Summary of the invention
The embodiment of the present invention provides a kind of pyrrole Lun Panai mouthfuls of molten films and preparation method thereof, provides a kind of pyrrole Lun Panai's
Novel form improves the convenience of medication.
The present invention provides a kind of pyrrole Lun Panai mouthfuls of molten films, the molten film of mouth includes partial size (D90) at 1-35 μm
Pyrrole Lun Panai particle, film forming agent and disintegrating agent.
Preferably, the molten film of the mouth further includes surfactant pluronic.
Preferably, the partial size (D90) of the pyrrole Lun Panai is at 10-20 μm.
Optionally, the film forming agent includes polyvinyl alcohol.
Optionally, the disintegrating agent includes sodium alginate.
Optionally, the molten film of the mouth further includes plasticizer polyethylene glycol.
Optionally, the molten film of the mouth further includes corrigent.
The present invention also provides a kind of preparation methods of above-mentioned pyrrole Lun Panai mouthfuls of molten films, which comprises
Pyrrole Lun Panai is subjected to micronization processes, obtains pyrrole Lun Panai particle of the partial size (D90) at 1-35 μm;
Pyrrole Lun Panai particle after micronization processes is dissolved in second alcohol and water with surfactant, film forming agent, disintegrating agent
In the mixed solvent, be uniformly mixing to obtain film forming matrix;
The film forming matrix is deaerated, is film-made, is dried to obtain the pyrrole Lun Panai mouthfuls of molten films.
Preferably, described that pyrrole Lun Panai is subjected to micronization processes, partial size (D90) is obtained in pyrrole Lun Panai of 1-35 μm
Son includes:
Pyrrole Lun Panai is subjected to micronization processes, obtains pyrrole Lun Panai particle of the partial size (D90) at 10-20 μm.
Preferably, the weight ratio of the in the mixed solvent, water and ethyl alcohol is 1:2-5.
Pyrrole Lun Panai mouthfuls of molten films provided by the invention and preparation method thereof, using the pyrrole Lun Panai particle of micron level,
Pyrrole Lun Panai is made to the molten film of mouth quickly dissolved in the oral cavity by the dissolubility for improving pyrrole Lun Panai, convenient anhydrous
Under the conditions of take, provide patient medication compliance and convenience.
Specific embodiment
It in order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below will be in the embodiment of the present invention
Technical solution be clearly and completely described, it is clear that described embodiments are some of the embodiments of the present invention, rather than
Whole embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art are not making creative work premise
Under every other embodiment obtained, shall fall within the protection scope of the present invention.
One embodiment of the invention provides a kind of pyrrole Lun Panai mouthfuls of molten films, this mouthful of molten film includes that partial size (D90) is less than
35 μm of pyrrole Lun Panai particle, film forming agent and disintegrating agent.
The pharmaceutical dosage form for the film-like that the molten film of mouth can at least partly dissolve in oral cavity.
The reagent of furtherance film supplemented by film forming agent, i.e., by the evaporation of solvent or carrier to the mixture containing film forming agent or
Solidification to the mixture for being mixed with film forming agent, can form continuous film.Coalescing agents are such as selected from polyvinyl alcohol, hydroxypropyl methyl
One of cellulose, sodium cellulose glycolate, hydroxypropyl cellulose, xanthan gum, pectin, polyoxyethylene and cornstarch are several
Kind.
Main ingredient pyrrole Lun Panai in the embodiment of the present invention is not soluble in water, and solubility in water is only 0.032g/L (25
℃).Lower solubility also results in lower bioavilability simultaneously.In order to solve this problem, the embodiment of the present invention is adopted
With the pyrrole Lun Panai particle of micron level, can be dispersed in the molten film of mouth.The ratio of pyrrole Lun Panai drug granule
Surface area influences whether its dissolved efficiency, and micro mist is thinner, and specific surface area is bigger, and the area contacted with external environment is bigger, drug
It is easy for dissolving, and then also improves bioavilability.The partial size (D90) of pyrrole Lun Panai particle in the embodiment of the present invention is less than
35μm.Partial size (D90) is the equivalent diameter of the largest particles when cumulative distribution is 90% in distribution curve.Such as partial size (D90)
It is 20 μm, i.e. particle of the partial size less than 20 μm accounts for all particles 90%.Micron level can be obtained by kinds of processes means
Drug particle.Such as pyrrole Lun Panai bulk pharmaceutical chemicals can be carried out with micronization processes to obtain the drug particle of micron level.
Disintegrating agent is that the molten film of mouth can be made to accelerate to split the substance for being broken into thin in the oral cavity.Disintegrating agent for example selected from
Sodium carboxymethyl starch, low-substituted hydroxypropyl methylcellulose, crosslinked polyvinylpyrrolidone, croscarmellose sodium, alginic acid
One or more of sodium, crospovidone and microcrystalline cellulose.Disintegrating agent is added in the embodiment of the present invention to help drug
The acceleration of pyrrole Lun Panai is dissolved and is absorbed.
Pyrrole Lun Panai mouthfuls of molten films provided in an embodiment of the present invention improve pyrrole using the pyrrole Lun Panai particle of micron level
Pyrrole Lun Panai is made to the molten film of mouth quickly dissolved in the oral cavity, conveniently in anhydrous conditions by the dissolubility of Lun Panai
It takes, provides the compliance and convenience of patient's medication.
In another embodiment of the present invention, the molten film of mouth further includes surfactant, and surfactant can be further
Increase the solvability of drug in a solvent.Surfactant is for example selected from fatty acid glyceride, sucrose fatty ester, lecithin
One of rouge, polysorbate, sucrose fatty ester, ten polyglyceryl laurates, lauryl sodium sulfate and pluronic
Or it is several.
In one embodiment of the invention, surfactant is pluronic.Pluronic is a kind of novel high score
Sub- nonionic surfactant, is polyoxyethylene poly-oxygen propylene aether block copolymer, and general formula is HO (C2H4O)a(C3H6O)b
(C2H4O)cH, it is 15-67 that wherein a and c, which is 2-130, b, and middle section is hydrophobic chain, and both ends are divided into hydrophilic chain.Pu Langni
Gram there is solubilizing effect for main ingredient, promotes main ingredient dissolution in a solvent.In addition, having compared to lauryl sodium sulfate etc.
For soap is similar to the surfactant of taste, pluronic odorless, tasteless is highly suitable to be applied for the molten film of mouth.In addition, general
Lang Nike without immunogene, dissolve in body fluid, drug can be promoted by blood-brain barrier, and then improve the biological utilisation of pyrrole Lun Panai
Degree.Specifically, in some embodiments of the invention, selecting pluronic F127, molecular formula is as above, wherein 101 a, c, and b is
56.In other embodiment of the invention, Pluronic F68 is selected, molecular formula is as above, a, c 79, b 28.Both classes
The pluronic of type is preferable to the compatibilization effect of main ingredient pyrrole Lun Panai.
For main ingredient pyrrole Lun Panai, although partial size is lower, specific surface area is bigger, is more conducive to dissolution and the medicine of drug
The bioavilability of object, but the problem of consider process costs simultaneously, the granularity of micro mist is also unsuitable too low, with pyrrole Lun Panai particle
Can be dispersed in film forming matrix is advisable.Therefore, in certain embodiments, the partial size (D90) of pyrrole Lun Panai particle is not small
In 1 μm, i.e., between 1-35 μm.Specifically, the partial size (D90) of pyrrole Lun Panai particle can be 1 μm, 5 μm, 10 μm, 15 μm, 20
μm,25μm,30μm,35μm.It is further preferred that in certain embodiments, the partial size of pyrrole Lun Panai particle 10-20 μm it
Between.Pyrrole Lun Panai particle in the range can take into account the cost of excellent in a solvent dispersibility and micromill process.
In some embodiments of the invention, the preferred polyvinyl alcohol of film forming agent.Optionally, as the polyvinyl alcohol of film forming agent
Molecular weight be 20-400KDa, degree of hydrolysis 85-90%.Specifically, in certain embodiments of the present invention, can use and divide
Son amount is 31KDa, the polyvinyl alcohol that degree of hydrolysis is 68.7-88.8% namely polyvinyl alcohol that trade name is Mowiol4-88
Product.In certain embodiments of the present invention, the polyvinyl alcohol that the degree of polymerization is 88 for 1700, alcoholysis degree can also be used.At this
It, can also be using the mixture of polyvinyl alcohol Mowiol4-88 and polyvinyl alcohol 1788 as film forming in some embodiments of invention
Agent, the weight ratio of the two for example 2:1-1:2 are formed by medicine film uniform ground using the polyethylene product of such film forming agent.
In another embodiment of the invention, disintegrating agent is sodium alginate.Sodium alginate is as disintegrating agent in application, being formed
The molten membrane surface of mouth it is smooth, without granular sensation.
In another embodiment of the present invention, in order to increase the plasticity of finished product film, the molten film of mouth further includes plasticizer.Increase
Mould agent for example selected from one of polyethylene glycol (PEG), glycerol, glyceryl triacetate, propylene glycol Chinese holly edge acid esters and Tween 80 or
It is several.Preferably, plasticizer is selected from polyethylene glycol (PEG).It is further preferred that the mixture that two kinds of polyethylene glycol can be selected is made
For plasticizer application.Such as select molecular weight 3000-6000Da PEG and molecular weight the PEG of 250-1000Da mixing
Object, more specifically, the mixture of PEG4000 and PEG400.Preferably, plasticizer is the mixture of PEG4000 and PEG400, and
The weight ratio of PEG4000 and PEG400 is 1-3:1, preferred 2:1.When the mixture of PEG4000 and PEG400 is as plasticizer,
The toughness of film is higher, the not cracky in storing process.
In order to which that improves the molten film of mouth takes mouthfeel, in certain embodiments, the molten film of mouth further includes corrigent.Corrigent
It may include sweetener and/or aromatic.Sweetening agents are such as selected from saccharin, Sucralose, neotame, A Litian, honey element, An Sai
One or more of honey, Aspartame and ammonium glycyrrhizinate.Aromatic is for example selected from petit grain oil, strawberry essence, vanilla flavour concentrate, Portugal
One or more of grape shaddock oil, Mint Essence, cinnamyl acetate, citral, citronella oil, Levomenthol and menthol.It is preferred that
Sucralose and Mint Essence are collectively as corrigent.
In addition, in certain embodiments, the molten film of mouth can also including colorant etc. other auxiliary agents.Colorant for example selected from
Water colo(u)r etc..
In some embodiments of the invention, each component accounts for the weight percentage of the molten film of finished product mouth are as follows: 5-20wt%
The film forming agent of main ingredient pyrrole Lun Panai, 20-60wt%, the plasticizer of 1-20wt%, the disintegrating agent of 10-25%, 1-15wt%
The corrigent of surfactant and 1-10wt%.
More preferably, in some embodiments of the invention, each component accounts for the weight percentage of the molten film of finished product mouth
Are as follows: the disintegration of the film forming agent, the plasticizer, 15-20% of 5-15wt% of main ingredient pyrrole Lun Panai, 40-50wt% of 10-15wt%
Agent, the surfactant of 6-10wt% and 3-6wt% corrigent.
Finally, it will be appreciated that usually also containing the acceptable balance solvent for not influencing medicine film storage, example in film
Such as water or the mixed solvent of water and ethyl alcohol.Accounting of the balance solvent in the molten film of mouth is 0.5-7wt%, specifically, for example
Accounting 0.5wt%, 1wt%, 2wt%, 3wt%, 4wt%, 5wt%, 6wt%, 7wt% etc..Preferably, 1-3wt%.By solvent
Content controls within this range, and the flexibility of the molten film of gained mouth is preferable.Solvent content is excessive, and film is not easily molded;Solvent content
Too low, film is easy drying and splits, not easy to maintain.
With the molten film of above-mentioned mouth correspondingly, the embodiment of the invention also provides the preparation methods of this mouthful of molten film.This method
Include the following steps.
Step 1: pyrrole Lun Panai being subjected to micronization processes, obtains pyrrole Lun Panai particle of the partial size (D90) less than 35 μm.
In this step, the partial size of pyrrole Lun Panai bulk pharmaceutical chemicals is reduced using micronization processes, such as makes its partial size (D90) be
1 μm, 5 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm or 35 μm etc..
Preferably, step 1 includes: that pyrrole Lun Panai is carried out micronization processes, obtains pyrrole of the partial size (D90) at 10-20 μm
Lun Panai particle.
Step 2: the pyrrole Lun Panai particle after micronization processes is dissolved in second with surfactant, film forming agent, disintegrating agent
The in the mixed solvent of alcohol and water, is uniformly mixing to obtain film forming matrix.
The selection such as description in the molten film embodiment of above-mentioned mouth of surfactant, film forming agent, disintegrating agent, it is no longer superfluous herein
It states.In addition, corresponding with the molten film embodiment of above-mentioned mouth, step 2 can also include that plasticizer, corrigent, colorant etc. is added
The step of auxiliary agent.
In this step, the weight ratio of the in the mixed solvent, water and ethyl alcohol is preferably 1:2-5, it is further preferred that weight
Than being preferably 1:3.The mixed solvent of the ratio is preferable to the solute effect of drug.
The selection of each component and content are for example, see the molten film embodiment of above-mentioned mouth in the molten film of mouth, and details are not described herein again.
Step 3: the film forming matrix being deaerated, is film-made, is dried to obtain the pyrrole Lun Panai mouthfuls of molten films.
The preparation method of pyrrole Lun Panai mouthfuls of molten films provided in an embodiment of the present invention, is first micronized pyrrole Lun Panai
Processing improves the dissolubility of pyrrole Lun Panai, and pyrrole Lun Panai is made to the molten film of mouth quickly dissolved in the oral cavity, is conveniently existed
It is taken under anhydrous condition, provides the compliance and convenience of patient's medication.
In one embodiment of the invention, in order to promote to dissolve, optionally, step 2 further include it is following step by step.
Step 21: by after micronization processes pyrrole Lun Panai particle and surfactant be dissolved in second alcohol and water mixing it is molten
Homogeneous solution is obtained in agent.
Step 22: film forming agent, disintegrating agent being added in the homogeneous solution and stirring makes it be uniformly dispersed, is formed a film
Matrix.
Corresponding with the molten film embodiment of above-mentioned mouth, step 22 can also include that plasticizer, corrigent, colorant etc. is added
The step of auxiliary agent.
The embodiment provided in order to better illustrate the present invention is said below by the mode for enumerating specific embodiment
It is bright.