CN102038661B - Oleanolic acid osmotic pump tablet and preparation method thereof - Google Patents
Oleanolic acid osmotic pump tablet and preparation method thereof Download PDFInfo
- Publication number
- CN102038661B CN102038661B CN201010596043A CN201010596043A CN102038661B CN 102038661 B CN102038661 B CN 102038661B CN 201010596043 A CN201010596043 A CN 201010596043A CN 201010596043 A CN201010596043 A CN 201010596043A CN 102038661 B CN102038661 B CN 102038661B
- Authority
- CN
- China
- Prior art keywords
- sheet
- oleanolic acid
- tablet
- mix homogeneously
- medicine
- 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
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of medicinal preparation and discloses an oleanolic acid osmotic pump tablet and a preparation method thereof. The oleanolic acid osmotic pump tablet comprises three parts, namely, a medicine-containing layer, a boosting layer and a coating layer, and is prepared by adopting a single punch tablet press and a two-time filling and two-time pressurizing method to press and prepare two-layer tablet core, and opening a medicine-releasing hole on the surface of one side of the medicine-containing layer. The medicine-containing layer comprises a main medicine, a suspending agent, a binding agent, a penetrating agent, an osmotic pressure active substance, a lubricating agent and the like. The boosting layer comprises a high-molecular swelling agent, the osmotic pressure active substance, the binding agent, the lubricating agent and the like. The coating layer mainly comprises a film-forming material, a plasticizer, a hole-forming agent and the like. In the invention, the preparation takes zero-order release dynamics as a characteristic, the medicine is released constantly, the concentrations of the blood and the medicine are stable, the effective time is long and the purpose of releasing the medicine in 24 hours, i.e. taking the medicine once everyday is achieved.
Description
Technical field
The invention belongs to controlled release preparation in the field of pharmaceutical preparations, relate to acute, the chronic hepatitis of a kind of treatment, the medicine of diseases such as liver cirrhosis is specifically related to oleanolic acid double-layer osmotic pump tablet and preparation method thereof.Said preparation can improve the release degree and the bioavailability of slightly solubility oleanolic acid, makes the release of medicine zero level speed, and control blood drug level level reduces toxic and side effects.
Background technology
(Oleanocid Acid is a kind of plant kingdom natural product composition OA) to oleanolic acid, extensively is present in food, the medical science herbaceous plant, belongs to oleanolic acid alkane type pentacyclic triterpenoid.Be white crystalline powder, nothing is smelt tasteless.Be insoluble in water, dissolve in ethanol, ether, chloroform, methanol, acetone and other organic solvent, unstable to soda acid.
Oleanolic acid has fat-soluble very by force, gets into liver organization easily, reaches higher drug level, can significantly reduce the activity of SAIT, lactic acid dehydrogenase and lipid peroxidation enzyme, plays good hepatoprotective effect.Also can make liver cell regeneration, suppress hair jelly fibril hypertrophy, suppress the generation of liver cirrhosis.Because of its toxic and side effects is little, be the active drug of treatment acute icterohepatitis and viral hepatitis again.
Clinical use oleanolic acid preparation is the tablet and the capsule of the oleanolic acid of treatment icterohepatitis, chronic animal migration hepatitis.Commercially available ordinary preparation is because it is extremely strong fat-soluble, absorbed in the body rapidly easily and reaches higher blood drug level, and the half-life is shorter; Eliminate rapid speed in the body; Add its strong-hydrophobicity, influenced it and discharged and absorb, make bioavailability generally lower at gastrointestinal.For keeping in the body long-term efficient blood drug level, needs of patients every day, repeatedly multiple dose was taken medicine, and increase trouble to the patient, and the blood concentration fluctuation amplitude was excessive, and drug effect and toxicity all are difficult to control.Therefore, how to improve curative effect of medication, keep blood drug level, reduce toxic and side effects, reduce patient's medication number of times, improve preparation stability, become the free-revving engine of current oleanolic acid preparation research.
Summary of the invention
The object of the invention is to overcome the deficiency of oleanolic acid ordinary preparation, and oleanolic acid double-layer osmotic pump tablet and preparation method thereof is provided.It is a characteristic with the zero level release dynamics, continues to discharge a certain amount of medicine with constant rate of speed, can effectively control blood drug level; Effectively longer duration can also be regulated rate of releasing drug through changing factors such as semipermeable membrane character, pore size, has nothing to do with extraneous factor, pharmaceutical properties; Do not receive the influence of variable factors such as gastrointestinal tract; The inside and outside dependency is good, improves drug bioavailability greatly, plays good controlled-release effect.Can eliminate the excessive untoward reaction that causes of blood concentration fluctuation, reduce toxic and side effects.Only need take medicine once every day, and sustainable 24 hours of drug effect reduces patient's medicining times, has improved safety, effectiveness and the compliance of Drug therapy greatly.
Oleanolic acid osmotic pump tablet provided by the invention utilizes the release principle of osmotic pressure, and moisture gets into label through semipermeable membrane, makes dissolving of push layer polymer substance and swelling, produces hyperosmosis.Coating membrane is the relative stiffness structure, gets into moisture, in label, produces higher hydrostatic pressing, forces drug solution from small delivery aperture, to continue to discharge with constant rate of speed.
Oleanolic acid osmotic pump preparation provided by the invention is made up of medicated layer, boosting layer, coatings three parts, and at medicine layer one side perforating of tablet and get.The principal agent oleanolic acid and the suspending agent of 1-1500 part, the low molecule infiltration of 1-500 part that comprise 1-1000 part in the said medicated layer are pressed active substance, the penetrating agent of 1-1500 part, the binding agent of 0.1-100 part, the lubricant of 0.1-50 part, the adjuvants such as fluidizer of 0.1-30 part; The low molecule infiltration that contains 1-500 part in the said boosting layer is pressed active substance, the macromolecule sweller of 1-1000 part, the binding agent of 0.1-100 part, the lubricant of 0.1-50 part and the coloring agent of 0.1-50 part etc.The coating solution of coatings contains the semipermeable polymer material of 1-100 part, the plasticizer of 0.1-40 part, the porogen of 0.1-40 part, Osmolyte regulator and 1000 parts of solvents of 0.1-40 part.
Principal agent is an oleanolic acid in the osmotic pump tablet medicated layer of the present invention.
Suspending agent can be selected polyoxyethylene, hypromellose, low-substituted hydroxypropyl cellulose, arabic gum etc. in the preparation medicated layer of the present invention.Oleanolic acid is embarrassed soluble substance, and the adding of suspending agent can make insoluble drug form suspension, improves bioavailability.The inventor selected several kinds of suspending agents to screen, and investigated their influence to drug release rate, as follows:
| The suspending agent kind | Consumption (mg/ sheet) | Accumulative total degree of release 24h (%) |
| |
60 | 99.8 |
| Low-substituted |
60 | 99.5 |
| |
60 | 95.2 |
| Hypromellose | 60 | 96.7 |
The result shows; Suspending agent in the oleanolic acid osmotic pump tablet medicated layer of the present invention is preferably polyoxyethylene or low-substituted hydroxypropyl cellulose, and polyoxyethylene and low-substituted hydroxypropyl cellulose influence there was no significant difference (P＜0.02) to oleanolic acid osmotic pump tablet accumulative total degree of release.
The penetrating agent that provides in the medicated layer of the present invention is carboxymethyl starch sodium or carboxymethylcellulose calcium.
Macromolecule sweller in the preparation boosting layer of the present invention can be selected the mixture of hypromellose, polyoxyethylene, arabic gum, Polyethylene Glycol, carboxymethyl cellulose, hydroxyethyl-cellulose, polyvinylpyrrolidone homopolymer or several kinds of materials; Preferred hypromellose, carboxymethyl cellulose, polyoxyethylene, more preferably polyoxyethylene.Macromolecule sweller volume after suction constantly increases, and the drug suspension that promotes the both sides medicated layer is through the empty release of release, to keep zero order release rate.The inventor screens several kinds of macromolecule swellers, examines and has wiped its influence to drug release rate.Different macromolecule swellers are seen accompanying drawing 1 to the release rate of drugs curve.
Osmotic pressure active substance in the preparation of the present invention in medicated layer and the boosting layer can selective chlorination sodium, potassium sulfate, magnesium sulfate, magnesium chloride, potassium chloride, tartaric acid, sorbitol, sucrose, mannitol one or more.Low molecule infiltration is pressed the adding of active substance, can produce enough osmotic pressuries and keep the constant relatively rate of release of medicine.The inventor therefrom chooses one or more low molecule infiltrations and presses active substance, adds to measure 24h accumulative total degree of release in the medicated layer after the compacting in flakes, investigates its influence to oleanolic acid osmotic pump tablet release degree in medicated layer, as follows:
| The osmotic pressure active substance | Consumption (mg/ sheet) | Accumulative total degree of release 24h (%) |
| |
20 | 99.4 |
| |
20 | 98.2 |
| |
20 | 98.6 |
| Mannitol | 20 | 96.7 |
The result shows that the low molecule infiltration in the oleanolic acid osmotic pump tablet presses active substance to be preferably sodium chloride.On other component basis of invariable, investigated of the influence of sodium chloride consumption, shown in accompanying drawing 2 to oleanolic acid osmotic pump tablet rate of releasing drug; Increase along with the sodium chloride consumption; The rate of releasing drug of oleanolic acid osmotic pump tablet is accelerated, and burst size increases, and especially early stage, rate of releasing drug was accelerated more obvious.This is because after the increase of osmotic pressure active substance consumption, osmotic pressure obviously increases, and impels drug release obviously to accelerate.
Semipermeable membrane property macromolecular material in the preparation coatings of the present invention can be chosen as ethyl cellulose, cellulose acetate, cellulose diacetate, preferred cellulose acetate.
The solvent of preparation coatings of the present invention is one or more in different proportion acetone, isopropyl alcohol, dichloromethane, the second alcohol and water.
Plasticizer in the preparation coatings of the present invention is the mixture of diethyl phthalate, Polyethylene Glycol or two kinds of materials, preferably the two mixture.The inventor has investigated the influence of the content ratio of each composition in Polyethylene Glycol and the diethyl phthalate mixture to oleanolic acid osmotic pump tablet rate of release; Find fixedly diethyl phthalate content; Increase the Polyethylene Glycol consumption; The method for releasing speed of oleanolic acid osmotic pump tablet increases progressively gradually, like Fig. 3; And fixing polyethyleneglycol content increases the consumption of Methyl Benzene-o-dicarboxylate, and the rate of release of oleanolic acid osmotic pump tablet descends gradually, like Fig. 4.
Porogen in the coatings of the present invention such as Macrogol 200,400,1500,4000, but when selecting PEG200 for use, coating membrane breaks easily, and select PEG1500 and for use at 4000 o'clock, the easy moisture absorption of coating membrane.Therefore, the preferred PEG 400 of the present invention.
Can also contain in the preparation of the present invention:
Osmolyte regulator such as Polyethylene Glycol, hydroxypropyl emthylcellulose, triacetyl glycerine.
Lubricant such as magnesium stearate, Pulvis Talci, sodium benzoate.
Coloring agent such as ferrum oxide.
The ethanol of binding agent such as starch, polyvinylpyrrolidone, different proportion.
Filler such as lactose, starch, microcrystalline Cellulose.
The present invention also provides the method for preparing of oleanolic acid double-layer osmotic pump tablet, and this method technological process is simple, is convenient to produce, and product is easy to preserve.Above-mentioned oleanolic acid osmotic pump tablet method for preparing comprises the steps:
1, oleanolic acid and each adjuvant grind the processing of sieving respectively.
2, the preparation medicated layer takes by weighing oleanolic acid and mix homogeneously such as suspending agent, osmotic pressure active substance after the pulverizing, adds the binding agent system soft material of 0.1-100 part, cross the 10-30 mesh sieve and granulate, under 40-80 ℃ dry 5-20 as a child, 10-30 order granulate.The lubricant that adds 0.1-50 part, mix homogeneously, subsequent use.
3, preparation boosting layer with mix homogeneously such as macromolecule sweller, osmotic pressure active substance, coloring agent, is crossed the 40-80 mesh sieve; Mix homogeneously; The binding agent system soft material that adds 0.1-100 part is crossed the 10-30 mesh sieve and is granulated, and dry 5-20 as a child crossed 10-30 order granulate under 40-80 ℃.Add the lubricant of 0.1-50 part, mix homogeneously is subsequent use.
4, with the mixing granulation compression moulding of step 2 kind, the mixing granulation that adds again in the step 3 is pressed into double-layer tablet.
5, in the lamella outsourcing with the semipermeable membrane coating material, preferred 40-80 ℃ dry 5-20 hour down.
6, simultaneously use machinery or laser boring closing on medicated layer, the release aperture is preferably 0.4-1.2mm.
In the said step 1, oleanolic acid is ground, cross 100 mesh sieves.
In the said step 2, after polyoxyethylene, sodium chloride, starch, HPC ground respectively, cross 100 mesh sieves, with the oleanolic acid mix homogeneously.Make soft material after adding 80% ethanol in the supplementary material, cross 24 mesh sieves and granulate.Drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate.Add 0.05% magnesium stearate, mix homogeneously.
In the said step 3, polyoxyethylene, sodium chloride, ferrum oxide etc. are pulverized respectively, crossed 100 mesh sieves, back mix homogeneously.Make soft material behind the ethanol of adding 80%, cross 24 mesh sieves and granulate.Drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate.Add 0.05% magnesium stearate, mix homogeneously.
In the said step 4, adopt single punch tablet machine, twice pressurization of twice filler to suppress double-deck label.
In the said step 5, cellulose acetate, PEG400 are dissolved in the mixed solution of acetone or alcohol and water, mix homogeneously gets coating solution.Label is put in the coating pan, till label outer coatings film increases to the heavy 5-20% of sheet, dry 12h under 40 ℃.Coating membrane thickness produces comparatively remarkable influence to oleanolic acid osmotic pump tablet rate of release.Coating membrane thickness is embodied by the label gain in weight, and with the increase of label weight, the rate of release of oleanolic acid osmotic pump tablet descends gradually.Weightening finish is an optimum selection 11%, and too thin meeting produces the too fast or coating membrane fracture phenomena of rate of release, and the blocked up rate of release that can make again is slow, does not have good controlled-release effect, like Fig. 5.
Said step 6 kind breaks into the aperture of 0.8mm with the machine drilling method on tablet medicated layer surface, promptly get.
The beneficial effect that oleanolic acid double-layer osmotic pump tablet of the present invention is compared with commercially available conventional tablet is: 1, discharge medicine with zero level speed, the valid density time keeps for a long time, reduces a day innerlich anwenden number of times.2, rate of releasing drug and extraneous factor are irrelevant, do not receive factor affecting such as gastrointestinal tract.3, make the basic held stationary of blood drug level, reduced Wave crest and wave trough and changed the side effect that produces.
Description of drawings:
Fig. 1 be in the push layer different macromolecule swellers to the influence curve of oleanolic acid osmotic pump tablet rate of release.
Fig. 2 is that low molecule infiltration is pressed the influence curve of active substance amount of sodium chloride to oleanolic acid osmotic pump tablet rate of release.
Fig. 3 be in the coating solution Polyethylene Glycol consumption to the influence curve of oleanolic acid osmotic pump tablet rate of release.
Fig. 4 be in the coating solution diethyl phthalate consumption to the influence curve of oleanolic acid osmotic pump tablet rate of release.
Fig. 5 is instance 1, instance 2, instance 3 oleanolic acid osmotic pump tablet drug accumulation release profiles.
Fig. 6 is instance 1 and commercially available conventional tablet drug accumulation release profiles.
The specific embodiment:
Below specifically describe the prescription of oleanolic acid double-layer osmotic pump tablet, it may be noted that these instances provide as the purpose of illustration, do not cause restriction to the scope of the invention through instance.
Embodiment one:
Medicated layer is formed:
| Component | Content (mg/ sheet) |
| |
30 |
| Polyoxyethylene | 77.5 |
| Sodium chloride | 18 |
| |
20 |
| Magnesium stearate | 1.5 |
The boosting layer is formed:
| Component | Content (mg/ sheet) |
| Polyoxyethylene Coagulant | 50.5 |
| Hypromellose | 44 |
| Sodium chloride | 5 |
| |
1 |
| |
1 |
Coatings is formed: (200ml coating solution)
| Component | Content |
| Cellulose acetate | 6g |
| PEG400 | 0.6ml |
| Diethyl phthalate | 0.8ml |
| Acetone | 200ml |
The method for preparing of above-mentioned oleanolic acid double-layer osmotic pump tablet is following:
The preparation medicated layer was ground 100 mesh sieves by recipe quantity respectively with oleanolic acid, polyoxyethylene 400, sodium chloride, carboxymethyl starch sodium, made soft material after adding 80% ethanol behind the mix homogeneously, crossed 24 mesh sieves and granulated.Drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate.Add the 1.5mg magnesium stearate, mix homogeneously is subsequent use.
After preparation boosting layer grinds recipe quantity polyoxyethylene, hypromellose, sodium chloride, ferrum oxide respectively, cross 100 mesh sieves, mix homogeneously is made soft material after adding 80% ethanol, crosses 24 mesh sieves and granulates.Drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate.Add 0.05% magnesium stearate, mix homogeneously is subsequent use.
Adopt single punch tablet machine, twice pressurization of twice filler to suppress double-deck label.
The preparation coatings is dissolved in recipe quantity cellulose acetate, PEG400, diethyl phthalate in the acetone soln, and mix homogeneously gets coating solution.Label is put in the coating pan, increased to until label outer coatings film and be 11% of tablet quality,, break into the aperture of 0.8mm then on tablet medicated layer surface with the machine drilling method, promptly get at 40 ℃ of dry 12h down.
Drug release determination:
Obtaining the oleanolic acid double-layer osmotic pump tablet sample of above-mentioned preparation, carry out drug release determination according to Pharmacopoeia of the People's Republic of China version second method in 2005, is release medium with 0.05% sodium lauryl sulphate 900ml, and the adjustment rotating speed is 100r/min; Temperature is (37 ± 0.5) ℃, respectively at 4,8; 12,16,20; The 24h 5ml that takes a sample in time replenishes with the volume blank medium, through 0.45 μ m membrane filtration; Precision is measured subsequent filtrate 20 μ L under the 210nm wavelength, measures the absworption peak area according to the HPLC method, and filler is an octadecylsilane chemically bonded silica, and mobile phase is methanol-water (95: 5), flow velocity 1ml/min, and 25 ℃ of column temperatures write down chromatogram respectively.By the bent medication amount of calculating of mark, draw the accumulative total release profiles and see accompanying drawing 5.Get linear equation y=22.68x-17.35, r through match
2=0.9896, meet zero level and discharge.
Embodiment two:
Medicated layer is formed:
| Component | Content (mg/ sheet) |
| |
30 |
| Polyoxyethylene | 58.5 |
| Lactose | 25 |
| Carboxymethyl starch sodium | 35 |
| Magnesium stearate | 1.5 |
The boosting layer is formed:
| Component | Content (mg/ sheet) |
| Polyoxyethylene | 42 |
| Hypromellose | 56 |
| Magnesium stearate | 1.5 |
| Ferrum oxide (pigment) | 1 |
Coatings is formed: (200ml coating solution)
| Component | Content |
| Cellulose acetate | 6g |
| PEG400 | 0.6ml |
| Diethyl phthalate | 0.8ml |
| Acetone | 200ml |
The method for preparing of above-mentioned oleanolic acid double-layer osmotic pump tablet is following:
The preparation medicated layer was ground 100 mesh sieves respectively with recipe quantity oleanolic acid, polyoxyethylene, lactose, carboxymethyl starch sodium, made soft material after adding 80% ethanol behind the mix homogeneously, crossed 24 mesh sieves and granulated.Drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate.Add magnesium stearate, mix homogeneously is subsequent use.
After preparation boosting layer grinds recipe quantity polyoxyethylene, hypromellose, ferrum oxide respectively, cross 100 mesh sieves, mix homogeneously is made soft material after adding 80% ethanol, crosses 24 mesh sieves and granulates.Drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate.Add magnesium stearate, mix homogeneously is subsequent use.Adopt single punch tablet machine, twice pressurization of twice filler to suppress double-deck label.
The preparation coatings is dissolved in recipe quantity cellulose acetate, PEG400, diethyl phthalate in the acetone soln, and mix homogeneously gets coating solution.Label is put in the coating pan, increased to until label outer coatings film and be 11% of tablet quality,, break into the aperture of 0.8mm then on tablet medicated layer surface with the machine drilling method, promptly get at 40 ℃ of dry 12h down.
Drug release determination:
Obtaining the oleanolic acid double-layer osmotic pump tablet sample of above-mentioned preparation, carry out drug release determination according to Pharmacopoeia of the People's Republic of China version second method in 2005, is release medium with 0.05% sodium lauryl sulphate 900ml, and the adjustment rotating speed is 100r/min; Temperature is (37 ± 0.5) ℃, respectively at 4,8; 12,16,20; The 24h 5ml that takes a sample in time replenishes with the volume blank medium, through 0.45 μ m membrane filtration; Precision is measured subsequent filtrate 20 μ L under the 210nm wavelength, measures the absworption peak area according to the HPLC method, and filler is an octadecylsilane chemically bonded silica, and mobile phase is methanol-water (95: 5), flow velocity 1ml/min, and 25 ℃ of column temperatures write down chromatogram respectively.By the bent medication amount of calculating of mark, draw the accumulative total release profiles and see accompanying drawing 5.Get linear equation y=18.35x-8.29, r through match
2=0.9881, meet zero level and discharge.
Instance three:
Medicated layer is formed:
| Component | Content (mg/ sheet) |
| |
30 |
| Low-substituted hydroxypropyl cellulose | 80.5 |
| Sodium chloride | 18 |
| |
20 |
| Pulvis Talci | 1.5 |
The boosting layer is formed:
| Component | Content (mg/ sheet) |
| Polyoxyethylene | 50.5 |
| Hypromellose | 44 |
| Sodium chloride | 5 |
| |
1 |
| |
1 |
Coatings is formed: (200ml coating solution)
| Component | Content |
| Cellulose acetate | 6g |
| PEG400 | 0.6ml |
| Diethyl phthalate | 0.8ml |
| 95% ethanol | 200ml |
The method for preparing of above-mentioned oleanolic acid double-layer osmotic pump tablet is following:
The preparation medicated layer was ground 100 mesh sieves by recipe quantity respectively with oleanolic acid, low-substituted hydroxypropyl cellulose, sodium chloride, carboxymethylcellulose calcium, made soft material after adding 80% ethanol behind the mix homogeneously, crossed 24 mesh sieves and granulated.Drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate.Add Pulvis Talci, mix homogeneously is subsequent use.
After preparation boosting layer grinds recipe quantity polyoxyethylene, hypromellose, sodium chloride, ferrum oxide respectively, cross 100 mesh sieves, mix homogeneously is made soft material after adding 80% ethanol, crosses 24 mesh sieves and granulates.Drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate.Add Pulvis Talci, mix homogeneously is subsequent use.
Adopt single punch tablet machine, twice pressurization of twice filler to suppress double-deck label.
The preparation coatings is dissolved in recipe quantity cellulose acetate, PEG400, diethyl phthalate in 95% alcoholic solution, and mix homogeneously gets coating solution.Label is put in the coating pan, increased to until label outer coatings film and be 11% of tablet quality,, break into the aperture of 0.8mm then on tablet medicated layer surface with the machine drilling method, promptly get at 40 ℃ of dry 12h down.
Drug release determination:
Obtaining the oleanolic acid double-layer osmotic pump tablet sample of above-mentioned preparation, carry out drug release determination according to Pharmacopoeia of the People's Republic of China version second method in 2005, is release medium with 0.05% sodium lauryl sulphate 900ml, and the adjustment rotating speed is 100r/min; Temperature is (37 ± 0.5) ℃, respectively at 4,8; 12,16,18; The 24h 5ml that takes a sample in time replenishes with the volume blank medium, through 0.45 μ m membrane filtration; Precision is measured subsequent filtrate 20 μ L under the 210nm wavelength, measures the absworption peak area according to the HPLC method, and filler is an octadecylsilane chemically bonded silica, and mobile phase is methanol-water (95: 5), flow velocity 1ml/min, and 25 ℃ of column temperatures write down chromatogram respectively.By the bent medication amount of calculating of mark, draw the accumulative total release profiles and see accompanying drawing 5.Get linear equation y=12.8x+26.68, r through match
2=0.9858, meet zero level and discharge.
" part " number average of principal agent described in the present specification and each adjuvant refers to weight portion.
Claims (2)
1. an oleanolic acid osmotic pump tablet comprises medicated layer, boosting layer, coatings three parts, it is characterized in that:
Described medicated layer consists of oleanolic acid 30mg/ sheet, polyoxyethylene 58.5mg/ sheet, lactose 25mg/ sheet, carboxymethyl starch sodium 35mg/ sheet, magnesium stearate 1.5mg/ sheet; Described boosting layer consists of polyoxyethylene 42mg/ sheet, hypromellose 56mg/ sheet, magnesium stearate 1.5mg/ sheet; Ferrum oxide 1mg/ sheet, described coatings consists of cellulose acetate 6g, PEG4000.6ml; Diethyl phthalate 0.8ml, acetone 200ml;
The method for preparing of described oleanolic acid osmotic pump tablet is following:
(1) preparation medicated layer: recipe quantity oleanolic acid, polyoxyethylene, lactose, carboxymethyl starch sodium were ground 100 mesh sieves respectively; Make soft material after adding 80% ethanol behind the mix homogeneously; Cross 24 mesh sieves and granulate, drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate; Add magnesium stearate, mix homogeneously is subsequent use;
(2) prepare the boosting layer: after recipe quantity polyoxyethylene, hypromellose, ferrum oxide are ground respectively, cross 100 mesh sieves, mix homogeneously; Make soft material after adding 80% ethanol, cross 24 mesh sieves and granulate, 50 ℃ dry 16 hours down; Cross 20 mesh sieve granulate, add magnesium stearate, mix homogeneously is subsequent use;
(3) adopt single punch tablet machine, twice pressurization of twice filler to suppress double-deck label;
(4) preparation coatings: recipe quantity cellulose acetate, PEG400, diethyl phthalate are dissolved in the acetone soln; Mix homogeneously gets coating solution; Label is put in the coating pan, increased to until label outer coatings film and be 11% of tablet quality, at 40 ℃ of dry 12h down; Break into the aperture of 0.8mm then with the machine drilling method on tablet medicated layer surface, promptly get.
2. an oleanolic acid osmotic pump tablet comprises medicated layer, boosting layer, coatings three parts, it is characterized in that:
Described medicated layer consists of oleanolic acid 30mg/ sheet, low-substituted hydroxypropyl cellulose 80.5mg/ sheet, sodium chloride 18mg/ sheet, carboxymethylcellulose calcium 20mg/ sheet, Pulvis Talci 1.5mg/ sheet; Described boosting layer consists of polyoxyethylene 50.5mg/ sheet, hypromellose 44mg/ sheet, sodium chloride 5mg/ sheet, ferrum oxide 1mg/ sheet, Pulvis Talci 1mg/ sheet; Described coatings consists of cellulose acetate 6g, PEG4000.6ml, diethyl phthalate 0.8ml, 95% ethanol 200ml;
The method for preparing of described oleanolic acid osmotic pump tablet is following:
(1) preparation medicated layer: oleanolic acid, low-substituted hydroxypropyl cellulose, sodium chloride, carboxymethylcellulose calcium were ground 100 mesh sieves respectively by recipe quantity; Make soft material after adding 80% ethanol behind the mix homogeneously; Cross 24 mesh sieves and granulate, drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate; Add Pulvis Talci, mix homogeneously is subsequent use;
(2) prepare the boosting layer: after recipe quantity polyoxyethylene, hypromellose, sodium chloride, ferrum oxide are ground respectively, cross 100 mesh sieves, mix homogeneously; Make soft material after adding 80% ethanol; Cross 24 mesh sieves and granulate, drying is 16 hours under 50 ℃, crosses 20 mesh sieve granulate; Add Pulvis Talci, mix homogeneously is subsequent use;
(3) adopt single punch tablet machine, twice pressurization of twice filler to suppress double-deck label;
(4) preparation coatings: recipe quantity cellulose acetate, PEG400, diethyl phthalate are dissolved in 95% alcoholic solution; Mix homogeneously gets coating solution; Label is put in the coating pan, increased to until label outer coatings film and be 11% of tablet quality, at 40 ℃ of dry 12h down; Break into the aperture of 0.8mm then with the machine drilling method on tablet medicated layer surface, promptly get.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010596043A CN102038661B (en) | 2010-12-20 | 2010-12-20 | Oleanolic acid osmotic pump tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010596043A CN102038661B (en) | 2010-12-20 | 2010-12-20 | Oleanolic acid osmotic pump tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102038661A CN102038661A (en) | 2011-05-04 |
| CN102038661B true CN102038661B (en) | 2012-10-10 |
Family
ID=43905430
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010596043A Expired - Fee Related CN102038661B (en) | 2010-12-20 | 2010-12-20 | Oleanolic acid osmotic pump tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102038661B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103599099B (en) * | 2013-11-18 | 2015-12-30 | 沈阳药科大学 | Bilobalide bi-layer osmotic pump control tablet and preparation method |
| CN114767872B (en) * | 2022-03-21 | 2023-08-22 | 则正(上海)生物科技有限公司 | Application of polacrilin potassium in preparation of osmotic pump boosting layer, nifedipine osmotic pump tablet and preparation method |
-
2010
- 2010-12-20 CN CN201010596043A patent/CN102038661B/en not_active Expired - Fee Related
Non-Patent Citations (3)
| Title |
|---|
| 张兰等."格列吡嗪双层渗透泵片的制备".《中国药剂学杂志》.2009,第7卷(第6期),20091130. |
| 王金超."盐酸哌唑嗪和齐墩果酸单层芯渗透泵片的研究".《中国优秀硕士论文电子期刊网》.2006,第28－34页. |
| 王金超."盐酸哌唑嗪和齐墩果酸单层芯渗透泵片的研究".《中国优秀硕士论文电子期刊网》.2006,第28-34页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102038661A (en) | 2011-05-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103655539B (en) | A kind of oral solid formulation of canagliflozin and preparation method thereof | |
| CN1946426B (en) | Sustained release formulation for oral administration of HMG-CoA reductase inhibitor and method for the preparation thereof | |
| US9283190B2 (en) | Highly efficient and long-acting slow-release formulation of poorly soluble drugs and preparation method thereof | |
| CN100393302C (en) | Controlled releasing penetrant pump prepn for insoluble medicine composition | |
| CN105326814A (en) | Topiramate sustained release preparation pharmaceutical composition | |
| CN104414992B (en) | Glipizide osmotic pump controlled release tablet and preparation method thereof | |
| US8962017B2 (en) | Formulation of silymarin with high efficacy and prolonged action and the preparation method thereof | |
| CN104586795B (en) | A kind of canagliflozin piece and preparation method thereof | |
| CN103191077B (en) | Gliclazide tablet and preparation method thereof | |
| US9023388B2 (en) | Formulation of silibinin with high efficacy and prolonged action and the preparation method thereof | |
| CN111450072A (en) | Ticagrelor controlled release tablet and preparation method thereof | |
| CN102038661B (en) | Oleanolic acid osmotic pump tablet and preparation method thereof | |
| CN103142532B (en) | Ginkgolide osmotic pump tablet and preparation method thereof | |
| CN104800184B (en) | The smooth sustained release agent pieces of butanedioic acid furan Luo Qu | |
| CN102247370B (en) | Compound repaglinide-metformin hydrochloride controlled release preparation | |
| CN100427084C (en) | Oral silybin sustained release agent and preparation thereof | |
| CN104706614B (en) | Tandospirone micropore permeation pump preparation | |
| CN100441201C (en) | Chinese medicine slow-release formulation containing asiatic pennywort herb water-soluble active ingredient, and its preparing method | |
| CN107050419A (en) | A kind of osmotic pump tablet of Perindopril and its salt and preparation method thereof | |
| CN109330995B (en) | Pellet coated with short-acting hypoglycemic agent and preparation method thereof | |
| CN103599086B (en) | Folium Ginkgo total flavones double-layer osmotic pump controlled-release tablet and preparation method | |
| CN104225608B (en) | Purposes of the natural dilatancy matrix in osmotic pump preparation from the sterculia seed | |
| CN102406620B (en) | Skeleton type lovastatin sustained-release micropill and preparation method thereof | |
| CN1332668C (en) | Cepharanthine slow releasing preparation | |
| CN110251475A (en) | A kind of 9-hydroxy-risperidone tablet and preparation method thereof |
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 | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121010 Termination date: 20121220 |
|
| DD01 | Delivery of document by public notice |
Addressee: Zhang Xiao Document name: Notification of Termination of Patent Right |