CN106692094A - Rolapitant medicine oral preparation and preparation method thereof - Google Patents
Rolapitant medicine oral preparation and preparation method thereof Download PDFInfo
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- CN106692094A CN106692094A CN201510769293.4A CN201510769293A CN106692094A CN 106692094 A CN106692094 A CN 106692094A CN 201510769293 A CN201510769293 A CN 201510769293A CN 106692094 A CN106692094 A CN 106692094A
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- rolapitant
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- 239000003814 drug Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- FIVSJYGQAIEMOC-ZGNKEGEESA-N rolapitant Chemical compound C([C@@](NC1)(CO[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=2C=CC=CC=2)C[C@@]21CCC(=O)N2 FIVSJYGQAIEMOC-ZGNKEGEESA-N 0.000 title abstract 9
- 229960001068 rolapitant Drugs 0.000 title abstract 9
- 238000004090 dissolution Methods 0.000 claims abstract description 12
- 239000007884 disintegrant Substances 0.000 claims abstract description 6
- 239000007767 bonding agent Substances 0.000 claims abstract description 5
- 239000000945 filler Substances 0.000 claims abstract description 5
- 239000000314 lubricant Substances 0.000 claims abstract description 5
- 229940079593 drug Drugs 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000007887 hard shell capsule Substances 0.000 claims description 3
- 239000003405 delayed action preparation Substances 0.000 claims 6
- 238000001514 detection method Methods 0.000 claims 1
- 238000005303 weighing Methods 0.000 claims 1
- 238000009826 distribution Methods 0.000 abstract description 7
- 239000006184 cosolvent Substances 0.000 abstract description 2
- 239000004615 ingredient Substances 0.000 abstract 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 238000002512 chemotherapy Methods 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 239000002994 raw material Substances 0.000 description 12
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 10
- 239000008107 starch Substances 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- 239000000370 acceptor Substances 0.000 description 7
- 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 description 6
- 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 description 6
- 206010047700 Vomiting Diseases 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000000853 adhesive Substances 0.000 description 5
- 230000001070 adhesive effect Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
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- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 235000020985 whole grains Nutrition 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 240000003864 Ulex europaeus Species 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
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- 239000002464 receptor antagonist Substances 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 2
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102000009493 Neurokinin receptors Human genes 0.000 description 2
- 108050000302 Neurokinin receptors Proteins 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 229960001021 lactose monohydrate Drugs 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- MMWCIQZXVOZEGG-UHFFFAOYSA-N 1,4,5-IP3 Natural products OC1C(O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(O)C1OP(O)(O)=O MMWCIQZXVOZEGG-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- MMWCIQZXVOZEGG-XJTPDSDZSA-N D-myo-Inositol 1,4,5-trisphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=O MMWCIQZXVOZEGG-XJTPDSDZSA-N 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 101000831616 Homo sapiens Protachykinin-1 Proteins 0.000 description 1
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 description 1
- QANDQRKVQCIBES-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CCCCCCCCCCCCCCCCCC(O)=O Chemical compound OC(=O)\C=C\C(O)=O.CCCCCCCCCCCCCCCCCC(O)=O QANDQRKVQCIBES-WLHGVMLRSA-N 0.000 description 1
- 208000031649 Postoperative Nausea and Vomiting Diseases 0.000 description 1
- 206010066963 Procedural vomiting Diseases 0.000 description 1
- 102100024304 Protachykinin-1 Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 102100037346 Substance-P receptor Human genes 0.000 description 1
- 102000003141 Tachykinin Human genes 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002460 anti-migrenic effect Effects 0.000 description 1
- 229960001372 aprepitant Drugs 0.000 description 1
- ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 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 1
- 239000001177 diphosphate Substances 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940078646 other antiemetics in atc Drugs 0.000 description 1
- CPZBLNMUGSZIPR-NVXWUHKLSA-N palonosetron Chemical compound C1N(CC2)CCC2[C@@H]1N1C(=O)C(C=CC=C2CCC3)=C2[C@H]3C1 CPZBLNMUGSZIPR-NVXWUHKLSA-N 0.000 description 1
- 229960002131 palonosetron Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- -1 phosphatidylinositol diphosphate Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
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- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
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- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to the technical field of medicine preparations containing organic effective ingredients, in particular to a rolapitant medicine oral preparation and a preparation method thereof. The rolapitant medicine oral preparation is composed of rolapitant, filler, disintegrant, lubricant, flow aid and bonding agent. Through special processing, rolapitant has extra-fine grain size, 90% of rolapitant has the grain size of 20 microns or below, and 99% of rolapitant has the grain size of 25 microns or below. The distribution is narrow, the solubility, stability, dissolution and the dissolving out speed of the medicine preparation are greatly increased, the rolapitant medicine oral preparation can be effectively and quickly released without cosolvent, the medicine bioavailability is greatly improved, and the rolapitant medicine oral preparation is suitable for large-scale production.
Description
Technical field
Pharmaceutical product technical field the present invention relates to contain organic effective component, specially smooth oral formulations of roller and preparation method thereof.
Background technology
The nausea and vomiting caused by chemotherapy（CINV）It is clinically very common, such as control it is bad will increase physician office visits, reduce Compliance With Chemotherapy, reduce chemotherapy, or even patient is refused further chemotherapy etc., have a strong impact on the quality of life and antineoplaston effect of patient.Therefore, the prevention and treatment of CINV are extremely important.CINV is the n and V caused by chemotherapy, and often 3 classes are divided into according to the time that vomiting occurs, acute（Occur within after chemotherapy starts first 24 hours）, Delayed onset（Occur at least 24 hours after chemotherapy starts）With expected property（Conditioned reflex, before betiding chemotherapy）.The drug factors such as species, the dosage and administration of chemotherapeutics are the influence most important determinants of CINV.
Tachykinin, such as P materials（SP）It is the peptide ligand of neurokinin receptor, neurokinin receptor, such as NK-1, NK-2, NK-3 participate in many biochemical processes.These three acceptors are G G-protein linked receptors, and wherein NK-1 acceptors distribution is most wide, also mostly important, only a few cell expression NK-2 acceptors and NK-3 acceptors.Wherein selective highest of the NK-1 acceptors to SP, binding ability is most strong, maincenter and peripheral nervous system are widely present in, are distributed in neuron, brain stem, vascular endothelial cell, muscle, intestines and stomach, urogenital tract, lung tissue, thyroid gland and various immunocytes.After NK-1 acceptors are with the SP combinations of its part, it is associated with phosphatidylinositol diphosphate second messenger system by G albumen, and the calcium channel on film is acted on by InsP3, cause the depolarising of film potential and the change of protein kinase activity, and then participate in pain and stress signal, played in inflammatory reaction and smooth muscle contraction process complexity physiological function.
" NK-1 " receptor antagonist has been shown as useful therapeutic agent, such as in treatment pain, inflammation, antimigraine, vomiting and grieved stimulation.The receptor antagonist of neurokinin 1（NK1RA）With antidepression, effect antianxity, and there is good therapeutic effect to the nausea and vomiting that chemotherapy causes；Being shared with other antiemetics can better control over Delayed emesis and postoperative vomiting.Go deep into to P materials and NK-1 acceptor researchs, the first granted NK-1 receptor antagonist pharmaceuticals Aprepitants for clinic are the Nausea and vomiting for preventing and treating chemotherapy induction within 2003（CINV）There is provided strong weapon.NEPA is first compound antiemetic, contains a kind of new high selectivity NK1RA class medicines（How appropriate pyrrole is smooth）With a kind of 5-HT3RA classes medicine（Palonosetron）.
On September 1st, 2015, FDA approval listing new drug rolapitant- rollers are smooth, for the related n and V of Prophylactic chemotherapy.It is a kind of oral NK1RA inhibitor of new high selectivity that roller pyrrole is smooth, and its plasma half-life is up to 180h.Identical with NEPA, the smooth tolerance of roller pyrrole is good, and it is consistent with expection with the security that antiemetic class medicine and chemotherapeutics are combined.From unlike aprepitant and NEPA, roller pyrrole is smooth can not to be induced or suppress CYP3A4.Therefore, when combination smooth with roller pyrrole, CYP3A4 is passed through without adjustment（Including DEX）The drug dose of metabolism.This may benefit some patientss, because drug interaction can be avoided well.
In order to reach good result of extraction, inventor takes the mode for carrying out specially treated smooth to raw material roller, being crushed using high pressure draught has carried out the mode of air-flow crushing to bulk drug, then according to common preparation process pelletizing press sheet or encapsulating capsule, in the case where any cosolvent is not added with, obtain result of extraction well, be adapted to the smooth tablet of roller of clinic needs.
The content of the invention
It is fast it is an object of the invention to provide a kind of dissolution release, preparation process is simple, it is suitable for preventing patient because of the pharmaceutical preparation of the related n and V of chemotherapy, predominantly tablet and hard shell capsules, the good purpose of result of extraction is reached, dissolution time is adapted to clinic needs, and bioavilability is high, and is adapted to industrialized production.
The formulation of the heretofore described smooth drug oral preparation of roller is tablet or hard shell capsules.
The composition and quality proportioning of the smooth drug oral preparation of heretofore described roller be：Roller smooth 12%~27%, the disintegrant 3.4~10% of filler 60~75%, lubricant 0.5~9.5%, glidant 0~0.75%, bonding agent 6~10%.Further, the filler is one or several the composition in lactose, starch, microcrystalline cellulose, mannitol, hydroxypropylcellulose.The lubricant is the one or two kinds of in magnesium stearate, stearic acid, fumaric acid stearic acid, talcum powder.The glidant is superfine silica gel powder.The disintegrant is the composition of one or more in sodium carboxymethyl starch, PVPP, Ac-Di-Sol.The bonding agent is the one kind in Hydroxypropyl methylcellulose, starch, PVP, sodium carboxymethylcellulose.
The dissolution complete time of the smooth drug oral preparation of roller of the present invention is -1.5 hours 40 minutes.
The dissolution of the smooth curative effect clinically of roller and its preparation is rapid, bioavilability is high very big relation.Can not merely solve the problems, such as to control dissolution time completely by the help of auxiliary material, in order to solve this problem, we are employed to be crushed the smooth raw material of roller by high pressure draught and are micronized, and filter out most suitable particle size distribution range：Below 25 microns, 99% particle diameter is below 20 microns for 90% particle diameter, so as to greatly improve the dissolution rate of preparation and control dissolution rate.
Then operated by following technique：Treated micronizing raw material is weighed into recipe quantity, the filler of recipe quantity, disintegrant is added to be well mixed, adding bonding agent carries out wet granulation, add the lubricant of recipe quantity, glidant carries out compressing tablet or encapsulating capsule after being well mixed, the direct tablet compressing that do not make pellet can be also taken in the technique of compressing tablet, can also take point mode for adding inside and outside disintegrant to carry out compressing tablet during particle is prepared.The present inventor has carried out integrated survey to the outward appearance and capsule appearance of tablet, mobility of particle, uniformity of dosage units simultaneously, and the quality of outward appearance is determined by following standard：
Outward appearance is main to be considered from surface smoothness, broken brittleness etc.：It is excellent to be ++++, good be +++, generally ++, difference for+
Result shows：Present composition outward appearance can reach requirement, and greatly improve the dissolution rate of the smooth oral formulations of roller, and the dissolution rate for making roller smooth more suits the requirements, medicine sustained effectiveness in vivo, allow clinical effectiveness to become more preferable.
Specific embodiment
Comparative example
90 grams of the smooth raw material of treated roller, 150 grams of lactose monohydrate, 75 grams of mannitol, 34 grams of sodium carboxymethyl starch are weighed by 1000 amounts to be well mixed, 5% Hydroxypropyl methylcellulose is added to prepare wet granular as adhesive in right amount, drying, 2 grams of magnesium stearate, 2 grams of superfine silica gel powder is added to be well mixed after whole grain, compressing tablet, Stress control in 7kg~10kg, per agreement that contracts a film or TV play to an actor or actress 380mg.
Hardness 8.5kg
Outward appearance ++
Embodiment 1
By the smooth raw material of roller by air-flow crushing, make particle size distribution range 90% less than 20 microns, 99% less than 25 microns, standby.90 grams of the smooth raw material of treated roller, 150 grams of lactose monohydrate, 75 grams of mannitol, 34 grams of sodium carboxymethyl starch are weighed by 1000 amounts to be well mixed, 5% Hydroxypropyl methylcellulose is added to prepare wet granular as adhesive in right amount, drying, 2 grams of magnesium stearate, 2 grams of superfine silica gel powder is added to be well mixed after whole grain, compressing tablet, Stress control in 7.5kg~10kg, per agreement that contracts a film or TV play to an actor or actress 380mg.
Hardness：9.8kg
Outward appearance：+++
Embodiment 2
By the smooth raw material of roller by air-flow crushing, make particle size distribution range 90% less than 20 microns, 99% less than 25 microns, standby.90 grams of the smooth raw material of treated roller, 120 grams of starch, 180 grams of microcrystalline cellulose, 15 grams of sodium carboxymethyl starch are weighed by 1000 amounts to be well mixed, concentration is added for 10% starch slurry prepares wet granular as adhesive in right amount, drying, 4 grams of magnesium stearate, 2 grams of superfine silica gel powder is added to be well mixed after whole grain, compressing tablet, Stress control in 7.5kg~10kg, per agreement that contracts a film or TV play to an actor or actress 438mg.
Hardness：7.4kg
Outward appearance：++++
Embodiment 3
By the smooth raw material of roller by air-flow crushing, make particle size distribution range 90% less than 20 microns, 99% less than 25 microns, standby.45 grams of the smooth raw material of treated roller, 120 grams of lactose, 120 grams of microcrystalline cellulose, 11 grams of PVPP are weighed by 1000 amounts to be well mixed, concentration is added for 5% (W/V) the Hydroxypropyl methylcellulose aqueous solution prepares wet granular as adhesive in right amount, drying, 4 grams of magnesium stearate is added to be well mixed after whole grain, compressing tablet, Stress control in 7.5kg~10kg, per agreement that contracts a film or TV play to an actor or actress 325mg.
Hardness：8.9kg
Outward appearance：+++ embodiment 4
By the smooth raw material of roller by air-flow crushing, make particle size distribution range 90% less than 20 microns, 99% less than 25 microns, standby.45 grams of the smooth raw material of treated roller, 80 grams of hydroxypropylcellulose, 75 grams of mannitol, 25 grams of starch, 15 grams of sodium carboxymethyl starch are weighed by 1000 amounts to be well mixed, concentration is added for 5% (W/V) PVP ethanol solution prepares wet granular as adhesive in right amount, drying, 4 grams of magnesium stearate, 2 grams of superfine silica gel powder is added to be well mixed after whole grain, compressing tablet, Stress control in 7kg~10kg, per agreement that contracts a film or TV play to an actor or actress 270mg.
Hardness：9.3kg
Outward appearance：++++
Result is investigated in dissolution release
Claims (6)
1. a kind of active component is the smooth drug oral sustained release preparation of roller, it is characterised in that said preparation is smooth comprising roller of 90% particle diameter below 20 microns.
2. a kind of active component is the smooth drug oral sustained release preparation of roller, it is characterised in that said preparation is smooth comprising roller of 99% particle diameter below 25 microns.
3. the smooth drug oral sustained release preparation of roller according to claim 2, it is characterised in that its formulation is tablet or hard shell capsules.
4. a kind of active component is the smooth drug oral sustained release preparation of roller, it is characterised in that the composition and quality proportioning of the preparation be：Roller smooth 12%~27%, the disintegrant 3.4~10% of filler 60~75%, lubricant 0.5~9.5%, glidant 0~0.75%, bonding agent 6~10%.
5. the smooth drug oral sustained release preparation of roller according to claim 1, it is characterised in that the said preparation dissolution complete time is -1.5 hours 40 minutes.
6. the smooth drug oral sustained release preparation of roller according to claim 1 and 2, it is characterised in that its preparation technology is as follows：First it is micronized roller is smooth by modes such as air-flow crushings, by detection, reaches particle diameter standby after requirement, the roller for then weighing recipe quantity is smooth, and other auxiliary materials of recipe quantity complete follow-up technique.
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| CN201510769293.4A CN106692094A (en) | 2015-11-12 | 2015-11-12 | Rolapitant medicine oral preparation and preparation method thereof |
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| CN201510769293.4A CN106692094A (en) | 2015-11-12 | 2015-11-12 | Rolapitant medicine oral preparation and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951885A (en) * | 2017-12-16 | 2018-04-24 | 侯瑞玲 | A kind of combination of oral medication for treating capillary leak syndrome |
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2015
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951885A (en) * | 2017-12-16 | 2018-04-24 | 侯瑞玲 | A kind of combination of oral medication for treating capillary leak syndrome |
| CN107951885B (en) * | 2017-12-16 | 2018-09-18 | 侯瑞玲 | A kind of combination of oral medication for treating capillary leak syndrome |
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