CN108272777A - A kind of solid composite medicament containing Repaglinide - Google Patents
A kind of solid composite medicament containing Repaglinide Download PDFInfo
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- CN108272777A CN108272777A CN201810327698.6A CN201810327698A CN108272777A CN 108272777 A CN108272777 A CN 108272777A CN 201810327698 A CN201810327698 A CN 201810327698A CN 108272777 A CN108272777 A CN 108272777A
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- repaglinide
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- solid composite
- film
- composite medicament
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
Abstract
For defect existing for Repaglinide bulk pharmaceutical chemicals, bulk pharmaceutical chemicals solid is scattered in oral quick-dissolving film preparation by inventor by way of preparing oral quick-dissolving film preparation, to increase the water solubility of preparation, increases its bioavilability.The decomposition of amido bond in bulk pharmaceutical chemicals is reduced by controlling the pH of the preceding solution of film drying.Increase corrigent in film simultaneously, improves the compliance of patient.Experiment proves that gained oral quick-dissolving film preparation dissolution rate is good, and good mouthfeel, stability test shows that degradation impurity A and C are suppressed significantly, and has achieved the purpose that of the invention initial.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of solid composite medicament and its system containing Repaglinide
Preparation Method and purposes.
Background technology
Diabetes refer to internal sugar, fat and albumen caused by insulin secretion is absolutely insufficient or relative deficiency
Matter metabolic disorder.Diabetes are a kind of metabolic diseases of more reasons, and common feature is chronic hyperglycemia, and clinical manifestation is blood
The performances, i.e., " more than three one such as containing in liquid has sugar in sugared excessively high or urine, clinical classical symptom may occur in which diuresis, more drinks, eat more, become thin
It is few " symptom.Chinese medicine diabetes are referred to as diabetes, refer to the meaning of polydipsia of becoming thin.
In specific clinical position, the people for having " three-many-one-little " has generally been in the diabetes middle and advanced stage stage, each
The complication puzzlement of kind various kinds, and in prediabetes usually not symptom.In addition, also substantial portion of people always will not table
Reveal typical symptom.
Ketoacidosis stupor and Non-ketotic hyperosmolar coma etc. can occur when serious for diabetes, and can be with various senses
Dye.The lesions such as course of disease elder may and go crazy, kidney and retina, and with macroangiopathy, the mainly heart, brain and lower limb
Vascular lesion.
In the past 30 years, China's diabetes prevalence dramatically increases.The epidemiology money of national 14 provinces and cities, 300,000 people in 1980
The illness rate of material display, diabetes is 0.67%.The diabetes that 1994 to nineteen ninety-five has carried out national 19 provinces and cities, 210,000 people are popular
Disease learns investigation, and the diabetes prevalence of 25~64 years old crowd is 2.5% (population standardized rate is 2.2%), and impaired glucose tolerance is
3.2% (population standardized rate is 2.1%).
Nearest 10 years, diabetes popularity was even more serious.Diabetes have been carried out while national nutrition survey in 2002
Popularity investigation.The investigation utilizes fasting blood-glucose>5.5mmol/L takes orally as screening index higher than this horizontal person
Dextrose tolerance test (OGTT).The diabetes prevalence of 18 years old or more urban populations is 4.5%, rural area 1.8%.City
In, the age is respectively 2.96%, 4.41% and in the diabetes prevalence of 18~44 years old, 45~59 years old and 60 years old or more crowd
13.13%, and the illness rate of the corresponding age bracket in rural area is respectively then 1.95%, 0.98% and 7.78%.2007 to 2008 years,
Under the tissue of diabetology branch of Chinese Medical Association (CDS), national 14 provinces and cities have carried out the epidemiological survey of diabetes.It is logical
Cross weighted analysis, after the factor for considering gender, age, town and country distribution and regional disparity, estimation China 20 years old or more adult's
Diabetes prevalence is 9.7%, and Chinese Adult diabetes sum is up to 9 240 ten thousand, wherein rural area about 43,100,000, city about 4930
Ten thousand.China national Center for Disease Controls in 2010 and endocrinology branch of Chinese Medical Association have investigated 18 years old Chinese or more crowd's sugar
The disease condition for urinating disease shows that diabetes prevalence is 9.7% using WHO diagnostic criteria in 1999, reconfirms that China can
The country that diabetes number of patients is most in the world can be had become, if simultaneously using glycosylated hemoglobin (HbA1c) >=6.5% as
Diabetes diagnostic criterion, then its illness rate is 11.6%.
Repaglinide (repaglinide) is a kind of novel non-sulfonylurea Insulin secretagogues, by thin with pancreas islet β
Specific receptor on after birth combines, and promotes to close with the ATP sensitive potassium channels of coupled receptors, inhibits potassium ion from β cells
Outflow, membrane depolarization, calcium channel open, and flow of calcium ions rapidly promotes insulin secretion, can imitate the life of insulin
Rationality is secreted, and postprandial hyperglycemia is effectively controlled.Being clinically used for diet control, losing weight and motion exercise cannot effectively control
Type II diabetes (non-insulin-depending type) patient of hyperglycemia, the glycosylated hemoglobin and meal of the person that can reduce type II diabetes
Blood glucose afterwards, the melbine use in conjunction with binding mode complementation, can mitigate β cell burdens, extend the existence of islet cells,
Remarkable curative effect is shown to isolatism postprandial hyperglycemia person, the 1st phase obstacle person of insulin secretion and the irregular person of diet.
Repaglinide belongs to II class in Biopharmaceutics Classification, and poorly water-soluble, permeability is high, and drug-eluting speed is drug
The rate-limiting step of absorption is difficult to dissolve out completely in enteron aisle or dissolution is slow, drug bioavailability can be caused to reduce, in preparation
In production, it may be considered that increase water solubility using suitable solid dispersions technique, improve dissolution rate, meet preparation dissolution
The requirement of degree.
Repaglinide (Repaglinide) is a kind of white to linen crystalline powder.Molecular formula is：C27H36N2O4,
Molecular weight is 452.59, is soluble in methanol, dichloromethane and n,N-Dimethylformamide, is slightly soluble in acetonitrile, is insoluble in water.Chemistry
It is entitled：(S) -2- ethyoxyls -4- [2- [3- methyl-1s-[2- (1- piperidyls) phenyl]-butane group]-amino] -2- carbonyl ethyl benzene
Formic acid, structural formula are as follows：
Repaglinide compressed tablets agent obtains FDA approvals for 1997, is developed by Novo Nordisk Co., Ltd, trade name PRANDI, advises
Lattice are 0.5mg, 1mg, 2mg.Auxiliary material used is：Calcium phosphate dibasic anhydrous, microcrystalline cellulose, cornstarch, polacrilin potassium, poly- second
Alkene is than pyrrolidone, glycerine (85%), meglumine, poloxamer, magnesium stearate.
Generate technique substantially, by polyvinylpyrrolidone, meglumine, poloxamer is dissolved in glycerine water solution, raw material
It is adhesive that medicine, which disperses or dissolves in this solution, and calcium phosphate dibasic anhydrous, microcrystalline cellulose and cornstarch mixing are used as filling
Agent and adhesive are pelletized by spray dryer, after particle drying, polacrilin potassium are added as disintegrant, magnesium stearate is made
For lubricant mixing, tabletting to obtain the final product.
From the formula above as can be seen that there are amido bonds in Repaglinide molecule, under alkaline condition, or and basic species
Matter (such as meglumine) Long Term Contact, it may occur that hydrolysis, amido bond fracture generate corresponding degradation impurity.European Pharmacopoeia
8.0 describe the relevant impurity A-E of Repaglinide, amount to 5.Wherein impurity A and impurity C are the product of amido bond fracture,
Structure is as follows：
It is clearly improper that alkaline matter meglumine is added in terms of this angle, in commercial preparation.
In addition, Repaglinide water solubility is very poor, for example, in the buffer solution that pH is 5.0, only 9 mcg/mls.Cause
Its bioavilability is extremely low, and in rat and dog body, absolute bioavailability is only 48%.
By retrieval, the prior art reduces preparation finished product and prepares and deposit there is no two aspects as above are taken into account simultaneously
Impurity A and impurity C content are to increase preparation stability during storage, and improve the oral preparation of oral preparation bioavilability
The research of prescription and technique.
The instant transmission system of drug (fast dissolving drug delivery systems) is developed in 20 generation earliest
It records the seventies, is broadly divided into oral quick disintegrating tablet (orally disintegrating tablets) and oral quick-dissolving film preparation (oral
thin film).Oral quick-dissolving film preparation, which need not drink water, to be taken, and is placed on instant on tongue, and is not easy to spue after sticking, has administration
Conveniently, the advantages that good patient compliance, it is especially suitable for the old man and children of dysphagia.
Invention content
As described above, amido bond is broken Repaglinide bulk pharmaceutical chemicals under alkaline condition, degrade, generate impurity A,
The impurity such as impurity C, and it is water-soluble very poor, cause its bioavilability low.
To reduce the generation of the degradation impurities such as hydrolysis impurity in preparation preparation and storing process and improving bioavilability, send out
A person of good sense obtains a kind of solid composite medicament containing Repaglinide by research, and by main ingredient Repaglinide, filmogen increases
Mould agent, disintegrant, saliva stimulant, corrigent, pH adjusting agent composition.The composition is further prepared into mouth as follows
The instant film of chamber：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant successively, Repaglinide adjusts pH, and stirring is spare；Step
Rapid three：Step 2 acquired solution is taken, dissolves plasticizer successively, filmogen disperses disintegrant, and stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
It is dry.Will blade coating obtain film stripping, shearing packing to get.
It is characterized in that, the filmogen is hydroxypropyl cellulose；Plasticizer is polyethylene glycol 400, and disintegrant is carboxylic
Methyl starch sodium, saliva stimulant are acetic acid, and corrigent is Aspartame, and pH adjusting agent is sodium hydroxide.
Moisture is less than 1.0% after the oral quick-dissolving film preparation drying.
Unit dose Repaglinide content is 0.25mg, 0.5mg, 1mg, 2mg.
The solid composite medicament containing Repaglinide, unit formulation composition are as follows：
The solid composite medicament containing Repaglinide, is further prepared into oral instant membrane as follows
Agent：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant acetic acid, Repaglinide successively, pH adjusting agent is used in stirring
PH to 4.5-5.5 is adjusted, it is spare；
Step 3：Step 2 acquired solution is taken, dissolves plasticizer polyethylene glycol 400 successively, filmogen hydroxypropyl cellulose divides
Disintegrating agent carboxymethyl base sodium starch is dissipated, stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
It is dry.Will blade coating obtain film stripping, shearing packing to get.
Patent application is further illustrated the present invention through the following experiment.
For defect existing for Repaglinide bulk pharmaceutical chemicals, inventor is quasi- by way of preparing oral quick-dissolving film preparation, will be former
Material medicine solid is scattered in oral quick-dissolving film preparation, to increase the water solubility of preparation, increases its bioavilability.By controlling film
The pH of solution and the moisture after drying before drying, to reduce the decomposition of amido bond in bulk pharmaceutical chemicals.Increase in film simultaneously
Corrigent improves the compliance of patient.
Experiment prove gained oral quick-dissolving film preparation dissolution rate it is good, good mouthfeel, stability test show degradation impurity A and
C is suppressed significantly, and has been achieved the purpose that of the invention initial.
Experiment one：Prescription screening is tested
Rule of thumb design following composition：
Preparation process：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant acetic acid, Repaglinide successively, pH adjusting agent is used in stirring
PH to 4.5-5.5 is adjusted, it is spare；
Step 3：Step 2 acquired solution is taken, dissolves plasticizer polyethylene glycol 400 successively, filmogen hydroxypropyl cellulose divides
Disintegrating agent carboxymethyl base sodium starch is dissipated, stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
It is dry.Will blade coating obtain film stripping, shearing packing to get.
Test result analysis：
By the way that the film prepared by three prescriptions, visual inspection primarily determines that prescription one is optimal prescription, membrane surface light
Sliding, be integrally translucent shape, and ductile strength is relatively preferable, conveniently stripped.
Its performance is further tested by the experiment of following nature examination：
Experiment two：Film thickness determination
It being measured using micrometer caliper (range 0~25mm, resolution ratio 0.001mm), each prescription takes three parts of samples, is repeated 3 times,
It is averaged, acquired results are as follows：
The property of 3 film prescription samples has been investigated respectively, as a result as shown above.The Repaglinide oral cavity of 3 prescriptions
The thickness of instant film is in 0.05mm or so, as to can be seen that film thickness obtained by three prescriptions uniform for upper table data.
Experiment two：Disintegration time
Film sample obtained by three prescriptions is taken respectively, three parts, is put into after being clamped with clip in the beaker equipped with 50mL distilled water,
(37 ± 1) DEG C water bath with thermostatic control, measures the disintegration time of film.Film is put into water-bath and starts timing, is repeated 3 times, is averaged
Acquired results are as shown in the table：
As shown above, the Repaglinide film of 3 prescriptions, disintegration time is in 20s or so, but prescription one is slightly shorter.
Experiment four:The measurement of film mechanical property
Good film must have suitable flexibility and tensile property, convenient for taking and storing, take respectively obtained by three prescriptions
Film sample, three parts, using BLD-200S electron detachment testing machines, will about 10cm × 1cm size films, with 50mmmin-1
Speed longitudinal stretching elasticity modulus, tensile strength and rate elongation are calculated by following equation until film is broken.
Elasticity modulus=applied stress/adaptability to changes/area of section.
Tensile strength=applied stress/cross-sectional area.
Percent elongation=length incrementss/the original length × 100%：
Tensile strength is in 120Nmm-2Left and right, elasticity modulus is in 23Nmm-2Left and right, extends percentage 10% or so,
With good toughness.
By above-mentioned film thickness, disintegration time, mechanical property measures, and further confirms that, prescription one is optimal prescription.
With reference to one 1.0mg film prescriptions of prescription, preparation specification is become into 0.25mg, 0.5mg, 2.0mg, supplementary product consumption is constant
It is as follows to obtain four specification film prescriptions：
0.25mg, 0.5mg are observed with method, 2.0mg specification piece appearances measure its thickness, disintegration time, mechanical property,
Acquired results are as follows：
Experiment five：Study on Dissolution
According to document, after being improved on the basis of USP35 paddle method, the homemade stainless (steel) wire for being used for fixing film is added
Dish is positioned over digestion instrument release bottom of a cup portion, 5.0 phosphate buffers of 100mL pH is housed (by 10.2g Citric Acid Monos in cup
It is dissolved in 1000L purified waters, is made with 18.6g phosphate dihydrate disodium hydrogens) it is medium, rotating speed 75rmin-1, 1,5,
10, fixed position takes 5mL release liquids when 20 and 30min, while supplementing medium.Content is measured, and calculates the accumulation of different time
Release rate.Investigate aforementioned four specification (embodiment 1-4) oral quick-dissolving film preparation and commercially available Repaglinide tablet (PRANDI,
0.5mg, this sample are fixed without stainless (steel) wire dish) dissolution in vitro, data are as follows：
The dissolution data of the 4 specification film samples measured is as shown above.By result it is found that film rate of release compared with
Soon, the dissolution rate in 10min is up to 80% or more, and release is complete substantially in 30min, and marketed tablet is molten in 30min
Out-degree is only 73% or so.
Experiment five：Accelerated stability experiment in 12 months
Above-mentioned 4 specification oral quick-dissolving film preparations (embodiment 1-4) are taken, containing packaging and commercially available product PRANDI, 0.5mg (containing packaging) five
Number A-E sets 40 DEG C ± 2 DEG C to group sample respectively respectively, is stored 12 months under the conditions of 75% ± 5%RH, respectively at 0 month, January, and 3
Month, in June, December is measured by sampling relevant nature, obtains corresponding data, as shown in the table：
5 embodiment 1-4 of table is compared with marketed tablet sample stability
According to prescription described in embodiment 1-4 of the present invention and the Rui Gelie prepared by technique it can be seen from upper table data
How film, at 40 DEG C ± 2 DEG C, under 75% ± 5%RH acceleration environments, after storage in 12 months, content, related substance is become
Change, but content, more than 98.5%, maximum list impurity is less than 0.09%, and total impurities are below 0.5%, and impurity A is less than
0.05%, impurity C are less than 0.05%, and dissolution rate is qualified and without significant changes；It corresponds, commercially available Repaglinide tablet warp
After crossing acceleration storage in 12 months, content falls to approximately 95%, and maximum list impurity rises to about 0.5%, and impurity A increases to about
0.4%, impurity C increase to about 0.4%, and total impurities are then more than 4.0%, and dissolution rate is slightly reduced compared with 0 month, with A-D group phases
Than significantly relatively low.
Based on analysis as above, according to prescription described in embodiment 1-4 of the present invention and the Repaglinide tablet prepared by technique
Under acceleration conditions, the data after storing 12 months show that stability is significantly better than marketed tablet, i.e., place through the invention
Side and technique make the stability of Repaglinide tablet be remarkably reinforced, and amido bond degradation impurity, impurity A and impurity C are obtained
It significantly inhibits, so that the present invention has substantive distinguishing features outstanding and marked improvement, and there is practicability.
Specific implementation mode
The advantageous effect further illustrated the present invention is tested by following.But it is not limited to following embodiments, this field
Technical staff on the basis of the present invention made by, do not depart from equivalent substitute or the transformation of substantive content of the present invention, also this
Within the protection domain of invention.
Preparation (the unit of 1 0.25mg specification Repaglinide oral quick-dissolving film preparations of embodiment：g)
Prescription：
Preparation process：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant acetic acid, Repaglinide successively, pH adjusting agent is used in stirring
PH to 4.5-5.5 is adjusted, it is spare；
Step 3：Step 2 acquired solution is taken, dissolves plasticizer polyethylene glycol 400 successively, filmogen hydroxypropyl cellulose divides
Disintegrating agent carboxymethyl base sodium starch is dissipated, stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
It is dry.Will blade coating obtain film stripping, shearing, with PVC/ In Aluminium Foil Packings to get.
Moisture is 0.94% after the drying of gained oral quick-dissolving film preparation.
Preparation (the unit of 2 0.5mg specification Repaglinide oral quick-dissolving film preparations of embodiment：g)
Prescription：
Preparation process：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant acetic acid, Repaglinide successively, pH adjusting agent is used in stirring
PH to 4.5-5.5 is adjusted, it is spare；
Step 3：Step 2 acquired solution is taken, dissolves plasticizer polyethylene glycol 400 successively, filmogen hydroxypropyl cellulose divides
Disintegrating agent carboxymethyl base sodium starch is dissipated, stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
It is dry.Will blade coating obtain film stripping, shearing, with PVC/ In Aluminium Foil Packings to get.
Moisture is 0.96% after the drying of gained oral quick-dissolving film preparation.
Preparation (the unit of 3 1.0mg specification Repaglinide oral quick-dissolving film preparations of embodiment：g)
Prescription：
Preparation process：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant acetic acid, Repaglinide successively, pH adjusting agent is used in stirring
PH to 4.5-5.5 is adjusted, it is spare；
Step 3：Step 2 acquired solution is taken, dissolves plasticizer polyethylene glycol 400 successively, filmogen hydroxypropyl cellulose divides
Disintegrating agent carboxymethyl base sodium starch is dissipated, stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
It is dry.Will blade coating obtain film stripping, shearing, with PVC/ In Aluminium Foil Packings to get.
Moisture is 0.91% after the drying of gained oral quick-dissolving film preparation.
Preparation (the unit of 4 2.0mg specification Repaglinide oral quick-dissolving film preparations of embodiment：g)
Prescription：
Preparation process：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant acetic acid, Repaglinide successively, pH adjusting agent is used in stirring
PH to 4.5-5.5 is adjusted, it is spare；
Step 3：Step 2 acquired solution is taken, dissolves plasticizer polyethylene glycol 400 successively, filmogen hydroxypropyl cellulose divides
Disintegrating agent carboxymethyl base sodium starch is dissipated, stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
It is dry.Will blade coating obtain film stripping, shearing, with PVC/ In Aluminium Foil Packings to get.
Moisture is 0.95% after the drying of gained oral quick-dissolving film preparation.
Claims (7)
1. a kind of solid composite medicament containing Repaglinide, by main ingredient Repaglinide, filmogen hydroxypropyl cellulose increases
Mould agent polyethylene glycol 400, disintegrating agent carboxymethyl base sodium starch, saliva stimulant acetic acid, corrigent Aspartame, pH adjusting agent hydrogen-oxygen
Change sodium composition, the composition is further prepared into oral quick-dissolving film preparation as follows：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant successively, pH adjusting agent, Repaglinide stirs, spare；
Step 3：Step 2 acquired solution is taken, dissolves plasticizer successively, filmogen disperses disintegrant, and stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
It is dry.Will blade coating obtain film stripping, shearing packing to get；
It is characterized in that, moisture is less than 1.0% after the oral quick-dissolving film preparation drying.
2. the solid composite medicament containing Repaglinide as described in claim 1, which is characterized in that unit dose Rui Gelie
How content is 0.25mg, 0.5mg, 1mg, 2mg.
3. the solid composite medicament containing Repaglinide as claimed in claim 2, which is characterized in that unit formulation prescription group
At as follows：
4. the solid composite medicament containing Repaglinide as claimed in claim 2, which is characterized in that unit formulation prescription group
At as follows：
5. the solid composite medicament containing Repaglinide as claimed in claim 2, which is characterized in that unit formulation prescription group
At as follows：
6. the solid composite medicament containing Repaglinide as claimed in claim 2, which is characterized in that unit formulation prescription group
At as follows：
7. any solid composite medicament containing Repaglinide as described in claim 1-6, it is characterised in that described to contain
The solid composite medicament of Repaglinide, is further prepared into oral quick-dissolving film preparation as follows：
Step 1：It takes Repaglinide bulk pharmaceutical chemicals to crush, sieves with 100 mesh sieve, it is spare；
Step 2：It takes 95% ethyl alcohol as solvent, dissolves saliva stimulant acetic acid, Repaglinide successively, pH adjusting agent is used in stirring
PH to 4.5-5.5 is adjusted, it is spare；
Step 3：Step 2 acquired solution is taken, dissolves plasticizer polyethylene glycol 400 successively, filmogen hydroxypropyl cellulose divides
Disintegrating agent carboxymethyl base sodium starch is dissipated, stirring is spare；
Step 4：Step 3 acquired solution is taken, is scratched to stainless steel plate with film applicator, the temperature between 50 DEG C to 60 DEG C is dried
Film stripping dry, that blade coating is obtained, shearing, with PVC/ In Aluminium Foil Packings to get.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101237781A (en) * | 2005-05-19 | 2008-08-06 | 麦克内尔-Ppc股份有限公司 | Confectionery products for the treatment of dry mouth |
| CN101466354A (en) * | 2006-06-16 | 2009-06-24 | Lts罗曼治疗方法有限公司 | Type-2 diabetes combination wafer |
| CN103211801A (en) * | 2013-04-02 | 2013-07-24 | 苏州人本药业有限公司 | Film agent quickly dissolved in oral cavity and preparation method thereof |
| CN103750323A (en) * | 2014-01-26 | 2014-04-30 | 宁夏医科大学 | Oral lutein instant membrane and preparation method thereof |
| CN105147643A (en) * | 2015-09-17 | 2015-12-16 | 北京联合大学 | Repaglinide membrane and preparation method thereof |
| EP3192499A1 (en) * | 2016-01-14 | 2017-07-19 | Hoffmann & Sommer GmbH und Co. KG | Cellulose fibre based support matrices for layered products for oral and peroral application and their preparation |
-
2018
- 2018-04-12 CN CN201810327698.6A patent/CN108272777A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101237781A (en) * | 2005-05-19 | 2008-08-06 | 麦克内尔-Ppc股份有限公司 | Confectionery products for the treatment of dry mouth |
| CN101466354A (en) * | 2006-06-16 | 2009-06-24 | Lts罗曼治疗方法有限公司 | Type-2 diabetes combination wafer |
| CN103211801A (en) * | 2013-04-02 | 2013-07-24 | 苏州人本药业有限公司 | Film agent quickly dissolved in oral cavity and preparation method thereof |
| CN103750323A (en) * | 2014-01-26 | 2014-04-30 | 宁夏医科大学 | Oral lutein instant membrane and preparation method thereof |
| CN105147643A (en) * | 2015-09-17 | 2015-12-16 | 北京联合大学 | Repaglinide membrane and preparation method thereof |
| EP3192499A1 (en) * | 2016-01-14 | 2017-07-19 | Hoffmann & Sommer GmbH und Co. KG | Cellulose fibre based support matrices for layered products for oral and peroral application and their preparation |
Non-Patent Citations (1)
| Title |
|---|
| 陈琼，等: "《中药制剂技术》", 30 November 2014, 北京：中国农业大学出版社 * |
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