CN103405390A - Preparation method of lecithin-bound iodine enteric-coated pellet tablet - Google Patents
Preparation method of lecithin-bound iodine enteric-coated pellet tablet Download PDFInfo
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- CN103405390A CN103405390A CN2013103704929A CN201310370492A CN103405390A CN 103405390 A CN103405390 A CN 103405390A CN 2013103704929 A CN2013103704929 A CN 2013103704929A CN 201310370492 A CN201310370492 A CN 201310370492A CN 103405390 A CN103405390 A CN 103405390A
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Abstract
The invention discloses a preparation method of a lecithin-bound iodine enteric-coated pellet tablet. The preparation method comprises the following steps: uniformly mixing lecithin-bound iodine with auxiliary materials, wherein the auxiliary materials include one or more of a disintegrating agent, an excipient and a diluent; adhering the mixed auxiliary materials onto the surface of a starch or lactose pellet to obtain pellet particles by an adhesive in a ratio of the adhesive to the auxiliary materials of (0.05-0.5) to 1; adding the pellet particles into the auxiliary materials after being wrapped with enteric coatings and then directly tabletting, or mixing the pellet particles with buffer particles which are prepared by a conventional method in a weight ratio of (1:1) to (2:8) to obtain the pellet tablet. Compared with the conventional preparation, the pellet tablet, which is prepared by the preparation method disclosed by the invention, has the characteristic that the distribution area is large, and has the advantages of being small in size, capable of dividing dosage and the like, so that patient compliance is increased; the pellet can be isolated from the air more stably, and a period of validity reaches three years or more,.
Description
Technical field
The present invention relates to a kind of or form and to be divided into pharmaceutical composition enteric coated micropill tablet of lecithin chelated iodine and preparation method thereof.
Background technology
Lecithin chelated iodine is the compound generated by complexation reaction by lecithin (phosphatidylcholine) and iodine, and iodine is used to treat nervous function disease, arteriosclerosis, asthma and thyroid disease etc. in the internal medicine field.In addition, iodine is used as antiinflammatory and antitypy medicine for a long time in field of ophthalmology, especially in retinal diseases treatment, and the goodish clinical effectiveness of demonstration place.Yet the medicine form of most iodide such as potassium iodide, sodium iodide and compound iodine solution all is not suitable for taking, and the untoward reaction of these iodine preparation, it is mainly the damage to stomach.Select suitable carrier to provide the required iodine for the treatment of pathological changes necessary.
Lecithin chelated iodine is brown yellow granule or powder; special odor is arranged; Yi Ji is in chloroform, carbon tetrachloride and benzene; be insoluble to ether and ethanol, in water, form colloid solution, amount of iodine 6.5～7.0%; stable in non-polar solven; by digestive tract, in blood, worked with the form of inorganic iodine, then be incorporated into thyroid and to owing to lacking goiter patient that iodine causes or child's hypothyroidism, working.Promote the rabbit retinal tissue to breathe, promote amphiblestroid metabolism.In anaphylaxis uvea (tunica uvea) inflammation or the uveitic experiment of fulminant to rabbit, obvious antiinflammatory action and the effect that improves ERG are arranged.
Lecithin chelated iodine is mainly used in treating vasospasm retinitis, hemorrhagic retinitis, vitreous hemorrhage, vitreous opacity, central vein closure retinitis and infantile asthma, bronchitis, goiter due to iodine deficiency, iodine deficiency hypothyroidism clinically.
Active substance iodine in lecithin chelated iodine is easy absorbed into serum in vivo, but unstable in gastric juice, discharges too fast easy stimulation gastric mucosa and causes the stomach damage, and have special odor, causes the patient to take inconvenience.The Chinese patent of the patent No. " 200610012274.8 " discloses lecithin chelated iodine soft capsule and preparation method thereof.The method has been covered drug smell, but can't avoid gastrointestinal stimulation.The patent No. discloses lecithin enteric coated capsule and preparation method thereof for the Chinese patent of " 201110124914.5 ", can avoid stomach to discharge, the stimulation of minimizing to stomach, but the isolated air effect of capsule preparations is little, easily produces the problems affect drug absorption such as not disintegrate of capsule softgel shell.
Pellet tablet is as a kind of desirable dosage form, not only has advantages of multiple unit type preparations such as being uniformly dispersed, reducing medicine irritation and reduction toxic and side effects at gastrointestinal tract, also have advantages of that production efficiency is high, taking convenience and the haplotype preparation such as dosage is divisible, after wherein cutting apart, still can keep the slow controlled release ability of multiple-unit is the most outstanding characteristics of pellet tablet preparation.
Lecithin chelated iodine enteric coated micropill sheet prepared by the present invention can avoid medicine to gastrointestinal stimulation, strengthens the absorption of medicine, and isolated drug smell, improve medicine stability, is easy to produce.
Summary of the invention
In order to overcome above-mentioned the deficiencies in the prior art, the invention provides a kind of lecithin chelated iodine enteric coated micropill sheet and can avoid medicine to gastrointestinal stimulation, strengthen the absorption of medicine, isolated drug smell, improve medicine stability, is easy to produce.
Lecithin chelated iodine enteric coated micropill sheet of the present invention mainly comprises the following steps:
(1) by lecithin chelated iodine and auxiliary materials and mixing, described adjuvant comprises one or more of disintegrating agent, excipient, diluent; Described disintegrating agent is selected from one or more of dried starch, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and carboxymethylcellulose calcium; Described excipient and diluent are selected from respectively one or more of starch, Icing Sugar, dextrin, lactose, pregelatinized Starch, microcrystalline Cellulose, mannitol and sorbitol;
(2) by weight binding agent: adjuvant=0.05～0.5: it is 1%～15% binder solution that 1 ratio water and/or ethanol are mixed with mass percentage concentration by binding agent;
Described binding agent is selected from one or more of hyprolose, sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, polyvidone, gelatin, Polyethylene Glycol, sodium alginate, lactose, polyvinyl alcohol;
(3) utilize binding agent the mixed material of step (1) to be sticked to the Blank Pellets surface prepared with lactose or starch, obtain micropill, the gross weight of the mixed material of described binding agent and step (1) and the weight ratio of Blank Pellets are 1: 5～2: 1;
(4) enteric-coating material dissolved or is distributed in solvent, being prepared into coating solution; To put into fluid bed to lecithin chelated iodine micropill prepared by step (3); Coating solution is placed in to liquid feeding end the lecithin chelated iodine micropill is carried out to coating, obtain the lecithin chelated iodine enteric coated micropill of equal particle diameter; The mass percent of described coating material solution and lecithin chelated iodine micropill is 1: 3-1: 15; Described enteric-coating material is selected from one or more in Lac, Cellulose Acetate Phthalate, alginate jelly, polyvinyl acetate phthalate, acrylic resin and hydroxypropyl methyl cellulose phthalate;
(5) by the enteric coated-pellet granule direct compression of step (4), or with buffering granule prepared by conventional method, mix rear tabletting by weight the ratio of 1: 1～9: 1, obtain pellet tablet.
In the present invention, disintegrating agent need to make tablet and micropill granule meet the rapid disintegrate of water, and disintegration time does not affect the release curve of film control micropill; Excipient need to have good adhesive force (can stick in the coated micropill surface under the help of binding agent), certain compressive resistance and compressibility (can in the tabletting process, resist ambient pressure, the protection coated micropill does not break) and good disintegrative (can under disintegrating agent helps rapid disintegrate and do not affect the drug release curve).Binding agent makes adjuvant stick to the coated micropill surface, and can dissolve rapidly under the disintegrating agent effect, does not affect the disintegration time of tablet and micropill granule.
Binding agent can water and/or ethanol in adhesion process, slowly add after being mixed with solution, allow the mixed material that is mixed with lecithin chelated iodine under the effect of binder solution, stick to the Blank Pellets surface prepared with lactose or starch, obtain micropill.The quality percentage composition of ethanol can be 20% ~ 80%.
The coating material of coated micropill is one or more of Lac, Cellulose Acetate Phthalate, alginate jelly, polyvinyl acetate phthalate, acrylic resin and hydroxypropyl methyl cellulose phthalate, and coating material is more than 10% of micropill weight percentage.The buffering granule is that conventional method prepares, and it can be one or more the mixture in adjuvant.
Preferably, for improving liquidity so that cushion granule and the micropill granule adheres to better, during step (5) tabletting, add fluidizer, described fluidizer is one or more of magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, sodium laurylsulfate, magnesium laurylsulfate, and described micropill granule and the gross weight of buffering granule and the weight ratio of described fluidizer are 50～100: 1.
Preferably, described disintegrating agent is cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone or sodium alginate; Described excipient and diluent are respectively lactose, pregelatinized Starch or microcrystalline Cellulose.
Preferably, described in step (2), the mass percentage concentration of binder solution is 1%-10%; Described in step (3), the percentage by weight of binding agent and mixed material gross weight and Blank Pellets is 1: 3-1: 1; Described in step (4), the mass percent of coating material solution and lecithin chelated iodine micropill is 1: 5-1: 10; Micropill granule described in step (5) is 1 with the weight ratio of buffering granule: 1-7: 3.
Below by further experiment, beneficial effect of the present invention is described:
(1) produce checking
According to the requirement of " Good Manufacturing Practice and Quality Control of Drug ", the embodiment of the present invention 1 is carried out to three batches of process certifications, the result shows technique reasonable of the present invention, can guarantee product quality, the results are shown in Table 1.
Table 1 is produced the result
(2) accelerated test
Get three batches of products of producing checking, the simulation commercially available back is placed under 40 ℃ ± 2 ℃ of temperature, relative humidity RH75% ± 5% condition to be placed 6 months.In 0,1,2,3 and June sampling once, according to the method for quality standard regulation, check.In 0 month with check microbial limit June, the every Index for examination of result is compared without significant change with 0 month result, all up to specification.
(3) long-term stable experiment
Get three batches of products of producing checking, the simulation commercially available back is placed under 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% condition to be placed 36 months.0, once, the method for stipulating according to quality standard checks in each sampling in 3,6,9,12,18,24 and 36 months.In 0,6,12,18,24 and 36 month, check microbial limit, the every Index for examination of result is compared without significant change with 0 month result, all up to specification.
The specific embodiment
Below by embodiment the present invention is further described the present invention.
Embodiment 1: the preparation of lecithin chelated iodine enteric coated micropill sheet comprises the following steps:
1. prepare the lecithin chelated iodine micropill by following each component materials of formula weighing:
80 order lactose ball core 700g
Lecithin chelated iodine (give money as a gift, pure, in iodine) 2g
Pregelatinized Starch 200g
Microcrystalline Cellulose 50g
Pulvis Talci 100g
Hydroxypropyl emthylcellulose 20g
Pure water 5000g
Hydroxypropyl emthylcellulose is dissolved in to pure water, is prepared into the aqueous solution of 1% content as binding agent; The material of lactose ball core being put to centrifugal coating granulator is indoor, separately the mixed-powder (120 order) of lecithin chelated iodine and pregelatinized Starch 200 g, microcrystalline Cellulose 50 g and Pulvis Talci 100g is put in solid feed hopper.The aqueous solution of take is wetting agent, starts centrifugal coating granulator by following parameter: engine speed 200 r/min, and air blast flux 20 * 20 L/min, spray air flow 15-20 L/min, whiff pressure 0.5 MPa, spray pump rotating speed 20 r/min, for powder speed 20 r/min.The 1% hydroxypropyl emthylcellulose aqueous solution of take is binding agent, and the whitewashing time is 5 min, when round as a ball, maintains pump speed 20 r/min, and the round as a ball time is 2 min, the rear 60 ℃ of oven dry that take the dish out of the pot, and 20-40 order lecithin chelated iodine micropill is chosen in screening.
2. prepare coated micropill
Press following each component materials of formula weighing:
Lecithin chelated iodine micropill 900g
Hydroxypropyl emthylcellulose 20g
Acrylic resin L30D-55 150g
The about 20g of micropowder silica gel
The about 1500g of pure water
Adopt the fluidized-bed coating machine coating.Take pill appropriate, put in the air-flow coating device, with 3% hydroxypropyl emthylcellulose aqueous solution bag contagion gown, 40 ℃ of dryings are 10 min approximately, then use acrylic resin L30D-55 aqueous dispersion enteric coated, 40 ℃ of drying 2 h.Coating thickness is counted 13%-14% to contain the pill core weightening finish.Art for coating condition: blower frequency: 27.5 Hz; Whiff pressure: 0.2 MPa; Hydrojet flow velocity: 1 mLmin-1; Stream temperature: 33 ℃.After coating completes by coated micropill and 0.2%(w) micropowder silica gel mix, be placed in 40 ℃ of baking oven ripening 24 h.
3. preparation buffering granule
Press following each component materials of formula weighing:
Microcrystalline Cellulose (PH102) 3500g
Lactose (80 order) 1500g
Hydroxypropyl emthylcellulose 50g
The about 2500g of pure water
The 50g hydroxypropyl emthylcellulose is dissolved in the 2500g pure water, is prepared into binder solution for granulating.By 3500g microcrystalline Cellulose and 1500g lactose mix homogeneously, put into one-step-granulating method, middling speed is started.After taking the dish out of the pot, will cushion granule and be placed in 60 ℃ of baking oven 4h, obtain dry buffering granule.Sieve, obtain 20-40 purpose buffering granule standby.
4. prepare pellet tablet
Buffering granule 5000g mix homogeneously by the lecithin chelated iodine enteric coated micropill 1000g of step 2 acquisition and step 3 acquisition, add magnesium stearate 30g, tabletting, tablet diameters is 8mm, the every heavily about 0.30g of sheet, tablet pressure is about 25N, obtains lecithin chelated iodine enteric coated micropill sheet.
Embodiment 2: the preparation of lecithin chelated iodine enteric coated micropill sheet comprises the following steps:
1. prepare the lecithin chelated iodine micropill by following each component materials of formula weighing:
80 order lactose ball core 700g
Lecithin chelated iodine (give money as a gift, pure, in iodine) 2g
Starch 200g
Microcrystalline Cellulose 50g
Pulvis Talci 100g
Polyvidone 150g
Ethanol 1000g
Pure water 5000g
Polyvidone is dissolved in to 70% alcoholic solution, is prepared into the aqueous solution of 10% content as binding agent; The material of lactose ball core being put to centrifugal coating granulator is indoor, separately the mixed-powder (120 order) of lecithin chelated iodine and starch 200 g, microcrystalline Cellulose 50 g and Pulvis Talci 100g is put in solid feed hopper.The water of take is wetting agent, starts centrifugal coating granulator by following parameter: engine speed 200 r/min, and air blast flux 20 * 20 L/min, spray air flow 15-20 L/min, whiff pressure 0.5 MPa, spray pump rotating speed 20 r/min, for powder speed 20 r/min.The 10% polyvidone alcoholic solution of take is binding agent, and the whitewashing time is 4 min, when round as a ball, maintains pump speed 20 r/min, and the round as a ball time is 2 min, the rear 60 ℃ of oven dry that take the dish out of the pot, and 20-40 order lecithin chelated iodine micropill is chosen in screening.
2. prepare coated micropill
Press following each component materials of formula weighing:
Lecithin chelated iodine micropill 900g
Su Teli (Sureteric) 150g
Hydroxypropyl emthylcellulose 20g
The about 20g of micropowder silica gel
The about 1500g of pure water
Adopt the fluidized-bed coating machine coating.Take pill appropriate, put in the air-flow coating device, with 3% hydroxypropyl emthylcellulose aqueous solution bag contagion gown, 40 ℃ of dryings are 10 min approximately, then use Su Te Lishui dispersion enteric coated, 40 ℃ of drying 2 h.Coating thickness is counted 12%-14% to contain the pill core weightening finish.Art for coating condition: blower frequency: 27.5 Hz; Whiff pressure: 0.2 MPa; Hydrojet flow velocity: 1 mLmin
-1Stream temperature: 35 ℃.After coating completes by coated micropill and 0.2%(w) micropowder silica gel mix, be placed in 40 ℃ of baking oven ripening 24 h.
3. prepare pellet tablet
Press following each component materials of formula weighing:
Microcrystalline Cellulose (Avicel PH102) 3500g
Spray-dried lactose (40-60 order) 1300g
Crospolyvinylpyrrolidone 200g
Magnesium stearate 30g
Lecithin chelated iodine enteric coated micropill 1000g and above-mentioned microcrystalline Cellulose, lactose and crospolyvinylpyrrolidone mix homogeneously by step 2 acquisition, add magnesium stearate 30g, tabletting, tablet diameters is 8mm, the every heavily about 0.30g of sheet, tablet pressure is about 25N, obtains lecithin chelated iodine enteric coated micropill sheet.
Claims (3)
1. lecithin enteric coated micropill sheet comprises the following steps:
(1) by lecithin chelated iodine and auxiliary materials and mixing, described adjuvant comprises one or more of disintegrating agent, excipient, diluent;
Described disintegrating agent is selected from one or more of dried starch, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and carboxymethylcellulose calcium;
Described excipient and diluent are selected from respectively one or more of starch, Icing Sugar, dextrin, lactose, pregelatinized Starch, microcrystalline Cellulose, Pulvis Talci, mannitol and sorbitol;
(2) by weight binding agent: adjuvant=0.05～0.5: it is 1%～15% binder solution that 1 ratio water and/or ethanol are mixed with mass percentage concentration by binding agent;
Described binding agent is selected from one or more of hyprolose, sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, polyvidone, gelatin, Polyethylene Glycol, sodium alginate;
(3) utilize binding agent the mixed material of step (1) to be sticked to the Blank Pellets surface prepared with lactose or starch, obtain the pastille micropill, the gross weight of the mixed material of described binding agent and step (1) and the weight ratio of Blank Pellets are 1: 5～2: 1;
(4) enteric-coating material dissolved or is distributed in solvent, being prepared into coating solution; To put into fluid bed to lecithin chelated iodine micropill prepared by step (3); Coating solution is placed in to liquid feeding end the lecithin chelated iodine micropill is carried out to coating, obtain the lecithin chelated iodine enteric coated-pellet; The mass percent of described coating material solution and lecithin chelated iodine micropill is 1: 3-1: 15;
(5) by the enteric coated-pellet granule direct compression of step (4), or with buffering granule prepared by conventional method, mix rear tabletting by weight the ratio of 1: 1～9: 1, obtain pellet tablet.
2. lecithin chelated iodine enteric coated micropill sheet according to claim 1 is characterized in that: step (5) is mixed direct compression afterwards by weight one or more of the ratio of 1: 1～9: 1 and disintegrating agent, excipient, diluent and is prepared lecithin chelated iodine enteric coated micropill sheet;
Described disintegrating agent is selected from one or more of dried starch, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and carboxymethylcellulose calcium;
Described excipient and diluent are selected from respectively one or more of starch, Icing Sugar, dextrin, lactose, pregelatinized Starch, microcrystalline Cellulose, Pulvis Talci, mannitol and sorbitol.
3. lecithin chelated iodine enteric coated micropill sheet according to claim 1, it is characterized in that: the described enteric-coating material of step (4) is selected from one or more in Lac, Cellulose Acetate Phthalate, alginate jelly, polyvinyl acetate phthalate, acrylic resin and hydroxypropyl methyl cellulose phthalate.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013103704929A CN103405390A (en) | 2013-08-23 | 2013-08-23 | Preparation method of lecithin-bound iodine enteric-coated pellet tablet |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013103704929A CN103405390A (en) | 2013-08-23 | 2013-08-23 | Preparation method of lecithin-bound iodine enteric-coated pellet tablet |
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| CN103405390A true CN103405390A (en) | 2013-11-27 |
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| CN2013103704929A Pending CN103405390A (en) | 2013-08-23 | 2013-08-23 | Preparation method of lecithin-bound iodine enteric-coated pellet tablet |
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