CN102085196A - Nefopam hydrochloride bilayer slow-release tablet and preparation method thereof - Google Patents
Nefopam hydrochloride bilayer slow-release tablet and preparation method thereof Download PDFInfo
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- CN102085196A CN102085196A CN2009102414068A CN200910241406A CN102085196A CN 102085196 A CN102085196 A CN 102085196A CN 2009102414068 A CN2009102414068 A CN 2009102414068A CN 200910241406 A CN200910241406 A CN 200910241406A CN 102085196 A CN102085196 A CN 102085196A
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- slow
- layer
- nefopam hydrochloride
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- release layer
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- CNNVSINJDJNHQK-UHFFFAOYSA-N hydron;5-methyl-1-phenyl-1,3,4,6-tetrahydro-2,5-benzoxazocine;chloride Chemical compound [Cl-].C12=CC=CC=C2C[NH+](C)CCOC1C1=CC=CC=C1 CNNVSINJDJNHQK-UHFFFAOYSA-N 0.000 title claims abstract description 53
- 229960004925 nefopam hydrochloride Drugs 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 239000007939 sustained release tablet Substances 0.000 claims abstract description 29
- 239000003826 tablet Substances 0.000 claims abstract description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 44
- 235000019359 magnesium stearate Nutrition 0.000 claims description 22
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 21
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 21
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 21
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 18
- 229920003081 Povidone K 30 Polymers 0.000 claims description 18
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 18
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 18
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 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 claims description 17
- 239000011230 binding agent Substances 0.000 claims description 16
- 229920002472 Starch Polymers 0.000 claims description 15
- 239000008187 granular material Substances 0.000 claims description 15
- 239000008107 starch Substances 0.000 claims description 15
- 235000019698 starch Nutrition 0.000 claims description 15
- 239000003085 diluting agent Substances 0.000 claims description 14
- 239000000314 lubricant Substances 0.000 claims description 14
- 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 13
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 13
- 239000011734 sodium Substances 0.000 claims description 13
- 229910052708 sodium Inorganic materials 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 229920000881 Modified starch Polymers 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000007605 air drying Methods 0.000 claims description 6
- 239000007779 soft material Substances 0.000 claims description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 4
- 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 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 229960003943 hypromellose Drugs 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- 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 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 2
- 229920001747 Cellulose diacetate Polymers 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229920003091 Methocel™ Polymers 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002301 cellulose acetate Polymers 0.000 claims description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 239000006185 dispersion Substances 0.000 claims description 2
- 229960004756 ethanol Drugs 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 2
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000011812 mixed powder Substances 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000002002 slurry Substances 0.000 claims description 2
- 229940032147 starch Drugs 0.000 claims description 2
- BAZVSMNPJJMILC-UHFFFAOYSA-N triadimenol Chemical compound C1=NC=NN1C(C(O)C(C)(C)C)OC1=CC=C(Cl)C=C1 BAZVSMNPJJMILC-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 10
- 230000036407 pain Effects 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 7
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
- 230000002411 adverse Effects 0.000 abstract 1
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 230000000202 analgesic effect Effects 0.000 description 11
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- 230000036592 analgesia Effects 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000031868 Calculus ureteric Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229940121954 Opioid receptor agonist Drugs 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
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- 241000018646 Pinus brutia Species 0.000 description 1
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- 231100000749 chronicity Toxicity 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229960004127 naloxone Drugs 0.000 description 1
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 239000003402 opiate agonist Substances 0.000 description 1
- 239000003401 opiate antagonist Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
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- 230000002980 postoperative effect Effects 0.000 description 1
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- 230000002035 prolonged effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
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- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention relates to a nefopam hydrochloride bilayer slow-release tablet and a preparation method thereof. The nefopam hydrochloride bilayer sustained-release tablet is characterized by being prepared by the step of jointly tabletting a quick release layer and a slow release layer into a bilayer tablet, wherein the proportion of nefopam hydrochloride as the main drug contained in the quick release layer and the slow release layer is (1:1)-(1:5). The invention belongs to the technical field of medical preparations and aims at providing the nefopam hydrochloride bilayer slow-release tablet capable of relieving pain rapidly and relieving and easing pain uniformly and persistently and a preparation method thereof. The bilayer slow-release tablet has the advantages of not only decreasing side effects of a common nefopam hydrochloride preparation to the gastrointestinal tract, but also lowering the medicine-taking frequency of patients, reducing adverse effects and improving patient compliance.
Description
Technical field
The present invention relates to a kind of nefopam hydrochloride double-layer sustained release tablets and preparation method thereof, it is characterized in that described double-layer sustained release tablets is to be pressed into double-layer tablet jointly by release layer and slow release layer, the proportion that wherein contains the principal agent nefopam hydrochloride in release layer and the slow release layer is 1: 1-1: 5.Belong to the pharmaceutical preparations technology field.
Background technology
Nefopam hydrochloride is a kind of novel potent analgesic of non-addiction, has slight analgesic and flesh pine effect.As analgesic, be widely used in clinically as far back as phase early 1970s, nefopam hydrochloride is being different from opiates analgesia and NSAID (non-steroidal anti-inflammatory drug), its no narcoticness, no toleration, no dependence aspect structure and the pharmacology; Non-opioid receptor agonist, its analgesic activity is not resisted by the opiate receptor antagonist naloxone; No aspirin is to the gastrointestinal stimulation, and tendency does not cause bleeding; Analgesic activity is strong, is used for moderate and severe pain, and is similar to the time graph of morphine analgesia effect, and antagonism not mutually, do not produce cross resistance mutually; Lighter to the respiration inhibition effect, do not suppress circulatory function yet, untoward reaction is starkly lower than other analgesic commonly used; Can with multiple medication combined application, no incompatibility.This medicine is widely used in clinical at home and abroad, and moderate and severe pain are had good analgesic activity.Be mainly used in postoperative analgesia, carcinoma pain, acute outer grieved, also be used for visceral smooth muscle angor such as acute gastritis, ascariasis of biliary tract, ureteral calculus.
The nefopam hydrochloride common formulations is an ordinary tablet, because of it is normal release formulation, about 45 minutes, can reach effective blood drug concentration after taking medicine, and action time is short, to chronicity pain such as cancer slight illness person, need adhere to medicining times and dosage for a long time, just can reach therapeutic effect, ordinary tablet blood drug level peak value fluctuation degree is big in addition, easily produces untoward reaction.In view of there is above deficiency in ordinary tablet, in order better to control nefopam hydrochloride blood drug level, guarantee clinical efficacy, reduce medicining times, improve compliance, the nefopam hydrochloride double-layer sustained release tablets has been developed in the generation of reduction untoward reaction.
Beneficial effect
1, the nefopam hydrochloride double-layer sustained release tablets has been developed its advantage, improve the deficiency of common formulations, because of it is made up of release layer and slow release layer, the rapid stripping of nefopam hydrochloride in the release layer of oral back, reach effective blood drug concentration, thereby play quickly alleviating pain, analgesic effect, slow release layer then slowly discharges, and can remain valid in a long time, stable blood concentration, reach even, persistent analgesic effect, analgesic effect was kept 12-24 hour.
2, can reduce medicine to the gastrointestinal side effect.Conventional formulation is made slow releasing preparation and can be reduced side effect because oral back disintegrate stripping in gastrointestinal tract is big to GI irritation.
3, pharmaceutical release time is obviously prolonged, therefore reduced medicining times, improve patient compliance, abirritate and untoward reaction.
Summary of the invention
An object of the present invention is to provide a kind of can quickly alleviating pain, again can be evenly, lasting pain relieving, analgesic nefopam hydrochloride double-layer sustained release tablets, this double-layer sustained release tablets not only reduced because of the nefopam hydrochloride ordinary preparation to the gastrointestinal side effect, also reduced simultaneously patient's medicining times, reduce untoward reaction, improved patient's compliance.
Another object of the present invention has provided the preparation method of described nefopam hydrochloride double-layer sustained release tablets.
The present invention relates to a kind of nefopam hydrochloride double-layer sustained release tablets, it is characterized in that described double-layer sustained release tablets is to be made of release layer and slow release layer, the proportion that wherein contains the principal agent nefopam hydrochloride in release layer and the slow release layer is 1: 1-1: 5, and release layer contains principal agent and disintegrating agent, diluent, binding agent, lubricant; Slow release layer contains principal agent and slow-release material, diluent, binding agent, lubricant.
Double-layer sustained release tablets of the present invention, it is characterized in that described slow-release material can select one or more in Sulisi aqueous dispersion, hydroxypropyl methylcellulose, ethyl cellulose, methylcellulose, cellulose acetate-phthalate, hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, the hydroxy methocel for use, preferred hydroxypropyl methylcellulose.
Double-layer sustained release tablets of the present invention, it is characterized in that described diluent can select one or more in microcrystalline Cellulose, mannitol, pregelatinized Starch, low-substituted hydroxypropyl cellulose, polyvinyl alcohol, Polyethylene Glycol, the ethanol for use, preferably microcrystalline cellulose, pregelatinized Starch.
Double-layer sustained release tablets of the present invention, it is characterized in that described disintegrating agent can select one or more in crospolyvinylpyrrolidone, carboxymethyl starch sodium, low substituted hydroxy-propyl methylcellulose, the cross-linking sodium carboxymethyl cellulose for use, preferred carboxymethyl starch sodium.
Double-layer sustained release tablets of the present invention is characterized in that in the optional water of described binding agent, ethanol, dehydrated alcohol, starch slurry, polyvidone, crospolyvinylpyrrolidone, the hydroxypropyl methylcellulose one or more, preferred polyvidone.
Double-layer sustained release tablets of the present invention is characterized in that described lubricant agent can select magnesium stearate, micropowder silica gel, Pulvis Talci, polyethylene glycols for use, month hang in the pure magnesium sulfate one or more, preferred magnesium stearate.
Double-layer sustained release tablets of the present invention, it is characterized in that described release layer by weight percentage: nefopam hydrochloride accounts for 10～50%, and is preferred 20～40%, and more preferably 25～35%; Diluent accounts for 15～60%, and is preferred 30～50%, and more preferably 35～45%; Disintegrating agent accounts for 5～40%, and is preferred 10～30%, and more preferably 15～35%; Binder constitutes 1～20%, preferred 2～15%, more preferably 5～13%; Lubricant accounts for 0～5%.
Double-layer sustained release tablets of the present invention, it is characterized in that described slow release layer by weight percentage: nefopam hydrochloride accounts for 10～50%, and is preferred 20～40%, and more preferably 25～35%; Slow-release material accounts for 10～50%, and is preferred 20～40%, and more preferably 25～35%; Diluent accounts for 5～50%, and is preferred 10～40%, and more preferably 20～30%; Binder constitutes 1～20%, preferred 5～15%; Lubricant accounts for 0～5%.
Double-layer sustained release tablets of the present invention is characterized in that comprising and is prepared as follows step:
(1) immediate-release granules preparation
Each component is crossed 100 mesh sieves respectively in will writing out a prescription, and is standby.With recipe quantity diluent, the abundant mixing of 1/2 amount disintegrating agent, again with equivalent incremental method and nefopam hydrochloride mix homogeneously, with binding agent system soft material, 20 mesh sieve system wet granulars, 50 ℃ of forced air dryings, 20 mesh sieve granulate add 1/2 amount disintegrating agent, lubricant mixing, measure intermediate content, it is heavy to calculate slice.
(2) slow-releasing granules preparation
Each component is crossed 100 mesh sieves respectively in will writing out a prescription, and is standby.With the mixed powder of recipe quantity slow-release material and diluent with the abundant mixing of equivalent incremental method, again with equivalent incremental method and nefopam hydrochloride mix homogeneously, with binding agent system soft material, 20 mesh sieve system wet granulars, 50 ℃ of forced air dryings, 20 mesh sieve granulate add the lubricant mixing, measure intermediate content, it is heavy to calculate slice.
(3) tabletting is suppressed double-layer tablet with two kinds of granules that (1) and (2) makes.
Specific embodiment
Embodiment 1
| Release layer: | |
| Nefopam hydrochloride | 15g |
| Pregelatinized Starch | 20g |
| Carboxymethyl starch sodium | 10g |
| 30 POVIDONE K 30 BP/USP 30 | 4g |
| Magnesium stearate | 0.5g |
| Slow release layer: | |
| Nefopam hydrochloride | 45g |
| Hydroxypropyl methylcellulose K100LV | 34g |
| Hypromellose E5 | 12g |
| Microcrystalline Cellulose 101 | 34g |
| 30 POVIDONE K 30 BP/USP 30 | 12g |
| Magnesium stearate | 2g |
| Make altogether | 1000 |
Preparation technology
(1) immediate-release granules preparation
Each component is crossed 100 mesh sieves respectively in will writing out a prescription, and is standby.With recipe quantity pregelatinized Starch, the abundant mixing of 1/2 amount carboxymethyl starch sodium, again with equivalent incremental method and nefopam hydrochloride mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 50 ℃ of forced air dryings, 20 mesh sieve granulate add 1/2 amount carboxymethyl starch sodium, magnesium stearate mixing, measure intermediate content, and it is heavy to calculate slice.
(2) slow-releasing granules preparation
Each component is crossed 100 mesh sieves respectively in will writing out a prescription, and is standby.With the mixture of recipe quantity hydroxypropyl methylcellulose 100LV and pregelatinized Starch, microcrystalline Cellulose 101 with the abundant mixing of equivalent incremental method, again with equivalent incremental method and nefopam hydrochloride mix homogeneously, with 10% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent system soft material, 20 mesh sieve system wet granulars, and 50 ℃ of forced air dryings, 20 mesh sieve granulate add the magnesium stearate mixing, measure intermediate content, and it is heavy to calculate slice.
(3) tabletting two kinds of granules usefulness compacting double-layer tablet that (1) and (2) makes.
Embodiment 2
| Release layer: | |
| Nefopam hydrochloride | 10g |
| Microcrystalline Cellulose 101 | 15g |
| Carboxymethyl starch sodium | 8g |
| 30 POVIDONE K 30 BP/USP 30 | 4g |
| Magnesium stearate | 0.5g |
| Slow release layer: | |
| Nefopam hydrochloride | 20g |
| Hydroxypropyl methylcellulose K100LV | 26g |
| Microcrystalline Cellulose 101 | 20g |
| 30 POVIDONE K 30 BP/USP 30 | 10g |
| Magnesium stearate | 1g |
| Make altogether | 1000 |
Preparation technology: with embodiment 1
Embodiment 3
| Release layer: | |
| Nefopam hydrochloride | 30g |
| Microcrystalline Cellulose 101 | 38g |
| Crospolyvinylpyrrolidone | 20g |
| 30 POVIDONE K 30 BP/USP 30 | 10g |
| Magnesium stearate | 0.8g |
| Slow release layer: | |
| Nefopam hydrochloride | 30g |
| Hydroxypropyl methylcellulose K100LV | 35g |
| Microcrystalline Cellulose 101 | 26g |
| 30 POVIDONE K 30 BP/USP 30 | 15g |
| Magnesium stearate | 2g |
| Make altogether | 1000 |
Preparation technology: with embodiment 1
Embodiment 4
| Release layer: | |
| Nefopam hydrochloride | 20g |
| Microcrystalline Cellulose 101 | 14g |
| Mannitol | 12g |
| Carboxymethyl starch sodium | 12g |
| 30 POVIDONE K 30 BP/USP 30 | 4g |
| Magnesium stearate | 0.5g |
| Slow release layer: | |
| Nefopam hydrochloride | 40g |
| Hydroxypropyl methylcellulose K100LV | 28g |
| Hypromellose K4M | 10g |
| Microcrystalline Cellulose 101 | 30g |
| 30 POVIDONE K 30 BP/USP 30 | 10g |
| Magnesium stearate | 2.5g |
| Make altogether | 1000 |
Preparation technology: with embodiment 1
Embodiment 5
| Release layer: | |
| Nefopam hydrochloride | 12g |
| Microcrystalline Cellulose 101 | 17g |
| Carboxymethyl starch sodium | 9g |
| 30 POVIDONE K 30 BP/USP 30 | 5g |
| Magnesium stearate | 0.5g |
| Slow release layer: | |
| Nefopam hydrochloride | 48g |
| Hydroxypropyl methylcellulose K100LV | 50g |
| Microcrystalline Cellulose 101 | 34g |
| 30 POVIDONE K 30 BP/USP 30 | 14g |
| Magnesium stearate | 2g |
| Make altogether | 1000 |
Preparation technology: with embodiment 1
Embodiment 6
| Release layer: | |
| Nefopam hydrochloride | 10g |
| Pregelatinized Starch | 14g |
| Carboxymethyl starch sodium | 8g |
| 30 POVIDONE K 30 BP/USP 30 | 4g |
| Magnesium stearate | 0.5g |
| Slow release layer: | |
| Nefopam hydrochloride | 50g |
| Hydroxypropyl methylcellulose K100LV | 37g |
| Hypromellose E5 | 15g |
| Microcrystalline Cellulose 101 | 36g |
| 30 POVIDONE K 30 BP/USP 30 | 14g |
| Magnesium stearate | 2g |
| Make altogether | 1000 |
Preparation technology: with embodiment 1
According to the drug release determination method, measure its burst size with the nefopam hydrochloride double-layer sustained release tablets of embodiment 1,2 preparation, and contrast buys commercially available common nefopam hydrochloride sheet, measure its stripping quantity, the result is as follows:
The nefopam hydrochloride double-layer sustained release tablets burst size of embodiment 1,2 preparations
Commercially available nefopam hydrochloride sheet (20mg/ sheet) stripping quantity
| Time | 0.25h | 0.5h | 0.45h | 1h | 3h | 6h |
| Stripping quantity (mg) | 4.19 | 8.73 | 15.12 | 18.21 | 19.72 | - |
Claims (7)
1. nefopam hydrochloride double-layer sustained release tablets, it is characterized in that described double-layer sustained release tablets is to be made of release layer and slow release layer, the proportion that wherein contains the principal agent nefopam hydrochloride in release layer and the slow release layer is 1: 1-1: 5, and release layer contains principal agent and disintegrating agent, diluent, binding agent, lubricant; Slow release layer contains principal agent and slow-release material, diluent, binding agent, lubricant.
2. the described double-layer sustained release tablets of claim 1 is characterized in that release layer is by weight percentage:
Nefopam hydrochloride accounts for 10～50%, and is preferred 20～40%, and more preferably 25～35%;
Diluent accounts for 15～60%, and is preferred 30～50%, and more preferably 35～45%;
Disintegrating agent accounts for 5～40%, and is preferred 10～30%, and more preferably 15～35%;
Binder constitutes 1～20%, preferred 2～15%, more preferably 5～13%;
Lubricant accounts for 0～5%.
3. the described double-layer sustained release tablets of claim 1 is characterized in that slow release layer is by weight percentage:
Nefopam hydrochloride accounts for 10～50%, and is preferred 20～40%, and more preferably 25～35%;
Slow-release material accounts for 10～50%, and is preferred 20～40%, and more preferably 25～35%;
Diluent accounts for 5～50%, and is preferred 10～40%, and more preferably 20～30%;
Binder constitutes 1～20%, preferred 5～15%;
Lubricant accounts for 0～5%.
4. the double-layer sustained release tablets described in the claim 1-3 is characterized in that:
Described slow-release material can be selected one or more in Sulisi aqueous dispersion, hydroxypropyl methylcellulose, ethyl cellulose, methylcellulose, cellulose acetate-phthalate, hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, the hydroxy methocel for use, preferred hydroxypropyl methylcellulose.
Described diluent can be selected one or more in microcrystalline Cellulose, mannitol, pregelatinized Starch, low-substituted hydroxypropyl cellulose, polyvinyl alcohol, Polyethylene Glycol, the ethanol for use, preferably microcrystalline cellulose, pregelatinized Starch.
Described disintegrating agent can be selected one or more in crospolyvinylpyrrolidone, carboxymethyl starch sodium, low substituted hydroxy-propyl methylcellulose, the cross-linking sodium carboxymethyl cellulose for use, preferred carboxymethyl starch sodium.
In the optional water of described binding agent, ethanol, dehydrated alcohol, starch slurry, polyvidone, crospolyvinylpyrrolidone, the hydroxypropyl methylcellulose one or more, preferred polyvidone.
Described lubricant agent can be selected one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, polyethylene glycols, month pure magnesium sulfate of extension, preferred magnesium stearate for use.
5. each described double-layer sustained release tablets among the claim 1-4 is characterized in that by weight, it consists of:
6. each described double-layer sustained release tablets among the claim 1-4 is characterized in that calculating by weight, and it consists of:
7. each described double-layer sustained release tablets among the claim 1-6 is characterized in that comprising and is prepared as follows step:
(1) immediate-release granules preparation
Each component is crossed 100 mesh sieves respectively in will writing out a prescription, and is standby.With recipe quantity diluent, the abundant mixing of 1/2 amount disintegrating agent, again with equivalent incremental method and nefopam hydrochloride mix homogeneously, with binding agent system soft material, 20 mesh sieve system wet granulars, 50 ℃ of forced air dryings, 20 mesh sieve granulate add 1/2 amount disintegrating agent, lubricant mixing, measure intermediate content, it is heavy to calculate slice.
(2) slow-releasing granules preparation
Each component is crossed 100 mesh sieves respectively in will writing out a prescription, and is standby.With the mixed powder of recipe quantity slow-release material and diluent with the abundant mixing of equivalent incremental method, again with equivalent incremental method and nefopam hydrochloride mix homogeneously, with binding agent system soft material, 20 mesh sieve system wet granulars, 50 ℃ of forced air dryings, 20 mesh sieve granulate add the lubricant mixing, measure intermediate content, it is heavy to calculate slice.
(3) tabletting is suppressed double-layer tablet with two kinds of granules that (1) and (2) makes.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009102414068A CN102085196A (en) | 2009-12-08 | 2009-12-08 | Nefopam hydrochloride bilayer slow-release tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102414068A CN102085196A (en) | 2009-12-08 | 2009-12-08 | Nefopam hydrochloride bilayer slow-release tablet and preparation method thereof |
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| CN102085196A true CN102085196A (en) | 2011-06-08 |
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| CN102727558A (en) * | 2012-07-04 | 2012-10-17 | 重庆市中药研究院 | Tripterygium Hypoglaucum Hutch root extract, and bi-layer extended release tablet and application thereof |
| CN103655505A (en) * | 2013-12-23 | 2014-03-26 | 闻晓光 | Pain relieving bilayer controlled-release tablet and preparation method thereof |
| CN106137984A (en) * | 2016-08-03 | 2016-11-23 | 山西国润制药有限公司 | A kind of nefopam hydrochloride injection and preparation method thereof |
| CN107998169A (en) * | 2017-09-26 | 2018-05-08 | 江西中医药大学 | A kind of cholagogic helps digestion, the preparation method of antidiarrheal double-layer tablets |
| US10137092B2 (en) | 2013-12-23 | 2018-11-27 | Xiaoguang WEN | Double-layer tablet and preparation method thereof |
| CN118873505A (en) * | 2024-07-05 | 2024-11-01 | 中国人民解放军空军军医大学 | Nefopam rapid/sustained release double-layer buccal tablet and preparation method thereof |
| RU2833481C2 (en) * | 2020-01-21 | 2025-01-22 | Атена Фармасьютикс Сас | Orally disintegrating pharmaceutical composition containing nefopam, and method for preparation thereof |
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- 2009-12-08 CN CN2009102414068A patent/CN102085196A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102727558A (en) * | 2012-07-04 | 2012-10-17 | 重庆市中药研究院 | Tripterygium Hypoglaucum Hutch root extract, and bi-layer extended release tablet and application thereof |
| CN103655505A (en) * | 2013-12-23 | 2014-03-26 | 闻晓光 | Pain relieving bilayer controlled-release tablet and preparation method thereof |
| CN103655505B (en) * | 2013-12-23 | 2016-10-26 | 闻晓光 | A kind of pain relieving class two-layer release-controlled tablet and preparation method thereof |
| US10137092B2 (en) | 2013-12-23 | 2018-11-27 | Xiaoguang WEN | Double-layer tablet and preparation method thereof |
| US10925836B2 (en) | 2013-12-23 | 2021-02-23 | Overseas Pharmaceuticals (Guangzhou) Ltd. | Double-layer tablet and painkiller tablet with same structure |
| US10940114B2 (en) | 2013-12-23 | 2021-03-09 | Overseas Pharmaceuticals (Guangzhou) Ltd. | Hypnotics tablet with double-layer structure |
| CN106137984A (en) * | 2016-08-03 | 2016-11-23 | 山西国润制药有限公司 | A kind of nefopam hydrochloride injection and preparation method thereof |
| CN107998169A (en) * | 2017-09-26 | 2018-05-08 | 江西中医药大学 | A kind of cholagogic helps digestion, the preparation method of antidiarrheal double-layer tablets |
| RU2833481C2 (en) * | 2020-01-21 | 2025-01-22 | Атена Фармасьютикс Сас | Orally disintegrating pharmaceutical composition containing nefopam, and method for preparation thereof |
| CN118873505A (en) * | 2024-07-05 | 2024-11-01 | 中国人民解放军空军军医大学 | Nefopam rapid/sustained release double-layer buccal tablet and preparation method thereof |
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Address after: 100083 Haidian District, Xueyuan Road, No. 30, A building, room No. 15, room, room 15 Applicant after: Beijing Kexin Bicheng Medicine Science & Technology Developing Co., Ltd. Address before: 100190, room 1410, satellite building, No. 63, Zhichun Road, Beijing, Haidian District Applicant before: Beijing Kexin Bicheng Medicine Science & Technology Developing Co., Ltd. |
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Application publication date: 20110608 |