Tadalafei of the present invention and preparation method thereof is：The Tadalafei solid dispersion system profit of the present invention
With 1-4 parts Tadalafei and the biological utilisation of 6-9 parts pharmaceutical carrier mixing synergy lifting Tadalafei solid dispersion system
Degree and stability, and the technological operation for preparing the Tadalafei is simple, reappearance is good.
Brief description of the drawings
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below by embodiment it is required use it is attached
Figure is briefly described, it will be appreciated that the following drawings illustrate only certain embodiments of the present invention, therefore be not construed as pair
The restriction of scope, for those of ordinary skill in the art, on the premise of not paying creative work, can also be according to this
A little accompanying drawings obtain other related accompanying drawings.
Fig. 1 is that the X-ray powder diffraction of embodiment 1 analyzes collection of illustrative plates；
Fig. 2 is the HPLC chromatogram analysis collection of illustrative plates of the Dissolution Rate Testing of experimental example 2；
Fig. 3 is the result figure of the accelerated stability test of experimental example 3；
Fig. 4 is the SD serum level curve maps of experimental example 4.
Embodiment
, below will be in the embodiment of the present invention to make the purpose, technical scheme and advantage of the embodiment of the present invention clearer
Technical scheme be clearly and completely described.Unreceipted actual conditions person, builds according to normal condition or manufacturer in embodiment
The condition of view is carried out.Agents useful for same or the unreceipted production firm person of instrument, it is the conventional production that can be obtained by commercially available purchase
Product.
In the description of the invention, it is necessary to which explanation, term " first ", " second " etc. are only used for distinguishing description, without
It is understood that to indicate or implying relative importance.
Tadalafei solid dispersion system of the embodiment of the present invention and preparation method thereof is specifically described below.
A kind of Tadalafei solid dispersion system provided in an embodiment of the present invention, it is mainly carried by Tadalafei and medicine
System into.Tadalafei and pharmaceutical carrier mutually act synergistically, and can lift the dissolution rate of Tadalafei, lift Tadalafei
Bioavilability.Meanwhile pharmaceutical carrier can reduce Tadalafei particle diameter, increase the surface area of Tadalafei particle so as to being lifted
Dissolution rate of the Tadalafei in human body, the utilization rate of Tadalafei is then lifted, meanwhile, the Ta Dala during release
Non-solid dispersion is non-hygroscopic, and dissolution release keeps stable.
Tadalafei (Tadalafil), it is a kind of specific inhibitor of oral novel phosphoric acid diesterase 5 (PDE-5), it is main
Treat erectile dysfunction, pulmonary hypertension and benign prostatic hyperplasis (BPH).Its molecular formula is C22H19N3O4, molecular weight
For 389.41, fusing point is up to 302 DEG C.The pKa value of Tadalafei is 16.68, shows that it in physiological pH range is that one kind can not be from
The medicine of sonization, belong to FDA Biopharmaceutical Classification system II classes medicines with low solubility (with strong hydrophobicity, in water
Solubility is only 3.21 μ g/mL) and high osmosis (octanol-water cloth coefficient logP is 2.48).
Further, pharmaceutical carrier is mannitol, and mannitol is the isomer of D-sorbite, soluble in water, is white
The transparent solid of color, there is the sweet taste of similar sucrose.It has highly-water-soluble, and class is as diuretics, hypertonic depressor in medicine
Or excipient.Mannitol main function is as small molecule crystallinity auxiliary material in embodiments of the present invention, it is possible to increase he reaches
Draw non-dissolution rate and bioavilability.
It is further preferred that Tadalafei solid dispersion system is prepared by Tadalafei and pharmaceutical carrier, this he
Up to drawing non-solid dispersion to be only prepared by two kinds of raw materials, the crystallite form of the Tadalafei of the solid dispersion system is good
It is good, and medicine stability is good, dissolution rate is also high, and bioavilability is high.
Further, in parts by weight, Tadalafei is 1-4 parts, and pharmaceutical carrier is 6-9 parts.Tadalafei and medicine carry
Body can ensure that the Tadalafei solid dispersion system stability that is prepared is good using aforementioned proportion, there is good dissolution speed
Rate, stable dissolution release then lift the bioavilability of solid dispersion system.It is further preferred that in parts by weight,
Tadalafei is 7-8 parts for 2-3 parts, pharmaceutical carrier.If the Tadalafei and the ratio of pharmaceutical carrier that use exceed above-mentioned model
Enclose the Tadalafei solid that may then cause to be prepared of the interior Tadalafei solid dispersion system that may cause to be prepared
The too high dissolution for suppressing Tadalafei on the contrary of active component content reduces the bioavilability of solid dispersion system in dispersion.
If ratio, less than that may be caused in solid dispersion system if aforementioned proportion, active medicine content is low, it is impossible to reaches good treatment effect
Fruit, and in the range of aforementioned proportion, the effective content of active component was both can guarantee that, while it is good also to ensure that solid dispersion system has
Good dissolution rate and bioavilability.
The embodiment of the present invention also provides a kind of method for preparing Tadalafei solid dispersion system, comprises the following steps：
In parts by weight, by Tadalafei and pharmaceutical carrier after 1-4 parts Tadalafei and 6-9 parts pharmaceutical carrier being mixed
Mixture carries out hot-melt extruded.
Hot-melt extruded method is that ground and mixed to after uniformly, is added to hot-melt extruded machine according to a certain percentage by medicine and carrier
In, mix in molten condition in the heated machine barrel of mixture and by the strong extrusion shearing of twin-screw, melted from head extrusion
The bar melted, through supercooling and the subsequent process steps crushed, 80 mesh is obtained to the solid dispersion powder of 120 mesh, can be used
Tabletting or filling capsule after appropriate formulation, such as addition auxiliary material is made as desired.
After hot-melt extruded, active component can exist one of in two forms：As the polymer phase for being embedded in hardening
In crystal, or as dissolving individual molecule in the polymer matrix.Unformed solid dispersions, medicine are divided equally with molecular water
Dissipate, so solid dispersions are metastable state forms, and medicine can recrystallize during storage from matrix.
The embodiment of the present invention can be high with microcrystalline form (particle diameter is less than 5 microns) effectively by Tadalafei using hot-melt extruded
Degree is dispersed in mannitol, and is increased Tadalafei wetability and improved the dissolution rate of Tadalafei.Specifically he is reached
Draw the mixture of non-sum mannitol to be added in hot-melt extruded machine and carry out heating melting, then change and slowly extrude.
Further, the temperature of hot-melt extruded is 130-190 DEG C, the mixing speed 50-100rpm of hot-melt extruded.In the temperature
Mannitol can be heated melting in the range of degree, and Tadalafei is dispersed in mannitol with microcrystalline form.Protected using said temperature
Card Tadalafei and mannitol will not go bad, and then ensure that the drug effect of the medicine of solid dispersion system.
It is further preferred that hot-melt extruded is to be squeezed after melting at a temperature of 160-190 DEG C at a temperature of 130-160 DEG C
Go out.First, under the conditions of 160-190 DEG C, Tadalafei and mannitol are heated and melt to solution status, and now, Tadalafei is micro-
It is brilliant fully with mannitol molecular mixing, the speed of Tadalafei molecule dissolution out of solid dispersion system is lifted, then in 130-
Solid dispersion system solidifies while extrusion under the conditions of 160 DEG C, and solid dispersions are ground into particle in an extruder, can be direct
Shaping, and ensure that the composition of the active medicine in solid dispersion system will not change.
Except using above-mentioned hot-melt extruded method, the embodiment of the present invention can also use other hot-melt extrudeds, such as hot
Molten extrusion directly can be extruded at a temperature of 160-190 DEG C, and now, the mixture of Tadalafei and mannitol, which is heated, to be melted
Melt, be then directly extruded at high temperature, solid dispersion system has been successfully prepared, and during extrusion, it is cooled and solidified by melting rapidly
Liquid is changed into solid-state.
Further, the rate of extrusion of hot-melt extruded is 0.5-20g/min.Rate of extrusion is prevented using above-mentioned rate of extrusion
It is too fast and destroy crystallite form in solid dispersion system, ensure stability of the Tadalafei in solid dispersion system inner structure.Adopt
The dissolution rate and bioavilability of solid dispersion system can be ensured with above-mentioned speed.
Further, the material obtained after hot-melt extruded is crushed, crushing can increase solid dispersion system with it is right
Answer the contact surface area of solvent then to be lifted, can then lift the dissolution rate of medicine in solid dispersion system, then be lifted
The bioavilability of medicine.
It is further preferred that crush be by the material elder generation mechanical crushing after hot-melt extruded be cake mass, then utilization
The head-on collision of sub-resonance molecule crushes cake mass.The material that hot-melt extruded is prepared is the larger thing of continuous unbroken volume
Matter, the material of small volume, such as cake mass are first crushed into, are easy to follow-up further crushing, it is more lower to obtain particle diameter
Particle or powder.Make it that Tadalafei solid dispersion system is in irregular shape using in general grinding mode, there are more arris
Angle, after human body is taken, the structure of more arris easily scratches human body cell, then adds Tadalafei solid dispersion system
Side effect.Therefore, the fine crushing that the embodiment of the present invention uses is that the head-on collision of quantizing resonance molecule crushes, using the grinding mode not
Only Tadalafei solid dispersion system is further crushed, and while crushing, by Tadalafei solid dispersions
It is that irregular corner angle remove in molecule so that Tadalafei solid dispersion system molecular surface is more smooth, and then reduces him
Up to the side effect for drawing non-solid dispersion.
Tadalafei solid dispersion system provided in an embodiment of the present invention is microcrystalline dispersion piece, compared to ordinary preparation and its
His solid dispersions, it has stability is good, bioavilability is high and the technique is simple, favorable reproducibility, product quality is stable.
The feature and performance of the present invention are described in further detail with reference to embodiments.
Embodiment 1
The present embodiment provides a kind of Tadalafei solid dispersion system (F1), and it is mainly by Tadalafei and pharmaceutical carrier
It is made, wherein, in terms of weight g, Tadalafei 1g, pharmaceutical carrier 9g, pharmaceutical carrier is mannitol.
The present embodiment provides also a kind of method for preparing Tadalafei solid dispersion system：
After 1g Tadalafeis and 9g mannitol are sufficiently mixed uniformly, the mixture being mixed to get is added to hot-melt extruded
Carry out heating melting and extrusion in machine.Specifically after mixture is melted at a temperature of 180 DEG C, and with 50rpm rotating speed
It is stirred, is extruded mixture with 1.2g/min speed at a temperature of 140 DEG C.Then the mixture of extrusion is crushed blocking
Shape material, cake mass are powder being crushed using the head-on collision of quantizing resonance molecule.
Embodiment 2
The present embodiment provides a kind of Tadalafei solid dispersion system (F2), and it is mainly by Tadalafei and pharmaceutical carrier
It is made, wherein, in terms of weight g, Tadalafei 2g, pharmaceutical carrier 8g, pharmaceutical carrier is mannitol.
The present embodiment provides also a kind of method for preparing Tadalafei solid dispersion system：
After 2g Tadalafeis and 8g mannitol are sufficiently mixed uniformly, the mixture being mixed to get is added to hot-melt extruded
Carry out heating melting and extrusion in machine.Specifically after mixture is melted at a temperature of 160 DEG C, and turned with 100rpm
Speed is stirred, and is extruded mixture with 0.5g/min speed at a temperature of 130 DEG C.Then the mixture of extrusion is ground into
Cake mass, cake mass are powder being crushed using the head-on collision of quantizing resonance molecule.
Embodiment 3
The present embodiment provides a kind of Tadalafei solid dispersion system (F3), and it is mainly by Tadalafei and pharmaceutical carrier
It is made, wherein, in terms of weight g, Tadalafei 3g, pharmaceutical carrier 7g, pharmaceutical carrier is mannitol.
The present embodiment provides also a kind of method for preparing Tadalafei solid dispersion system：
After 3g Tadalafeis and 7g mannitol are sufficiently mixed uniformly, the mixture being mixed to get is added to hot-melt extruded
Carry out heating melting and extrusion in machine.Specifically after mixture is melted at a temperature of 190 DEG C, and with 70rpm rotating speed
It is stirred, is extruded mixture with 20g/min speed at a temperature of 130 DEG C.Then the mixture of extrusion is crushed blocking
Shape material, cake mass are powder being crushed using the head-on collision of quantizing resonance molecule.
Embodiment 4
The present embodiment provides a kind of Tadalafei solid dispersion system (F4), and it is mainly by Tadalafei and pharmaceutical carrier
It is made, wherein, in terms of weight g, Tadalafei 4g, pharmaceutical carrier 6g, pharmaceutical carrier is mannitol.
The present embodiment provides also a kind of method for preparing Tadalafei solid dispersion system：
After 4g Tadalafeis and 6g mannitol are sufficiently mixed uniformly, the mixture being mixed to get is added to hot-melt extruded
Carry out heating melting and extrusion in machine.Specifically after mixture is melted at a temperature of 190 DEG C, and turned with 100rpm
Speed is stirred, while is extruded mixture with 15g/min speed.The mixture of extrusion is then ground into cake mass,
Cake mass is powder being crushed using the head-on collision of quantizing resonance molecule.
Experimental example
Experimental example 1
Prepared by embodiment 1-4 carries out X-ray powder diffraction analysis to Tadalafei solid dispersion system (F1-F4).
Same amount of Tadalafei solid dispersion system sample (F1-F4) is weighed respectively to be homogeneously disposed in vinyl disc respectively,
It is then placed in x-ray powder diffraction instrument, using Cu target K alpha rays, X-ray tube accelerating potential is 40kV, and acceleration electric current is
40mA, the scanning range at 2 θ angles is 5~30 °, and sweep speed is 12 °/min.Referring specifically to Fig. 1.
As shown in Figure 1, Tadalafei has strong crystal structure, and its diffraction maximum angle is 7.25,10.60,12.53,
13.46,14.51,15.55,15.77,16.92,18.42,21.65,24.17 and 24.98 °, the diffraction maximum angle of mannitol is
10.42,14.58,18.72,20.40,21.07,23.36,28.27 and 29.44 °.As shown in Figure 1, F1~F4 XRD spectrum can
To be considered the mixing of Tadalafei crystal and sweet dew alcohol crystals, both do not change at crystal formation, may be due to being squeezed through heating
Quick cooling, crystal have little time to grow up after going out, and cause diffraction peak intensity low, Tadalafei/mannitol hot-melt extruded solid disperses
In body Tadalafei with microcrystalline form it is scattered with auxiliary material mannitol, it was demonstrated that Tadalafei/mannitol hot-melt extruded solid disperses
Body is Tadalafei solid microcrystalline suspension dispersion.
Experimental example 2
Prepared by embodiment 1-4 carries out solid dispersions dissolution rate examination to Tadalafei solid dispersion system (F1-F4)
Test.
This experiment uses Tadalafei bulk drug that it is solid to weigh Tadalafei bulk drug, Tadalafei respectively to contrast reference
Body dispersion (F1~F4) 5mg, every kind of sample is parallel 3 parts, according to 2015 editions《Chinese Pharmacopoeia》The regulation of the 4th 0931,
Determined using paddle method, dissolution medium is the 0.2%SDS aqueous solution, volume 1000ml.At 37 ± 0.5 DEG C, rotating speed is temperature control
75rpm.Sample time is 5,10,20,30,45 and 60min.Sample volume is 1ml, 0.45 μm of miillpore filter filtration, is drawn continuous
The μ l of filtrate 50 add 50 μ l dilution in acetonitrile, vortex 10s, are completely dissolved Tadalafei in sample into sample injection bottle internal lining pipe, prevent
Only separate out, take supernatant to be analyzed using HPLC chromatogram sample introduction.HPLC chromatogram condition is：Chromatographic column：BDS Hypersil C18
(2.1 × 50mm, 2.4 μm, U.S. Thermo Scientific), mobile phase：Water-acetonitrile (62:38, v/v), flow velocity：400μl/
Min, column temperature：35 DEG C, Detection wavelength：220nm, sample size：5μl.
Specific testing result as shown in Figure 2, after adding hydrophilic carrier, can effectively improve the molten of Tadalafei referring to Fig. 2
Go out, improve dissolution rate.The dissolution rate for the Tadalafei solid dispersions that the embodiment of the present invention is prepared is above bulk drug,
It is obviously improved the In Vitro Dissolution of Tadalafei.Bulk drug dissolution rate in 60min only has 67.74%, may be due to Tadalafei
Hydrophobicity is too strong, and degree of wetting is poor, and the strong crystalline structure of Tadalafei makes drug molecule be difficult to be dissolved in medium, limits dissolving
Speed and dissolution rate.And in 60min, F1, F2, F3 and F4 dissolution rate are respectively 90.01%, 90.49%, 88.39% and
86.53%, respectively the 1.32,1.33,1.29 and 1.27 of bulk drug dissolution rate times.Illustrate the Ta Dala that the present invention is prepared
Non-solid dispersion has good dissolution rate.
Experimental example 3
Prepared by embodiment 1-4 carries out accelerated stability test to Tadalafei solid dispersion system (F1-F4).
Weigh same amount of F1~F4 sample respectively, sample is directly open exposed avoid light place in 75%RH, 40 DEG C
One month in climatic chamber, take out, observe sample appearance.Concrete outcome is referring to Fig. 3.
From the figure 3, it may be seen that Tadalafei solid dispersion powder is positioned over 75%RH, one month in 40 DEG C of closed environment
Afterwards, the solid disperse powders of 10%~40% drugloading rate are almost non-hygroscopic, and outward appearance does not change, do not lump, and keep preferable
The pulverulence of mobility.
Experimental example 4
Prepared by embodiment 1-4 carries out SD bioavailability in rats examinations to Tadalafei solid dispersion system (F1-F4)
Test.
Sprague-Dawley rats 40, male, body weight 180-220g, by Traditional Chinese Medicine University Of Guangzhou's experimental animal center
There is provided, animal productiong licensing numbering is SCXK (Guangdong) 2013-0020.
40 SD rats are randomly divided into Tadalafil groups, and totally 5 groups of F1-F4, every group of 8 rats.Before respectively testing
Rat Fast 12h, free water, every rat dosage are Tadalafei 1.8mg/kg, suspension gastric infusion, after administration
Retroorbital venous clump takes the μ l of blood about 300 to 0.5,1,2,4,8,12 and 24h respectively, is placed in sodium heparinized centrifuge tube, stands
30min, 5000rpm centrifuge 5min, separated plasma, are placed in -80 DEG C of refrigerator stored frozens, standby.Respectively at 2h, 4h, 8h, 12h,
The SD rat plasmas of 24h collections, are prepared into plasma sample, and same day batch is calculated according to the retinue standard curve of detection same day measure
All blood plasma blood concentration.As a result Fig. 4 is seen.
As shown in Figure 4, reference, the SD of 1-4 of the embodiment of the present invention four solid dispersions are made with Tadalafei bulk drug
Blood concentration is improved in rat body, and reaches maximum plasma concentration in 1~2h.
PKSolver pharmacokinetics software for calculation is then used, using non-compartment model-extravascular administration pattern to being surveyed
Drug-time curve data carry out calculating pharmacokinetic parameters, and carry out statistical analysis, are shown in Table 1.
The pharmacokinetic parameters of table 1 (n=8,)
As shown in Table 1, because medicine belongs to the medicine that dissolution limitation absorbs, dissolution rate is fast, and absorption rate faster, reaches
Peak time is shorter, and tmax may be higher, because the property being metabolized only with medicine of medicine in itself is relevant, several solid dispersions
Solid dispersion system its bioavilability that the speed surface of absorption is prepared using the embodiment of the present invention can at least improve 1.7
Times.
In summary, Tadalafei solid dispersion system that 1-4 of the embodiment of the present invention is provided and preparation method thereof.This is scattered
System is microcrystalline dispersion piece, compared to ordinary preparation and other solid dispersions, it has stability is good, bioavilability is high and
The technique is simple, favorable reproducibility, and product quality is stable.
Embodiments described above is part of the embodiment of the present invention, rather than whole embodiments.The reality of the present invention
The detailed description for applying example is not intended to limit the scope of claimed invention, but is merely representative of the selected implementation of the present invention
Example.Based on the embodiment in the present invention, what those of ordinary skill in the art were obtained under the premise of creative work is not made
Every other embodiment, belongs to the scope of protection of the invention.
Claims (10)
- A kind of 1. Tadalafei solid dispersion system, it is characterised in that it is mainly made up of Tadalafei and pharmaceutical carrier, its In, in parts by weight, the Tadalafei is 1-4 parts, and the pharmaceutical carrier is 6-9 parts.
- 2. Tadalafei solid dispersion system according to claim 1, it is characterised in that the Tadalafei solid disperses System is prepared by the Tadalafei and the pharmaceutical carrier, in parts by weight, the Tadalafei for 2-3 parts, The pharmaceutical carrier is 7-8 parts.
- 3. Tadalafei solid dispersion system according to claim 1 or 2, it is characterised in that the pharmaceutical carrier is sweet Reveal alcohol.
- A kind of 4. method for preparing Tadalafei solid dispersion system, it is characterised in that comprise the following steps：In parts by weight, The mixture of the Tadalafei and the pharmaceutical carrier is carried out after 1-4 parts Tadalafei and 6-9 parts pharmaceutical carrier are mixed Hot-melt extruded.
- 5. the method according to claim 4 for preparing Tadalafei solid dispersion system, it is characterised in that hot-melt extruded Temperature is 130-190 DEG C, the mixing speed 50-100rpm of hot-melt extruded.
- 6. the method according to claim 5 for preparing Tadalafei solid dispersion system, it is characterised in that hot-melt extruded is Extruded after thawing at a temperature of 160-190 DEG C at a temperature of 130-160 DEG C.
- 7. the method according to claim 4 for preparing Tadalafei solid dispersion system, it is characterised in that the mixture It is extruded at a temperature of 160-190 DEG C.
- 8. according to the method for preparing Tadalafei solid dispersion system described in claim 4-7 any one, it is characterised in that The rate of extrusion of hot-melt extruded is 0.5-20g/min.
- 9. the method according to claim 7 for preparing Tadalafei solid dispersion system, it is characterised in that by hot-melt extruded The material obtained afterwards is crushed.
- 10. the method according to claim 9 for preparing Tadalafei solid dispersion system, it is characterised in that crushing be by Material elder generation mechanical crushing after hot-melt extruded is cake mass, then crushes the block using the head-on collision of quantizing resonance molecule Matter.
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| CN105496965A (en) * | 2015-12-17 | 2016-04-20 | 浙江华海药业股份有限公司 | Method for preparing Tadalafil solid dispersion and medicinal preparation of Tadalafil solid dispersion |
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- 2017-07-21 CN CN201710602004.0A patent/CN107334737A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
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