CN101181226A - System for slowing and controlling to release gas bag floationg - Google Patents
System for slowing and controlling to release gas bag floationg Download PDFInfo
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- CN101181226A CN101181226A CNA2007101583553A CN200710158355A CN101181226A CN 101181226 A CN101181226 A CN 101181226A CN A2007101583553 A CNA2007101583553 A CN A2007101583553A CN 200710158355 A CN200710158355 A CN 200710158355A CN 101181226 A CN101181226 A CN 101181226A
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Abstract
The invention discloses a sustained-release and controlled-release balloon floating system, which can ensure that the drug can float at the top layer of the stomach contents after entering body and can not enter into small intestine along with the evacuation of foods, so as to improve the drug efficacy. The invention includes a balloon which can provide buoyancy to allow the system to be floated at liquid surface and a sustained/controlled-release preparation containing pharmacological active substances. The system includes three parts: a balloon shell I, gas II and the sustained-release and controlled-release preparation III containing drugs, wherein the gas II occupies one end of the balloon shell I, and the other end is occupied by the sustained-release and controlled-release preparation III, and the two are or are not separated by a partition board/diaphragm IV. The floating preparation which is prepared by the method of the invention can respectively and independently regulate the controlled-release time and the floating time during the prescription and process designs, and when the characteristics of one part of the two parts change, the characteristics of the other part do not be affected, thus, the exploration processes of the prescription and process can be greatly simplified.
Description
Technical field
The present invention relates to technical field of medicine, relate in particular to a kind of slow, controlled release floating system of bladder-type.
Background technology
Slow, controlled release preparation is pressed drug release type branch, can be divided into three kinds: constant speed, location and delayed release.The constant speed release tech refers to that preparation discharges medicine in vivo with given pace, meets zero level release dynamics rule substantially.Constant speed discharges can reduce blood concentration fluctuation, increases the compliance of patient's medication.Slow, controlled release preparation belongs to the constant speed release type, and common technology has: film control and framework controlled release.Be convenient to realize that the technology of suitability for industrialized production has: multilamellar slow releasing tablet and coated slow release chip technology, extrude round as a ball pill making craft, the miscible expressing technique of medicine and macromolecule, insoluble polymeric solid dispersion technology etc.Also can control the release of medicine by means of the geometry that changes tablet, as laminated diffusion matrix tablet, double concave coated tablet with holes, ring skeleton sheet etc.The location discharges can be increased local therapeutic effects or increase the absorption of specific absorption position to medicine.As gastric retention system, stomach floating system, gastric expansion system, bio-adhesive system are arranged; Small intestinal navigation system (enteric coated preparation) and colon targeting preparation etc. can avoid medicine in gastric degraded or to the stimulation of stomach, improve the curative effect of some medicines.Regularly discharge the medicine that can discharge requirement, make medicine performance optimum curative effect according to biological temporal rhythm characteristics.Regularly release is called pulse release again, and easily in the characteristics of special time outbreak, research can discharge the preparation of medicine in the specific time after taking medicine at some disease.
The known constant speed preparation of people mainly contains skeleton sustained-release and controlled release preparation, film coating sustained-release and controlled release preparation and osmotic pump type sustained-release preparation at present.Skeleton sustained-release and controlled release preparation is one of more slow, controlled release preparation of present clinical practice, by its used framework material difference, can be divided into insoluble matrix sustained release tablet, waxiness matrix sustained release tablet, hydrophilic gel matrix sustained release tablet and composite material matrix sustained release tablet etc.Film coating sustained-release and controlled release preparation is to pack the suitable clothing layer of one deck on the surface of label and piller, it is dissolved under certain condition or is partly dissolved and discharges medicine, can reach the sustained-release and controlled release effect.Its principle belongs to diffusion and discharges, and the energy is based on the osmotic pressure of film intracavity, or the stripping dispersal behavior of drug molecule in polymer.The osmotic pump type sustained-release preparation is the oral formulations that utilizes the osmotic pressure principle to make.The Oros type sustained-release preparation of research and development has single chamber and multicell osmotic pump preparation at present.Its sheet type is identical with ordinary tablet with size, and medicine and adjuvant are pressed into label, and the semipermeable insoluble polymer film-coat of outsourcing one deck is made a call to a hole with laser or machinery on film, and in gastrointestinal tract, water can see through clothing film, dissolved substance.Osmotic pressure is higher than outside gastro-intestinal Fluid in the tablet, and water just constantly infiltrates the sheet heart, and big thereby sheet heart volume constantly becomes, drug solution or suspension constantly are released from aperture.
The known location of people delivery formulations mainly contains gastric retention system, small intestinal navigation system and colon targeting preparation etc. at present.Gastric retention system includes bio-adhesive system, obstructive type gastric retention system stomach function regulating floating system again.The special adhesion power that bioadhesion type gastric retention system produces biological mucosa by means of some macromolecular material and adhere to the mucous epithelium position, thus prolong drug promotes the absorption of medicine in the stop and the release time of keypoint part, improves bioavailability.The obstructive type gastric retention system mainly prolongs its holdup time at stomach by avoiding medicine to be discharged by the stomach pylorus.Avoid being mainly contained control volume size, preparation being carried out the shape modification and makes three kinds of intumescent gastric retention systems by the mode that the stomach pylorus is discharged.The float type gastric retention system mainly refers to according to the system fluid dynamic equilibrium principle design, can keep floating state in gastric juice.It is generally acknowledged that the bulk density of this system makes it keep floating state to reduce or to eliminate the gastric emptying influence at gastric less than gastric juice density, improves gastric transit time.Along with the appearance of effervescent system, the bulk density of preparation no longer is an essential condition less than gastric content density.Can be divided into non-effervescence type floating system and the floating gastric retention system of effervescence type again according to this system of buoyant mechanism.Non-effervescent float type gastric retention system utilizes autologous density to be floating state less than gastric content density in gastric juice.The material of forming this system mainly contain hydrophilic polymer (as hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl-cellulose (HEC), methylcellulose (MC)), the relative materials with smaller of density (aliphatic alcohols, esters, fatty acid or wax class) and regulate the material of drug release (accelerate drug release rate as lactose, mannitol; Slow down drug release rate as acrylic resin) etc.Effervescent float type gastric retention system mainly utilizes the effervescent composition to run into gastric acid release gas or makes the fluid matrix gasification produce a kind of motion that makes progress and keep floating state.The effervescent composition mainly is sodium bicarbonate/sodium carbonate and citric acid/tartaric acid or the fluid matrix that can gasify in vivo.All there are deficiency in above-mentioned constant speed delivery formulations and gastric gaseous-waste holdup system.The constant speed delivery formulations has certain requirement to medicine, the medicine that promptly is used to be prepared into slow release or controlled release will have good absorption at full intestinal, so there are many medicines to be not suitable for: 1. because of the intestinal pH medicine that dissolubility reduces that raises, as domperidone, furosemide etc.; 2. the medicine that mainly plays a role under one's belt is as ranitidine etc.; 3. the medicine that only absorbs at privileged sites is as riboflavin etc.; 4. many acidic drugs that absorb from stomach are as norfloxacin etc.Gastric retention system then is that gastric sticks, the change clearly of gastric choke system the normal physiological state of stomach, can make the patient who takes this kind medicine produce uncomfortable sensation.Existing stomach floating system, along with the release of medicine, the system that constantly enters of moisture, the very fast decline of flotation property, the preparation that has is in suspended state at the very start always, along with the feed stomach function regulating the emptying medicine be easy to enter the intestinal from stomach.Advantage of the present invention is that when this floating system contact Biomedia, air bag makes system swim in the Biomedia the superiors just as a lifebuoy; Wherein the slow/controlled release preparation discharges medicine with a constant speed.Because Biomedia can not see through airbag wall such as water and enter air bag, tangible change can not take place so air bag is kept the buoyant performance of whole system all the time in the process of drug release, system also can remain buoyant state.Discharge slow, controlled release system with known constant speed and compare, the spendable medicine of this system is more extensive, and the medicine that from then on is used to prepare the constant speed delivery formulations no longer is subjected to the restriction of " good absorption being arranged at full intestinal "; Compare with known floating in stomach system, this system's flotation property is more secure, is difficult for the release along with medicine, the influence of moisture and obviously change flotation property; The gentle controlled release properties of flotation property can be regulated and control respectively, is difficult for interacting; Take the back system bulk and bigger change can not take place so that stop up pylorus, be difficult for causing uncomfortable sensation.
Summary of the invention
The present invention relates to a kind of slow, controlling to release gas bag floationg system, comprising one can provide buoyancy make system can swim in the air bag of liquid surface and one contain pharmacological active substance, profile under certain condition can fixed slow/controlled release preparation.
Air bag is the key device that buoyancy is provided among the present invention, surrounds a gas II by air bag shell I and forms.The profile of air bag shell I can be the shape of conventional capsule body or capsule cap, also can be other shape (spherical, square, Y shape, polygon etc.), but has at least a part to combine with slow, controlled release preparation.Air bag shell I can make transparent, also can make opaque; Can not add pigment, also can add the air bag shell that pigment is made different colours.
Air bag shell I can be water insoluble, especially is insoluble to hydrochloric acid.Preparation air bag shell should use has especially insoluble polymer in the acid of good mouldability, water-insoluble.The material that is suitable for has the cellulose derivative of non-swellability, and such material comprises cellulose esters, cellulose ether and cellulose esters-ether (as cellulose acetate, ethyl cellulose etc.) and other insoluble materials (as zein etc.).
Air bag shell I can be an enteric solubility, should use the enteric solubility material with good mouldability during preparation air bag shell.Comprise acrylic resin, hydroxypropyl methylcellulose acetate succinate, phthalic acid polyvinyl alcohol ester (PVAP), styrene maleic acid copolymer (StyMA), hydroxypropylmethyl cellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), Lac etc.
Air bag shell I can dissolve or corrosion behind certain hour, should use soluble material with good mouldability and/or can be during preparation air bag shell by the material of corrosion, with above-mentioned insoluble material and/or enteric solubility material mixing or not with above-mentioned insoluble material and/or enteric solubility material mixing, the air bag shell of preparing is slowly dissolving and/or corrosion in a set time, treats just all to dissolve and/or corrosion after drug release fully.The material that is suitable for comprises gel rubber material, as hydroxypropyl emthylcellulose (HPMC), methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, polyoxyethylene (PEO) etc.; The corrosion material is as Cera Flava, hydrogenated vegetable oil, stearic acid, Brazil wax, glyceryl stearate, propylene glycol stearate and octadecanol etc.; Other soluble materials are as polyvidone (PVP), Polyethylene Glycol, sorbitol, xylitol etc.
Air bag shell I does not add or adds that suitably plasticizer (plasticizer comprises Polyethylene Glycol, phthalate) directly makes with above-mentioned material, also can use above-mentioned material not add or adds that suitably plasticizer makes in existing commercially available solubility capsule shells outer coatings.Can contain tiny duct on the air bag shell I.
Gas II generally refers to air, also can be other gas, as in order to prevent that oxidation of drug gas II from can be nitrogen or carbon dioxide.Gas II even can not be gas is as vacuum (this situation is rarer).
The formation of air bag can be when preparation air bag shell, promptly when preparation air bag shell, just seal a certain amount of gas II, a among Fig. 1 for example, wherein be used for the material that the dividing plate IV of sealing gas II should gentle softgel shell I, colors etc. are identical, because dividing plate IV itself is exactly the part of air bag shell, certain material of dividing plate IV in some cases, gentle softgel shell I such as color also can be different; The formation of air bag also can be, controlled release preparation gentle at the air bag shell in conjunction with the time, the air bag shell that promptly ought not have a sealing gas gentle, sealed a certain amount of gas II when controlled release preparation is bonded, thereby formed air bag, b among Fig. 1 for example.
Bonded slow, controlled release preparation III is that profile can fixed all slow, that controlled release preparation is finished medicine slow, controlled-release functions under certain condition with air bag.The slow/controlled release preparation comprises matrix type, film controlling type and osmotic pump type from its release mechanism, and dosage form comprises slow/controlled release sheet, slow/controlled release capsule, slow/controlled release pill etc.
The slow/controlled release sheet is seen in shape from it and is comprised cylindricality sheet, lenticular, double concave sheet, ring segment and special-shaped sheet etc.; On size, comprise 2～No. 14 towards (ordinary tablet that Φ 2～14mm) suppresses, and the microplate that Φ＜the 2mm punching press is made.The sheet surface can be smooth or be carved with word/pattern.The slow/controlled release sheet comprises single-layer sheet, double-layer tablet and multilayer tablet, and double-layer tablet and multilayer tablet can be regulated different drug release rates, and different medicines was discharged in the different time.The slow/controlled release capsule comprises conventional capsule and soft capsule.The slow/controlled release pill comprises ordinary pill and micropill.
Air bag and sustained-release preparation can combine and make sustained-release preparation be difficult for splitting away off from air bag, and what mainly lean on is frictional force between the gentle softgel shell I of preparation; When air bag be air bag shell I and sustained-release preparation III in conjunction with the time when forming, if sustained-release preparation III will come off from air bag shell I, also must overcome the inside and outside pressure differential of air bag, because when sustained-release preparation III outwards comes off, it is big that the air bag volume becomes relatively, the air bag internal gas pressure just diminishes, less than the outer atmospheric pressure of air bag.
Certainly, can suitably add binding agent to strengthen the combination of air bag shell I and sustained-release preparation III.Can also be at air bag and sustained-release preparation in conjunction with the back coating, or add medicated cap at the preparation end.
Pharmacological active substance of the present invention can be any material slow, controlled release system that is applicable to, the pharmacological active substance that is suitable for almost comprises all materials that can be used for treating, for example anti-arrhythmic, vasodilation, antihypertensive, beta-blocker, oral antidiabetic, antirheumatic, antibiotic medicine, antidepressants, diuretic, antuepileptic, tranquilizer, antibiotic, analgesic, vitamin, hormone, antibacterial, polypeptide, enzyme and mucopolysaccharide and various Chinese medicine extract.
The example of pharmacological active substance has: Licardipine Hydrochloride, nisoldipine, nifedipine, amlodipine, nimodipine, nitrendipine, glipizide, gliclazide, glibenclamide, venlafaxine, diclofenac sodium, meloxicam, piroxicam, vinpocetine, famotidine, nicotinic acid, folic acid, propranolol, vitamin B12 etc.
The beneficial effect that the present invention significantly is better than existing floating preparation has three: 1. use the floating preparation flotation property of the present invention's preparation good, it never is suspended state, the superiors of gastric content can be swum in after can guaranteeing in the body, small intestinal can be do not entered rapidly along with the emptying of food; 2. use the floating preparation flotation time of the present invention's preparation very long, 12 hours floating, 24 hours floating, floatingly all can realize in 36 hours, even can the floating longer time; 3. use method of the present invention to prepare floating preparation, when prescription and technological design, can distinguish and regulate slow controlled release time and flotation time separately, the prescription of sustained-release preparation and technology and air bag can be regulated and control respectively, can not influence the characteristic of another part during the wherein a part of characteristic changing of two parts, can simplify the process of groping of prescription and technology so greatly.
Description of drawings
Fig. 1 a be delay, the vertical section structural map during controlled release floating system band dividing plate/barrier film.
Fig. 1 b be delay, the vertical section structural map of controlled release floating system during not with dividing plate/barrier film.
Among the figure: I. air bag shell, II. gas, III. comprise the sustained-release preparation of medicine, IV. dividing plate/barrier film.
Fig. 2 is the two chambers of famotidine monolayer gas bag floationg osmotic pumps release profiles.
Fig. 3 is a famotidine gel skeleton type gas bag floationg preparation release profiles.
Fig. 4 is a famotidine gel-type gas bag floationg preparation release profiles.
Fig. 5 is a VENLAFAXINE HCL gel skeleton type gas bag floationg preparation release profiles.
Fig. 6 is a dipyridamole capsules floating release profiles.
N=6 among Fig. 2-6, and 6 preparations of each prescription remain afloat in external stripping experimentation.
The specific embodiment
Embodiment 1
A kind of insoluble air bag shell
Take by weighing cellulose acetate 30g and be dissolved in 500ml acetone, constantly be stirred to dissolving fully then.2gPEG6000 is dissolved in the 30ml pure water again, constantly is stirred to dissolving fully.Above-mentioned two solution are mixed, stir then.Quiet straightening to removing bubble in the solution liquid.The glue of resting is put into and is stained with the glue groove, and being stained with in the glue groove temperature of limb liquid and being 40 ℃, indoor environment temperature is 20-25 ℃, is stained with glue automatically, dries, pulls out shell, cutting through the capsule shells template, promptly obtains insoluble air bag shell.Can obtain the different air bag shell of internal diameter according to capsule shells template difference.
The two chambers of famotidine monolayer gas bag floationg osmotic pumps
Among the embodiment 1, air bag shell I is No. 0 enteric coated capsule medicated cap as shown in Figure 1; The sustained-release preparation III that comprises medicine is a famotidine mono-layer osmotic pump sheet.
Famotidine mono-layer osmotic pump sheet:
Sheet heart prescription:
Famotidine 13.3%
Glucose 46.7%
Tragakanta 33.3%
Microcrystalline Cellulose 13.3%
5%PVP ethanol liquid is an amount of
Magnesium stearate is an amount of
1000
Coating solution:
Cellulose acetate 30g
PEG4000 24g
Dibutyl phthalate 4g
Acetone 1000ml
Water 100ml
Supplementary materials such as famotidine, glucose, tragakanta, microcrystalline Cellulose, polyethylene pyrrole sieve alkane ketone (PVPK90), magnesium stearate are pulverized until crossing 80 mesh sieves.Take by weighing famotidine 20g, glucose 70g, tragakanta 50g, microcrystalline Cellulose 20g, and with its mix homogeneously.With the 5%PVP alcoholic solution is binding agent system soft material, crosses 18 mesh sieves and granulates, and 40 ℃ were dried by the fire 30 minutes down, crossed 20 mesh sieve granulate, and 40 ℃ of oven dry became dried granule in 5 hours.Take by weighing weight for doing particulate 0.5% magnesium stearate, with dried granule mixing, to play lubricated fluidizer effect.Next charge and attack sheet with No. 7 scrobiculas, the heavily about 150mg of sheet is called the sheet heart.
Taking by weighing cellulose acetate 30g is dissolved in the 1000ml acetone, measure water 100ml, other takes by weighing dibutyl phthalate 4g and adds in the cellulose acetate acetone soln, wash in the cellulose acetate acetone soln with the dibutyl phthalate that low amounts of water will stick on the beaker, taking by weighing PEG4000 24g again is dissolved in about 60ml water, add in the cellulose acetate acetone soln, the PEG that will stick on the beaker with remaining water washes in the cellulose acetate acetone soln.When each material mix homogeneously promptly gets coating solution.
Next, be the process of coating.The sheet heart is put in the coating pan 35 rev/mins of coating pan rotating speeds, 40 ℃ of sheet bed tempertaures, coating solution flow velocity 7ml/min.When being 11%, the coating weightening finish stops coating.Coated tablet was dried 12 hours down at 40 ℃ then.
After the coated tablet oven dry, the hole of stamping 1.0mm with the method for machinery or laser on the two sides of sheet respectively.
With the opening part of sheet plug to 0 enteric coated capsule medicated cap, beat the hole of 0.4mm again with the method for machinery or laser at air bag shell top at last, promptly make the two chambers of famotidine monolayer gas bag floationg osmotic pumps.Its release profiles as shown in Figure 2.Preparation was in floating state in 16 hours, began after 16 hours to sink.
Embodiment 3
Famotidine gel skeleton type gas bag floationg preparation
Among the embodiment 1, air bag shell I is No. 0 enteric coated capsule as shown in Figure 1; The sustained-release preparation III that comprises medicine is the famotidine gel matrix tablet.
The famotidine gel matrix tablet:
Sheet heart prescription:
Famotidine 26.7%
Polyoxyethylene (molecular weight 300,000) 33.3%
Sodium chloride 6.7%
5%PVP ethanol liquid is an amount of
Magnesium stearate is an amount of
1000
Supplementary materials such as famotidine, polyoxyethylene, sodium chloride, polyethylene pyrrole sieve alkane ketone (PVPK30), magnesium stearate are pulverized until crossing 80 mesh sieves.Take by weighing famotidine 40g, sodium chloride 10g, polyoxyethylene 90g, and with its mix homogeneously.With the 5%PVP alcoholic solution is binding agent system soft material, crosses 18 mesh sieves and granulates, and 40 ℃ were dried by the fire 30 minutes down, crossed 20 mesh sieve granulate, and 40 ℃ of oven dry became dried granule in 5 hours.Take by weighing weight for doing particulate 1% magnesium stearate, with dried granule mixing, to play lubricated fluidizer effect.Next charge and attack sheet with No. 7 scrobiculas, the heavily about 150mg of sheet is called the sheet heart.
With the opening part of sheet plug to 0 enteric coated capsule, promptly make famotidine gel skeleton type gas bag floationg preparation at last.Its release profiles as shown in Figure 3.Preparation does not dissolve at gel skeleton and is in floating state constantly, begins to sink after the gel skeleton dissolving.
Famotidine corrosion matrix type gas bag floationg preparation
Among the embodiment 1, air bag shell I is No. 0 enteric coated capsule as shown in Figure 1; The sustained-release preparation III that comprises medicine is a famotidine corrosion matrix tablet.
Famotidine corrosion matrix tablet:
Sheet heart prescription:
Famotidine 11.7%
River wax 11.7%
PEG20000 11.7％
Microcrystalline Cellulose 35.3%
Sodium chloride 17.6%
PVPK90 is an amount of
Magnesium stearate is an amount of
1000
Supplementary materials such as famotidine, river wax, PEG20000, microcrystalline Cellulose, sodium chloride, polyethylene pyrrole sieve alkane ketone (PVPK590), magnesium stearate are pulverized until crossing 80 mesh sieves.Take by weighing famotidine 20g, river wax 20g, PEG20000 30g, microcrystalline Cellulose 60g, sodium chloride 30g, PVPK90 8g, magnesium stearate 2g, and with its mix homogeneously.Next charge and attack sheet with No. 7 scrobiculas, the heavily about 170mg of sheet.
With the opening part of sheet plug to 0 enteric coated capsule, cover the ease of solubility capsule cap at last No. 0 at last, promptly make famotidine corrosion matrix type gas bag floationg preparation.Preparation is in floating state when medicine has not discharged, begin after medicine discharges fully to sink.
Embodiment 5
Famotidine matrix type gas bag floationg preparation
As shown in Figure 1 among the embodiment 1, the air bag shell of preparation among the air bag shell I embodiment 1, internal diameter 6mm; The sustained-release preparation III that comprises medicine is two of famotidine matrix tablets.
Famotidine corrosion matrix tablet:
Sheet heart prescription:
Polyoxyethylene (molecular weight 100,000) 79%
Magnesium stearate is an amount of
1000
Supplementary materials such as famotidine, polyoxyethylene, magnesium stearate are pulverized until crossing 80 mesh sieves.Take by weighing famotidine 20g, polyoxyethylene 80g, and with its mix homogeneously.With 95% alcoholic solution is binding agent system soft material, crosses 18 mesh sieves and granulates, and 40 ℃ were dried by the fire 30 minutes down, crossed 20 mesh sieve granulate, and 40 ℃ of oven dry became dried granule in 3 hours.Take by weighing weight for doing particulate 0.5% magnesium stearate, with dried granule mixing, to play lubricated fluidizer effect.Next put down with No. 6 and charge and attack sheet, the heavily about 100mg of sheet is called the sheet heart.
With the opening part of two sheet heart plug to air bag shells, promptly make famotidine matrix type gas bag floationg preparation at last.Its release profiles as shown in Figure 4.Preparation is in floating state when medicine has not discharged, begin after medicine discharges fully to sink.
VENLAFAXINE HCL gel skeleton type gas bag floationg preparation
Among the embodiment 1, air bag shell I is No. 0 insoluble capsule as shown in Figure 1; The sustained-release preparation III that comprises medicine is the VENLAFAXINE HCL gel matrix tablet.
The VENLAFAXINE HCL gel matrix tablet:
Sheet heart prescription:
VENLAFAXINE HCL 37.5%
PEO?WSRN750 59％
5%PVP ethanol liquid is an amount of
Magnesium stearate is an amount of
1000
Supplementary materials such as VENLAFAXINE HCL, polyoxyethylene, polyethylene pyrrole sieve alkane ketone (PVPK30), magnesium stearate are pulverized until crossing 80 mesh sieves.Take by weighing VENLAFAXINE HCL 37.5g, PEO WSRN75059g, and with its mix homogeneously.With the 5%PVP alcoholic solution is binding agent system soft material, crosses 18 mesh sieves and granulates, and 40 ℃ were dried by the fire 30 minutes down, crossed 20 mesh sieve granulate, and 40 ℃ of oven dry became dried granule in 5 hours.Take by weighing weight for doing particulate 1% magnesium stearate, with dried granule mixing, to play lubricated fluidizer effect.Next charge and attack sheet with No. 6 scrobiculas, the heavily about 100mg of sheet.
With No. 1 insoluble capsule cap inwall of a small amount of 5%PVP ethanol liquid spraying, at last before ethanol does not volatilize with the sheet plug to opening part, dried 12 hours, and promptly made VENLAFAXINE HCL gel skeleton type gas bag floationg preparation for 40 ℃.Its release profiles as shown in Figure 5.Preparation is in floating state when medicine has not discharged, begin after medicine discharges fully to sink.
Embodiment 7
The two chambers of dipyridamole monolayer gas bag floationg osmotic pumps
Among the embodiment 1, air bag shell I is a kind of air bag shell for preparing of embodiment, internal diameter 7mm as shown in Figure 1; The sustained-release preparation III that comprises medicine is a dipyridamole mono-layer osmotic pump sheet.
Dipyridamole mono-layer osmotic pump sheet:
Sheet heart prescription:
Dipyridamole 25%
Microcrystalline Cellulose 15%
Glucose 35%
Citric acid 24%
Magnesium stearate is an amount of
1000
Coating solution:
Cellulose acetate 30g
PEG4000 10g
Acetone 1000ml
Water 60ml
Supplementary materials such as dipyridamole, microcrystalline Cellulose, glucose, citric acid, magnesium stearate are pulverized until crossing 80 mesh sieves.Take by weighing dipyridamole 50g, microcrystalline Cellulose 30g, glucose 70g, citric acid 48g, and with its mix homogeneously.Add 1% magnesium stearate, to play lubricated fluidizer effect.Next under the low temperature and low humidity condition, charge and attack sheet with No. 7 scrobiculas, the heavily about 200mg of sheet is called the sheet heart.
Take by weighing cellulose acetate 30g and be dissolved in the 1000ml acetone, measure water 60ml, take by weighing PEG400010g and be dissolved in about 40ml water, add in the cellulose acetate acetone soln, wash in the cellulose acetate acetone soln with the PEG aqueous solution that remaining water will stick on the beaker.When each material mix homogeneously promptly gets coating solution.
Next, be the process of coating.The sheet heart is put in the coating pan 30 rev/mins of coating pan rotating speeds, 30 ℃ of sheet bed tempertaures, coating solution flow velocity 7ml/min.When being 8%, the coating weightening finish stops coating.Coated tablet was dried 12 hours down at 40 ℃ then.
After the coated tablet oven dry, the hole of stamping 0.7mm with the method for machinery or laser on the two sides of sheet respectively.
With the opening part of sheet plug to the air bag shell, the two chambers of dipyridamole monolayer gas bag floationg osmotic pumps is promptly made in the hole that 0.4mm has been stamped with the method for machinery or laser in air bag shell top at last.Preparation was in floating state in 18 hours, began after 18 hours to sink.
The two chambers of dipyridamole gas bag floationg micropore permeation pump
Among the embodiment 1, air bag shell I is No. 1 insoluble capsule cap as shown in Figure 1; The sustained-release preparation III that comprises medicine is the dipyridamole micro-porous osmotic pump tablet.
The dipyridamole micro-porous osmotic pump tablet:
Sheet heart prescription:
Dipyridamole 25%
Microcrystalline Cellulose 15%
Glucose 35%
Citric acid 24%
Magnesium stearate is an amount of
1000
Coating solution:
Cellulose acetate 30g
PEG4000 10g
PVPK90 3g
Acetone 1000ml
Water 60ml
Supplementary materials such as dipyridamole, microcrystalline Cellulose, glucose, citric acid, magnesium stearate are pulverized until crossing 80 mesh sieves.Take by weighing dipyridamole 50g, microcrystalline Cellulose 30g, glucose 70g, citric acid 48g, and with its mix homogeneously.Add 1% magnesium stearate, to play lubricated fluidizer effect.Next under the low temperature and low humidity condition, charge and attack sheet with No. 7 scrobiculas, the heavily about 200mg of sheet is called the sheet heart.
Taking by weighing cellulose acetate 30g is dissolved in the 1000ml acetone, measure water 60ml, take by weighing PEG400010g, PVPK90 3g and be dissolved in about 40ml water, add in the cellulose acetate acetone soln, wash in the cellulose acetate acetone soln with the PEG aqueous solution that remaining water will stick on the beaker.When each material mix homogeneously promptly gets coating solution.
Next, be the process of coating.The sheet heart is put in the coating pan 30 rev/mins of coating pan rotating speeds, 30 ℃ of sheet bed tempertaures, coating solution flow velocity 7ml/min.When being 8%, the coating weightening finish stops coating.Coated tablet was dried 12 hours down at 40 ℃ then.
With the opening part of sheet plug, promptly make the two chambers of dipyridamole gas bag floationg micropore permeation pump after the coated tablet oven dry to the air bag shell.Preparation was in floating state in 18 hours, began after 18 hours to sink.
Embodiment 9
Dipyridamole capsules floating (micropill)
Among the embodiment 1, air bag shell I is No. 0 capsule cap as shown in Figure 1; The sustained-release preparation III that comprises medicine is a dipyridamole micropill slow releasing capsule.
Taking by weighing microcrystalline Cellulose 300g puts in the centrifugal coating pelletizing machine, with water is binding agent, engine speed is 200r/min, regulate whiff pressure 0.1～0.3MPa, air blast flux is 15 * 20L/min, jet flow 10～20L/min, the whitewashing flow changed with the pelletize time, be initially big flow whitewashing (25r/min) in 2 minutes, make powder wetted at short notice, avoid dust from flying; Control medium speed's whitewashing flow (15r/min) then, ongoing operation a period of time also begins for powder, control powder slurry is than (1: 1), finish the molding growth process of centrifugal granulating, finish the back and open discharging opening, take out finished product, room temperature is dried in the air and is done near, dry in 60 ℃ of baking ovens, the ball nuclear of screening 32-24 order particle diameter is standby again.
Taking by weighing microcrystalline Cellulose ball nuclear 300g (32～24 order) puts in the centrifugal coating pelletizing machine; dipyridamole powder (crossing 100 mesh sieves) is put in the loading hopper for powder; with 1% hydroxypropyl methylcellulose (5cps) aqueous solution is binding agent; start centrifugal coating pelletizing machine by following parameter: engine speed 200r/min; air blast flux is 15 * 20L/min, whiff pressure 0.1～0.3MPa, jet flow 12～18 L/min; spray pump rotating speed 10～15r/min is for powder speed 10～20r/min.To the whole laminations of powder till on the parent nucleus.Finish the back room temperature and dry, screening promptly gets the dipyridamole micropill.Micropill drug loading 27.5～25.6%.
With the dipyridamole micropill capsule of packing into No. 0, dosage 100mg/ capsule, and add a cover No. 0 capsule cap at the capsule cap place.The aforementioned medicated cap capsule that adds is put in the coating pan 35 rev/mins of coating pan rotating speeds, 40 ℃ of sheet bed tempertaures, coating solution (cellulose acetate 30g, PEG400010g, acetone 1000ml, water 60ml) flow velocity 7ml/min.The coating weightening finish stops coating when being 5%.Coated tablet was dried 12 hours down at 40 ℃ then.Last each beats the hole of 0.8mm with laser at the capsule two ends, promptly makes dipyridamole gas bag floationg capsule.Its release profiles as shown in Figure 6.Preparation was in floating state in 16 hours, began after 16 hours to sink.
Claims (10)
1. controlling to release gas bag floationg system, it is characterized in that: comprising one can provide buoyancy make system can swim in the air bag of liquid surface and one contain pharmacological active substance, profile under certain condition can fixed slow/controlled release preparation, provide buoyant buoyancy with air bag, finish slow, the controlled-release function of medicine to be embedded in sustained-release preparation on the air bag
2. controlling to release gas bag floationg according to claim 1 system, it is characterized in that: the gas bag floationg system comprises three parts; Air bag shell I, gas II, comprise the sustained-release preparation III of medicine, gas II occupies the end of air bag shell I, and the other end is sustained-release preparation III, between the two with or put out without dividing plate/barrier film IV.
3. controlling to release gas bag floationg according to claim 1 system is characterized in that: the air bag shell can be water insoluble, especially be insoluble to hydrochloric acid, preparation air bag shell should use the especially sour insoluble polymer of water-insoluble; The air bag shell can be an enteric solubility, and preparation air bag shell should use the enteric solubility material; The air bag shell can dissolve or corrosion behind certain hour, and preparation air bag shell should use soluble material and/or can be by the material of corrosion, with above-mentioned insoluble material or enteric solubility material mixing or not with above-mentioned insoluble material and/or enteric solubility material mixing.
4. controlling to release gas bag floationg according to claim 3 system, it is characterized in that: the especially sour insoluble polymer of described water-insoluble is cellulose esters, cellulose ether and cellulose esters-ether and other insoluble materials.
5. controlling to release gas bag floationg according to claim 3 system is characterized in that: described enteric solubility material is acrylic resin, hydroxypropyl methylcellulose acetate succinate, phthalic acid polyvinyl alcohol ester or claims PVAP, styrene maleic acid copolymer or claim StyMA, hydroxypropylmethyl cellulose phthalate or claim HPMCP, cellulose acetate phthalate or claim CAP, Lac.
6. controlling to release gas bag floationg according to claim 3 system is characterized in that: described soluble material and/or can be gel rubber material, hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, polyoxyethylene by the material of corrosion; Corrosion material, Cera Flava, hydrogenated vegetable oil, stearic acid, Brazil wax, glyceryl stearate, propylene glycol stearate and octadecanol); Other soluble materials, polyvidone, Polyethylene Glycol, sorbitol, xylitol.
7. according to claim 3 or 4 or 5 or 6 described controlling to release gas bag floationg systems, it is characterized in that: the air bag shell can be not add or add that suitably plasticizer directly makes with above-mentioned material, and perhaps above-mentioned material does not add or adds that suitably plasticizer makes in existing commercially available solubility capsule shells outer coatings; The air bag shell does not have any hole or has one or more apertures.
8. controlling to release gas bag floationg according to claim 1 and 2 system, it is characterized in that: gas is air, carbon dioxide or nitrogen in the air bag.
9. controlling to release gas bag floationg according to claim 1 system, it is characterized in that: the sustained-release preparation that is embedded on the air bag is the slow/controlled release sheet, one or more in slow/controlled release capsule or the slow/controlled release pill.
10. controlling to release gas bag floationg according to claim 1 and 2 system, it is characterized in that: air bag combines what mainly lean on sustained-release preparation be frictional force between air bag shell and the preparation, also can suitably add binding agent to strengthen the combination of air bag shell and sustained-release preparation, can also add medicated cap in conjunction with the back coating or at the preparation end at air bag and sustained-release preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101583553A CN101181226A (en) | 2007-11-19 | 2007-11-19 | System for slowing and controlling to release gas bag floationg |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101583553A CN101181226A (en) | 2007-11-19 | 2007-11-19 | System for slowing and controlling to release gas bag floationg |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101181226A true CN101181226A (en) | 2008-05-21 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101583553A Pending CN101181226A (en) | 2007-11-19 | 2007-11-19 | System for slowing and controlling to release gas bag floationg |
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| Country | Link |
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| CN (1) | CN101181226A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010020098A1 (en) * | 2008-08-18 | 2010-02-25 | 北京天衡药物研究院 | Gastric retention drug delivery system, preparation method and use thereof |
| CN112021272A (en) * | 2020-09-17 | 2020-12-04 | 山西农业大学 | Grapholitha molesta sex pheromone release system |
| CN112716916A (en) * | 2019-10-14 | 2021-04-30 | 蒋海松 | Sustained-release micro-tablet capsule of 5-hydroxytryptamine, norepinephrine and dopamine reuptake inhibitor and preparation method thereof |
| CN113382721A (en) * | 2018-12-14 | 2021-09-10 | Dpl医药有限公司 | Solid oral pharmaceutical composition comprising a composite monolithic matrix for the time-varying administration of drugs in the gastrointestinal tract |
-
2007
- 2007-11-19 CN CNA2007101583553A patent/CN101181226A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010020098A1 (en) * | 2008-08-18 | 2010-02-25 | 北京天衡药物研究院 | Gastric retention drug delivery system, preparation method and use thereof |
| CN113382721A (en) * | 2018-12-14 | 2021-09-10 | Dpl医药有限公司 | Solid oral pharmaceutical composition comprising a composite monolithic matrix for the time-varying administration of drugs in the gastrointestinal tract |
| CN113382721B (en) * | 2018-12-14 | 2023-06-09 | Dpl医药有限公司 | Solid oral pharmaceutical composition comprising a composite monolithic matrix for drug chronologically-administered in the gastrointestinal tract |
| CN112716916A (en) * | 2019-10-14 | 2021-04-30 | 蒋海松 | Sustained-release micro-tablet capsule of 5-hydroxytryptamine, norepinephrine and dopamine reuptake inhibitor and preparation method thereof |
| CN112021272A (en) * | 2020-09-17 | 2020-12-04 | 山西农业大学 | Grapholitha molesta sex pheromone release system |
| CN112021272B (en) * | 2020-09-17 | 2021-11-30 | 山西农业大学 | Grapholitha molesta sex pheromone release system |
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Application publication date: 20080521 |