[summary of the invention]
The objective of the invention is to improve existing stem and leaf of Radix Ginseng total saponins aspect peroral dosage form deficiency, provide a kind of taking convenience, absorption is rapid-action, bioavailability is high ginseng stem and leaf total saponin oral disintegration tablet to extensive patients and medical personnel.Needn't drink water when the present invention relates to take, in the oral cavity, only need tens seconds can rapid disintegrate or dissolving, the ginseng stem and leaf total saponin oral disintegrating tablet and the preparation technology thereof that can finish to take medicine with saliva hypopharynx.
One, prescription
The ginseng stem and leaf total saponin oral disintegrating tablet that reaches of the present invention comprises the material medicine stem and leaf of Radix Ginseng total saponins, needs following former, the auxiliary material of 9 classes altogether, wherein: when not making Cotton seeds, then do not use coating material, effervescent and binding agent also can for selecting adjuvant for use as one sees fit.Calculate with weight percentage, stem and leaf of Radix Ginseng total saponins (5-50) %, binding agent (0-5) %, filler (10-80) %, disintegrating agent (2-35) %, correctives (1-40) %, coating material (0-40) %, effervescent (0-30) %, fluidizer (0.01-5) %, lubricant (0.3-3) %, and it is prepared from by following method:
(1) stem and leaf of Radix Ginseng total saponins with filler, disintegrating agent, correctives, fluidizer mixing, adds the lubricant mixing with granulate back or do not deal with of binding agent, and the gained material detects through intermediate, determine that sheet is heavy after, send into the tablet machine tabletting promptly; Perhaps
(2) stem and leaf of Radix Ginseng total saponins is with behind the coating material powder coating, and with filler, disintegrating agent, correctives, fluidizer, lubricant mixing, the gained material detects through intermediate, determine that sheet is heavy after, send into the tablet machine tabletting promptly; Perhaps
(3) after stem and leaf of Radix Ginseng total saponins and effervescent were granulated with binding agent, with filler, disintegrating agent, correctives, fluidizer, lubricant mixing, the gained material detected through intermediate, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
Wherein:
Binding agent includes but are not limited to starch, pregelatinized Starch, dextrin, maltodextrin, sucrose, arabic gum, gelatin, methylcellulose, carboxymethyl cellulose, ethyl cellulose, polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone (PVP), alginic acid and alginate, xanthan gum, hydroxypropyl cellulose and hydroxypropyl emthylcellulose (HPMC), can use use also capable of being combined separately.
Filler includes but are not limited to mannitol (granular or powdery), xylitol, sorbitol, maltose, erithritol, microcrystalline Cellulose, PROSOLV
SMCC (silicified microcrystalline cellulose), polymerization sugar (EMDEX
), coupling sugar, glucose, lactose, sucrose, dextrin and starch etc., can use separately, also can applied in any combination, consumption is generally (10-80) %.
Disintegrating agent includes but are not limited to crospolyvinylpyrrolidone (PVPP), carboxymethyl starch sodium (CMS-Na), low substituted hydroxy-propyl methylcellulose (L-HPC), cross-linking sodium carboxymethyl cellulose (CCNa) and soybean polysaccharide (EMCOSOY
) etc., can use use also capable of being combined separately.
Correctives includes but are not limited to mannitol, xylitol, stevioside, lactose, fructose, sucrose, protein sugar, maltose alcohol, glycyrrhizin, Sodium Cyclamate, gelatin, aspartame, flavoring banana essence, flavoring pineapple essence, vanillin, fragrant citrus essence, flavoring orange essence, Herba Menthae essence, ginseng essence, strawberry essence, citric acid, citric acid etc., can use use also capable of being combined separately.
Coating material includes but are not limited to gelatin, arabic gum, alginate, chitosan, carboxymethyl cellulose salt, cellulose acetate phthalate ester, ethyl cellulose, methylcellulose, hypromellose, crylic acid resin (homemade acrylic resin I, II, III, IV, Eudragit
Series), polyvinyl alcohol, polyvinylpyrrolidone, Polyethylene Glycol etc., can use use also capable of being combined separately.
Fluidizer includes but are not limited to micropowder silica gel, Pulvis Talci, Cab-O-sil, Arosil, hydrated sodium aluminosilicate etc., can use use also capable of being combined separately.
Lubricant includes but are not limited to magnesium stearate, calcium stearate, zinc stearate, glyceryl monostearate, Polyethylene Glycol, hydrogenated vegetable oil, sodium stearyl fumarate, polyoxyethylene monostearate, single Laurel sucrose acid ester, sodium laurylsulfate, magnesium laurylsulfate, Stepanol MG and Pulvis Talci etc., can use use also capable of being combined separately.
Effervescent includes but are not limited to the mixture of malic acid, citric acid or citric acid and sodium bicarbonate or sodium carbonate.
Two, preparation method
The ginseng stem and leaf total saponin oral disintegrating tablet that reaches of the present invention, its preparation method is a direct compression process, the manufacturer with preparation conventional tablet all can adopt.
The stem and leaf of Radix Ginseng total saponins bitter in the mouth, the present invention can adopt two kinds of distinct methods to carry out flavoring or taste masking: 1. adopt the direct flavoring of correctives; 2. in advance stem and leaf of Radix Ginseng total saponins is carried out powder coating with taste masking.
Concrete preparation method is as follows:
The preprocess method of first step stem and leaf of Radix Ginseng total saponins:
1. directly the flavoring method---this law is granulated to the stem and leaf of Radix Ginseng total saponins raw material or is not dealt with, and directly enters for second step;
2. powder coating taste masking---get selected coating material, with the dissolving of the solvent that adapts with it and to be diluted to debita spissitudo standby, getting stem and leaf of Radix Ginseng total saponins again places ebullated bed to make boiling, spray into above-mentioned solution with suitable speed then and carry out powder coating, get stem and leaf of Radix Ginseng total saponins powder coating granule, dry back sieving for standby;
Second step took by weighing correctives and stem and leaf of Radix Ginseng total saponins or the feed particles after first step taste masking processing according to quantity, and mix homogeneously is standby;
The 3rd step took by weighing filler, disintegrating agent, effervescent, fluidizer and mix homogeneously according to quantity, made evenly again with through second mixing of materials that goes on foot gained, and adding lubricant mixing is standby;
The 4th step gained material detects through intermediate, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
Specifically, powder coating taste masking method of the present invention prepares the method for described ginseng stem and leaf total saponin oral disintegrating tablet, is made up of following steps:
The first step is got coating material, uses suitable solvent dissolving and be diluted to debita spissitudo standby;
Second step got stem and leaf of Radix Ginseng total saponins and places ebullated bed to make boiling, and the solution that sprays into the first step with suitable speed carries out powder coating then, stem and leaf of Radix Ginseng total saponins powder coating granule, dry back sieving for standby;
The 3rd step is even with filler, disintegrating agent, correctives, fluidizer, mix lubricant, and is standby with the back coated granule mixing that sieves in second step again;
The 4th step the 3rd step gained material detects through intermediate, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
The hardness of the tablet that said method obtains is between 10 to 45 newton, and disintegration time is at 1-60 in second.
[beneficial effect]
Tablet is a kind of conventional dosage forms, because of its steady quality, dosage accurately, take, easy to carry, mechanization degree is high, low one of the at present the most frequently used dosage form that becomes of production cost, but because of the tablet extrusion forming, disintegrate is slow, bioavailability is lower, and part patient swallows comparatively difficult, thereby promoting the use of to a certain extent of tablet is restricted.The oral administration solid quick releasing formulation becomes a focus, particularly oral cavity disintegration tablet of new drug development in recent years for this reason, because of its taking convenience, rapid-action, bioavailability is high, the good emphasis that becomes tablet exploitation of mouthfeel.
Oral cavity disintegration tablet is meant not to be needed water or only needs low amounts of water, need not to chew, and tablet places lingual surface, meets after saliva separates rapidly or collapse, and borrows and swallows power, and medicine can be gone into the tablet of stomach onset.The characteristics of oral cavity disintegration tablet are that absorption is fast, bioavailability is high, and intestinal is residual few, and side effect is low, avoids liver first-pass effect etc.
According to the requirement of " formulation characteristic of oral cavity disintegration tablet and quality control meeting summary ", oral cavity disintegration tablet has essential leap than the disintegration rate of drop pill and ordinary tablet, and the disintegrate of oral cavity disintegration tablet generally in 30 seconds, is no more than 1 minute at most.
[specific embodiment]
For the preparation method of ginseng stem and leaf total saponin oral disintegrating tablet of the present invention better is described, in conjunction with directly flavoring method and powder coating taste masking method are as follows for an embodiment respectively:
Embodiment one direct flavoring method
One. prescription
1. raw material---stem and leaf of Radix Ginseng total saponins 25.0g;
2. binding agent---polyvinylpyrrolidone K-30 0.5g;
3. filler---mannitol 53.5g;
PROSOLV
SMCC 5.0g;
4. correctives---aspartame 1.0g;
Ginseng essence 1.0g;
5. disintegrating agent---crospolyvinylpyrrolidone 8.0g;
L-HPC 4.0g;
6. fluidizer---micropowder silica gel 1.0g;
7. lubricant---sodium stearyl fumarate 1.0g.
Gross weight 100g makes 1000 altogether.
Two. preparation method
1) get the stem and leaf of Radix Ginseng total saponins raw material pulverizing, granulate, cross 26 mesh sieves with polyvinylpyrrolidone K-30, standby;
2) with micropowder silica gel, ginseng essence, PROSOLV
SMCC and aspartame are crossed 40 mesh sieves respectively, and mix homogeneously adds the stem and leaf of Radix Ginseng total saponins granule of having granulated again, and mix homogeneously is standby;
3) get mannitol, L-HPC and crospolyvinylpyrrolidone and cross 40 mesh sieves respectively, mix homogeneously will add and mix homogeneously through the raw material of flavoring again, adds sodium stearyl fumarate and mix homogeneously at last;
4) intermediate content detection, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
Embodiment two powder coating taste masking methods
One. prescription
1. raw material---stem and leaf of Radix Ginseng total saponins 25.0g;
2. coating material---Eudragit
E100 3.5g;
Eudragit
NE30D (doing) 1.5g;
3. filler---mannitol 50.5g;
Microcrystalline Cellulose 5.0g;
4. correctives---aspartame 1.0g;
Ginseng essence 1.0g;
5. disintegrating agent---crospolyvinylpyrrolidone 6.0g;
L-HPC 4.0g;
6. fluidizer---micropowder silica gel 1.5g;
7. lubricant---sodium stearyl fumarate 1.0g.
Gross weight 100g makes 1000 altogether.
Two. preparation method
1) gets Eudragit
E100 and Eudragit
NE30D is with the dissolving of the medicinal industrial alcohol more than 95% and to be diluted to finite concentration standby;
2) get stem and leaf of Radix Ginseng total saponins and place ebullated bed to seethe with excitement, spray into above-mentioned solution by certain speed and carry out powder coating, make stem and leaf of Radix Ginseng total saponins powder coating granule, dry back is standby;
3) with mannitol, microcrystalline Cellulose, micropowder silica gel, PVPP, L-HPC, aspartame, sodium stearyl fumarate and ginseng essence mix homogeneously, again and sieve after the coated granule mixing standby;
4) intermediate content detection, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
Embodiment three effervescent flavoring methods
One. prescription
1. raw material---stem and leaf of Radix Ginseng total saponins 25.0g;
2. binding agent---polyvinylpyrrolidone K-30 0.5g;
3. effervescent---citric acid 12.5g;
Sodium bicarbonate 10.0g;
4. filler---mannitol 28.0g;
PROSOLV
SMCC 5.0g;
5. correctives---aspartame 1.0g;
Fragrant citrus essence 1.0g;
6. disintegrating agent---crospolyvinylpyrrolidone 10.0g;
L-HPC 5.0g;
7. fluidizer---micropowder silica gel 1.0g;
8. lubricant---sodium stearyl fumarate 1.0g.
Gross weight 100g makes 1000 altogether.
Two. preparation method
1) get stem and leaf of Radix Ginseng total saponins and citric acid raw material and mix the back pulverizing, granulate, cross 26 mesh sieves with polyvinylpyrrolidone K-30, standby;
2) get sodium bicarbonate and pulverize, granulate, cross 26 mesh sieves with polyvinylpyrrolidone K-30, standby;
3) adjuvant that all the other are all is crossed mix homogeneously behind 40 mesh sieves respectively, adds the granule of having granulated again, and mix homogeneously is standby;
4) intermediate content detection, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
Disintegration that the sample of the foregoing description is measured and slice, thin piece hardness are as follows:
Embodiment | Disintegration (second) | Slice, thin piece hardness (newton) |
1 2 3 | 11-22 13-29 15-28 | 18-26 15-24 16-25 |