CN104027306A - Paroxetine oral suspension and preparation method thereof - Google Patents
Paroxetine oral suspension and preparation method thereof Download PDFInfo
- Publication number
- CN104027306A CN104027306A CN201410287053.6A CN201410287053A CN104027306A CN 104027306 A CN104027306 A CN 104027306A CN 201410287053 A CN201410287053 A CN 201410287053A CN 104027306 A CN104027306 A CN 104027306A
- Authority
- CN
- China
- Prior art keywords
- salt
- paroxetine
- mixed suspension
- oral administration
- acid
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title description 6
- 229940076382 paroxetine oral suspension Drugs 0.000 title 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims abstract description 24
- 229960002296 paroxetine Drugs 0.000 claims abstract description 22
- 229920005989 resin Polymers 0.000 claims abstract description 18
- 239000011347 resin Substances 0.000 claims abstract description 18
- 235000019640 taste Nutrition 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 6
- 239000000725 suspension Substances 0.000 claims description 26
- 229920001429 chelating resin Polymers 0.000 claims description 16
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 14
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 10
- 229940085605 saccharin sodium Drugs 0.000 claims description 10
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 9
- 239000000600 sorbitol Substances 0.000 claims description 9
- 230000002421 anti-septic effect Effects 0.000 claims description 8
- 239000005711 Benzoic acid Substances 0.000 claims description 7
- 235000010233 benzoic acid Nutrition 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 239000004033 plastic Substances 0.000 claims description 6
- 229920003023 plastic Polymers 0.000 claims description 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- 239000000796 flavoring agent Substances 0.000 claims description 5
- 235000019634 flavors Nutrition 0.000 claims description 5
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 4
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 4
- 229960004998 acesulfame potassium Drugs 0.000 claims description 4
- 239000000619 acesulfame-K Substances 0.000 claims description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003729 cation exchange resin Substances 0.000 claims description 3
- 238000005728 strengthening Methods 0.000 claims description 3
- 239000000375 suspending agent Substances 0.000 claims description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound 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 GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 244000144730 Amygdalus persica Species 0.000 claims description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- 244000241257 Cucumis melo Species 0.000 claims description 2
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 claims description 2
- 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 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 241000628997 Flos Species 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 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 claims description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 235000006040 Prunus persica var persica Nutrition 0.000 claims description 2
- 239000004376 Sucralose Substances 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical compound NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 claims description 2
- 235000009508 confectionery Nutrition 0.000 claims description 2
- 229940109275 cyclamate Drugs 0.000 claims description 2
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000012907 honey Nutrition 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 150000004702 methyl esters Chemical class 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 229960003975 potassium Drugs 0.000 claims description 2
- 229940043243 saccharin calcium Drugs 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- 230000001430 anti-depressive effect Effects 0.000 abstract description 3
- 239000000935 antidepressant agent Substances 0.000 abstract description 3
- 229940005513 antidepressants Drugs 0.000 abstract description 3
- 229940100692 oral suspension Drugs 0.000 abstract 2
- 235000019658 bitter taste Nutrition 0.000 description 10
- 239000007788 liquid Substances 0.000 description 7
- 206010002091 Anaesthesia Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000037005 anaesthesia Effects 0.000 description 6
- 230000035807 sensation Effects 0.000 description 6
- 235000019615 sensations Nutrition 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 5
- 241000220223 Fragaria Species 0.000 description 4
- 235000016623 Fragaria vesca Nutrition 0.000 description 4
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 4
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 229960002216 methylparaben Drugs 0.000 description 4
- 229960005183 paroxetine hydrochloride Drugs 0.000 description 4
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 4
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
- 235000013599 spices Nutrition 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000052 comparative effect Effects 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
- 239000000203 mixture Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 235000019636 bitter flavor Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 230000014860 sensory perception of taste Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses oral suspension containing medicine resin salt of Paroxetine and salts of Paroxetine. The oral suspension is an antidepressant, is stable in property and is good in taste.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, more relate to a kind of oral mixed suspension solution of the medical resin salt that comprises paroxetine (Paroxetine) and salt thereof, its stable in properties and there is good mouthfeel.
Background technology
Paroxetine (Paroxetine), its chemical name is:
(-)-trans-4R-(4-fluorophenyl)-3S-{[3 ', 4 '-(methylene-dioxy) phenoxy group] methyl }-piperidines(1:1) salt acid-addition salts.Be usually used in clinically depression and compulsive treatment.
Paroxetine is the antidepressants of a kind of selective serotonin reuptake inhibithors (SSRI) type, its drug form is paroxetine hydrochloride (Paroxetine hydrochloride), commodity " seroxat " by name ordinary tablet (Seroxat), it is a kind of high selectivity serotonin reuptake inhibitor, by what stop 5-hydroxy tryptamine, absorb again the concentration that improves 5-hydroxy tryptamine in nerve synapse gap, enhancing maincenter 5-hydroxy tryptamine function of nervous system, thus antidepressant effect produced.
This compound is used for human body by approval, and as the many countries sale in the whole world of a kind of antidepressant preparation.Paroxetine listing dosage form is mainly oral tablet at present, yet some patient for example: child and old man are taking the problem that often runs into dysphagia, therefore need to develop the row of being obedient to that oral liquid improves patient.But because paroxetine has very strong bitterness, during with drink form, this bitterness is obvious especially, secondly, stability of Oral is poor, and effect duration is short.So be prepared into suspension, can not only effectively cover bitterness, can also increase greatly the stability of preparation, improve effect duration.
Summary of the invention
The present invention discloses a kind of stable in properties, the good oral administration mixed suspension of mouthfeel, and described suspension comprises effective ingredient
(-)-trans-4R-(4-fluorophenyl)-3S-{[3 ', 4 '-(methylene-dioxy) phenoxy group] methyl }-piperidinesand the medical resin salt of salt and Amberlite series plastics, described suspension is included in this suspension and adds suspending agent, antiseptic, and correctives, and its acid-base value is adjusted between pH3-8.
The present invention coordinates Amberlite series plastics formation medical resin with paroxetine, and adds aerosil to be prepared into suspension, and adds antiseptic, can effectively improve the stability of preparation.At propylene glycol: prepare medical resin salt in water (1:1) medium standby, high temperature 70-80 ℃ aqueous medium adds preservative and sweetener, adds suspending agent under stirring condition, and the cooling medical resin salt that adds, obtains oral administration mixed suspension to be prepared next time.
Wherein (-)-trans-4R-(4-fluorophenyl)-3S-{[3 ', 4 '-(methylene-dioxy) phenoxy group] methyl } the medicine and pharmacology acceptable addition salt of-piperidines is 1:1 salt acid-addition salts.
Wherein the mol ratio of Amberlite and paroxetine is 1:2-2:1.
Wherein Amberlite series plastics is weak-acid cation-exchange resin, is selected from Amberlite IRP-88, wherein one or more of Amberlite IRP-64 and Amberlite IRP-69.Amberlite series weak-acid cation-exchange resin can coordinate with medicine formation medical resin, effectively covers the bitterness of medicine.
The antiseptic that described paroxetine oral administration mixed suspension comprises is benzoic acid, and its concentration, between 0.1mg/mL to 2 mg/mL, is damaged oral administration mixed suspension in order to prophylaxis of microbial.
Wherein pharmaceutically acceptable sweetener packets contains the preferably sweeting agent of at least one reinforcement, for example: glucide, saccharin sodium and calcium, aspartame, Ai Si divide potassium, cyclamate, acesulfame potassium, LaspartylLphenylalanine methylester, encircle dithiocarbamic acid sodium, Ali is sweet, dihydro is looked into ketone, Mo Lin, Flos Chrysanthemi essence, 1,4,6-sucralose, acesulfame potassium, preferably is saccharin sodium.The bulk sweetener needing, such as: Sorbitol, mannitol, fructose, sucrose, maltose, lactose, glucose, xylitol etc.
The sweeting agent of strengthening is generally used under low concentration, and for example the concentration of saccharin sodium is between 0.01% to 0.1%w/v, and preferably approximately 0.05%.Bulk sweetener, for example Sorbitol can be effectively for relatively large scope, and approximately 30% to 50%w/v, and preferably approximately 40%.
Essence pharmaceutically acceptable, that can cover bitter principle, preferably is fruit-like flavour, for example: Fructus Pruni pseudocerasi, honey peach, Fructus Fragariae Ananssae, orange taste, Herba Menthae local flavor, hami melon etc. are at pharmaceutically acceptable strong taste essence.Preferably essence concentration between 0.05% to 1%w/v.The combination of this strong taste spice of use that can be favourable, preferably makes its sense of taste and color under the acid condition of formula not have any change or forfeiture, and does not affect the character of other compositions in formula while using spice.
specific embodiment:
1mol paroxetine hydrochloride is joined to a certain amount of propylene glycol with the AmberliteIRP-64 of 0.5,1,2mol respectively: in water (1:1) solution, as for allowing toner be dispersed in solution in water bath with thermostatic control agitator, shaken overnight under room temperature.Adopt vacuum filter by resin salt and fluid separation applications, afterwards by a small amount of water cleaning resin salt three times, the resin after sucking filtration is placed on the medical resin salt that dried overnight in 60 degrees Celsius of vacuum drying ovens obtains paroxetine.
The oral liquid of the paroxetine-AmberliteIRP-64 medical resin salt that contains different mol ratio according to table 1 preparation, selects 10 volunteers to evaluate bitterness by blind method research oral administration mixed suspension at random, is recorded as 1 to 5 minute.The taste masking effect of assessment AmberliteIRP-64 to paroxetine.
The impact of table 1 AmberliteIRP-64 consumption on mouthfeel
| Compound | Prescription 1 | Prescription 2 | Prescription 3 |
| Medical resin salt | 2:1 | 1:1 | 1:2 |
| Microcrystalline Cellulose CL611 | 30 mg/mL | 30 mg/mL | 30 mg/mL |
| Orange taste essence | 1mg/mL | 1mg/mL | 1mg/mL |
| Sorbitol 70%(w/v) | 400mg/mL | 400mg/mL | 400mg/mL |
| Methyl parahydroxybenzoate | 0.5mg/mL | 0.5mg/mL | 0.5mg/mL |
| Propyl p-hydroxybenzoate | 0.5mg/mL | 0.5mg/mL | 0.5mg/mL |
The affect result of table 2 AmberliteIRP-64 consumption on mouthfeel
| Experimenter | Prescription 1 | Prescription 2 | Prescription 3 |
| A | 1 | 3 | 4 |
| B | 3 | 2 | 3 |
| C | 2 | 4 | 4 |
| D | 3 | 3 | 3 |
| E | 3 | 3 | 3 |
| F | 1 | 2 | 3 |
| G | 2 | 3 | 2 |
| H | 2 | 2 | 4 |
| I | 3 | 4 | 3 |
| J | 4 | 4 | 3 |
| Average score | 2.4 | 3 | 3.2 |
Note: 5-mouthfeel is very good, and 4-mouthfeel is better, and 3-mouthfeel is general, and 1-mouthfeel is bad
When the mol ratio of paroxetine and AmberliteIRP-64 is 1:1, can play the effect of significantly covering bitterness.When the consumption of AmberliteIRP-64 continues to increase the effect that has not improved significantly.So select paroxetine: the medical resin salt that the ratio of AmberliteIRP-64 is 1:1.In order further to improve mouthfeel, intend regulating kind and the consumption of correctives in prescription.
Embodiment 2: comparative study
2 kinds of essence (orange taste essence and strawberry essence) and two kinds of sweeting agents (Sorbitol 70%(w/v) and saccharin sodium merge are used in assessment) after the taste of feeling and pleasant impression.10 volunteers of random selection evaluate its sugariness, fruity, the sensations such as bitterness by blind method research to including the oral mixed suspension formula of liquid (as shown in table 2) of one of two kinds of spice.
The impact on mouthfeel of table 3 sweeting agent and essence
| Compound | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 |
| Orange taste essence (mg/mL) | 0.5 | 1.5 | ? | ? |
| Strawberry essence (mg/mL) | - | - | 0.5 | 1.5 |
| Sorbitol 70%(w/v) (mg/mL) | 300 | 500 | 300 | 500 |
| Saccharin sodium (mg/mL) | 0.5 | 0.5 | 1.0 | 1.0 |
| Methyl parahydroxybenzoate (mg/mL) | 0.5 | 0.5 | 0.5 | 0.5 |
| Propyl p-hydroxybenzoate (mg/mL) | 0.5 | 0.5 | 0.5 | 0.5 |
With this two formula, delivering 10 volunteers tests.Compliance response variables (sugariness, fruity, the mark of bitterness sensation) is recorded as 1 to 5 minute.Whether the unidirectional ANOVA method of usage data analytical data has significant difference.
Table 4 sweeting agent and the essence result on mouthfeel impact
| Experimenter | Prescription 4 | Prescription 2 | Prescription 3 | Prescription 4 |
| A | 3 | 4 | 2 | 3 |
| B | 3 | 5 | 3 | 5 |
| C | 5 | 3 | 4 | 4 |
| D | 3 | 2 | 3 | 3 |
| E | 3 | 5 | 3 | 3 |
| F | 4 | 3 | 5 | 4 |
| G | 3 | 5 | 3 | 2 |
| H | 4 | 4 | 2 | 3 |
| I | 3 | 4 | 3 | 3 |
| J | 4 | 3 | 4 | 4 |
| Average score | 3.5 | 3.8 | 3.2 | 3.4 |
Note: 5-mouthfeel is very good, and 4-mouthfeel is better, and 3-mouthfeel is general, the bad (*: P<.0.05) of 1-mouthfeel
In general, saccharin sodium is at concentration 0.5mg/mL, and Sorbitol (70%w/v) has preferably score when concentration is 500mg/mL.Orange taste essence is better than strawberry essence, and the sugariness of orange taste essence is little compared with strawberry essence, and has fruit-like flavour.But all formulas all have slight anesthesia sensation on tongue.P-Hydroxybenzoate odorless or have slight special aroma, mildly bitter flavor, the fiber crops of burning, so the anesthesia sense on this tongue may be from the p-Hydroxybenzoate using as antiseptic, so we adopt benzoic acid further to compare research.
Embodiment 3: comparative study
The random oral mixed suspension formula of liquid of selecting 10 volunteers to adopt one of two kinds of antiseptic of blind method research (p-Hydroxybenzoate or benzoic acid), evaluates its its sugariness, fruity, bitterness and the sensations such as anesthesia sense on tongue
The impact of table 5 antiseptic on mouthfeel
| Compound | Prescription 1 | Prescription 2 |
| Orange taste essence (mg/mL) | 1 | 1 |
| Sorbitol 70%(w/v) (mg/mL) | 500 | 500 |
| Saccharin sodium (mg/mL) | 0.5 | 0.5 |
| Methyl parahydroxybenzoate (mg/mL) | 0.5 | - |
| Propyl p-hydroxybenzoate (mg/mL) | 0.5 | - |
| Benzoic acid (mg/mL) | - | 1.0 |
According to this two formulated oral liquid, deliver 10 volunteers and test.Compliance response variables (sugariness, fruity, the mark of bitterness and anesthesia sensation) is recorded as 1 to 5 minute.Whether the unidirectional ANOVA method of usage data analytical data has significant difference.
The result of table 6 antiseptic on mouthfeel impact
| Experimenter | Prescription 1 | Prescription 1 |
| A | 3 | 5 |
| B | 4 | 4 |
| C | 5 | 3 |
| D | 4 | 5 |
| E | 3 | 4 |
| F | 3 | 4 |
| G | 5 | 5 |
| H | 4 | 4 |
| I | 5 | 4 |
| J | 4 | 5 |
| Average score | 4.0 | 4.3 |
Note: 5-mouthfeel is very good, and 4-mouthfeel is better, and 3-mouthfeel is general, the bad (*: P<.0.05) of 1-mouthfeel
Generally speaking, under benzoic acid exists, do not feel the sensation of anesthesia, in the oral liquid that includes methyl parahydroxybenzoate and propyl p-hydroxybenzoate, can feel slight anesthesia sense.Table 4 is listed the compositions of the most extensively being recommended by volunteer.
The better oral liquid prescription of table 7
| Compound | Concentration (mg/mL) |
| Paroxetine hydrochloride: Amberlite IRP-64 | 1:1 |
| Microcrystalline Cellulose CL611 | 30 |
| Orange taste essence | 1.0 |
| Sorbitol 70%(w/v) | 500 |
| Saccharin sodium | 0.5 |
| Aerosil | 30 |
| Benzoic acid | 1.0 |
Add sodium hydroxide and regulate pH to 5.0.
Claims (10)
1. the oral mixed suspension solution of a medical resin salt that contains paroxetine (Paroxetine) and salt thereof, its soda acid pH value is between 3-8, wherein comprise (-)-trans-4R-(4-fluorophenyl)-3S-{[3 ', 4 '-(methylene-dioxy) phenoxy group] methyl } the medical resin salt of-piperidines and salt and Amberlite series plastics.
2. the oral mixed suspension solution of a kind of medical resin salt that contains paroxetine (Paroxetine) and salt thereof as claimed in claim 1, wherein further comprises benzoic acid.
3. as claimed in claim 1, wherein Amberlite series plastics is weak-acid cation-exchange resin, is selected from Amberlite IRP-88, wherein one or more of Amberlite IRP-64 and Amberlite IRP-69.
4. oral administration mixed suspension as claimed any one in claims 1 to 3, wherein the mol ratio of Amberlite and paroxetine is 1:2-2:1.
5. oral administration mixed suspension as claimed any one in claims 1 to 3, wherein (-)-trans
-4R-(4-fluorophenyl)-3S-{[3 ', 4 '-(methylene-dioxy) phenoxy group] methyl }-piperidinesmedicine and pharmacology acceptable addition salt be 1:1 salt acid-addition salts.
6. the oral administration mixed suspension as described in claim 1,2, wherein benzoic consumption is between 0.1 mg/mL to 2mg/mL.
7. oral administration mixed suspension as claimed any one in claims 1 to 3, wherein soda acid pH value is between 3-8.
8. oral administration mixed suspension as claimed any one in claims 1 to 3, further contains bulk sweetener, its concentration between 30% to 50%w/v; The sweeting agent of strengthening, its concentration between 0.01% to 0.1%w/v; And essence, concentration between 0.05% to 1%w/v.
9. the oral administration mixed suspension as described in claim 1-8, wherein bulk sweetener is wherein one or more of Sorbitol, mannitol, fructose, sucrose, maltose, lactose, glucose, xylitol; The sweeting agent of strengthening is that glucide, saccharin sodium and calcium, aspartame, Ai Si divide potassium, cyclamate, acesulfame potassium, LaspartylLphenylalanine methylester, encircle dithiocarbamic acid sodium, Ali is sweet, dihydro is looked into ketone, Mo Lin, Flos Chrysanthemi essence, 1,4,6-sucralose, wherein one or more of acesulfame potassium, preferably is saccharin sodium; Essence, preferably is fruit-like flavour, as Fructus Pruni pseudocerasi, honey peach, Fructus Fragariae Ananssae, orange taste, Herba Menthae local flavor, wherein one or more such as hami melon.
10. a stable in properties, the good oral administration mixed suspension of mouthfeel, described suspension comprises effective ingredient
(-)-trans-4R-(4-fluorophenyl)-3S-{[3 ', 4 '-(methylene-dioxy) phenoxy group] methyl }-piperidinesand the medical resin salt of salt and Amberlite series plastics, described suspension is included in this suspension and adds suspending agent, antiseptic, and correctives, and its acid-base value is adjusted between pH3-8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410287053.6A CN104027306A (en) | 2014-06-25 | 2014-06-25 | Paroxetine oral suspension and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410287053.6A CN104027306A (en) | 2014-06-25 | 2014-06-25 | Paroxetine oral suspension and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104027306A true CN104027306A (en) | 2014-09-10 |
Family
ID=51458458
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410287053.6A Pending CN104027306A (en) | 2014-06-25 | 2014-06-25 | Paroxetine oral suspension and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104027306A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309363A (en) * | 2016-09-24 | 2017-01-11 | 万特制药(海南)有限公司 | Paroxetine hydrochloride oral suspension and preparation method thereof |
| CN108926529A (en) * | 2017-05-25 | 2018-12-04 | 万特制药(海南)有限公司 | Paroxetine hydrochloride oral administration mixed suspension and its preparation process |
| CN113209017A (en) * | 2021-06-02 | 2021-08-06 | 上海美优制药有限公司 | Paroxetine hydrochloride suspension and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1140411A (en) * | 1994-02-03 | 1997-01-15 | 史密丝克莱恩比彻姆有限公司 | Oral liquid compositions contg. paroxetine resinate |
| CN1249686A (en) * | 1997-01-15 | 2000-04-05 | 史密丝克莱恩比彻姆有限公司 | Paroxetine compositions |
| CN1294512A (en) * | 1998-03-24 | 2001-05-09 | 史密丝克莱恩比彻姆有限公司 | Paroxetine compsns. |
| US20100166858A1 (en) * | 2006-03-16 | 2010-07-01 | Tris Pharma, Inc. | Modified release formulations containing drug-ion exchange resin complexes |
-
2014
- 2014-06-25 CN CN201410287053.6A patent/CN104027306A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1140411A (en) * | 1994-02-03 | 1997-01-15 | 史密丝克莱恩比彻姆有限公司 | Oral liquid compositions contg. paroxetine resinate |
| CN1249686A (en) * | 1997-01-15 | 2000-04-05 | 史密丝克莱恩比彻姆有限公司 | Paroxetine compositions |
| CN1294512A (en) * | 1998-03-24 | 2001-05-09 | 史密丝克莱恩比彻姆有限公司 | Paroxetine compsns. |
| US20100166858A1 (en) * | 2006-03-16 | 2010-07-01 | Tris Pharma, Inc. | Modified release formulations containing drug-ion exchange resin complexes |
Non-Patent Citations (1)
| Title |
|---|
| 韦超等: "《药剂学（第2版）》", 31 August 2012, 河南科学技术出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309363A (en) * | 2016-09-24 | 2017-01-11 | 万特制药(海南)有限公司 | Paroxetine hydrochloride oral suspension and preparation method thereof |
| CN108926529A (en) * | 2017-05-25 | 2018-12-04 | 万特制药(海南)有限公司 | Paroxetine hydrochloride oral administration mixed suspension and its preparation process |
| CN113209017A (en) * | 2021-06-02 | 2021-08-06 | 上海美优制药有限公司 | Paroxetine hydrochloride suspension and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6391886B1 (en) | Oral compositions having improved consumer aesthetics | |
| KR101551506B1 (en) | Medical composition containing rebamipide | |
| CN110035741B (en) | Oral solutions containing atomoxetine hydrochloride and methods thereof | |
| KR102226833B1 (en) | Complex granule formulation having improved stability comprising levocetirizine and montelukast | |
| KR20100135316A (en) | Liquid preparation for diperipron with rich flavor | |
| CN104027306A (en) | Paroxetine oral suspension and preparation method thereof | |
| JP4190769B2 (en) | Oral liquid composition | |
| CN108430469A (en) | ST-246 (tecavirin monohydrate) suspension preparation | |
| JP2012136492A (en) | Chinese oral liquid medicine improved in medicine-taking feeling | |
| TW200413027A (en) | Oral liquid tolterodine composition | |
| JP2004161679A (en) | Liquid for internal use | |
| CN101103968A (en) | Ambroxol oral liquid with good taste | |
| JP4373649B2 (en) | Oral solution | |
| JP5009707B2 (en) | Solution for oral administration of quinolone antibacterial agent masked with unpleasant taste | |
| JP4216916B2 (en) | Drinking liquid composition | |
| KR102323708B1 (en) | Fast dissolving granulate | |
| CN103736098A (en) | Intranasal medicinal composition containing bilastine and mometasone furoate | |
| WO2011148794A1 (en) | Dimemorfan-containing liquid preparation for internal administration | |
| JPH10167988A (en) | Oral liquid preparation | |
| JPH1036252A (en) | Belladonna (total) alkaloid-containing oral liquid | |
| JP6794758B2 (en) | Oral liquid pharmaceutical composition | |
| CN109999201B (en) | A kind of taste-masking companion agent and its application | |
| JPH09286723A (en) | Improved oral solution | |
| JP2006131625A (en) | Isosorbide preparation with improved taste quality | |
| JP2013155142A (en) | Bitter-masked oral solution of quinolone-based antimicrobial agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140910 |
|
| RJ01 | Rejection of invention patent application after publication |