CN101695482B - Glipizide orally disintegrating tablet and preparation process thereof - Google Patents
Glipizide orally disintegrating tablet and preparation process thereof Download PDFInfo
- Publication number
- CN101695482B CN101695482B CN2009101863799A CN200910186379A CN101695482B CN 101695482 B CN101695482 B CN 101695482B CN 2009101863799 A CN2009101863799 A CN 2009101863799A CN 200910186379 A CN200910186379 A CN 200910186379A CN 101695482 B CN101695482 B CN 101695482B
- Authority
- CN
- China
- Prior art keywords
- glipizide
- grams
- fatty acid
- acid ester
- gram
- 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.)
- Expired - Fee Related
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a glipizide orally disintegrating tablet which comprises the following ingredients in proportions by weight: 5g of glipizide, 30.64g of mannitol, 15g of microcrystalline cellulose, 9g of crospovidone, 0.06g of aspartame, 0.3g of magnesium stearate, 0.9g of 2% povidone K30 ethanol solution in percentage by weight, 8.5g of sucrose fatty acid ester and 3g of erythritol. The glipizide orally disintegrating tablet has the effects for most type 2 diabetes and can reduce fasting blood-glucose and postprandial blood glucose. Hypoglycemic medicines are required to be taken before meals, and in order to provide the convenience for a patient to take medicine under various conditions, the orally disintegrating tablet is a more ideal dosage form. The orally disintegrating tablet is characterized by being disintegrated quickly just by very little amount of water or spittle without gritty texture, is favorable in mouthfeel and easy to swallow. The optimal auxiliary materials can enable the glipizide orally disintegrating tablet to be disintegrated more quickly and considers the hardness and the friability simultaneously so as to facilitate the molding of the orally disintegrating tablet.
Description
Technical field
The present invention relates to drug port disintegrating tablet technical field, relate in particular to a kind of oral cavity disintegration tablet and preparation technology thereof of glipizide.
Background technology
The not enough situation that Glipizide orally disintegrating tablet exists at present is that disintegration rate reached about 40 seconds, and such speed is slow partially, and Glipizide orally disintegrating tablet is as antidiabetic drug, and disintegration rate is significant sooner.In addition, conventional disintegrating agent still is difficult to obtain quickly disintegrated effect through a large amount of screenings, this is because except satisfying quick disintegrate, oral cavity disintegration tablet itself also needs to satisfy the requirement of certain rigidity and brittleness, the too poor oral cavity disintegration tablet of hardness and brittleness is not easy to transportation and keeping, is considered as substandard product.
And when making oral cavity disintegration tablet, be contradiction between hardness or brittleness and the disintegration time usually.Lift a simple case, under the equal conditions, tabletting reaches the fine and close obvious disintegration time of slice, thin piece and will prolong.Such as adopting high-strength and heavy dose of disintegrating agent, reach requirement as disintegration time, but the hardness of slice, thin piece, friability are defective; Hardness, friability as slice, thin piece are qualified, and the disintegration time of slice, thin piece is defective again.
The disintegrating agent of the routine in the Glipizide orally disintegrating tablet still is difficult to shorten significantly in disintegration time through a large amount of screenings, and the hardness of slice, thin piece, friability improve comprehensively.
Above-mentioned situation imbody is hereinafter:
Glipizide is that Chinese Pharmacopoeia two ones of versions in 2000 are recorded kind, is second filial generation sulfonylurea antidiabetic drug.Effective to most of II paradiabetes patients, can make on an empty stomach and the post-prandial glycemia reduction.Antidiabetic drug requires taking before the meal, and the patient can take medicine on time in all cases for convenience, and oral cavity disintegration tablet is a kind of comparatively ideal dosage form.The formulation characteristic of oral cavity disintegration tablet is that little water or saliva just can make the quick disintegrate of slice, thin piece, there is no sand type, good mouthfeel, swallow easily, to the oral mucosa nonirritant, according to the characteristics of dosage form and the characteristic of principal agent, can select the good disintegrating agents of disintegrating property such as well behaved disintegrating agent such as cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium for use, the filler of good mouthfeel such as mannitol, sorbitol, trehalose, microcrystalline Cellulose etc., in addition an amount of sweeting agent carries out prescription screening to regulate mouthfeel.
Oral cavity disintegration tablet is a kind of novel pharmaceutical formulation that development in recent years is got up, and glipizide has multiple dosage form, and the oral cavity disintegration tablet of glipizide also has report.For example there is prescription the Jiangxi Prov. Medicine Inst in the record of a kind of blood sugar lowering oral cavity disintegration tablet of on July 27th, 2004 application and preparation technology CN200410055438.6 thereof: glipizide 5 grams, mannitol 30.64 grams, microcrystalline Cellulose PH101 15 grams, polyvinylpolypyrrolidone 9 grams, aspartame 0.06 gram, magnesium stearate 0.3 gram, 2% 30 POVIDONE K 30 BP/USP, 30 pure liquid 0.9 grams are made 1000.Technology: take by weighing glipizide, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame respectively by recipe quantity and adopt the equivalent method of progressively increasing to add in the mixing channel, abundant mix homogeneously, alcoholic solution (alcoholic solution with 60% prepares povidone solution) system soft material with 2% polyvidone, 40 mesh sieves are granulated, 50-60 ℃ of forced air drying with 40 mesh sieve granulate, adds the magnesium stearate mix homogeneously, with φ 6mm stamping, packing promptly after the assay was approved.Get the said goods and test, assay is as follows:
Table 1
| Lot number | Outward appearance | Disintegration time | Dissolution (%) | Content (%) |
| 801 | White tablets, disintegrate rapidly, no sand type, good mouthfeel in the oral cavity | Whole disintegrates are also by 40 mesh sieves during to 37 seconds | 100.63 | 99.96 |
| 802 | White tablets, disintegrate rapidly, no sand type, good mouthfeel in the oral cavity | Whole disintegrates are also by 40 mesh sieves during to 43 seconds | 102.14 | 101.33 |
| 803 | White tablets, disintegrate rapidly, no sand type, good mouthfeel in the oral cavity | Whole disintegrates are also by 40 mesh sieves during to 42 seconds | 99.73 | 100.98 |
Above-mentioned prescription and production technology are after transferring the applicant, and the applicant has done suitable technological improvement.Improved target is: adopt better prescription and technology, so that from obtaining disintegration time faster, simplify production technology and save production cost, suitably reduce glipizide the stimulation of stomach, the reasonable hardness of tablet molding, the broken brittleness and quick disintegrate two aspect improvement effects taken into account.
Oral cavity disintegration tablet mainly is suitable for following situation: (1) can turn over the first-aid medicine of film absorption or the medicine of the rapid onset of palpus through the oral cavity, as nitroglycerin, nifedipine, salbutamol sulfate etc.: the patient of (2) dysphagia (as the esophageal carcinoma patient) medication, as the Bendectin ondansetron, Ramosetron HCls etc.: (3) patient is not initiatively or mismatch medication under the situation, as the antidepressants Lizakuputan benzoate, Zolmitriptan etc.: the medicine that (4) need to increase contact area or reduce GI irritation, as aspirin, ibuprofen etc.: (5) child, the old man, difficult change of bed position and hydropenia condition are foretold patient's medication.
Because Rezulin patient quantity is very huge, thereby patient's the absolute quantity of old man, child, psychotic, dysphagia of suffering from Rezulin is also very many, and oral cavity disintegration tablet just can make the quick disintegrate of slice, thin piece because of little water or saliva, uses so the oral cavity disintegration tablet of glipizide is fit to suffer from old man, child, the psychotic of Rezulin very much.Certainly general patient also very is fit to use the oral cavity disintegration tablet of glipizide.
But adopt the prescription and the arts demand 37-42 of the record of CN200410055438.6 could well finish disintegrate second.This takes the requirement leeway that still is significantly improved fast apart from the patient's of old man, child, psychotic, dysphagia.
The disintegration time of external a lot of oral cavity disintegration tablets is all finished about 15 seconds, and this need do a large amount of improvements at adjuvant and process aspect, removes Freeze Drying Technique such as adopting.But these complex process domesticly lack the supporting production equipment that is fit to produce with lyophilization oral cavity disintegration tablet.Therefore the production of the domestic overwhelming majority's oral cavity disintegration tablet.
The most effective traditional oral cavity disintegration tablet disintegrating agent is low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, their disintegrate principle mainly is a suction back volume swelling significantly, thereby oral cavity disintegration tablet is collapsed out.
In that disintegration time is reduced to about 10 seconds from the 37-42 of prior art second significantly is unusual difficulty, this is because glipizide is almost insoluble in water, the present invention has screened conventional combination such as a large amount of low-substituted hydroxypropyl celluloses, carboxymethyl starch sodium, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, polyvidone, all very difficult disintegration time is controlled at about 15 seconds.
Technology is direct powder compression:
Table 2 filler screening test prescription
Technology is direct powder compression
Table 3 filler screening test result
Table 4 disintegrating agent screening test prescription
Table 5 disintegrating agent The selection result
Summary of the invention
The purpose of this invention is to provide a kind of Glipizide orally disintegrating tablet and preparation technology thereof, conveniently take to better meet needs of medical treatment.The technical solution used in the present invention can obviously shorten the time of disintegrate, and keeps good hardness and friability.Aspect disintegration time, disintegrate hardness, the disintegrate friability three comprehensive lifting is being arranged.
Technical scheme of the present invention has following:
A kind of Glipizide orally disintegrating tablet, wherein: each constituent weight proportion is: glipizide 5 grams, mannitol 30.64 grams, microcrystalline Cellulose 15 grams, polyvinylpolypyrrolidone 9 grams, aspartame 0.06 gram, magnesium stearate 0.3 gram, concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, sucrose fatty acid ester 8.5 grams, erythritol 3 grams.
A kind of preparation technology of Glipizide orally disintegrating tablet, wherein: it is stand-by to take by weighing glipizide, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, sucrose fatty acid ester, erythritol respectively by formula ratio; Earlier with glipizide and sucrose fatty acid ester, the first mix homogeneously of erythritol, again to wherein adding mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, abundant mix homogeneously, the reuse concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, add water 15 again and restrain soft material, 40 mesh sieves are granulated, and 50-60 ℃ of forced air drying is with 40 mesh sieve granulate, add the magnesium stearate mix homogeneously, with the mould stamping of φ 6mm, make 1000 after the assay was approved, packing is promptly.
Being prepared as follows of sucrose fatty acid ester: in first reactor, add 1200 gram stearic acid, 46.2 gram sulphuric acid, 2200 gram ethanol stir 70-80 ℃ on the limit, normal pressure reacted 6-8 hour down, excess ethanol is reclaimed in distillation then, washes product earlier with water till the pH=7, obtains the intermediate product ethyl stearte of the first step; Get intermediate product ethyl stearte 48 grams of the above-mentioned first step, sucrose 50 grams, propylene glycol 158 grams, potassium carbonate 6.3 grams join in second reactor successively, stir on the limit, reaction adds 1.2 gram citric acids after 10 hours under 80 ℃ the condition, propylene glycol is reclaimed in distilling under reduced pressure again; With product in second reactor and concentration is that 12% sodium chloride solution mixes, and stirs with the intact sucrose of flush away unreacted; Standing demix also separates sub-cloud liquid; The upper strata product promptly gets the sucrose fatty acid ester crude product after drying; Hybrid extraction liquid by weight 1: 1 proportional arrangement isobutyl alcohol and water is stand-by, 1: 3 ratio of example is put into the sucrose fatty acid ester crude product hybrid extraction liquid of isobutyl alcohol and water by weight, sucrose fatty acid ester enter isobutanol mutually in, the sucrose impurity of complete reaction does not enter aqueous phase; Carry out extract and separate, isobutanol is reclaimed in distillation, obtains purified sucrose fatty acid ester.
The present invention considers as follows in design:
Glipizide apparent in view to gastrointestinal stimulation, the therefore suitable coating that carries out, it is significant reducing its stimulation to stomach.
" earlier with glipizide and sucrose fatty acid ester, the erythritol elder generation mix homogeneously; again to wherein adding mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, abundant mix homogeneously " that relates in the preparation process of the present invention embodied the technology point that sucrose fatty acid ester and erythritol is used to wrap up glipizide.
The adding erythritol has the effect of the abnormal flavour of shielding glipizide.
It is little sweet that the present invention adopts erythritol itself to have, and relative sweetness 0.65 has the characteristics of refrigerant sense, and caloric value is low, is about 1/10th of sucrose caloric value.But erythritol can provide the mouthfeel of similar sucrose, and simultaneously erythritol can only see through kidney and drain in the urine from blood and discharge, and not involved in sugar metabolism and change of blood sugar are so be suitable for patients with diabetes mellitus.Erythritol provides the mouthfeel of similar sucrose can cover the bad mouthfeel of glipizide to the oral cavity.
The present invention adopts sucrose fatty acid ester parcel glipizide, and reducing it on the one hand stimulates gastrointestinal, utilizes the lipophilic group parcel of sucrose fatty acid ester glipizide on the other hand, and the hydrophilic group of sucrose fatty acid ester is assist in dissolving outwardly, quickens to finish disintegrate.And newly add sucrose fatty acid ester, erythritol, cooperation direct compression and aspect disintegration time shortening, disintegrate hardness, the disintegrate friability three comprehensive lifting is being arranged.
In that disintegration time is reduced to about 10 seconds from the 37-42 of prior art second significantly is unusual difficulty, this is because glipizide is almost insoluble in water, the present invention has screened conventional combination such as a large amount of low-substituted hydroxypropyl celluloses, carboxymethyl starch sodium, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, polyvidone, all very difficult disintegration time is controlled at about 15 seconds.
The kind of sucrose fatty acid ester is many, synthesis technique is also many, and the new method that the present invention adopts goes the sucrose fatty acid ester that obtains can be reasonable to be used with other pharmaceutic adjuvants to obtain disintegration time, disintegrate hardness, disintegrate friability three aspects comprehensive lifting is arranged.The sucrose fatty acid ester that the method that the present invention adopts goes to obtain can reasonablely cooperate with other pharmaceutic adjuvants, has reached the effect of quickening disintegrate in 12 seconds.
Rare especially is that the technology that preferred embodiment 1 provides can shorten disintegration time significantly, and the hardness of oral cavity disintegration tablet, friability improve comprehensively.Disintegrating agent as the routine in the Glipizide orally disintegrating tablet of introducing in the background technology of the present invention still is difficult to disintegration time is shortened significantly through a large amount of screenings.
The related content of the detection of hardness of the present invention and friability has:
Hardness generally is meant case hardness, and mainly is meant crushing strength (Crushingstrength) in tablet.Method for measuring is that tablet is stood between two pressing plates, along the direction pressurization slowly of diameter, up to fragmentation, measures required power.The result of this mensuration also is called tensile strength (Tensile strength).
Be called hardness in tablet is measured, tablet was complete when meaning was to guarantee to pack and transport.Measure tablet hardness instrument commonly used Meng Shandou (Monsanto) type or the calculating of Strong-cobb type intensity etc. are arranged.The latter is with the hydraulic press pressurization, shows pressure with Pressure gauge.Meng Shan type is by a bolt one spring to be pressurizeed, and promotes pressing plate by spring tablet is pressurizeed; The size that is reflected power by the spring length variations, the power when observing fragmentation is hardness.Homemade tablet four-function analyzer is measured structural principle partly, and all type is similar to Meng Shan, uses the motor drive bolt, and pressurization evenly.It is become with compression spring set by two plunger pistons, and left plunger contacts with tablet, and right plunger is controlled by electronic bolt.When bolt rotated, pressure passed on the slice, thin piece by the compression spring, and when compression spring pressurized, the pointer on the tube moves along the outer wall scale, the pressure that is born when demonstrating the medicine fragmentation simultaneously.The chieftain touched microswitch when tablet was broken, made the motor stall.Stir reversing switch, pointer is return zero point.
The mensuration of friability (Friability) is replenishing of piezometry hardness.Because finished product is hard and crisp, can not stand the concussion in the packed and transported equally.Friability is meant the degree of crushing that tablet causes through shaking, colliding.Broken or top is split if any tablet, represents that promptly the hardness of tablet is undesirable, as does not have cracked or the top is split, and accurately claims the fixed weight of loss altogether, and represents that with percentage ratio if sample weightlessness is lower than at 0.8% o'clock, its friability is commonly considered as satisfactory.Instrument has sieve to be permitted (Roche) type when measuring friability, during use tablet is placed the drum of a rotation, tablet is ground mutually and collides certain hour (being generally 4 minutes), judges friability by above-mentioned requirements then.Tablet then is to utilize back and forth vibrations to measure with Instrument measuring friability part, and standard is the same.
Glipizide orally disintegrating tablet of the present invention is effective to most of II paradiabetes patients, can make on an empty stomach and the post-prandial glycemia reduction.Antidiabetic drug requires taking before the meal, and the patient can take medicine on time in all cases for convenience, and oral cavity disintegration tablet is a kind of comparatively ideal dosage form.The formulation characteristic of oral cavity disintegration tablet is that little water or saliva just can make the quick disintegrate of slice, thin piece, there is no sand type, and good mouthfeel is swallowed easily.The preferred adjuvant of the present invention can make the Glipizide orally disintegrating tablet disintegrate more quick.
The usage of Glipizide orally disintegrating tablet of the present invention and consumption: a 3-5 sheet, 2 times on the one.
The specific embodiment:
Embodiment 1: a kind of Glipizide orally disintegrating tablet, wherein: each constituent weight proportion is: by glipizide 5 grams, mannitol 30.64 grams, microcrystalline Cellulose 15 grams, polyvinylpolypyrrolidone 9 grams, aspartame 0.06 gram, magnesium stearate 0.3 gram, concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, sucrose fatty acid ester 8.5 grams, erythritol 3 grams.
A kind of preparation technology of Glipizide orally disintegrating tablet, wherein: it is stand-by to take by weighing glipizide, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, sucrose fatty acid ester, erythritol respectively by formula ratio; Earlier with glipizide and sucrose fatty acid ester, the first mix homogeneously of erythritol, again to wherein adding mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, abundant mix homogeneously, the reuse concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, add water 15 again and restrain soft material, 40 mesh sieves are granulated, and 50-60 ℃ of forced air drying is with 40 mesh sieve granulate, add the magnesium stearate mix homogeneously, with the mould stamping of φ 6mm, make 1000 after the assay was approved, packing is promptly.
Being prepared as follows of sucrose fatty acid ester: in first reactor, add 1200 gram stearic acid, 46.2 gram sulphuric acid, 2200 gram ethanol stir 70-80 ℃ on the limit, normal pressure reacted 6-8 hour down, excess ethanol is reclaimed in distillation then, washes product earlier with water till the pH=7, obtains the intermediate product ethyl stearte of the first step; Get intermediate product ethyl stearte 48 grams of the above-mentioned first step, sucrose 50 grams, propylene glycol 158 grams, potassium carbonate 6.3 grams join in second reactor successively, stir on the limit, reaction adds 1.2 gram citric acids after 10 hours under 80 ℃ the condition, propylene glycol is reclaimed in distilling under reduced pressure again; With product in second reactor and concentration is that 12% sodium chloride solution mixes, and stirs with the intact sucrose of flush away unreacted; Standing demix also separates sub-cloud liquid; The upper strata product promptly gets the sucrose fatty acid ester crude product after drying.
Hybrid extraction liquid by weight 1: 1 proportional arrangement isobutyl alcohol and water is stand-by, 1: 3 ratio of example is put into the sucrose fatty acid ester crude product hybrid extraction liquid of isobutyl alcohol and water by weight, sucrose fatty acid ester enter isobutanol mutually in, enter aqueous phase such as the sucrose impurity of complete reaction not; Carry out extract and separate, isobutanol is reclaimed in distillation, obtains purified sucrose fatty acid ester.
Embodiment 2: glipizide 5 grams, and mannitol 30.64 grams, microcrystalline Cellulose PH101 15 grams, polyvinylpolypyrrolidone 9 grams, aspartame 0.06 gram, magnesium stearate 0.3 gram, 2% 30 POVIDONE K 30 BP/USP, 30 pure liquid 0.9 grams are made 1000.Technology: take by weighing glipizide, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame respectively by recipe quantity and adopt the equivalent method of progressively increasing to add in the mixing channel, abundant mix homogeneously, alcoholic solution (alcoholic solution with 60% prepares povidone solution) system soft material with 2% polyvidone, 40 mesh sieves are granulated, 50-60 ℃ of forced air drying with 40 mesh sieve granulate, adds the magnesium stearate mix homogeneously, with φ 6mm stamping, packing promptly after the assay was approved.
Embodiment 3: a kind of Glipizide orally disintegrating tablet, wherein: each constituent weight proportion is: by glipizide 5 grams, mannitol 30.64 grams, microcrystalline Cellulose 15 grams, polyvinylpolypyrrolidone 9 grams, aspartame 0.06 gram, magnesium stearate 0.3 gram, concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, sucrose fatty acid ester 30 grams, erythritol 3 grams.All the other are with embodiment 1.
Embodiment 4: a kind of Glipizide orally disintegrating tablet, wherein: each constituent weight proportion is: by glipizide 5 grams, mannitol 30.64 grams, microcrystalline Cellulose 15 grams, polyvinylpolypyrrolidone 9 grams, aspartame 0.06 gram, magnesium stearate 0.3 gram, concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, sucrose fatty acid ester 14 grams, erythritol 1 gram.All the other are with embodiment 1.
Embodiment 5: a kind of Glipizide orally disintegrating tablet, wherein: each constituent weight proportion is: by glipizide 5 grams, mannitol 30.64 grams, microcrystalline Cellulose 15 grams, polyvinylpolypyrrolidone 9 grams, aspartame 0.06 gram, magnesium stearate 0.3 gram, concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, sucrose fatty acid ester 2 grams, erythritol 1 gram.All the other are with embodiment 1.
The test data contrast is as follows:
Table 6
| Embodiment 2 | Embodiment 5 | Embodiment 4 | Embodiment 3 | Embodiment 1 | |
| Disintegration time | 40 seconds | 36 seconds | 10 seconds | 20 seconds | 12 seconds |
| Disintegrate hardness | 2.0kg/cm 2 | 1.2kg/cm 2 | 0.8kg/cm 2 | 1.6kg/cm 2 | 2.5kg/cm 2 |
| The disintegrate friability | 0.6％ | 1.5％ | 1.4％ | 0.9％ | 0.4％ |
The result shows: embodiment 1 adding sucrose fatty acid ester, erythritol, cooperation direct compression are having comprehensive lifting aspect disintegration time, disintegrate hardness, the disintegrate friability three.Embodiment 3,4,5 can't improve comprehensively.
Claims (2)
1. Glipizide orally disintegrating tablet, it is characterized in that: each constituent weight proportion is: glipizide 5 grams, mannitol 30.64 grams, microcrystalline Cellulose 15 grams, polyvinylpolypyrrolidone 9 grams, aspartame 0.06 gram, magnesium stearate 0.3 gram, concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, sucrose fatty acid ester 8.5 grams, erythritol 3 grams; Being prepared as follows of sucrose fatty acid ester: in first reactor, add 1200 gram stearic acid, 46.2 gram sulphuric acid, 2200 gram ethanol stir 70-80 ℃ on the limit, normal pressure reacted 6-8 hour down, excess ethanol is reclaimed in distillation then, washes product earlier with water till the pH=7, obtains the intermediate product ethyl stearte of the first step; Get intermediate product ethyl stearte 48 grams of the above-mentioned first step, sucrose 50 grams, propylene glycol 158 grams, potassium carbonate 6.3 grams join in second reactor successively, stir on the limit, reaction adds 1.2 gram citric acids after 10 hours under 80 ℃ the condition, propylene glycol is reclaimed in distilling under reduced pressure again; With product in second reactor and concentration is that 12% sodium chloride solution mixes, and stirs with the intact sucrose of flush away unreacted; Standing demix also separates sub-cloud liquid; The upper strata product promptly gets the sucrose fatty acid ester crude product after drying;
Hybrid extraction liquid by weight 1: 1 proportional arrangement isobutyl alcohol and water is stand-by, 1: 3 ratio of example is put into the sucrose fatty acid ester crude product hybrid extraction liquid of isobutyl alcohol and water by weight, sucrose fatty acid ester enter isobutanol mutually in, the sucrose impurity of complete reaction does not enter aqueous phase; Carry out extract and separate, isobutanol is reclaimed in distillation, obtains purified sucrose fatty acid ester.
2. the preparation technology of a Glipizide orally disintegrating tablet as claimed in claim 1 is characterized in that: it is stand-by to take by weighing glipizide, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, sucrose fatty acid ester, erythritol respectively by formula ratio; Earlier with glipizide and sucrose fatty acid ester, the first mix homogeneously of erythritol, again to wherein adding mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, abundant mix homogeneously, the reuse concentration expressed in percentage by weight is 2% 30 POVIDONE K 30 BP/USP 30 ethanol liquid 0.9 gram, add water 15 again and restrain soft material, 40 mesh sieves are granulated, and 50-60 ℃ of forced air drying is with 40 mesh sieve granulate, add the magnesium stearate mix homogeneously, with the mould stamping of φ 6mm, make 1000 after the assay was approved, packing is promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101863799A CN101695482B (en) | 2009-10-29 | 2009-10-29 | Glipizide orally disintegrating tablet and preparation process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101863799A CN101695482B (en) | 2009-10-29 | 2009-10-29 | Glipizide orally disintegrating tablet and preparation process thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101695482A CN101695482A (en) | 2010-04-21 |
| CN101695482B true CN101695482B (en) | 2011-08-10 |
Family
ID=42140635
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101863799A Expired - Fee Related CN101695482B (en) | 2009-10-29 | 2009-10-29 | Glipizide orally disintegrating tablet and preparation process thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101695482B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102232953B (en) * | 2010-04-28 | 2013-06-05 | 成都康弘药业集团股份有限公司 | Medicinal composition containing Esopiclone and preparation method thereof |
| CN104997747B (en) * | 2015-08-11 | 2019-10-25 | 瑞阳制药有限公司 | Glipizide tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1726916A (en) * | 2004-07-27 | 2006-02-01 | 江西省药物研究所 | Oral disintegration tablet for dropping blood sugar and preparation method |
| CN101134021A (en) * | 2006-08-31 | 2008-03-05 | 海南海灵制药厂有限公司 | Glipizide oral cavity disintegrating lyophilized tablets and method for preparing the same |
-
2009
- 2009-10-29 CN CN2009101863799A patent/CN101695482B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1726916A (en) * | 2004-07-27 | 2006-02-01 | 江西省药物研究所 | Oral disintegration tablet for dropping blood sugar and preparation method |
| CN101134021A (en) * | 2006-08-31 | 2008-03-05 | 海南海灵制药厂有限公司 | Glipizide oral cavity disintegrating lyophilized tablets and method for preparing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101695482A (en) | 2010-04-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI314866B (en) | Guaifenesin sustained release formulation and tablets | |
| Puttewar et al. | Formulation and evaluation of orodispersible tablet of taste masked doxylamine succinate using ion exchange resin | |
| RU2492853C2 (en) | Tablets of ulipristal acetate | |
| CN105147662A (en) | Pharmaceutical composition comprising glucopyranosyl diphenylmethane derivatives, pharmaceutical dosage form thereof, process for their preparation and uses thereof for improved glycemic control in a patient | |
| WO2018071678A1 (en) | Tablets comprising 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde | |
| CN103751193A (en) | Pharmaceutical composition comprising linagliptin and optional SGLT2 inhibitor and uses thereof | |
| CN101234105A (en) | Pharmaceutical composition containing diabetosan and vildagliptin and preparation thereof | |
| CN101904824A (en) | Olanzapine orally-disintegrating tablet preparation and preparation method thereof | |
| US20060240101A1 (en) | Orally disintegrating pharmaceutical tablet formulations of olanzapine | |
| CN105943554A (en) | Capsule and powder formulations containing lanthanum compounds | |
| CN102805736A (en) | Albendazol dispersible tablets and preparation method thereof | |
| CN105233300B (en) | A kind of stable vildagliptin composition and preparation method thereof | |
| CN101695482B (en) | Glipizide orally disintegrating tablet and preparation process thereof | |
| CN101822646B (en) | Fexofenadine hydrochloride orally disintegrating tablet and preparation method thereof | |
| CN101461811A (en) | Loratadine orally disintegrating tablet and technique for preparing the same | |
| CN101011362A (en) | Dispersible tablet of pidotimod and its preparing process and use | |
| CN102614140B (en) | Iloperidone oral cavity disintegration tablet and preparation method thereof | |
| WO2013177833A1 (en) | Dysmenorrhea-treating medicament and preparation method therefor | |
| CN102631332A (en) | Voglibose tablet and preparation method thereof | |
| CN111728946A (en) | Acarbose tablet composition and preparation method thereof | |
| CN102000040A (en) | Febuxostat capsule drug combination and preparation method thereof | |
| CN102335153B (en) | Piperazine ferulate sustained-release tablet and its preparation method | |
| CN106551927A (en) | Pharmaceutical composition comprising vildagliptin and metformin hydrochloride and preparation method thereof | |
| CN106176761B (en) | Application of composition containing isosorbide mononitrate and ivabradine | |
| CN104523653B (en) | Acarbose capsules agent pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110810 Termination date: 20211029 |