CN104434854A - Minodronic acid tablet and preparation process thereof - Google Patents
Minodronic acid tablet and preparation process thereof Download PDFInfo
- Publication number
- CN104434854A CN104434854A CN201410757564.XA CN201410757564A CN104434854A CN 104434854 A CN104434854 A CN 104434854A CN 201410757564 A CN201410757564 A CN 201410757564A CN 104434854 A CN104434854 A CN 104434854A
- Authority
- CN
- China
- Prior art keywords
- minodronic acid
- tablet
- lactose
- magnesium stearate
- minodronic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a minodronic acid tablet and a preparation process thereof. According to the preparation process, a direct tabletting method is used, Flowac100 type spray-dried lactose is used as a filling agent and polylactic acid is added at the same time, so that the prepared minodronic acid tablet is uniform in content and favorable to release; and compared with the prior art, the direct tabletting method is capable of solving the problem that the minodronic acid tablets obtained via powder direct tableting are easy to crack and not good for coating, so that the medicine quality is ensured.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of minodronic acid tablet and preparation method thereof.
Background technology
Osteoporosis is thought the second disease of the major healthcare issue being only second to cardiovascular disease now by World Health Organization (WHO).Statistics show, in the population of China more than 60 years old, the prevalence of osteoporosis more than 30%, the existing aging population of China nearly 200,000,000, patients with osteoporosis at least 6,000 ten thousand.The sickness rate of osteoporosis was also in the gesture risen overally in recent years, and wherein the overwhelming majority is the old people of more than 50 years old, and the old man of postclimacteric women and more than 70 years old, often increase by 5 years old, ill danger will double.
Minodronic acid is the nitrogenous fragrant heterocycle Diphosphonate of the third generation, is mainly applicable to treat osteoporosis.Minodronic acid, by suppressing the farnesylpyrophosphate synzyme in osteoclast, suppresses the bone resorption function of osteoclast, and then bone metabolism circulation is gone down.
Minodronate tablets is researched and developed jointly by Japanese ONO Pharmaceutical Co., Ltd. and Japanese Astellas Pharmaceutical Co., Ltd, in January, 2009 goes on the market at Japanese health ministry, can be used as a line medication for the treatment of osteoporosis, compare third generation diphosphate alendronic Acid, minodronic acid has similar curative effect, but using dosage then obviously declines, and (alendronic Acid is 10mg/day, minodronic acid is 1mg/day), improve the compliance of patient and decrease the common gastrointestinal untoward reaction of diphosphate.
Patent CN102144982B discloses a kind of prescription and preparation method of minot phosphoric acid sheet, Polyethylene Glycol and polyvinyl alcohol are applied in minodronic acid tablet recipe, although have received good effect in reduction zest and raising absorption rate, but its preparation technology is very complicated, and polyvinyl alcohol is plasticizer.
Patent CN1102114025A, CN102204923A, CN103565771A disclose a kind of pharmaceutical composition, minodronic acid has wherein been carried out micronization processes, in order to promote drug-eluting, improve vitro Drug dissolution rate, but, raw material, after micronization, easily produces electrostatic, and crystal formation is unstable.
Patent CN1102078232A discloses a kind of preparation technology, in minodronic acid preparation, adds the additives such as sodium carbonate, and in order to improve drug dissolution, but sodium carbonate has certain alkalescence, has certain zest to stomach.
Patent CN102949358A discloses a kind of prescription and preparation method of minot phosphoric acid sheet, adds hydroxypropylβ-cyclodextrin, carry out wet granule compression tablet in prescription.This method is conducive to the dissolution improving minodronate tablets.But wet granulation complex procedures, production cost is higher, wayward to end product quality.
In general the hardness of tablet should reach 30,40N, and friability is less than 0.1%, and guarantee tablet quality meets movement requirement.
Minodronic acid has temperature sensitivity, the present invention on the basis of existing technology, the method of direct powder compression is adopted to prepare a kind of minodronate tablets, overcome responsive to temperature sex chromosome mosaicism, but find in preparation process, adopt direct powder compression, the easy sliver of gained minodronic acid tablet, be unfavorable for coating, simultaneously, the problem of the also existence and stability difference of the tablet after coating, for this reason, the present invention adds a kind of polymeric material polylactic acid in formula, in coating material, also add a small amount of polylactic acid simultaneously, eliminate the problem of sliver and coated tablet instability, meet quality standard, meet again the technological requirement of direct powder compression.For minodronic acid direct powder compression provides new method.
Summary of the invention
The object of the present invention is to provide the minodronic acid tablet that a kind of steady quality, result of extraction are good.
Minodronic acid tablet of the present invention, for thin membrane coated tablet, every 1000, the weight of each component of element sheet consists of: minodronic acid monohydrate 0.5-2g, spraying dry Flowlac100 lactose 60-90g, corn starch 0.5-15g, polylactic acid 8-12g, hydroxypropyl cellulose 1-15g, magnesium stearate 0.5-1.5g, film coating after said components tabletting, film coating liquid is prepared from by following material: Opadry 20g, polylactic acid 5g is dissolved in the ethanol of 200g80% (v/v), and mix homogeneously obtains.
Preferably, minodronic acid tablet of the present invention, every 1000, the weight of each component of plain sheet consists of: minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 70g, corn starch 12g, polylactic acid 10g, hydroxypropyl cellulose 6g, magnesium stearate weight are 1g.
Another object of the present invention is the preparation method providing minodronic acid tablet, comprises the following steps:
1) minodronic acid monohydrate raw material is crossed 160 mesh sieves; Spraying dry Flowlac100 lactose, corn starch, hydroxypropyl cellulose, magnesium stearate cross 60 mesh sieves respectively.
2) by minodronic acid raw material, vertical compression lactose, corn starch, polylactic acid, hydroxypropyl cellulose put into three-dimensional motion mixer mixing after 30 minutes, then added magnesium stearate and mix 5 minutes, mixed material adds high speed rotary tablet press tabletting, coating and get final product after tabletting.
Formula composition of the present invention obtains based on the former medicine prescription screening that grinds, and screening process is as follows:
The screening of element slice prescription
Formula 1, minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 80g, polyvidone 12g, hydroxypropyl cellulose 6g, magnesium stearate 1g.
Formula 2, minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 80g, microcrystalline Cellulose 12g, hydroxypropyl cellulose 6g, magnesium stearate 1g.
Formula 3, minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 80g, pregelatinized Starch 12g, hydroxypropyl cellulose 6g, magnesium stearate 1g.
Formula 4, minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 80g, corn starch 12g, polylactic acid 10g, hydroxypropyl cellulose 6g, magnesium stearate 1g.
Carry out screening experiment with friability, hardness for index, result is as follows:
| Inspection target | Formula 1 | Formula 2 | Formula 3 | Formula 4 |
| Friability % | 0.27 | 0.2 | 0.15 | 0.12％ |
| Hardness | 4～5 | 5～6 | 7～8 | 8～10 |
Through experiment, found that, formula 4 fragment rate is minimum, and can meet coating needs, and other formula are difficult to the requirement meeting coating, determines to carry out film coating to the tablet of formula 4 for this reason.
Common Opadry aqueous solution film coating is carried out to the tablet of the above-mentioned formula of the present invention 4, found that, the stability existing problems of the tablet after coating.
Proceed following screening experiment, the present invention finds the tablet using formula 6 to prepare unexpectedly, and stability improves greatly, and the tablet of experiment is as follows:
Formula 5, minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 80g, corn starch 12g, polylactic acid 10g, hydroxypropyl cellulose 6g, magnesium stearate 1g, Opadry aqueous solution coating.
Formula 6, minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 80g, corn starch 12g, polylactic acid 10g, hydroxypropyl cellulose 6g, magnesium stearate 1g, use Opadry 20g, and polylactic acid 5g is dissolved in the coating solution coating in the ethanol of 200g80% (v/v).
With accelerated stability experiment related substance item for index carries out screening experiment, result is as follows:
| Accelerate June | Formula 5 | Formula 6 |
| Total assorted % | 0.31 | 0.11 |
| Adventitia variable color or speckle | Have | Nothing |
| Disintegrate | Slowly | Hurry up |
| Tablet is broken into two with one's hands into two | There is disintegrating slag | Nothing |
Whether break into two with one's hands and take phenomenon common in household remedy, therefore being broken into two with one's hands by tablet complete is judge whether tablet is applicable to a kind of index of domestic, if broken disintegrating slag into two with one's hands, has been unfavorable for accurately grasping dosage, is unfavorable for domestic.After have passed through the conclusion that above experiment obtains, finally determine formula 6 of the present invention and preparation method.
Advantage main manifestations of the present invention is as follows:
(1) the present invention is by a large amount of experimentatioies, Flowac100 type spray-dried lactose is applied in minodronic acid tablet recipe, make the minodronate tablets content prepared very even, the present invention adopts technique of direct powder compression, mobility and compressibility good, simplify the production process of minodronic acid solid preparation, technique is simple, easily operates, with the wet granulation of routine compared with dry granulation, production technology cycle time 50%, uniformity of dosage units improves about 40%; Save the energy, improve drug quality, be applicable to suitability for industrialized production, reduce preparation cost.
(2) dissolution of the preparation prepared by is greater than 85% in 30 minutes, related-substance impurities is very low, be only about 0.11%, decrease the process procedures such as conventional wet lay granulation, oven dry, granulate and cause impurity, add the stability of said preparation, reach the quality of the former triturate of import, ensure that medicine is stablized.
Detailed description of the invention
Further describe the present invention by following examples, embodiment only for the object of illustration, does not limit the scope of the invention.Meanwhile, the apparent change made according to the present invention of those of ordinary skill in the art and modification are also contained within the scope of the invention.
Embodiment 1
Every 1000, the weight of each component of label consists of: minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 80g, corn starch 12g, polylactic acid 10g, hydroxypropyl cellulose 6g, magnesium stearate 1g,
Coating solution: use Opadry 20g, polylactic acid 5g is dissolved in the coating solution coating in the ethanol of 200g80% (v/v).
Preparation method, step is as follows:
1) minodronic acid monohydrate raw material is crossed 160 mesh sieves; Spraying dry Flowlac100 lactose, corn starch, hydroxypropyl cellulose, magnesium stearate cross 60 mesh sieves respectively.
2) by minodronic acid raw material, vertical compression lactose, corn starch, polylactic acid, hydroxypropyl cellulose put into three-dimensional motion mixer mixing after 30 minutes, then added magnesium stearate and mix 5 minutes, mixed material adds high speed rotary tablet press tabletting, coating and get final product after tabletting.
Embodiment 2
Every 1000, the weight of each component of label consists of: minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 70g, corn starch 12g, polylactic acid 10g, hydroxypropyl cellulose 6g, magnesium stearate 1g, film coating after said components tabletting, film coating liquid is prepared from by following material: Opadry 20g
Polylactic acid 5g is dissolved in the ethanol of 200g80%, and mix homogeneously obtains.
Preparation method, step is as follows:
1) minodronic acid monohydrate raw material is crossed 160 mesh sieves; Spraying dry Flowlac100 lactose, corn starch, hydroxypropyl cellulose, magnesium stearate cross 60 mesh sieves respectively.
2) by minodronic acid raw material, vertical compression lactose, corn starch, polylactic acid, hydroxypropyl cellulose put into three-dimensional motion mixer mixing after 30 minutes, then added magnesium stearate and mix 5 minutes, mixed material adds high speed rotary tablet press tabletting, coating and get final product after tabletting.
Embodiment 3:
Every 1000, the weight of each component of label consists of: minodronic acid monohydrate 2g, spraying dry Flowlac100 lactose 59.5g, corn starch 15g, polylactic acid 12g, hydroxypropyl cellulose 10g, magnesium stearate 1.5g, film coating after said components tabletting, film coating liquid is prepared from by following material: Opadry 20g, polylactic acid 5g is dissolved in the ethanol of 200g80%, and mix homogeneously obtains.
Preparation method, step is as follows:
1) minodronic acid monohydrate raw material is crossed 160 mesh sieves; Spraying dry Flowlac100 lactose, corn starch, hydroxypropyl cellulose, magnesium stearate cross 60 mesh sieves respectively.
2) by minodronic acid raw material, vertical compression lactose, corn starch, polylactic acid, hydroxypropyl cellulose put into three-dimensional motion mixer mixing after 30 minutes, then added magnesium stearate and mix 5 minutes, mixed material adds high speed rotary tablet press tabletting, coating and get final product after tabletting.
According to dissolution determination method (Chinese Pharmacopoeia version in 2010 two annex), measure the minodronic acid tablet prepared by the embodiment of the present invention 1,2,3, with 900ml water for medium, rotating speed is 50 revs/min, respectively at sampling in 5,10,15,20,30,45,60 minutes, detect sample dissolution, in table 1.
Table 1 is former grinds medicine and the dissolution of embodiment 1,2,3 in aqueous medium
According to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex), measure content and the uniformity of dosage units of the minodronic acid tablet prepared by the embodiment of the present invention 1,2,3, in table 2.
Table 2 is former grinds medicine and embodiment 1,2,3 content and uniformity of dosage units result table
According to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex), measure the related substance of the minodronic acid tablet prepared by the embodiment of the present invention 1,2,3, in table 2.
Table 3 is former grinds medicine and embodiment 1,2,3 related substance result table
As shown in Table 1: the minodronate tablets dissolved corrosion prepared by the present invention and former to grind medicine basically identical.
As shown in Table 2: the minodronate tablets content prepared by the present invention and former grind basically identical; Uniformity of dosage units mark is far away higher than the requirement of A+1.8S≤15 of States Pharmacopoeia specifications.
As shown in Table 3: the minodronate tablets impurity size prepared by the present invention and former grind basically identical.
According to the preparation method of minodronate tablets of the present invention, produce minodronate tablets indices is all qualified, this process stabilizing, can be used for suitability for industrialized production as seen.
By embodiment 1 supplementary material formula and preparation method, the preparation of test agent in three batches that have produced under having carried out pilot-scale condition with reference to drug research guideline, and according to through checking the method for inspection test.Assay is in table 4.
Table 4 three batches of pilot scale sample survey result tables
In three batches, test agent is aluminum-plastic packaged is placed on temperature 40 degree, and under relative humidity 75% ± 5% condition, carry out Acceleration study, Acceleration study the results are shown in Table 5.
Table 5 is former grinds medicine and middle test agent accelerated test result in June table
Three batch samples keep sample for a long time to check for 24 months and the results are shown in Table 6.
Table 6 is former grinds medicine and middle test agent long term test 24 months result tables
Can be confirmed by above test, the prescription of minodronate tablets of the present invention is reasonable, and stable preparation process is feasible, is suitable for suitability for industrialized production.
Claims (3)
1. a minodronic acid tablet, it is characterized in that, for thin membrane coated tablet, every 1000, the weight of each component of element sheet consists of: minodronic acid monohydrate 0.5-2g, spraying dry Flowlac100 lactose 60-95g, corn starch 10-15g, polylactic acid 8-12g, hydroxypropyl cellulose 1-15g, magnesium stearate 0.5-1.5g, film coating after said components tabletting, film coating liquid is prepared from by following material: Opadry 20g, polylactic acid 5g is dissolved in the ethanol of 200g 80%, and mix homogeneously obtains.
2. minodronic acid tablet according to claim 1, it is characterized in that, every 1000, the weight of each component of plain sheet consists of: minodronic acid monohydrate 1g, spraying dry Flowlac100 lactose 70g, corn starch 12g, polylactic acid 10g, hydroxypropyl cellulose 6g, magnesium stearate weight are 1g.
3. the preparation method of minodronic acid tablet according to claim 1, it is characterized in that, step is as follows:
1) minodronic acid monohydrate raw material is crossed 160 mesh sieves; Spraying dry Flowlac100 lactose, corn starch, hydroxypropyl cellulose, magnesium stearate cross 60 mesh sieves respectively;
2) by minodronic acid raw material, vertical compression lactose, corn starch, polylactic acid, hydroxypropyl cellulose put into three-dimensional motion mixer mixing after 30 minutes, then added magnesium stearate and mix 5 minutes, mixed material adds high speed rotary tablet press tabletting, coating and get final product after tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410757564.XA CN104434854B (en) | 2014-12-10 | 2014-12-10 | A kind of minodronic acid tablet recipe and its preparation technology |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410757564.XA CN104434854B (en) | 2014-12-10 | 2014-12-10 | A kind of minodronic acid tablet recipe and its preparation technology |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104434854A true CN104434854A (en) | 2015-03-25 |
| CN104434854B CN104434854B (en) | 2017-03-29 |
Family
ID=52882122
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410757564.XA Active CN104434854B (en) | 2014-12-10 | 2014-12-10 | A kind of minodronic acid tablet recipe and its preparation technology |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104434854B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105125575B (en) * | 2015-08-07 | 2018-06-08 | 康臣药业(内蒙古)有限责任公司 | A kind of preparation method for treating hyperphosphatemia disease drug |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003028653A2 (en) * | 2001-10-03 | 2003-04-10 | Glaxo Group Limited | Sustained release pharmaceutical compositions |
| WO2005072747A1 (en) * | 2004-02-02 | 2005-08-11 | Ono Pharmaceutical Co., Ltd. | Bone resorption inhibitors |
| CN102144982A (en) * | 2011-03-30 | 2011-08-10 | 江苏神龙药业有限公司 | Minodronate tablets and preparation method thereof |
| CN103494781A (en) * | 2013-08-30 | 2014-01-08 | 哈药集团技术中心 | Montelukast sodium chewing tablet prescription and preparation process thereof |
-
2014
- 2014-12-10 CN CN201410757564.XA patent/CN104434854B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003028653A2 (en) * | 2001-10-03 | 2003-04-10 | Glaxo Group Limited | Sustained release pharmaceutical compositions |
| WO2005072747A1 (en) * | 2004-02-02 | 2005-08-11 | Ono Pharmaceutical Co., Ltd. | Bone resorption inhibitors |
| CN102144982A (en) * | 2011-03-30 | 2011-08-10 | 江苏神龙药业有限公司 | Minodronate tablets and preparation method thereof |
| CN103494781A (en) * | 2013-08-30 | 2014-01-08 | 哈药集团技术中心 | Montelukast sodium chewing tablet prescription and preparation process thereof |
Non-Patent Citations (1)
| Title |
|---|
| 刘书春，刘昌治: "《罕见病治疗药物II》", 31 December 2012, 江苏科学技术出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105125575B (en) * | 2015-08-07 | 2018-06-08 | 康臣药业(内蒙古)有限责任公司 | A kind of preparation method for treating hyperphosphatemia disease drug |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104434854B (en) | 2017-03-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104161752B (en) | A kind of vildagliptin composition | |
| CN105078915A (en) | Rivaroxaban tablets and preparation method for same | |
| CN106176640A (en) | Pharmaceutical composition containing tofacitinib citrate and preparation method thereof | |
| CN102688252A (en) | Acarbose oral solid preparation composition and preparation method thereof | |
| CN105233300B (en) | A kind of stable vildagliptin composition and preparation method thereof | |
| CN105012264B (en) | Sustained-release Sodium Valproate and its preparation process and purposes | |
| CN104688700A (en) | Tenofovir disoproxil fumarate tablet that is easy to dissolve and preparation method thereof | |
| CN103768063A (en) | Moxifloxacin hydrochloride pharmaceutical composition and preparation method thereof | |
| CN102302466A (en) | Capecitabine medicinal composition capable of direct powder tableting, and application thereof | |
| CN104434854A (en) | Minodronic acid tablet and preparation process thereof | |
| CN103877043A (en) | Sitgliptin phosphate dispersible tablet and preparation method thereof | |
| CN108175755A (en) | A kind of vildagliptin tablet and preparation method thereof | |
| CN104352534B (en) | A kind of poria cortex total triterpene dispersible tablet and preparation method thereof | |
| CN104644598A (en) | Tenofovir disoproxil fumarate tablets | |
| CN104367562A (en) | Pramipexole dihydrochloride slow-release tablets and preparation method thereof | |
| CN102370629B (en) | Entecavir liquid capsule and preparation method thereof | |
| CN103142533B (en) | Enteric coated tablet of etoposide | |
| CN105193758A (en) | Gliclazide sustained release tablets and preparation method thereof | |
| CN102525981B (en) | A kind of propranolol hydrochloride tablet and preparation method thereof | |
| CN105232481A (en) | Meloxicam dispersible tablet and preparation method thereof | |
| CN103284973A (en) | Adefovir dipivoxil composition and preparation method thereof | |
| CN105030707A (en) | Method for preparing clotrimazole buccal tablets on basis of all-powder direct pressing of modified glucose | |
| CN104645322A (en) | Phosphoesterases complex enteric-coated tablet and preparation method and application thereof | |
| CN104337783B (en) | A kind of capecitabine tablet and preparation method thereof | |
| CN102988322B (en) | Arginine ibuprofen tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221026 Address after: No. 68, Limin West 4th Street, Limin Development Zone, Harbin, Heilongjiang 150500 Patentee after: HARBIN PHARMACEUTICAL GROUP HOLDING Co.,Ltd. Patentee after: HARBIN PHARMACEUTICAL Group TECHNOLOGY CENTER Address before: No.98 Tongsheng Road, Limin Development Zone, Harbin City, Heilongjiang Province Patentee before: HARBIN PHARMACEUTICAL Group TECHNOLOGY CENTER |