CN109106693A - Rifampicin capsules and preparation method thereof - Google Patents
Rifampicin capsules and preparation method thereof Download PDFInfo
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- CN109106693A CN109106693A CN201710488562.9A CN201710488562A CN109106693A CN 109106693 A CN109106693 A CN 109106693A CN 201710488562 A CN201710488562 A CN 201710488562A CN 109106693 A CN109106693 A CN 109106693A
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- Prior art keywords
- rifampin
- rifampicin
- crystalline substance
- type crystalline
- medicine composition
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- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 title claims abstract description 133
- 229960001225 rifampicin Drugs 0.000 title claims abstract description 131
- 239000002775 capsule Substances 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title abstract description 27
- 239000000126 substance Substances 0.000 claims abstract description 58
- 239000000203 mixture Substances 0.000 claims abstract description 38
- 239000003814 drug Substances 0.000 claims abstract description 34
- 239000000463 material Substances 0.000 claims abstract description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 28
- 229920002261 Corn starch Polymers 0.000 claims description 16
- 239000008120 corn starch Substances 0.000 claims description 16
- 229940099112 cornstarch Drugs 0.000 claims description 16
- 229920000881 Modified starch Polymers 0.000 claims description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims description 14
- 239000000945 filler Substances 0.000 claims description 11
- DMBUODUULYCPAK-UHFFFAOYSA-N 1,3-bis(docosanoyloxy)propan-2-yl docosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCCCCCC DMBUODUULYCPAK-UHFFFAOYSA-N 0.000 claims description 10
- 239000000314 lubricant Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- -1 glycerol Ester Chemical class 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 238000007796 conventional method Methods 0.000 claims description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 4
- 239000002253 acid Substances 0.000 claims 2
- 125000002511 behenyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 239000013049 sediment Substances 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 12
- 238000009434 installation Methods 0.000 abstract description 2
- 239000013078 crystal Substances 0.000 description 25
- 239000011812 mixed powder Substances 0.000 description 18
- 102220042174 rs141655687 Human genes 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- UKMSUNONTOPOIO-UHFFFAOYSA-N Behenic acid Natural products CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 235000021357 Behenic acid Nutrition 0.000 description 3
- 229940116226 behenic acid Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 238000009940 knitting Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- JQXXHWHPUNPDRT-KCFDLMDRSA-N [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-[(Z)-(4-methylpiperazin-1-yl)iminomethyl]-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(29),2,4,9,19,21,25,27-octaen-13-yl] acetate Chemical compound CO[C@H]1\C=C\O[C@@]2(C)Oc3c(C2=O)c2c(O)c(\C=N/N4CCN(C)CC4)c(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)c(O)c2c(O)c3C JQXXHWHPUNPDRT-KCFDLMDRSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- DKXULEFCEORBJK-UHFFFAOYSA-N magnesium;octadecanoic acid Chemical compound [Mg].CCCCCCCCCCCCCCCCCC(O)=O DKXULEFCEORBJK-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940100691 oral capsule Drugs 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229960003292 rifamycin Drugs 0.000 description 1
- SQTCRTQCPJICLD-KTQDUKAHSA-N rifamycin B Chemical compound OC1=C(C(O)=C2C)C3=C(OCC(O)=O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O SQTCRTQCPJICLD-KTQDUKAHSA-N 0.000 description 1
- SQTCRTQCPJICLD-OQQFTUDCSA-N rifomycin-B Natural products COC1C=COC2(C)Oc3c(C)c(O)c4c(O)c(NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C)cc(OCC(=O)O)c4c3C2=O SQTCRTQCPJICLD-OQQFTUDCSA-N 0.000 description 1
- 229940049560 rimactane Drugs 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 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
- A61K31/495—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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to technical field of pharmaceuticals, and in particular to a kind of rifampicin capsules and preparation method thereof.The invention discloses a kind of rifampicin medicine composition, the rifampicin medicine composition is made of rifampin II type crystalline substance and pharmaceutically acceptable auxiliary material；The rifampin II type crystalline substance D90 is 30 μm -150 μm；The mass percent of the rifampin II type crystalline substance and auxiliary material is 60~85%:15~40%.The present invention by II type crystalline substance rifampin granularity control in reasonable range, thus obtain it is a kind of dissolution meet the requirements, the rifampicin capsules that quality is more stable, bioavilability is high.Rifampicin capsules preparation method of the invention is simple, easy to operate, is not necessarily to special installation, it is easy to accomplish industrialization.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, and in particular to a kind of rifampicin capsules and preparation method thereof.
Background technique
Rifampin chemical name is 3- [[(4- methyl-1-piperazinyl) imino group] methyl]-rifamycin, molecular formula
C43H58N4O12, molecular weight 822.95, No. CAS: 13292-46-1, chemical structural formula is shown below.
Rifampin is a kind of semisynthetic antibiotics obtained from rifamycin B, belongs to macrolactams antibiotic, can be pressed down
DNA of bacteria transcription synthesis RNA processed, clinically for treating pulmonary tuberculosis or other tuberculosis.As the phthisical line medicine for the treatment of
Object, rifampin dosage account for a quarter or so of the total dosage of antituberculotic.The single preparations of ephedrine of rifampin include tablet, capsule,
A variety of dosage forms such as injection.Rifampicin capsules 1967 for the first time in Italy by Sanofi-Aventis company Initial Public Offering pin
It sells, trade name1971.05.21 granted in U.S.'s list marketing, trade nameThe rule of approval
Lattice are 300mg；1981.07.15 increasing the listing of 150mg specification product.The rifampicin capsules of country's listing is imitation medicine, specification
For 150mg and 300mg.
Rifampin is currently known there are polymorphism there are I, II and SV crystal form and the forms such as unformed, wherein I and
II crystal form is medicinal effective crystal form and extensive use.The crystal form of rifampin and its physicochemical property, bioavilability and clinical efficacy
It is closely related.Rifampin I type crystal, crystalline density is small (>=0.5g/ml), crystal habit be large knitting needle shape, product adhesion compared with
Greatly, it is easy absorption bonding, mobility is poor.I type crystal is stable crystal form, and II type crystal is metastable crystal form.In terms of stability, benefit
The flat I type crystalline substance of good fortune is more stable, is not susceptible to change.In rifampin II type crystalline substance long term storage, easily there is impurity increase, content is bright
Aobvious decline, there is also crystal phenomenon under wet heat condition.And rifampicin capsules domestic at present is that I type is brilliant.
Since rifampicin capsules listing is of the remote past, in relation to taking orally the formulation and technology research of folk prescription capsule preparations or reporting very
It is few.Open or authorization patent relates generally to the composition of compound preparation or the Rimactane of preparation or other administration route.In
State patent 201510680756.X discloses a kind of rifampin semisolid capsule and preparation method thereof.The capsule is by semisolid content
Object, capsule shells and capsule shells coating material composition；Semisolid content includes the rifampin of 30wt%-40wt%, 40wt%-
The fat-soluble matrix of 55wt%, the solubilizer of 10wt%-20wt%；Capsule shells coating material quality is semisolid content quality
5wt%-15wt%.Preparation method is to be filled in fat-soluble matrix, solubilizer, rifampin mixing in hard capsule case simultaneously
Sealing；The semisolid capsule prepared is subjected to Cotton seeds once or twice with coating solution again, obtains product.The capsule and its
Preparation method solves rifampin semisolid capsule preparations uniformity of dosage units and Product transport in the process since thermal extremes are made
The problem of revealing at capsule keeps drug quality relatively reliable, and stock management, transport and sale are more convenient.This rifampin half
Although capsule fortreating AIDS quality is stablized, dissolution rate is high, composition and complex process, high production cost.
In view of domestic rifampicin capsules is that I type is brilliant, compared with external original grinds product, because crystal form difference is likely to deposit
In quality difference, especially efficacy and saferry difference.In order to improve domestic rifampicin capsules quality, therefore using the brilliant benefit of II type
Good fortune is flat to be used as raw material, obtains more stable rifampicin capsules medicine while not influencing preparation dissolution by researching and developing one kind.
Summary of the invention
In view of this, the purpose of the present invention is to provide a kind of rifampicin medicine composition and its rifampin glue of preparation
Capsule, rifampicin capsules of the invention is with good stability, and preparation method is simple, stablizes, favorable reproducibility.
Inventor is through reversed the study found that original grinds rifampicin capsulesIt is brilliant using II type, bulk pharmaceutical chemicals partial size compared with
It is small, about 10-15 μm of D90.Inventor takes II type crystalline substance rifampin to obtain similar particle sizes by air-flow crushing, finds the particle size range
Bulk pharmaceutical chemicals have very strong Electrostatic Absorption, and mobility is very poor, bring certain difficulty to mixing fill process operation.Inventor is by original
Composition is ground, by the D90 rifampin II type crystalline substance bulk pharmaceutical chemicals for being about 10 μm and filler cornstarch, lubricant tristearin magnesium acid-mixed
After closing uniformly, No. 2 gelatine capsules are filled, then capsule is subjected to 60 DEG C of high temperature and high humidity RH92.5% factors influencing, as a result
Medicament contg decreases, and impurity increases significantly, and the sample that super-humid conditions are investigated, which has also appeared, turns crystalline substance.Analyzing reason may be II
Type is brilliant originally as meta-stable crystal form, and partial size is smaller to will increase specific surface area, and surface can increase, and increase drug risk of instability.
Since rifampin belongs to low-solubility drug, reducing granularity can be improved solution rate, but in order to improve II type crystalline substance rifampin glue
The stability of capsule, granularity should not be too small, should control in reasonable range.It is studied by experiment sieving, it is determined that the brilliant sharp good fortune of II type
Flat granularity control range, and prepare with the bulk pharmaceutical chemicals composition and method of capsule meets to obtain a kind of dissolution
It is required that, quality is more stable, the simple and feasible rifampicin capsules of production.
To achieve the above object, the technical solution of the present invention is as follows:
A kind of rifampicin medicine composition, the rifampicin medicine composition is by rifampin II type crystalline substance and pharmaceutically acceptable
Auxiliary material composition；The rifampin II type crystalline substance D90 is 30 μm -150 μm；The mass percent of the rifampin II type crystalline substance and auxiliary material
For 60~85%:15~40%.
The crystal form of rifampin and its physicochemical property, bioavilability and clinical efficacy are closely related.Rifampin I type crystal,
Its crystalline density is small (>=0.5g/ml), crystal habit be large knitting needle shape, product adhesion is larger, be easy absorption bonding, mobility compared with
Difference.Rifampin II type crystal, crystalline density is big (>=0.7g/ml), and crystal form is the square piece shape of rule, and product adhesion is smaller,
Mobility is preferable.I type crystal is stable crystal form, and II type crystal is metastable crystal form.Although rifampin I type is brilliant in terms of stability
It is more stable, it is not susceptible to change, but in terms of dissolubility, II type crystalline substance dissolution rate and I type crystal phase are seemingly or brilliant fast compared with I type.Also,
There is experiment to show that II type crystalline substance rifampin is higher than I type crystalline substance in the Heavy metal of enteron aisle；It is brilliant that II type crystalline substance bioavilability is higher than I type.
Therefore, although rifampin II type crystalline substance is stablized not as good as I type crystalline substance, consider that II type crystalline substance has bright from preparation production and bioavilability
Aobvious advantage.
Further, the rifampin II type crystalline substance D90 is 50 μm -75 μm；The quality hundred of the rifampin II type crystalline substance and auxiliary material
Divide than being 75~83%:17~25%.
The dosage form that the rifampicin medicine composition can be prepared is capsule.
In order to improve domestic rifampicin capsules quality, the present invention revalues in research in progress rifampicin capsules, and discovery is adopted
II type crystalline substance rifampin is used, because granularity is meticulous, to there is stronger Electrostatic Absorption, medicine when granularity D90 is at 5~20 μm as bulk pharmaceutical chemicals
Object is reunited, poor fluidity, and it is larger that capsule fills loading amount deviation.Product is after high temperature, high humidity influence factor study on the stability, impurity
Increase significant, content reduction, especially high humidity investigation sample has also appeared crystal phenomenon.As granularity increases, drug electrostatic is inhaled
It echos mobility to make moderate progress, and capsule obtained, after study on the stability, impurity amount of increase is substantially reduced, and content is more stable, it is brilliant
Type is also stable.Since rifampin is BCSII class drug, i.e., low dissolution Thief zone drug, granularity will affect its dissolved corrosion.Pass through
Experiment sieving obtains more stable rifampicin capsules while in order to not influence preparation dissolution, and II type grain size is preferably controlled in D90
It is 30 μm -150 μm, preferably D90 is 50-75 μm.
Further, the auxiliary material includes filler and lubricant.
Further, the mass percent of the filler and lubricant is 12-23%:2-5%.
Further, the filler includes cornstarch or partially pregelatinized starch.
Cornstarch and partially pregelatinized starch are all very stable starch fillers, and hygroscopicity is small, self-lubricity
Good, disintegration is strong, good with the compatibility of rifampin.
Further, the lubricant includes magnesium stearate or Compritol 888 ATO.
Magnesium stearate or Compritol 888 ATO, lubricity is good, good with the compatibility of rifampin.
Further, the rifampicin medicine composition is composed of the following components by mass percentage:
Rifampin II type crystalline substance 60~85%, cornstarch or partially pregelatinized starch 10-38%, magnesium stearate or behenic acid
Glyceride 2-5%；The rifampin II type crystalline substance D90 is 30 μm -150 μm.
Further, the rifampicin medicine composition is composed of the following components by mass percentage:
Rifampin II type crystalline substance 75-83%, cornstarch or partially pregelatinized starch 12-23%, magnesium stearate or behenic acid
Glyceride 2-5%；The rifampin II type crystalline substance D90 is 50 μm -75 μm.
The second object of the present invention is to provide the side that rifampicin medicine composition described in one kind prepares rifampicin capsules
Method, comprising the following steps:
1) the rifampin II type crystalline substance and mix lubricant of above-mentioned mass ratio is uniform, after 80~120 meshes, obtain mixture
I；
2) mixture described in step 1) is uniformly mixed with the filler of above-mentioned mass ratio, obtains mixture II；
3) mixture II is prepared into rifampicin capsules according to a conventional method.
Above-mentioned technological operation is carried out in GMP workshop condition.
The third object of the present invention is to provide a kind of rifampicin capsules that the method is prepared.
The object of the invention is also to provide a kind of rifampicin capsules treatment pulmonary tuberculosis or other lungy answer
With.
The beneficial effects of the present invention are:
(1) rifampicin capsules of the invention uses the II type crystalline substance rifampin for controlling granularity as bulk pharmaceutical chemicals, by II type
The control of brilliant rifampin granularity is in reasonable range, to obtain that a kind of dissolution meets the requirements, quality is more stable, bioavilability is high
Rifampicin capsules.
(2) rifampicin capsules of the invention, preparation method is simple, easy to operate, is not necessarily to special installation, it is easy to accomplish industry
Change.
Specific embodiment
It detailed description of a preferred embodiment of the present invention will be given below.The reality of actual conditions is not specified in preferred embodiment
Proved recipe method, usually according to normal condition, illustrated embodiment are but not to be to preferably be illustrated to the contents of the present invention
The contents of the present invention are only limitted to illustrated embodiment.So those skilled in the art are according to foregoing invention content to embodiment party
Case carries out nonessential modifications and adaptations, still falls within protection scope of the present invention.
In following embodiment, prepared rifampicin capsules, specification 150mg.
First part's rifampicin capsules of the invention
Embodiment 1
The rifampicin capsules of the present embodiment forms as follows:
| 1000 | It forms (g) |
| Rifampin (D90=32 μm) | 150 |
| Cornstarch | 34 |
| Magnesium stearate | 6 |
Preparation step is as follows:
(1) it by II type crystalline substance rifampin (granularity D90 is 32 μm) and magnesium stearate, puts into granulator and is stirred 5min,
Obtain mixed-powder I；
(2) cornstarch is put into granulator, is stirred 10min, obtain mixed-powder II；
(3) by the filling capsule of mixed-powder II；
Embodiment 2
The rifampicin capsules of the present embodiment forms as follows:
| 1000 | It forms (g) |
| Rifampin (D90=50 μm) | 150 |
| Cornstarch | 36 |
| Magnesium stearate | 4 |
Preparation step is as follows:
(1) it by II type crystalline substance rifampin (granularity D90 is 50 μm) and magnesium stearate, puts into granulator and is stirred 5min,
Obtain mixed-powder I；
(2) cornstarch is put into granulator, is stirred 10min, obtain mixed-powder II；
(3) by the filling capsule of mixed-powder II；
Embodiment 3
The rifampicin capsules of the present embodiment forms as follows:
| 1000 | It forms (g) |
| Rifampin (D90=75 μm) | 150 |
| Pregelatinized starch | 36 |
| Compritol 888 ATO | 4 |
Preparation step is as follows:
(1) it by II type crystalline substance rifampin (granularity D90 is 75 μm) and Compritol 888 ATO, puts into granulator and is stirred
5min obtains mixed-powder I；
(2) pregelatinized starch is put into granulator, is stirred 10min, obtain mixed-powder II；
(3) by the filling capsule of mixed-powder II.
Embodiment 4
The rifampicin capsules of the present embodiment forms as follows:
| 1000 | It forms (g) |
| Rifampin (D90=146 μm) | 150 |
| Pregelatinized starch | 36 |
| Compritol 888 ATO | 4 |
Preparation step is as follows:
(1) it by II type crystalline substance rifampin (granularity D90 is 146 μm) and Compritol 888 ATO, puts into granulator and is stirred
5min obtains mixed-powder I；
(2) pregelatinized starch is put into granulator, is stirred 10min, obtain mixed-powder II；
(3) by the filling capsule of mixed-powder II.
Second part comparative example
Embodiment 5
The rifampicin capsules of the present embodiment forms as follows:
| 1000 | It forms (g) |
| Rifampin (D90=12 μm) | 150 |
| Cornstarch | 33 |
| Magnesium stearate | 7 |
Preparation step is as follows:
(1) it by II type crystalline substance rifampin (granularity D90 is 12 μm) and magnesium stearate, puts into granulator and is stirred 5min,
Obtain mixed-powder I；
(2) cornstarch is put into granulator, is stirred 10min, obtain mixed-powder II；
(3) by the filling capsule of mixed-powder II.
Embodiment 6
The rifampicin capsules of the present embodiment forms as follows:
| 1000 | It forms (g) |
| Rifampin (D90=180 μm) | 150 |
| Pregelatinized starch | 36 |
| Compritol 888 ATO | 4 |
Preparation step is as follows:
(1) it by II type crystalline substance rifampin (granularity D90 is 180 μm) and Compritol 888 ATO, puts into granulator and is stirred
5min obtains mixed-powder I；
(2) pregelatinized starch is put into granulator, is stirred 10min, obtain mixed-powder II；
(3) by the filling capsule of mixed-powder II.
Part III experimental example
Experimental example 1
The rifampicin capsules of Example 1-6 preparation, in 900ml 0.1M hydrochloric acid medium, 100 Rotating shakers are dissolved out
Detection, as a result as follows:
It sees from the above, the rifampicin capsules of embodiment 1-5 preparation, dissolution rate, which meets Chinese Pharmacopoeia quality standard, to be wanted
(45min dissolution is not less than 75%) is asked, and bulk pharmaceutical chemicals granularity is smaller, dissolves out faster.And 6 dissolution rate of embodiment is undesirable,
This spends big related with raw material powder in prescription.
Experimental example 2
Rifampicin capsules prepared by embodiment 1,4,5 is investigated 10 days respectively at 60 DEG C of high temperature and high humidity RH92.5%, knot
Fruit is as follows:
In terms of result, embodiment 1 and 4 crystal form of embodiment do not change, and embodiment 5 occurs to turn under conditions of high humidity
Crystalline substance, and the amount of increase of the impurity of embodiment 5 under high temperature and super-humid conditions is all higher than embodiment 1 and embodiment 4.Illustrate raw material powder
Degree becomes smaller, unstable increased risk.Therefore, comprehensively consider from dissolution and stability, oral capsule is prepared with II type crystalline substance rifampin
Wafer, bulk pharmaceutical chemicals granularity should be controlled in suitable range.
Experimental example 3
By rifampin bulk pharmaceutical chemicals (D90=75 μm), cornstarch, partially pregelatinized starch, microcrystalline cellulose, stearic acid
Magnesium, Compritol 888 ATO, talcum powder mix in appropriate proportion respectively, investigate 10 days in 60 DEG C of high temperature and high humidity RH92.5%,
As a result as follows:
By supplementary material compatibility test, rifampin and cornstarch, partially pregelatinized starch, magnesium stearate and behenic acid
The compatibility of glyceride is preferable, and microcrystalline cellulose and talcum powder are investigated under high temperature and super-humid conditions with rifampin, occurs
Impurity significantly increases, therefore is not suitable as the filler and lubricant of this product.
Finally, it is stated that the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although referring to compared with
Good embodiment describes the invention in detail, those skilled in the art should understand that, it can be to skill of the invention
Art scheme is modified or replaced equivalently, and without departing from the objective and range of technical solution of the present invention, should all be covered at this
In the scope of the claims of invention.
Claims (10)
1. rifampicin medicine composition, which is characterized in that the rifampicin medicine composition is by rifampin II type crystalline substance and pharmaceutically
Acceptable auxiliary material composition；The rifampin II type crystalline substance D90 is 30 μm -150 μm；The quality of the rifampin II type crystalline substance and auxiliary material
Percentage is 60-85%:15~40%.
2. rifampicin medicine composition according to claim 1, which is characterized in that the rifampin II type crystalline substance D90 is 50 μ
m-75μm；The mass percent of the rifampin II type crystalline substance and auxiliary material is 75~83%:17~25%.
3. rifampicin medicine composition according to claim 1, which is characterized in that the auxiliary material includes filler and lubrication
Agent.
4. rifampicin medicine composition according to claim 3, which is characterized in that the quality of the filler and lubricant
Percentage is 12-23%:2-5%.
5. rifampicin medicine composition according to claim 3, the filler is that cornstarch or part pregelatinated form sediment
Powder.
6. rifampicin medicine composition according to claim 3, the lubricant is magnesium stearate or Compritol 888 ATO.
7. rifampicin medicine composition according to claim 1-6, which is characterized in that the rifampicin medicine group
It is composed of the following components by mass percentage to close object:
Rifampin II type crystalline substance 60~85%, cornstarch or partially pregelatinized starch 10-38%, magnesium stearate or behenyl acid glycerol
Ester 2-5%；The rifampin II type crystalline substance D90 is 30 μm -150 μm.
8. rifampicin medicine composition according to claim 1-6, which is characterized in that the rifampicin medicine group
It is composed of the following components by mass percentage to close object:
Rifampin II type crystalline substance 75-83%, cornstarch or partially pregelatinized starch 12-23%, magnesium stearate or behenyl acid glycerol
Ester 2-5%；The rifampin II type crystalline substance D90 is 50 μm -75 μm.
9. the method that rifampicin medicine composition described in any one of claims 1-6 prepares rifampicin capsules, which is characterized in that
The following steps are included:
1) the rifampin II type crystalline substance and mix lubricant of above-mentioned mass ratio is uniform, 80~120 meshes are crossed, mixture I is obtained；
2) mixture described in step 1) is uniformly mixed with the filler of above-mentioned mass ratio, obtains mixture II；
3) mixture II is prepared into rifampicin capsules according to a conventional method.
10. the rifampicin capsules that claim 9 the method is prepared.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112022831A (en) * | 2020-09-04 | 2020-12-04 | 四川制药制剂有限公司 | Preparation method of rifampicin capsule |
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| US4613496A (en) * | 1983-03-07 | 1986-09-23 | Ciba-Geigy Corporation | Pharmaceutical capsules of Rifampicin with uniform elution properties |
| US20050186267A1 (en) * | 2002-09-13 | 2005-08-25 | Thompson Diane O. | Capsules containing aqueous fill compositions stabilized with derivatized cyclodextrin |
| CN101897681A (en) * | 2009-05-27 | 2010-12-01 | 华北制药集团制剂有限公司 | Method for preparing rifampicin oral preparation |
| CN105287427A (en) * | 2015-10-20 | 2016-02-03 | 沈阳红旗制药有限公司 | Semi-solid rifampicin capsule and preparation method thereof |
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2017
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|---|---|---|---|---|
| US4613496A (en) * | 1983-03-07 | 1986-09-23 | Ciba-Geigy Corporation | Pharmaceutical capsules of Rifampicin with uniform elution properties |
| US20050186267A1 (en) * | 2002-09-13 | 2005-08-25 | Thompson Diane O. | Capsules containing aqueous fill compositions stabilized with derivatized cyclodextrin |
| CN101897681A (en) * | 2009-05-27 | 2010-12-01 | 华北制药集团制剂有限公司 | Method for preparing rifampicin oral preparation |
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| CN112022831A (en) * | 2020-09-04 | 2020-12-04 | 四川制药制剂有限公司 | Preparation method of rifampicin capsule |
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