CN105796526A - Cephalosporin medicine capsule and preparing method thereof - Google Patents
Cephalosporin medicine capsule and preparing method thereof Download PDFInfo
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- CN105796526A CN105796526A CN201610181383.6A CN201610181383A CN105796526A CN 105796526 A CN105796526 A CN 105796526A CN 201610181383 A CN201610181383 A CN 201610181383A CN 105796526 A CN105796526 A CN 105796526A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
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Abstract
The invention provides a cephalosporin medicine capsule preparation.A capsule shell of the cephalosporin medicine capsule preparation is an empty capsule shell containing hydroxypropyl starch.The capsule preparation has good vitro dissolution and bioavailability, solves bitter taste regurgitation of cephalosporin medicine, and reduces adverse reactions such as nausea, diarrhea, stomachache, stomach discomfort, burning senseation, inappetence and inappetence.
Description
Technical field
The present invention relates to the capsule preparations of a kind of cephalosporins medicine, be specially a kind of cephalosporins medicine capsule adopting hydroxypropyl starch Capsules shell to prepare, belong to pharmaceutical technology field.
Background technology
Capsule is widely used in pharmaceuticals industry, as the capsule shells of one of main component, is a kind of shell protecting medicine, and it can not only protect medicine not to be destroyed, and also reduces medicine to respiratory tract and Alimentary stimulation.
But, there is multiple security risk in tradition gelatine capsule, because tradition gelatine capsule is that the animal proteinum colloid gelatin prepared using the skin of animal, bone hydrolysis is as capsule shell material.Due to limited source, illegal businessman utilizes the processing leftover pieces of industrial hides, or the non-leather that reclaims is treated makes the animal derived Capsules that edible or pharmagel thus supports and would be likely to occur heavy metals exceeding standard, water content is too high, cholesterol levels is high and causes the security risks such as animal sources infectious disease.
Hydroxypropyl starch capsule then possesses the remarkable advantages such as natural safety, long shelf-life, adaptation be wide.Starch capsule derives from natural Maninot esculenta crantz., and starch is after degenerative treatments, it is possible to effectively improve the character of gelatinized corn starch, strengthens the hydrophilic of gelatinized corn starch, makes the transparency of gelatinized corn starch and stability increase to some extent, not easily precipitate, good film-forming property, have excellent toughness.The many advantages such as not only have that raw material sources are natural, safety good, wide adaptability, storage are stable, it is thus also avoided that the zoonosis of conventional capsules.
Prior art as, CN104083768A discloses one and prepares Capsules shell, is made up of the composition of following weight proportion: component A: starch and derivant 15-30 part thereof；Component B: plant gum 2-13 part；Component C: coloring agent 0-5 part.Wherein, starch described in component A and combination that derivant is starch and hydroxypropyl starch thereof.
Cephalosporins has become clinical practice antibiotic the most widely, is generally divided into oral and injection by route of administration, and peroral dosage form includes tablet (including dispersible tablet etc.), capsule, granule, dry suspension etc..But, cephalosporins all has bad taste of smelling, and the medicines such as cephalo esters such as CEFUROXIME AXETIL also have strong bitterness, and patient's compliance is poor, common cephalosporins medicine capsule, when patient takes, there is the bitterness that reflux causes patient uncomfortable.Additionally, cephalosporins medicine there is also the untoward reaction such as nauseating, diarrhoea, stomachache, stomach discomfort, burn feeling, inappetence, constipation.
Although, prior art is instructed capsule can cover the bad of cephalosporins medicine and smell taste, but general capsule is when dissolution test, dissolution medium (water or gastric juice etc.) gelation met by medicine, medium can not continue deeper into inside, and drug dissolution is very low, causes that bioavailability is low, therefore, the research and development predicament of cephalosporins medicine capsule is caused.
At present, cephalosporins medicine capsule, in storing process, is subject to extraneous factor impact, it is easy to open loop is decomposed, and polymer content increases, and causes that its stability reduces.
Present inventors have surprisingly found that the capsule of cephalosporins medicine prepared by the employing Capsules shell containing hydroxypropyl starch can solve above-mentioned technical problem well.
Summary of the invention
It is an object of the invention to provide the capsule preparations of a kind of cephalosporins medicine, not only there is good In Vitro Dissolution and bioavailability, but also solve its bitterness reflux, reduce such as feel sick, diarrhoea, stomachache, stomach discomfort, burn feeling, inappetence, the untoward reaction such as constipation.
It is an object of the invention to provide a kind of cephalosporins medicine capsule preparations, it is characterised in that softgel shell is the Capsules shell containing hydroxypropyl starch.
It is an object of the invention to provide a kind of cephalosporins medicine capsule preparations, it is characterised in that softgel shell is that cephalosporins medicine preferably is selected from containing hydroxypropyl starch Capsules shell: cefradine, cefalexin, CEFUROXIME AXETIL.
Cefradine, respiratory tract infection, urogenital infections and the skin soft-tissue infection etc. such as acute pharyngitis caused by sensitive organism, tonsillitis, otitis media, bronchitis and pneumonia.Cefradine Capsules content is white to off-white color or pale yellow powder or granule, specification 0.25g and 0.5g.
Cefalexin, respiratory tract infection, urinary tract infection and the skin soft-tissue infection etc. such as acute tonsillitis caused by sensitive organism, angina, otitis media, sinusitis, bronchitis, pneumonia.Cefradine Capsules content is white to micro-yellow powder or granule, and specification 0.125g, 0.25g and 0.5g are (with C16H17N3O4S counts).
CEFUROXIME AXETIL, for sensitive microbial infection.Ceruroxime axetil capsules content is white or off-white powder or granule, and specification 0.125g, 0.25g and 0.5g are (with C16H16N4O8S counts).
As one of specific embodiments of the present invention, in the softgel shell of Capsules except hydroxypropyl starch, also can add gellant, help the conventional additives such as gellant, plasticizer, wetting agent.
Gellant, includes but not limited to arabic gum, xanthan gum, carrageenan, chitosan, trehalose Konjac glucomannan, carrageenin；
Help gellant, include but not limited to sodium salt or the potassium salt of citric acid, tartaric acid, phosphoric acid, acetic acid and ethylenediaminetetraacetic acid；
Plasticizer, includes but not limited to glycerol, sorbitol, mannitol, triethyl citrate, stearic acid, sucrose, fructose；
Wetting agent, includes but not limited to sodium lactate, propylene glycol, PEG400, sorbitol, polyvidone.
As one of specific embodiments of the present invention, thing in the capsule of Capsules, except cephalosporins medicine, the auxiliary additive being suitable to active medicine can be added, include but not limited to filler, lubricant, binding agent, disintegrating agent, fluidizer etc..
Filler, includes but not limited to starch, microcrystalline Cellulose, lactose, mannitol, dextrin, pregelatinized Starch, mannitol, sorbitol etc..
Lubricant, includes but not limited to magnesium stearate, Pulvis Talci, Glyceryl Behenate, Polyethylene Glycol, sodium lauryl sulphate etc..
Binding agent, includes but not limited to starch slurry, polyvidone, hypromellose, polyoxyethylene stearate (40) ester, hydroxypropylcellulose, arabic gum, xanthan gum, sodium carboxymethyl cellulose etc..
Disintegrating agent, includes but not limited to carboxymethylstach sodium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose etc..
Fluidizer, includes but not limited to silicon dioxide, Pulvis Talci etc..
Another object of the present invention, it is provided that a kind of preparation method prepared containing hydroxypropyl starch softgel shell, it is characterised in that including:
(1) glue is changed: by purified water to entering glue tank, heating, to 80～100 DEG C, is subsequently adding hydroxypropyl starch, insulated and stirred 90～180min；It is subsequently adding gellant, helps gellant, plasticizer and/or wetting agent, stir 10～15min, add activated carbon stirring decolouring 15min, filter to heat-preserving container temporary；
(2) sol solution obtained is made hydroxypropyl starch Capsules by full-automatic hollow capsule manufacture machining.
Another object of the present invention, it is provided that a kind of method preparing cephalo medicament capsule preparation, it is characterised in that including:
(1) weigh raw material and the adjuvant mix homogeneously of recipe quantity, granulate according to feedstock property selectivity, wet granulation or dry granulation；
(2) by the mixed-powder or particles filled in capsule of preparation.
Accompanying drawing explanation
Hereinafter, describe embodiment of the present invention in detail in conjunction with accompanying drawing, wherein:
The Cefradine Capsules plasma concentration curve figure of Fig. 1 different batches.
The cefalexin capsule plasma concentration curve figure of Fig. 2 different batches.
The Ceruroxime axetil capsules plasma concentration curve figure of Fig. 3 different batches.
Detailed description of the invention
Following example are further illustrating the present invention, but are definitely not limitation of the scope of the invention.It is further elaborated on the present invention referring to embodiment, it should be appreciated to those skilled in the art that the preparation method that the present invention is not limited to these embodiments and use.And, the present invention can be carried out equivalent replacement, combination, improvement according to description of the invention or modify by those skilled in the art, but these are intended to be included in the scope of the present invention.
Embodiment 1The preparation of the capsule shells containing hydroxypropyl starch
Prescription:
| Supplementary material | Consumption |
| Hydroxypropyl starch | 80g |
| Carrageenan | 7g |
| Chitosan | 5g |
| Sodium citrate | 3.5g |
| Triethyl citrate | 2.7g |
| Propylene glycol | 2g |
Preparation method:
(1) glue is changed: by purified water to entering glue tank, heating, to 80～100 DEG C, is subsequently adding hydroxypropyl starch, insulated and stirred 90～180min；It is subsequently adding residual components, stirs 10～15min, add activated carbon stirring decolouring 15min, filter to heat-preserving container temporary；
(2) sol solution obtained is made hydroxypropyl starch Capsules by full-automatic hollow capsule manufacture machining.
Comparative example 1aThe preparation of the capsule shells without hydroxypropyl starch
Prescription:
| Supplementary material | Consumption |
| Gelatin | 39g |
| Polyvinyl alcohol | 30.75g |
| Starch succinic acid | 26g |
| Hetastarch | 26.25g |
Preparation method:
(1) supplementary material of recipe quantity is become gelatin solution by changing gluing equipment boiling；Change glue temperature to control, at 56～75 DEG C, to be finally 63 DEG C；
(2) Capsules is made by full-automatic hollow capsule manufacture machining.
Comparative example 1bPreparation containing hydroxypropyl starch He other excipient capsule shells
Prescription:
Preparation method:
(1) after taking hydroxypropyl starch 100g, starch 200g mixing, adding 90 DEG C of purified water 4L, stirring becomes thick liquid, is incubated 2h.Then liquid entrance centrifugal spraying spray dryer carries out spray drying, and controlling inlet temperature is 180 DEG C, and leaving air temp is 90 DEG C, obtains mixed-powder A.
(2) after taking arabic gum 8g, carrageenan 20g, guar gum 8g, xanthan gum 20g mixing, add purified water 600ml, stirring becomes thick liquid, add decolorization and impurity removal by active carbon again, filtering, filtrate adds ethanol 280ml precipitation, filtration under diminished pressure, vacuum drying under 50 DEG C of conditions, obtains mixed powder B.
(3) take 120g mixed-powder A, 20g mixed powder B and 3g light blue mixes in proportion.
(4) in the powder of mix homogeneously, add purified water, be uniformly mixing to obtain glue；Capsules is made by full-automatic hollow capsule manufacture machining.
Comparative example 1cThe preparation of the capsule shells containing gelatin
Prescription:
| Supplementary material | Consumption |
| Gelatin | 80g |
| Carrageenan | 7g |
| Chitosan | 5g |
| Sodium citrate | 3.5g |
| Triethyl citrate | 2.7g |
| Propylene glycol | 2g |
Preparation method:
(1) glue is changed: by purified water to entering glue tank, heating, to 80～100 DEG C, is subsequently adding gelatin, insulated and stirred 90～180min；It is subsequently adding gellant, helps gellant, plasticizer and wetting agent, stir 10～15min, add activated carbon stirring decolouring 15min, filter to heat-preserving container temporary；
(2) sol solution obtained is made hydroxypropyl starch Capsules by full-automatic hollow capsule manufacture machining.
Embodiment 2a-2dPrepare thing in the capsule of Cefradine Capsules (0.25g specification, 1000)
| Excipient | Embodiment 2a | Embodiment 2b | Embodiment 2c | Embodiment 2d |
| Cefradine | 250g | 250g | 250g | 250g |
| Cross-linking sodium carboxymethyl cellulose | 75g | |||
| Microcrystalline Cellulose | 50g | |||
| Sodium bicarbonate | 52.5g | |||
| Polyoxyethylene stearate (40) ester | 4.2g | |||
| Silicon dioxide | 5g | 2.8g | 6.25g | |
| Magnesium stearate | 6.9g | 6.25g | ||
| Hydroxypropyl cellulose | 13.9g | 35g | ||
| Lactose | 45g |
Preparation process:
Embodiment 2a
1, cefradine and the silicon dioxide of recipe quantity, mix homogeneously are weighed.
Embodiment 2b
1, after cross-linking sodium carboxymethyl cellulose being mixed homogeneously with cefradine, mix with microcrystalline Cellulose, then mix with sodium bicarbonate.
Embodiment 2c
1, being mixed in prescription ratio with silicon dioxide by polyoxyethylene stearate (40) ester, and pulverize and sieve, sieve number is 60 orders；Hydroxypropylcellulose, magnesium stearate and cefradine crude drug sieve respectively, and sieve number is 80 orders；
2, weigh, by recipe quantity, each raw material that step 1 prepares, first the mixed powder of polyoxyethylene stearate (40) ester and silicon dioxide and magnesium stearate are mixed and mix, then press equal increments method to mix with hydroxypropylcellulose, it is eventually adding cefradine crude drug, mixer mixes 20 minutes, the content needed for capsule must be filled.
Embodiment 2d
1, the cefradine of recipe quantity, lactose being crossed 200 mesh sieves, hydroxypropylcellulose, magnesium stearate mixed 60 mesh sieves, and silicon dioxide crosses 120 mesh sieves；Cefradine raw material and lactose were mixed 60 mesh sieves, standby；
2, by the mixture of gained cefradine Yu lactose, add three-dimensional motion mixer mix 45 minutes together with remaining hydroxypropylcellulose, magnesium stearate, silicon dioxide, the mixed powder being uniformly mixed.
Embodiment 3 prepares Cefradine Capsules
Preparation method:
By thing in the capsule capsule of embodiment 2a-2d, it is respectively charged into embodiment 1, in the Capsules shell of comparative example 1a-1c.
Embodiment 4a-4dPrepare thing in cefalexin capsule capsule (0.25g specification, 1000)
| Excipient | Embodiment 4a | Embodiment 4b | Embodiment 4c | Embodiment 4d |
| Cefalexin | 250g | 250g | 250g | 250g |
| Cross-linking sodium carboxymethyl cellulose | 75g | |||
| Microcrystalline Cellulose | 50g | 50g | ||
| Sodium bicarbonate | 52.5g | |||
| Pulvis Talci | 6g | |||
| Polyoxyethylene stearate (40) ester | 4.2g | |||
| Silicon dioxide | 2.8g | 6.25g | ||
| Magnesium stearate | 6.9g | 6.25g | ||
| Hydroxypropyl cellulose | 13.9g | 35g | ||
| Lactose | 45g |
Preparation process:
Embodiment 4a
1, the cefalexin of recipe quantity, microcrystalline Cellulose and Pulvis Talci, mix homogeneously are weighed.
Embodiment 4b
1, after cross-linking sodium carboxymethyl cellulose being mixed homogeneously with cefalexin, mix with microcrystalline Cellulose, then mix with sodium bicarbonate.
Embodiment 4c
1, being mixed in prescription ratio with silicon dioxide by polyoxyethylene stearate (40) ester, and pulverize and sieve, sieve number is 60 orders；Hydroxypropylcellulose, magnesium stearate and cefalexin crude drug sieve respectively, and sieve number is 80 orders；
2, weigh, by recipe quantity, each raw material that step 1 prepares, first the mixed powder of polyoxyethylene stearate (40) ester and silicon dioxide and magnesium stearate are mixed and mix, then press equal increments method to mix with hydroxypropylcellulose, it is eventually adding cefalexin crude drug, mixer mixes 20 minutes, the content needed for capsule must be filled.
Embodiment 4d
1, the cefalexin of recipe quantity, lactose being crossed 200 mesh sieves, hydroxypropylcellulose, magnesium stearate mixed 60 mesh sieves, and silicon dioxide crosses 120 mesh sieves；Cefalexin raw material and lactose were mixed 60 mesh sieves, standby；
2, by the mixture of gained cefalexin Yu lactose, add three-dimensional motion mixer mix 45 minutes together with remaining hydroxypropylcellulose, magnesium stearate, silicon dioxide, the mixed powder being uniformly mixed.
Embodiment 5 prepares cefalexin capsule
| Combination | Embodiment 4a | Embodiment 4b | Embodiment 4c | Embodiment 4d |
| Embodiment 1 | 4a1 | 4b1 | 4c1 | 4d1 |
| Comparative example 1a | 4a1a | 4b1a | 4c1a | 4d1a |
| Comparative example 1b | 4a1b | 4b1b | 4c1b | 4d1b |
| Comparative example 1c | 4a1c | 4b1c | 4c1c | 4d1c |
Preparation method:
By thing in the capsule capsule of embodiment 4a-4d, it is respectively charged into embodiment 1, in the Capsules shell of comparative example 1a-1c.
Embodiment 6a-6dPrepare thing in Ceruroxime axetil capsules capsule (0.25g specification, 1000)
| Excipient | Embodiment 6a | Embodiment 6b | Embodiment 6c | Embodiment 6d |
| CEFUROXIME AXETIL | 250g | 250g | 250g | |
| Cross-linking sodium carboxymethyl cellulose | 75g | |||
| Microcrystalline Cellulose | 50g | 50g | ||
| Sodium bicarbonate | 52.5g | |||
| Glyceryl Behenate | 6g | |||
| Polyoxyethylene stearate (40) ester | 4.2g | |||
| Silicon dioxide | 2.8g | 6.25g | ||
| Magnesium stearate | 6.9g | 6.25g | ||
| Hydroxypropyl cellulose | 13.9g | 35g | ||
| Lactose | 45g |
Preparation process:
Embodiment 6a
1, CEFUROXIME AXETIL and microcrystalline Cellulose mix homogeneously, the dry granulation of recipe quantity are weighed；
2, in granule, add the Glyceryl Behenate of recipe quantity, mix homogeneously.
Embodiment 6b
1, after cross-linking sodium carboxymethyl cellulose being mixed homogeneously with CEFUROXIME AXETIL, mix with microcrystalline Cellulose, then mix with sodium bicarbonate.
Embodiment 6c
1, being mixed in prescription ratio with silicon dioxide by polyoxyethylene stearate (40) ester, and pulverize and sieve, sieve number is 60 orders；Hydroxypropylcellulose, magnesium stearate and CEFUROXIME AXETIL crude drug sieve respectively, and sieve number is 80 orders；
2, weigh, by recipe quantity, each raw material that step 1 prepares, first the mixed powder of polyoxyethylene stearate (40) ester and silicon dioxide and magnesium stearate are mixed and mix, then press equal increments method to mix with hydroxypropylcellulose, it is eventually adding CEFUROXIME AXETIL crude drug, mixer mixes 20 minutes, the content needed for capsule must be filled.
Embodiment 6d
1, the CEFUROXIME AXETIL of recipe quantity, lactose being crossed 200 mesh sieves, hydroxypropylcellulose, magnesium stearate mixed 60 mesh sieves, and silicon dioxide crosses 120 mesh sieves；CEFUROXIME AXETIL raw material and lactose were mixed 60 mesh sieves, standby；
2, by the mixture of gained CEFUROXIME AXETIL Yu lactose, add three-dimensional motion mixer mix 45 minutes together with remaining hydroxypropylcellulose, magnesium stearate, silicon dioxide, the mixed powder being uniformly mixed.
Embodiment 7 prepares Ceruroxime axetil capsules
| Combination | Embodiment 6a | Embodiment 6b | Embodiment 6c | Embodiment 6d |
| Embodiment 1 | 6a1 | 6b1 | 6c1 | 6d1 |
| Comparative example 1a | 6a1a | 6b1a | 6c1a | 6d1a |
| Comparative example 1b | 6a1b | 6b1b | 6c1b | 6d1b |
| Comparative example 1c | 6a1c | 6b1c | 6c1c | 6d1c |
Preparation method:
By thing in the capsule capsule of embodiment 6a-6d, it is respectively charged into embodiment 1, in the Capsules shell of comparative example 1a-1c.
Test example 1 Cefradine Capsules detects
Test example 1-1 study on the stability
Sample 2a1-2d1c amounts to 16 samples detect, is subsequently placed in 40 DEG C ± 2 DEG C, place 6 months under relative humidity 75% ± 5% condition, respectively at 1,2,3, detection in June, detection moisture and polymer, result is as follows:
Brief summary: from above-mentioned test data, the Cefradine Capsules of the different prescriptions that the Capsules containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, moist and the cefradine polymer accelerated test of drawing of its content is investigated and is far smaller than comparative example 1a and comparative example 1c and contain the Cefradine Capsules that the Capsules shell of hydroxypropyl starch is made, absolutely proved Cefradine Capsules that the present invention adopts hydroxypropyl starch capsule shells to prepare control to draw moist with cefradine polymer in superiority.
Test example 1-2 dissolution in vitro detects
Sample 2a1-2d1c amounting to 16 samples and carries out dissolution in vitro detection, result is as follows:
| Sample | Dissolution (%) |
| Sample 2a1 | 95.8 |
| Sample 2b1 | 96.3 |
| Sample 2c1 | 94.9 |
| Sample 2d1 | 96.1 |
| Sample 2a1a | 89.8 |
| Sample 2b1a | 87.6 |
| Sample 2c1a | 85.9 |
| Sample 2d1a | 88.2 |
| Sample 2a1b | 97.0 |
| Sample 2b1b | 96.6 |
| Sample 2c1b | 95.9 |
| Sample 2d1b | 97.3 |
| Sample 2a1c | 86.7 |
| Sample 2b1c | 85.8 |
| Sample 2c1c | 84.4 |
| Sample 2d1c | 87.0 |
Brief summary: from above-mentioned test data, the Cefradine Capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, its dissolution in vitro does not contain, more than comparative example 1a and comparative example 1c, the Cefradine Capsules that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved Cefradine Capsules that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in improving dissolution in vitro.
Test example 1-3 bioavailability
Sample 2a1-2d1c amounting to 16 samples and carries out vivo biodistribution equivalence trial, blood drug level is detected, result is shown in accompanying drawing 1.
Brief summary: from above-mentioned test data, the Cefradine Capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, its internal blood drug level does not contain, more than comparative example 1a and comparative example 1c, the Cefradine Capsules that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved Cefradine Capsules that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in improving vivo biodistribution availability.
Test example 1-4 bitterness reflux
Sample 2a1-2d1c amounting to 16 samples when carrying out vivo biodistribution equivalence trial, to taking medicine, volunteer carries out 24h monitoring, to whether there being bitterness reflux to be tracked after taking, often organizes 20 cases, and result is as follows.
Brief summary: from above-mentioned test data, the Cefradine Capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, after it is taken, internal bitterness reflux phenomenon is far smaller than comparative example 1a and comparative example 1c and contain the Cefradine Capsules that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved Cefradine Capsules that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in suppression cephalosporins medicine bitterness reflux phenomenon.
Test example 1-5 untoward reaction
Sample 2a1-2d1c amounting to 16 samples when carrying out vivo biodistribution equivalence trial, to taking medicine, volunteer carries out 24h monitoring, is tracked taking rear untoward reaction, often organizes 20 cases, and result is as follows.
Brief summary: from above-mentioned test data, the Cefradine Capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, it is taken rear patient's untoward reaction phenomenon and is not contained, far less than comparative example 1a and comparative example 1c, the Cefradine Capsules that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved Cefradine Capsules that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in reducing cephalosporins medicine untoward reaction.
Test example 2 cefalexin capsule detects
Test example 2-1 study on the stability
Sample 4a1-4d1c amounts to 16 samples detect, is subsequently placed in 40 DEG C ± 2 DEG C, place 6 months under relative humidity 75% ± 5% condition, respectively at 1,2,3, detection in June, detection moisture and polymer, result is as follows:
Brief summary: from above-mentioned test data, the cefalexin capsule of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, moist and the cefalexin polymer accelerated test of drawing of its content is investigated and is far smaller than comparative example 1a and comparative example 1c and contain the Cefradine Capsules that the Capsules shell of hydroxypropyl starch is made, absolutely proved cefalexin capsule that the present invention adopts hydroxypropyl starch capsule shells to prepare control to draw moist with cefalexin polymer in superiority.
Test example 2-2 dissolution in vitro detects
Sample 4a1-4d1c amounting to 16 samples and carries out dissolution in vitro detection, result is as follows:
| Sample | Dissolution (%) |
| Sample 4a1 | 98.8 |
| Sample 4b1 | 97.9 |
| Sample 4c1 | 96.5 |
| Sample 4d1 | 99.1 |
| Sample 4a1a | 91.0 |
| Sample 4b1a | 87.8 |
| Sample 4c1a | 89.2 |
| Sample 4d1a | 88.5 |
| Sample 4a1b | 98.9 |
| Sample 4b1b | 99.6 |
| Sample 4c1b | 98.8 |
| Sample 4d1b | 99.7 |
| Sample 4a1c | 85.9 |
| Sample 4b1c | 87.6 |
| Sample 4c1c | 89.2 |
| Sample 4d1c | 88.8 |
Brief summary: from above-mentioned test data, the cefalexin capsule of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, its dissolution in vitro does not contain, more than comparative example 1a and comparative example 1c, the cefalexin capsule that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved cefalexin capsule that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in improving dissolution in vitro.
Test example 2-3 bioavailability
Sample 4a1-4d1c amounting to 16 samples and carries out vivo biodistribution equivalence trial, blood drug level is detected, result is shown in accompanying drawing 2.
Brief summary: from above-mentioned test data, the cefalexin capsule of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, its internal blood drug level does not contain, more than comparative example 1a and comparative example 1c, the cefalexin capsule that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved cefalexin capsule that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in improving vivo biodistribution availability.
Test example 2-4 bitterness reflux
Sample 4a1-4d1c amounting to 16 samples when carrying out vivo biodistribution equivalence trial, to taking medicine, volunteer carries out 24h monitoring, to whether there being bitterness reflux to be tracked after taking, often organizes 20 cases, and result is as follows.
Brief summary: from above-mentioned test data, the cefalexin capsule of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, after it is taken, internal bitterness reflux phenomenon is far smaller than comparative example 1a and comparative example 1c and contain the cefalexin capsule that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved cefalexin capsule that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in suppression cephalosporins medicine bitterness reflux phenomenon.
Test example 2-5 untoward reaction
Sample 4a1-4d1c amounting to 16 samples when carrying out vivo biodistribution equivalence trial, to taking medicine, volunteer carries out 24h monitoring, is tracked taking rear untoward reaction, often organizes 20 cases, and result is as follows.
| Sample | Feel sick | Stomach discomfort | Stomachache | Burning sensation | Amount to |
| Sample 4a1 | 0 | 1 | 1 | 0 | 2 |
| Sample 4b1 | 1 | 0 | 1 | 1 | 3 |
| Sample 4c1 | 0 | 1 | 0 | 1 | 2 |
| Sample 4d1 | 1 | 1 | 0 | 0 | 2 |
| Sample 4a1a | 3 | 2 | 1 | 2 | 7 |
| Sample 4b1a | 2 | 1 | 2 | 2 | 7 |
| Sample 4c1a | 3 | 2 | 0 | 3 | 8 |
| Sample 4d1a | 1 | 1 | 2 | 2 | 6 |
| Sample 4a1b | 1 | 0 | 0 | 0 | 1 |
| Sample 4b1b | 1 | 0 | 1 | 0 | 2 |
| Sample 4c1b | 0 | 1 | 0 | 0 | 1 |
| Sample 4d1b | 0 | 0 | 0 | 1 | 1 |
| Sample 4a1c | 1 | 2 | 2 | 3 | 8 |
| Sample 4b1c | 2 | 1 | 2 | 1 | 6 |
| Sample 4c1c | 0 | 2 | 3 | 1 | 6 |
| Sample 4d1c | 1 | 2 | 2 | 1 | 6 |
Brief summary: from above-mentioned test data, the cefalexin capsule of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, it is taken rear patient's untoward reaction phenomenon and is not contained, far less than comparative example 1a and comparative example 1c, the cefalexin capsule that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved cefalexin capsule that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in reducing cephalosporins medicine untoward reaction.
Test example 3 Ceruroxime axetil capsules detects
Test example 3-1 study on the stability
Sample 6a1-6d1c amounts to 16 samples detect, is subsequently placed in 40 DEG C ± 2 DEG C, place 6 months under relative humidity 75% ± 5% condition, respectively at 1,2,3, detection in June, detection moisture and polymer, result is as follows:
Brief summary: from above-mentioned test data, the Ceruroxime axetil capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, moist and the cefuroxime ester polymer accelerated test of drawing of its content is investigated and is far smaller than comparative example 1a and comparative example 1c and contain the Ceruroxime axetil capsules that the Capsules shell of hydroxypropyl starch is made, absolutely proved Ceruroxime axetil capsules that the present invention adopts hydroxypropyl starch capsule shells to prepare control to draw moist with cefuroxime ester polymer in superiority.
Test example 3-2 dissolution in vitro detects
Sample 6a1-6d1c amounting to 16 samples and carries out dissolution in vitro detection, result is as follows:
Brief summary: from above-mentioned test data, the Ceruroxime axetil capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, its dissolution in vitro does not contain, more than comparative example 1a and comparative example 1c, the Ceruroxime axetil capsules that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved Ceruroxime axetil capsules that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in improving dissolution in vitro.
Test example 3-3 bioavailability
Sample 6a1-6d1c amounting to 16 samples and carries out vivo biodistribution equivalence trial, blood drug level is detected, result is shown in accompanying drawing 3.
Brief summary: from above-mentioned test data, the Ceruroxime axetil capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, its internal blood drug level does not contain, more than comparative example 1a and comparative example 1c, the Ceruroxime axetil capsules that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved Ceruroxime axetil capsules that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in improving vivo biodistribution availability.
Test example 3-4 bitterness reflux
Sample 6a1-6d1c amounting to 16 samples when carrying out vivo biodistribution equivalence trial, to taking medicine, volunteer carries out 24h monitoring, to whether there being bitterness reflux to be tracked after taking, often organizes 20 cases, and result is as follows.
Brief summary: from above-mentioned test data, the Ceruroxime axetil capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, after it is taken, internal bitterness reflux phenomenon is far smaller than comparative example 1a and comparative example 1c and contain the Ceruroxime axetil capsules that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved Ceruroxime axetil capsules that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in suppression cephalosporins medicine bitterness reflux phenomenon.
Test example 3-5 untoward reaction
Sample 6a1-6d1c amounting to 16 samples when carrying out vivo biodistribution equivalence trial, to taking medicine, volunteer carries out 24h monitoring, is tracked taking rear untoward reaction, often organizes 20 cases, and result is as follows.
| Sample | Feel sick | Stomach discomfort | Stomachache | Burning sensation | Amount to |
| Sample 6a1 | 0 | 1 | 0 | 0 | 1 |
| Sample 6b1 | 1 | 0 | 0 | 1 | 2 |
| Sample 6c1 | 0 | 0 | 1 | 0 | 1 |
| Sample 6d1 | 1 | 1 | 0 | 0 | 2 |
| Sample 6a1a | 3 | 2 | 1 | 3 | 9 |
| Sample 6b1a | 2 | 3 | 1 | 2 | 8 |
| Sample 6c1a | 3 | 2 | 2 | 0 | 7 |
| Sample 6d1a | 1 | 2 | 3 | 1 | 7 |
| Sample 6a1b | 0 | 1 | 1 | 0 | 2 |
| Sample 6b1b | 0 | 0 | 1 | 0 | 1 |
| Sample 6c1b | 2 | 0 | 0 | 1 | 3 |
| Sample 6d1b | 0 | 1 | 1 | 0 | 2 |
| Sample 6a1c | 1 | 2 | 2 | 2 | 7 |
| Sample 6b1c | 2 | 2 | 3 | 1 | 8 |
| Sample 6c1c | 1 | 1 | 1 | 3 | 6 |
| Sample 6d1c | 2 | 2 | 3 | 2 | 9 |
Brief summary: from above-mentioned test data, the Ceruroxime axetil capsules of the different prescriptions that the Capsules shell containing hydroxypropyl starch prepared by employing embodiment 1 and comparative example 1b is made, it is taken rear patient's untoward reaction phenomenon and is not contained, far less than comparative example 1a and comparative example 1c, the Ceruroxime axetil capsules that the Capsules shell of hydroxypropyl starch is made, and has absolutely proved Ceruroxime axetil capsules that the present invention adopts hydroxypropyl starch capsule shells the to prepare superiority in reducing cephalosporins medicine untoward reaction.
Claims (6)
1. a cephalosporins medicine capsule preparations, it is characterised in that softgel shell is the capsule shells containing hydroxypropyl starch.
2. cephalosporins medicine capsule preparations according to claim 1, it is characterised in that described cephalosporins medicine is selected from cefradine, cefalexin, CEFUROXIME AXETIL.
3. cephalosporins medicine capsule preparations according to claim 1, it is characterised in that in described Capsules shell except hydroxypropyl starch, also can add gellant, help the conventional additives such as gellant, plasticizer, wetting agent.
4. the cephalosporins medicine capsule preparations according to any one of claim 1-3, it is characterized in that thing in capsule, except cephalosporins medicine, the auxiliary additive being suitable to active medicine can be added, include but not limited to filler, lubricant, binding agent, disintegrating agent, fluidizer etc..
5. the preparation method prepared containing hydroxypropyl starch softgel shell, it is characterised in that including:
(1) glue is changed: by purified water to entering glue tank, heating, to 80～100 DEG C, is subsequently adding hydroxypropyl starch, insulated and stirred 90～180min；It is subsequently adding gellant, helps gellant, plasticizer and/or wetting agent, stir 10～15min, add activated carbon stirring decolouring 15min, filter to heat-preserving container temporary；
(2) sol solution obtained is made hydroxypropyl starch Capsules shell by full-automatic hollow capsule manufacture machining.
6. the method preparing cephalosporins medicine capsule, it is characterised in that including:
(1) weigh raw material and the adjuvant mix homogeneously of recipe quantity, granulate according to feedstock property selectivity, wet granulation or dry granulation；
(2) by the mixed-powder or particles filled in capsule of preparation.
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| CN110613697A (en) * | 2019-10-30 | 2019-12-27 | 长春迪瑞制药有限公司 | Cefalexin capsule and preparation method thereof |
| CN112972416A (en) * | 2021-03-30 | 2021-06-18 | 海南海力制药有限公司 | Preparation method of cefradine capsule |
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| CN110613697A (en) * | 2019-10-30 | 2019-12-27 | 长春迪瑞制药有限公司 | Cefalexin capsule and preparation method thereof |
| CN112972416A (en) * | 2021-03-30 | 2021-06-18 | 海南海力制药有限公司 | Preparation method of cefradine capsule |
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Application publication date: 20160727 |