CN105534941A - Minocycline hydrochloride sustained release tablets and preparation method - Google Patents
Minocycline hydrochloride sustained release tablets and preparation method Download PDFInfo
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- CN105534941A CN105534941A CN201610005488.6A CN201610005488A CN105534941A CN 105534941 A CN105534941 A CN 105534941A CN 201610005488 A CN201610005488 A CN 201610005488A CN 105534941 A CN105534941 A CN 105534941A
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- minocycline hydrochloride
- sustained release
- hydrochloride sustained
- release tablet
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Abstract
The invention relates to minocycline hydrochloride sustained release tablets and a preparation method thereof and belongs to the technical field of pharmaceutical products. The minocycline hydrochloride sustained release tablets consist of tablet cores and coatings, wherein the tablet cores are prepared from minocycline hydrochloride, a sustained release material, a filler, an anti-adhesion agent, a flow aid and an adhesive. The prepared minocycline hydrochloride sustained release tablets have good reproducibility, high medicine compliance, small toxic and side effects and the like.
Description
Technical field
The present invention relates to a kind of minocycline hydrochloride sustained release tablet and preparation method thereof, belong to pharmaceutical products technical field.
Background technology
Minocycline hydrochloride (MinocyclineHydrochloride) is semi-synthetic tetracycline medication, have another name called minocycline, this medicine, on the basis of tetracycline chemical structure, 6,7 side chains is modified, and forms two formyl ammonia-6-demethyl-6 deoxytetra cycline of 7-.Minocycline belongs to extensive pedigree antibiotic, by disturbing bacterioprotein to synthesize to the AA-tRNA retardation that acceptor site is combined on RNA ribosome complex.This medicine all has antibacterial activity to gram positive bacteria, gram-negative bacteria, rickettsia and chlamydia etc., thus there is good curative effect to infectious disease, be mainly applicable to the infection because staphylococcus, streptococcus, streptococcus pneumoniae, Diplococcus gonorrhoeae, dysentery bacterium, escherichia coli, klebsiella, Bacillus proteus, bacillus pyocyaneus, treponema pallidum and chlamydia etc. cause the pathogen of this product sensitivity.Compared with tetracycline, minocycline hydrochloride has that antibacterial action is strong, and Resistant strain is few, long half time and the feature such as untoward reaction is few, its safety confirm by clinical practice.
SOLODYN (minocycline hydrochloride) for Medicis company be used for the treatment of 12 years old and above patient non-nodular in the slow releasing tablet of inflammatory damage that causes to severe acne vulgaris.This medicine gets the Green Light in May, 2006 first in the U.S..In 12 months before 30 days November in 2007, U.S.'s sales volume of SOLODYN slow releasing tablet is about 2.167 hundred million dollars.According to the data statistics of IMS2011 JIUYUE, the Solodyn slow releasing tablet sales volume of Medicis is up to 7.5 hundred million dollars.
But in the actual course of processing, due to the defect in technique and on formula, all the time the interference that its toxic and side effects causes patient treatment cannot be overcome, ordinary preparation medication once a day easily causes peak plasma concentrations higher, and then cause nervus centralis side reaction, and batch between differ greatly, product stability is not good; Although not so significantly, its cost is higher, and cost performance is low, and universality is poor for the above-mentioned defect of external import medicine.
Based on this, make the application.
Summary of the invention
Of the present invention to provide a kind of take minocycline hydrochloride as the slow releasing preparation of main component, and this slow-releasing agent can reduce the toxic and side effects of Dynacin, is beneficial to the long-term treatment of sufferer, improves medication compliance.
For achieving the above object, the technical scheme taked of the present invention is as follows:
A kind of minocycline hydrochloride sustained release tablet, be made up of label and coating, the mass ratio of label and coating is 20:1, and described label is made up of each component of following percentage by weight:
Further, as preferably:
Described slow-release material is hydrophilic gel framework material, preferred, described slow-release material be in hypromellose K15M, HPMC K4M one or both.
Described binding agent selects Brazil wax.
Described filler selects lactose.
Described antitackiness agent selects micropowder silica gel.
Described fluidizer is selected from magnesium stearate.
Described coating material is selected from Opadry.
Slow releasing tablet of the present invention is by taking minocycline hydrochloride as principal agent, slow-release material, filler are as adjuvant, be equipped with antitackiness agent, fluidizer, binding agent and coating material etc. again, principal agent and the mutual compatibility of adjuvant, and using hydrophilic gel framework material as slow-release material, make slow releasing tablet form skeleton construction, this skeleton construction gives whole slow releasing tablet with framework controlled release, its stability is better than coating type slow release formulation, not easily causes the prominent of medicine to release because of the change of outer coating.And employ at the outermost layer of slow releasing tablet the stability that film coating improves medicine, reduce illumination, humidity, temperature to the impact of medicine, improve drug quality.
In slow releasing tablet of the present invention, the effective dose of minocycline hydrochloride, between 30-200mg, is preferably 45mg-115mg, to adapt to the use of different crowd, and main formation 55mg and 80mg two kinds of specifications; The medication object of the corresponding different weight of different size, when dose level is at 0.5-2mg/kg, experiment in vivo shows that the parameters of the interior medicine dynamics of the minocycline sheet of different size is identical, meets slow release effect and the demand of sufferer treatment to blood drug level.
In the course of processing, form intermediate with label, slow releasing tablet is then formed by this Intermediate Preparation, without the need to changing prescription composition, only total consumption need be regulated can to obtain the minocycline hydrochloride sustained release tablet of different size.
Slow releasing tablet of the present invention, its preparation method obtains the powder body of mix homogeneously after adopting the adjuvant of prescription ratio and major ingredient to stir a period of time in mixing and blending machine, adopts top spray fluid bed to spray into the granule that binding agent can obtain suitable particle diameter.
Detailed description of the invention
A kind of minocycline hydrochloride of the present embodiment, with minocycline hydrochloride and slow-release material for major ingredient, filler as adjuvant, then is equipped with the compositions such as antitackiness agent, fluidizer, binding agent and coating material, and above-mentioned each component processes in accordance with the following steps:
1. preprocessing raw material and auxiliary material: API (active constituents of medicine, in the application, refers to minocycline hydrochloride), binding agent cross 80 mesh sieves once, for subsequent use.
2. mixing of materials: take the API of recipe quantity, slow-release material, binding agent mix homogeneously, then the filler mixing adding recipe quantity, cross 60 mesh sieves once, remix evenly.
3. wet granulation: get mixed material and pour basin into, adds water appropriate, manually granulates, cross 30 mesh sieve wet granulars.
4. dry: 25 DEG C of forced air dryings, within being dried to moisture 4%.
5. granulate: cross 30 mesh sieve granulate, weigh, the materials such as additional fluidizer.
6. tabletting: according to answering the heavy 400mg of tabletting, hardness is at about 7-11Kg.
Be prepared for products of different specifications below.
Embodiment 1
The present embodiment minocycline hydrochloride sustained release tablet is prepared according to ratio shown in table 1.
The quality proportioning of minocycline hydrochloride prepared by table 1 embodiment 1
In the present embodiment, the effective dose of slow releasing tablet is about 55mg.
Embodiment 2
The present embodiment minocycline hydrochloride sustained release tablet is prepared according to ratio shown in table 2.
The quality proportioning of minocycline hydrochloride prepared by table 2 embodiment 2
In the present embodiment, the effective dose of slow releasing tablet is about 80mg.
Embodiment 3
The present embodiment minocycline hydrochloride sustained release tablet is prepared according to ratio shown in table 3.
The quality proportioning of minocycline hydrochloride prepared by table 3 embodiment 3
In the present embodiment, the effective dose of slow releasing tablet is about 55mg.
Embodiment 4
The present embodiment minocycline hydrochloride sustained release tablet is prepared according to ratio shown in table 4.
The quality proportioning of minocycline hydrochloride prepared by table 4 embodiment 4
In the present embodiment, the effective dose of slow releasing tablet is about 80mg.
Embodiment 5
The present embodiment minocycline hydrochloride sustained release tablet is prepared according to ratio shown in table 5.
The quality proportioning of minocycline hydrochloride prepared by table 5 embodiment 5
In the present embodiment, the effective dose of slow releasing tablet is about 55mg.
Embodiment 6
The present embodiment minocycline hydrochloride sustained release tablet is prepared according to ratio shown in table 6.
The quality proportioning of minocycline hydrochloride prepared by table 6 embodiment 6
In the present embodiment, the effective dose of slow releasing tablet is about 80mg.
Embodiment 7
The present embodiment minocycline hydrochloride sustained release tablet is prepared according to ratio shown in table 7.
The quality proportioning of minocycline hydrochloride prepared by table 7 embodiment 7
In the present embodiment, the effective dose of slow releasing tablet is about 55mg.
The vitro release test of minocycline slow releasing tablet:
SOLODYN have 8 specifications 45,135,65,115,105,80,55mg, wherein first three specification Yuan Yan producer delisting.Wherein RLD (RLD=referencelistdrug) hurdle, " YES " is write at 80mg, 55mg specification place, with it for imitated object, In vitro-in vivo correlation evaluation must carried out when showing this product imitated, only have RLD to be that the product of " YES " is only the legal qualified object copied.The different size of identical product, due to their integrity, the comprehensive difference such as clinical data, technological parameter, may only have a kind of specification can as reference preparation, select this RLD to be that the specification of " YES " is researched and developed so only have during this product imitated, after carry out change specification.To need with RLD " yes " when being BE, be generally most high standard, due to 135mg delisting, BE will be with 80mg+55mg.
Physical property is carried out and biochemical property is verified and compares by minocycline hydrochloride prepared by the application, test above-described embodiment is prepared into the vitro release of 55mg minocycline slow releasing tablet and commercially available minocycline slow releasing tablet, whether with the mild release of the speed of design, whether similar release characteristics can be had to commercially available slow releasing tablet to assess slow releasing preparation of the present invention.
Stripping results contrast (undiluted) in the water of preparation and reference preparation prepared by table 8 the application
Stripping results contrast (dilution) in the water of preparation and reference preparation prepared by table 9 the application
As can be seen from table 8 and 9 contrast experiments, adopt the buffer substrate tablet prepared by the application, itself and reference preparation similarity are higher, in use, the higher nervus centralis side reaction caused of peak plasma concentrations that ordinary preparation medication once a day brings can be reduced, ensure that preparation release differences between batches are little, good stability, can substitute import minocycline preparation completely simultaneously; Simultaneously, the application is by preparing the label of different size, thus realize the processing of different effective dose minocycline buffer substrate tablet, effectively can reduce the toxic and side effects of sour minocycline preparation, its people's experiment in vivo shows that daily a minocycline hydrochloride sustained-release preparation can ensure concentration in 24 hours bodies, and energy stability contorting plasma drug level peak value reduces the side effect that medicine brings, and improves the bioavailability of medicine to ensure curative effect, be conducive to the long-term treatment of sufferer, improve medication compliance.
Above content is the further description done provided technical scheme in conjunction with the preferred implementation of the invention; can not assert that the invention is specifically implemented to be confined to these explanations above-mentioned; for the invention person of an ordinary skill in the technical field; without departing from the concept of the premise of the invention; some simple deduction or replace can also be made, all should be considered as the protection domain belonging to the invention.
Claims (9)
1. a minocycline hydrochloride sustained release tablet, is made up of label and coating, it is characterized in that, the mass ratio of label and coating is 20:1, and described label is made up of each component of following percentage by weight:
Minocycline hydrochloride 10≤content≤30%
Slow-release material 5≤content≤15%
Filler 50≤content≤80%
Antitackiness agent 0 < content≤2%
Fluidizer 0 < content≤5%
Binding agent 5≤content≤20%.
2. a kind of minocycline hydrochloride sustained release tablet as claimed in claim 1, is characterized in that: described slow-release material is hydrophilic gel framework material.
3. a kind of minocycline hydrochloride sustained release tablet as claimed in claim 2, is characterized in that: described slow-release material be in hypromellose K15M, HPMC K4M one or both.
4. a kind of minocycline hydrochloride sustained release tablet as claimed in claim 1, is characterized in that: described binding agent selects Brazil wax.
5. a kind of minocycline hydrochloride sustained release tablet as claimed in claim 1, is characterized in that: described antitackiness agent selects micropowder silica gel.
6. a kind of minocycline hydrochloride sustained release tablet as claimed in claim 1, is characterized in that: described filler selects lactose.
7. a kind of minocycline hydrochloride sustained release tablet as claimed in claim 1, is characterized in that: described fluidizer is selected from magnesium stearate.
8. a kind of minocycline hydrochloride sustained release tablet as claimed in claim 1, is characterized in that: described coating material is selected from Opadry.
9. the preparation method of minocycline hydrochloride sustained release tablet as described in any one of claim 1-8, is characterized in that comprising the steps:
(1) once filter: minocycline hydrochloride, binding agent are sieved and choose the following granule of 80 order, for subsequent use;
(2) secondary filter: in proportion by after the minocycline hydrochloride of step (1), slow-release material, binding agent mix homogeneously, then add filler, crosses 60 mesh sieve mix homogeneously;
(3) wet granulation: add water the mixture of step (2) granulation, and cross 30 mesh sieves formation wet granulars;
Dry: forced air drying to granule water content below 4%;
(5) on dried granule, add tabletting process after fluidizer and antitackiness agent, Hardness Control is at 7-11Kg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610005488.6A CN105534941A (en) | 2016-01-04 | 2016-01-04 | Minocycline hydrochloride sustained release tablets and preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610005488.6A CN105534941A (en) | 2016-01-04 | 2016-01-04 | Minocycline hydrochloride sustained release tablets and preparation method |
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| CN105534941A true CN105534941A (en) | 2016-05-04 |
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| CN201610005488.6A Pending CN105534941A (en) | 2016-01-04 | 2016-01-04 | Minocycline hydrochloride sustained release tablets and preparation method |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2414668A (en) * | 2004-06-03 | 2005-12-07 | Dexcel Ltd | Sustained release delivery system for tetracycline compounds |
| CN101322694A (en) * | 2008-08-01 | 2008-12-17 | 海南百那医药发展有限公司 | Piclofenac potassium sustained release tablets and preparing technique thereof |
| WO2010046932A2 (en) * | 2008-10-21 | 2010-04-29 | Jubilant Organosys Limited | Extended release pharmaceutical composition of minocycline and process thereof |
| CN101940560A (en) * | 2010-09-16 | 2011-01-12 | 孙卫东 | Minocycline hydrochloride sustained-release tablets and method for preparing same with different specifications |
| CN102772384A (en) * | 2012-08-07 | 2012-11-14 | 四川百利药业有限责任公司 | Minocycline hydrochloride sustained release tablet and preparation method thereof |
-
2016
- 2016-01-04 CN CN201610005488.6A patent/CN105534941A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2414668A (en) * | 2004-06-03 | 2005-12-07 | Dexcel Ltd | Sustained release delivery system for tetracycline compounds |
| CN101322694A (en) * | 2008-08-01 | 2008-12-17 | 海南百那医药发展有限公司 | Piclofenac potassium sustained release tablets and preparing technique thereof |
| WO2010046932A2 (en) * | 2008-10-21 | 2010-04-29 | Jubilant Organosys Limited | Extended release pharmaceutical composition of minocycline and process thereof |
| CN101940560A (en) * | 2010-09-16 | 2011-01-12 | 孙卫东 | Minocycline hydrochloride sustained-release tablets and method for preparing same with different specifications |
| CN102772384A (en) * | 2012-08-07 | 2012-11-14 | 四川百利药业有限责任公司 | Minocycline hydrochloride sustained release tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| R. V. KENY ET AL: "Formulation and Evaluation of Once Daily Minocycline Hydrochloride Extended Release Matrix Tablets", 《INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
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Application publication date: 20160504 |