CN110403902A - A kind of preparation method of Tacrolimus paste - Google Patents
A kind of preparation method of Tacrolimus paste Download PDFInfo
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- CN110403902A CN110403902A CN201910838177.1A CN201910838177A CN110403902A CN 110403902 A CN110403902 A CN 110403902A CN 201910838177 A CN201910838177 A CN 201910838177A CN 110403902 A CN110403902 A CN 110403902A
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- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 title claims abstract description 55
- 229960001967 tacrolimus Drugs 0.000 title claims abstract description 55
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 41
- 239000002075 main ingredient Substances 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 25
- 239000003883 ointment base Substances 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 13
- SIXOAUAWLZKQKX-UHFFFAOYSA-N carbonic acid;prop-1-ene Chemical compound CC=C.OC(O)=O SIXOAUAWLZKQKX-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000007765 cera alba Substances 0.000 claims abstract description 11
- 229940057995 liquid paraffin Drugs 0.000 claims abstract description 11
- 239000012188 paraffin wax Substances 0.000 claims abstract description 11
- 238000009826 distribution Methods 0.000 claims abstract description 10
- 239000002245 particle Substances 0.000 claims abstract description 7
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 239000002562 thickening agent Substances 0.000 claims abstract description 6
- 238000009472 formulation Methods 0.000 claims abstract description 5
- 239000004615 ingredient Substances 0.000 claims abstract description 5
- 239000000314 lubricant Substances 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 239000011159 matrix material Substances 0.000 claims description 33
- 239000000498 cooling water Substances 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 16
- 239000002674 ointment Substances 0.000 claims description 13
- 239000000839 emulsion Substances 0.000 claims description 11
- 239000000758 substrate Substances 0.000 claims description 11
- 238000001514 detection method Methods 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 239000013067 intermediate product Substances 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 10
- 238000012360 testing method Methods 0.000 claims description 10
- 238000005352 clarification Methods 0.000 claims description 5
- 238000007599 discharging Methods 0.000 claims description 5
- 238000004090 dissolution Methods 0.000 claims description 5
- 239000011521 glass Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 5
- 239000000155 melt Substances 0.000 claims description 5
- 238000012856 packing Methods 0.000 claims description 5
- 238000005507 spraying Methods 0.000 claims description 5
- 230000000007 visual effect Effects 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 230000008676 import Effects 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 239000006210 lotion Substances 0.000 abstract description 3
- -1 allyl ester Chemical class 0.000 abstract description 2
- 238000001816 cooling Methods 0.000 description 5
- 238000010422 painting Methods 0.000 description 3
- 238000009827 uniform distribution Methods 0.000 description 3
- 230000002411 adverse Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
- G01N15/0205—Investigating particle size or size distribution by optical means
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Analytical Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Physics & Mathematics (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to technical field of medicine, a kind of a kind of preparation method of Tacrolimus paste: formulation ingredients ratio of Tacrolimus paste are as follows: main ingredient: tacrolimus 0.1%, solvent: propene carbonate 2%~5%, thickener: cera alba 3%~4%, lubricant: liquid paraffin 10%~12%, curing agent: paraffin 2%~4% and ointment bases: albolene 70%~80%, a kind of preparation method of Tacrolimus paste, the Adding Way of main ingredient solution in the technical program, compared with traditional dripping method, feed time is shorter, it is more efficient, compared with a traditional addition method, in obtained lotion product, the size droplet diameter of carbonic allyl ester solution is smaller, particle size distribution range is smaller, and (95% size droplet diameter is distributed between 5-10 μm, and import original grinds product Size droplet diameter distribution are as follows: 95% size droplet diameter is distributed between 5-25 μm), the uniformity of dosage units of main ingredient is more preferable, and the release in vitro and Transdermal absorption of main ingredient are more preferable, and curative effect is also just more preferable.
Description
Technical field
The present invention relates to technical field of medicine, specially a kind of preparation method of Tacrolimus paste.
Background technique
The product formula of each family of Tacrolimus paste of country's listing is inconsistent, our present product prescriptions and state's exogenesis
Grind Tacrolimus paste (Pood that) unanimously, quality standard is also consistent.But production process is different, currently on the market mostly
In process of production, the phenomenon that small lump that ointment bases are easy to produce in fast cooling, is (micro- for number Tacrolimus pastes
See under the microscope, the original of external import, which is ground in drug, just a small amount of this small lump), there is small lump in ointment bases,
By to drug release in vitro and Transdermal absorption have an adverse effect.
Summary of the invention
(1) the technical issues of solving
In view of the deficiencies of the prior art, the present invention provides a kind of preparation method of Tacrolimus paste, have and effectively keep away
The advantages that the phenomenon that having exempted from the small lump that ointment bases are easy to produce in fast cooling.
(2) technical solution
For the mesh for realizing above-mentioned the phenomenon that effectively preventing the small lump that ointment bases are easy to produce in fast cooling
, the invention provides the following technical scheme: a kind of preparation method of Tacrolimus paste: a kind of prescription of Tacrolimus paste at
Divide ratio are as follows: main ingredient: tacrolimus 0.1%, solvent: propene carbonate 2%~5%, thickener: cera alba 3%~4%, profit
Lubrication prescription: liquid paraffin 10%~12%, curing agent: paraffin 2%~4% and ointment bases: albolene 70%~80%.
A kind of preparation method of Tacrolimus paste, comprising the following steps:
S10, supplementary material is weighed by recipe quantity, it is spare；
S20, matrix preparation is carried out；
S30, main ingredient is dissolved；
S40, main ingredient solution is added in matrix；
S50, ointment preparation is carried out:
S60, intermediate products are detected；
S70, after intermediate product testing is qualified, unlatchings scraper plate speed of agitator is 40 turns/min, opens vacuum pump, control is very
Reciprocal of duty cycle is -0.06MPa~-0.08MPa, and opening cooling water makes matrix be cooled to 35 DEG C hereinafter, discharging；
S80, finally according to loading amount area requirement loading amount being set, loading amount debugging is qualified, check weighing scale rejects loading amount rejected product,
Start formal packing.
Preferably, the step of prepared by the matrix are as follows:
Step 1: albolene, cera alba, paraffin, the liquid paraffin of prescription batch are added into oily phase tank, steam is opened
70 DEG C~80 DEG C are heated to, stirring (speed of agitator is 300~500 turns/min) is opened, melts material to clarification；
Step 2: opening vacuum pump, the matrix in oily phase tank is filtered into emulsion tank (100 mesh of sieve mesh number), is opened
Stirring (scraper plate speed of agitator is 40 turns/min), opening cooling water, (cooling water temperature is controlled by heat exchanger, temperature range 33
DEG C~37 DEG C), so that substrate temperature is down to 38 DEG C~40 DEG C.
Preferably, the technique of the main ingredient dissolution are as follows: the tacrolimus of recipe quantity is added in propene carbonate, is stirred
Make to dissolve, be transferred in liquid spraying can.
Preferably, the step of main ingredient solution is added are as follows:
Step 1: keeping emulsion tank scraper plate speed of agitator is 40 turns/min, 1200 turns/min~2500 of homogeneous revolving speed are set
Turn/min, opens homogeneous；
Step 2: opening compressed air, control hydrojet pressure inside the tank is 0.01MPa~0.04MPa, adjusts hydrojet flow and opens
It closes, coutroi velocity is 0..15L/min~0.4L/min, and tacrolimus solution is sprayed into matrix.
Preferably, the technique of the ointment preparation are as follows: holding scraper plate speed of agitator is 40 turns/min, and homogeneous revolving speed is 1200
Turn/min~2500 turn/min, substrate temperature is maintained at 38 DEG C~40 DEG C, opens vacuum pump, and control vacuum degree is -0.06MPa
~-0.08MPa continues homogeneous and stirs 30min, shuts down sample detection.
Preferably, the sample detection method are as follows: it takes test sample appropriate, is placed on glass slide and applies straticulation, thin layer area
It is equivalent to coverslip area, 3 are applied altogether, according to granularity and determination of particle size distribution (Chinese Pharmacopoeia version general rule 0,982 first in 2015
Method) measurement, the drug drop in the visual field is inspected under 400 times of microscope, drop should be uniformly distributed, and 95% drop should be less than
25μm。
(3) beneficial effect
Compared with prior art, the present invention provides a kind of preparation methods of Tacrolimus paste, have following beneficial to effect
Fruit:
1, a kind of preparation method of Tacrolimus paste, the addition of main ingredient solution is by opening compression in the technical program
Air, control hydrojet pressure inside the tank are 0.01MPa~0.04MPa, adjust hydrojet flow switch, coutroi velocity 0.15L/min
~0..4L/min sprays into tacrolimus solution in matrix, and compared with traditional dripping method, feed time is shorter, and efficiency is more
Height, compared with a traditional addition method, in obtained lotion product, the size droplet diameter of carbonic allyl ester solution is smaller, grain
Diameter distribution is smaller, and (95% size droplet diameter is distributed between 5-10 μm, and import original grinds the size droplet diameter distribution model of product
Enclose are as follows: 95% size droplet diameter is distributed between 5-25 μm), the uniformity of dosage units of main ingredient is more preferable, the release in vitro of main ingredient and thoroughly
Skin absorbs more preferably, and curative effect is also just more preferable.
2, a kind of preparation method of Tacrolimus paste, the preparation of the technical program mesostroma, which passes through, opens vacuum pump,
Matrix in oily phase tank is filtered into emulsion tank (100 mesh of sieve mesh number), open stirring (scraper plate speed of agitator be 40 turns/
Min), cooling water (cooling water temperature is controlled by heat exchanger, and temperature range is 33 DEG C~37 DEG C) is opened, substrate temperature is down to
38 DEG C~40 DEG C, using 33 DEG C~37 DEG C of hot water rather than ointment bases drop in the conventional lower tap water of temperature
Temperature, cooling rate is slower, and ointment bases heat transfer is more effective in tank, ointment bases more uniform temperature, effectively prevents lotion
The phenomenon that small lump that matrix is easy to produce in fast cooling, (microscopically observation saw that the original of external import is ground in drug
Just have a small amount of this small lump), there is small lump in ointment bases, by drug release in vitro and Transdermal absorption generate
Adverse effect.
3, a kind of preparation method of Tacrolimus paste, main ingredient in the Tacrolimus paste as made from the technical program
Solution partial size is smaller, particle size distribution range is smaller, the drug content uniformity is more preferable, to improve curative effect, while also avoiding medicine
Occurs small lump in product.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical solution in the embodiment of the present invention is clearly and completely retouched
It states, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based on the present invention
In embodiment, every other implementation obtained by those of ordinary skill in the art without making creative efforts
Example, shall fall within the protection scope of the present invention.
Embodiment one:
A kind of preparation method of Tacrolimus paste:
A kind of formulation ingredients ratio of Tacrolimus paste are as follows: main ingredient: tacrolimus 0.1%, solvent: propene carbonate
2%, thickener: cera alba 3%, lubricant: liquid paraffin 10%%, curing agent: paraffin 2% and ointment bases: albolene
70%；
A kind of preparation method of Tacrolimus paste, comprising the following steps:
S10, supplementary material is weighed by recipe quantity, it is spare；
S20, matrix preparation is carried out；
S30, main ingredient is dissolved；
S40, main ingredient solution is added in matrix；
S50, ointment preparation is carried out:
S60, intermediate products are detected；
S70, after intermediate product testing is qualified, unlatchings scraper plate speed of agitator is 40 turns/min, opens vacuum pump, control is very
Reciprocal of duty cycle is -0.06MPa~-0.08MPa, and opening cooling water makes matrix be cooled to 35 DEG C hereinafter, discharging；
S80, finally according to loading amount area requirement loading amount being set, loading amount debugging is qualified, check weighing scale rejects loading amount rejected product,
Start formal packing.
The step of prepared by matrix are as follows:
Step 1: albolene, cera alba, paraffin, the liquid paraffin of prescription batch are added into oily phase tank, steam is opened
70 DEG C~80 DEG C are heated to, stirring (speed of agitator is 300~500 turns/min) is opened, melts material to clarification；
Step 2: opening vacuum pump, the matrix in oily phase tank is filtered into emulsion tank (100 mesh of sieve mesh number), is opened
Stirring (scraper plate speed of agitator is 40 turns/min), opening cooling water, (cooling water temperature is controlled by heat exchanger, temperature range 33
DEG C~37 DEG C), so that substrate temperature is down to 38 DEG C~40 DEG C.
The technique of main ingredient dissolution are as follows: the tacrolimus of recipe quantity is added in propene carbonate, is stirred to dissolve, is shifted
Into liquid spraying can.
The step of main ingredient solution is added are as follows:
Step 1: keeping emulsion tank scraper plate speed of agitator is 40 turns/min, 1200 turns/min~2500 of homogeneous revolving speed are set
Turn/min, opens homogeneous；
Step 2: opening compressed air, control hydrojet pressure inside the tank is 0.01MPa~0.04MPa, adjusts hydrojet flow and opens
It closes, coutroi velocity is 0..15L/min~0.4L/min, and tacrolimus solution is sprayed into matrix.
Ointment preparation technique are as follows: holdings scraper plate speed of agitator be 40 turns/min, homogeneous revolving speed for 1200 turns/min~
2500 turns/min, substrate temperature is maintained at 38 DEG C~40 DEG C, opens vacuum pump, control vacuum degree for -0.06MPa~-
0.08MPa continues homogeneous and stirs 30min, shuts down sample detection, sample detection method are as follows: take test sample appropriate, be placed in glass slide
Upper painting straticulation, thin layer area are equivalent to coverslip area, 3 are applied altogether, according to granularity and determination of particle size distribution (Chinese Pharmacopoeia
0,982 first method of version general rule in 2015) measurement, the drug drop in the visual field is inspected under 400 times of microscope, drop should be uniform
Distribution, 95% drop should be less than 25 μm.
According to Tacrolimus paste character made from above-mentioned formula and technique are as follows: white to faint yellow ointment.
Embodiment two:
A kind of preparation method of Tacrolimus paste:
A kind of formulation ingredients ratio of Tacrolimus paste are as follows: main ingredient: tacrolimus 0.1%, solvent: propene carbonate
2.5%, thickener: cera alba 3.5%, lubricant: liquid paraffin 11%, curing agent: paraffin 3% and ointment bases: Bai Fanshi
Woods 75%；
A kind of preparation method of Tacrolimus paste, comprising the following steps:
S10, supplementary material is weighed by recipe quantity, it is spare；
S20, matrix preparation is carried out；
S30, main ingredient is dissolved；
S40, main ingredient solution is added in matrix；
S50, ointment preparation is carried out:
S60, intermediate products are detected；
S70, after intermediate product testing is qualified, unlatchings scraper plate speed of agitator is 40 turns/min, opens vacuum pump, control is very
Reciprocal of duty cycle is -0.06MPa~-0.08MPa, and opening cooling water makes matrix be cooled to 35 DEG C hereinafter, discharging；
S80, finally according to loading amount area requirement loading amount being set, loading amount debugging is qualified, check weighing scale rejects loading amount rejected product,
Start formal packing.
The step of prepared by matrix are as follows:
Step 1: albolene, cera alba, paraffin, the liquid paraffin of prescription batch are added into oily phase tank, steam is opened
70 DEG C~80 DEG C are heated to, stirring (speed of agitator is 300~500 turns/min) is opened, melts material to clarification；
Step 2: opening vacuum pump, the matrix in oily phase tank is filtered into emulsion tank (100 mesh of sieve mesh number), is opened
Stirring (scraper plate speed of agitator is 40 turns/min), opening cooling water, (cooling water temperature is controlled by heat exchanger, temperature range 33
DEG C~37 DEG C), so that substrate temperature is down to 38 DEG C~40 DEG C.
The technique of main ingredient dissolution are as follows: the tacrolimus of recipe quantity is added in propene carbonate, is stirred to dissolve, is shifted
Into liquid spraying can.
The step of main ingredient solution is added are as follows:
Step 1: keeping emulsion tank scraper plate speed of agitator is 40 turns/min, 1200 turns/min~2500 of homogeneous revolving speed are set
Turn/min, opens homogeneous；
Step 2: opening compressed air, control hydrojet pressure inside the tank is 0.01MPa~0.04MPa, adjusts hydrojet flow and opens
It closes, coutroi velocity is 0..15L/min~0.4L/min, and tacrolimus solution is sprayed into matrix.
Ointment preparation technique are as follows: holdings scraper plate speed of agitator be 40 turns/min, homogeneous revolving speed for 1200 turns/min~
2500 turns/min, substrate temperature is maintained at 38 DEG C~40 DEG C, opens vacuum pump, control vacuum degree for -0.06MPa~-
0.08MPa continues homogeneous and stirs 30min, shuts down sample detection, sample detection method are as follows: take test sample appropriate, be placed in glass slide
Upper painting straticulation, thin layer area are equivalent to coverslip area, 3 are applied altogether, according to granularity and determination of particle size distribution (Chinese Pharmacopoeia
0,982 first method of version general rule in 2015) measurement, the drug drop in the visual field is inspected under 400 times of microscope, drop should be uniform
Distribution, 95% drop should be less than 25 μm.
According to Tacrolimus paste character made from above-mentioned formula and technique are as follows: white to faint yellow ointment.
Embodiment three:
A kind of preparation method of Tacrolimus paste:
A kind of formulation ingredients ratio of Tacrolimus paste are as follows: main ingredient: tacrolimus 0.1%, solvent: propene carbonate
5%, thickener: cera alba 4%, lubricant: liquid paraffin 12%, curing agent: paraffin 4% and ointment bases: albolene
80%；
A kind of preparation method of Tacrolimus paste, comprising the following steps:
S10, supplementary material is weighed by recipe quantity, it is spare；
S20, matrix preparation is carried out；
S30, main ingredient is dissolved；
S40, main ingredient solution is added in matrix；
S50, ointment preparation is carried out:
S60, intermediate products are detected；
S70, after intermediate product testing is qualified, unlatchings scraper plate speed of agitator is 40 turns/min, opens vacuum pump, control is very
Reciprocal of duty cycle is -0.06MPa~-0.08MPa, and opening cooling water makes matrix be cooled to 35 DEG C hereinafter, discharging；
S80, finally according to loading amount area requirement loading amount being set, loading amount debugging is qualified, check weighing scale rejects loading amount rejected product,
Start formal packing.
The step of prepared by matrix are as follows:
Step 1: albolene, cera alba, paraffin, the liquid paraffin of prescription batch are added into oily phase tank, steam is opened
70 DEG C~80 DEG C are heated to, stirring (speed of agitator is 300~500 turns/min) is opened, melts material to clarification；
Step 2: opening vacuum pump, the matrix in oily phase tank is filtered into emulsion tank (100 mesh of sieve mesh number), is opened
Stirring (scraper plate speed of agitator is 40 turns/min), opening cooling water, (cooling water temperature is controlled by heat exchanger, temperature range 33
DEG C~37 DEG C), so that substrate temperature is down to 38 DEG C~40 DEG C.
The technique of main ingredient dissolution are as follows: the tacrolimus of recipe quantity is added in propene carbonate, is stirred to dissolve, is shifted
Into liquid spraying can.
The step of main ingredient solution is added are as follows:
Step 1: keeping emulsion tank scraper plate speed of agitator is 40 turns/min, 1200 turns/min~2500 of homogeneous revolving speed are set
Turn/min, opens homogeneous；
Step 2: opening compressed air, control hydrojet pressure inside the tank is 0.01MPa~0.04MPa, adjusts hydrojet flow and opens
It closes, coutroi velocity is 0..15L/min~0.4L/min, and tacrolimus solution is sprayed into matrix.
Ointment preparation technique are as follows: holdings scraper plate speed of agitator be 40 turns/min, homogeneous revolving speed for 1200 turns/min~
2500 turns/min, substrate temperature is maintained at 38 DEG C~40 DEG C, opens vacuum pump, control vacuum degree for -0.06MPa~-
0.08MPa continues homogeneous and stirs 30min, shuts down sample detection, sample detection method are as follows: take test sample appropriate, be placed in glass slide
Upper painting straticulation, thin layer area are equivalent to coverslip area, 3 are applied altogether, according to granularity and determination of particle size distribution (Chinese Pharmacopoeia
0,982 first method of version general rule in 2015) measurement, the drug drop in the visual field is inspected under 400 times of microscope, drop should be uniform
Distribution, 95% drop should be less than 25 μm.
According to Tacrolimus paste character made from above-mentioned formula and technique are as follows: white to faint yellow ointment.
The sequencing of above embodiments is not only for ease of description, represent the advantages or disadvantages of the embodiments.
It although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
A variety of variations, modification, replacement can be carried out to these embodiments without departing from the principles and spirit of the present invention by understanding
And modification, the scope of the present invention is defined by the appended.
Claims (7)
1. a kind of Tacrolimus paste, it is characterised in that: a kind of formulation ingredients ratio of Tacrolimus paste are as follows: main ingredient:
Tacrolimus 0.1%, solvent: propene carbonate 2%~5%, thickener: cera alba 3%~4%, lubricant: liquid paraffin
10%~12%, curing agent: paraffin 2%~4% and ointment bases: albolene 70%~80%.
2. a kind of preparation method of Tacrolimus paste, which comprises the following steps:
S10, supplementary material is weighed by recipe quantity, it is spare；
S20, matrix preparation is carried out；
S30, main ingredient is dissolved；
S40, main ingredient solution is added in matrix；
S50, ointment preparation is carried out:
S60, intermediate products are detected；
S70, after intermediate product testing is qualified, unlatchings scraper plate speed of agitator is 40 turns/min, opens vacuum pump, control vacuum degree
For -0.06MPa~-0.08MPa, opening cooling water makes matrix be cooled to 35 DEG C hereinafter, discharging；
S80, finally according to loading amount area requirement loading amount is set, loading amount debugging is qualified, check weighing scale rejects loading amount rejected product, starts
Formal packing.
3. a kind of preparation method of Tacrolimus paste according to claim 2, it is characterised in that: the matrix preparation
Step are as follows:
Step 1: albolene, cera alba, paraffin, the liquid paraffin of prescription batch are added into oily phase tank, steam heating is opened
To 70 DEG C~80 DEG C, stirring (speed of agitator is 300~500 turns/min) is opened, melts material to clarification；
Step 2: opening vacuum pump, the matrix in oily phase tank is filtered into emulsion tank (100 mesh of sieve mesh number), opens stirring
(scraper plate speed of agitator be 40 turns/min), open cooling water (cooling water temperature is controlled by heat exchanger, temperature range for 33 DEG C~
37 DEG C), so that substrate temperature is down to 38 DEG C~40 DEG C.
4. a kind of preparation method of Tacrolimus paste according to claim 2, it is characterised in that: the main ingredient dissolution
Technique are as follows: the tacrolimus of recipe quantity is added in propene carbonate, is stirred to dissolve, is transferred in liquid spraying can.
5. a kind of preparation method of Tacrolimus paste according to claim 2, it is characterised in that: the main ingredient solution adds
The step of entering are as follows:
Step 1: keep emulsion tank scraper plate speed of agitator for 40 turns/min, setting 1200 turns/min~2500 turn of homogeneous revolving speed/
Min opens homogeneous；
Step 2: opening compressed air, control hydrojet pressure inside the tank is 0.01MPa~0.04MPa, adjusts hydrojet flow switch,
Coutroi velocity is 0..15L/min~0.4L/min, and tacrolimus solution is sprayed into matrix.
6. a kind of preparation method of Tacrolimus paste according to claim 2, it is characterised in that: the ointment preparation
Technique are as follows: holding scraper plate speed of agitator is 40 turns/min, and homogeneous revolving speed is 1200 turns/min~2500 turn/min, and substrate temperature is protected
It holds at 38 DEG C~40 DEG C, opens vacuum pump, control vacuum degree is -0.06MPa~-0.08MPa, continues homogeneous and stirs 30min, stops
Machine sample detection.
7. a kind of preparation method of Tacrolimus paste according to claim 6, it is characterised in that: the sample detection side
Method are as follows: take test sample appropriate, be placed on glass slide and apply straticulation, thin layer area is equivalent to coverslip area, 3 is applied altogether, according to grain
Degree and determination of particle size distribution (Chinese Pharmacopoeia 0,982 first method of version general rule in 2015) measurement, are inspected under 400 times of microscope
Drug drop in the visual field, drop should be uniformly distributed, and 95% drop should be less than 25 μm.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112022798A (en) * | 2020-08-11 | 2020-12-04 | 四川大学华西医院 | Quick-acting tacrolimus ointment, preparation method and application |
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| WO2010041684A1 (en) * | 2008-10-08 | 2010-04-15 | 高田製薬株式会社 | Tacrolimus preparation for external applications |
| CN105687161A (en) * | 2014-11-27 | 2016-06-22 | 黑龙江省智诚医药科技有限公司 | Tacrolimus slow-release mini-pill and preparation method thereof |
| CN105769752A (en) * | 2016-04-08 | 2016-07-20 | 湖北生物医药产业技术研究院有限公司 | Method for preparing tacrolimus ointment and tacrolimus ointment |
| CN106166138A (en) * | 2016-07-31 | 2016-11-30 | 合肥远志医药科技开发有限公司 | A kind of Tacrolimus paste preparation and preparation method thereof |
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2019
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010041684A1 (en) * | 2008-10-08 | 2010-04-15 | 高田製薬株式会社 | Tacrolimus preparation for external applications |
| CN105687161A (en) * | 2014-11-27 | 2016-06-22 | 黑龙江省智诚医药科技有限公司 | Tacrolimus slow-release mini-pill and preparation method thereof |
| CN105769752A (en) * | 2016-04-08 | 2016-07-20 | 湖北生物医药产业技术研究院有限公司 | Method for preparing tacrolimus ointment and tacrolimus ointment |
| CN106166138A (en) * | 2016-07-31 | 2016-11-30 | 合肥远志医药科技开发有限公司 | A kind of Tacrolimus paste preparation and preparation method thereof |
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| CN112022798A (en) * | 2020-08-11 | 2020-12-04 | 四川大学华西医院 | Quick-acting tacrolimus ointment, preparation method and application |
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