CN104146985A - Preparation method of phenoxymethylpenicillin potassium capsule - Google Patents
Preparation method of phenoxymethylpenicillin potassium capsule Download PDFInfo
- Publication number
- CN104146985A CN104146985A CN201410396192.2A CN201410396192A CN104146985A CN 104146985 A CN104146985 A CN 104146985A CN 201410396192 A CN201410396192 A CN 201410396192A CN 104146985 A CN104146985 A CN 104146985A
- Authority
- CN
- China
- Prior art keywords
- capsule
- preparation
- potassium
- filling
- calcium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a phenoxymethylpenicillin potassium capsule and a production process thereof. The phenoxymethylpenicillin potassium capsule provided by the invention has the advanategs of simple manufacturing process, low cost, no need to add flavoring agent, stable product quality, and benefit for industrialized production.
Description
Technical field
The invention belongs to pharmaceutical field, relate to a kind of preparation method of penicillin medicine, particularly, relate to the preparation method of potassium v calcium capsule.
Background technology
Penicillin V (penicillin V) is the Phenoxymethyl derivant of benzylpenicillin, potassium v calcium (penicillin V potassium, phenoxymethylpenicillin potassium) be the potassium salt of penicillin V, chemical name is (2S, 5R, 6R)-3,3-dimethyl-7-oxo-6-(2-phenoxy group acetylamino)-4-thia-1-azabicyclo [3.2.0]-heptane-2-formic acid potassium salt, its molecular formula is C
16h
17kN
2o
5s, molecular weight is 388.5.Potassium v calcium is that first,, for oral natural antibiotics, is also the beta-lactam antibiotic that has clinical value of second natural generation after benzylpenicillin in the world, since nineteen fifty-three listing, has obtained applying very widely.
Penicillin V is a kind of biosynthetic, stable antibiotic of stable, the non-penicillinase of acid, and it can check the biosynthesis of the pathogen cells wall of propagation and sensitivity.The antimicrobial spectrum of penicillin V comprises: the gram-positive bacterium of aerobic and anaerobism is (as corynebacterium, Listerella, shuttle shape bacillocin genus, anthrax bacillus, actinomycetes, enterococcus and generate except the staphylococcus of penicillinase), the Gram-negative coccus of aerobic and anaerobism (meningococcus, bacteroides oralis belong to kind, fusobacterium especially fusobacterium nucleatum, Veilonclla and fermentation coccus).This product is acidproof, is not destroyed after oral, and approximately 60% absorbs at duodenum.Within after oral 0.5g approximately 1 hour, reach blood peak concentration of drug, be 3～5mg/L.Food can reduce the absorption of this product, and protein binding rate is 80%.20%～35% of dosage is discharged through urine with original shape.The blood plasma elimination half-life of this product is about 1 hour.
Potassium v calcium is applicable to light, the grade and moderate infection due to penicillin sensitive strain, comprises tonsillitis due to streptococcus, pharyngolaryngitis, scarlet fever, erysipelas etc.; Skin soft-tissue infection due to bronchitis due to streptococcus pneumoniae, pneumonia, otitis media, sinusitis and responsive staphylococcus etc.Potassium v calcium also, as the prophylactic of rheumatic fever recurrence and infective endocarditis, also can be used for spirochaete infection.
The former medicine of potassium v calcium is white or off-white color granule or powder, has a kind of stronger abnormal smells from the patient, is not easy to be accepted by patient.Patent documentation CN101002767A discloses a kind of dispersion tablets of penicillin V potassium and preparation method thereof, in this invention by the former powder of potassium v calcium and supplementary product starch and alcoholic solution are mixed and make soft material, and then granulation, tabletting is made.While taking, dispersible tablet disintegrate in water forms suspension, can swallow, chews, contain and suck.In this patent documentation, be mainly by adding stevioside as correctives.
The prescription of potassium v calcium conventional tablet is relatively complicated at present, and mainly adopt the method for wet granulation to produce, and under the condition of high humidity, high temperature, oxidation, penicillins product easily produces degradation reaction, thereby cause the stability of penicillin V potassium bad, keeping life is short, simultaneously the technological process complexity of wet granulation and technological process is long, production cost is high.
Patent documentation CN103893150A discloses a kind of potassium v calcium microcapsule and preparation method thereof.Microcapsule is to use natural or synthetic macromolecular material that molecule is wrapped in to the technology in cyst membrane, and its particle radius is generally in micrometer range.Material in microcapsule is because tunica material intercepts, so external environment is less on the impact of capsule-core, thereby keeps stable.And there is the adverse drug of covering abnormal smells from the patient, improve medicine stability, weaken medicine to features such as gastrointestinal zests.Meanwhile, under proper condition, capsule-core medicine can discharge from capsule material again, by suitable means, can reach controlled-release effect.But the preparation of microcapsule needs special technology and instrument, and cost is higher.
Need a kind of simple process, with low cost, and do not need to add the preparation method of the potassium v calcium peroral dosage form of correctives.
Summary of the invention
A first aspect of the present invention provides a kind of potassium v calcium capsule formulation.
Potassium v calcium capsule of the present invention comprises and is placed in the former medicine 0.236g of potassium v calcium (40Wan unit) of gelatine capsule and the adjuvant magnesium stearate of former medicine weight 1%, and the hard sheet of polrvinyl chloride solid medicinal and the drug packaging aluminium foil that cover outward.
A second aspect of the present invention provides the manufacturing process of above-mentioned potassium v calcium capsule, and this manufacturing process mainly comprises the following steps:
(1) supplementary material is prepared;
(2) weigh;
(3) always mixed;
(4) filling;
(5) aluminum-plastic packaged;
(6) outsourcing.
Preferably, according to flow process shown in Fig. 1, manufacture.
In a specific embodiment, the concrete operation step of above-mentioned steps (1) comprising: according to batch production ordering, get this batch of required raw and auxiliary material from warehouse, after sloughing outer package, use the towel of drinking water moistening by inner bag wiped clean, use again 75% ethanol spray disinfectant, stick the appointed area, chamber of getting the raw materials ready between placing car after material state sign temporary.
In a specific embodiment, in above-mentioned steps (2) according to batch production ordering to each material weigh, labelling.Every crowd of former medicine 404.57kg of 1,500,000 needs potassium v calciums (potassium v calcium moisture content is by 87.5%), magnesium stearate 4.05kg.
In a specific embodiment, the concrete operation step of above-mentioned steps (3) comprising: load weighted former, adjuvant is added in HDA-1000 type Mixers with Multi-direction Movement by vacuum feeding successively, mix 5 minutes, as one, produce batch.Mixed medicated powder is contained in the bucket of inner lining plastic bag, carries out the status indication of material after weighing, hands over intermediate station to preserve.The condition of storage of mixed medicated powder is shading, airtight, dry, and the storage time is no more than 15 days.
In a specific embodiment, in above-mentioned steps (4), use NJP-2000 type fully-automatic capsule filling machine to carry out filling, technological parameter is as follows: powder disc thickness 14～16mm, 1500～2000/minute of filling velocities, vacuum 0.02～0.06MPa.Capsule after filling is stored in intermediate station and does honest material status indication.The condition of storage of the capsule after filling is shading, sealing, dry, and the storage time is no more than 18 days.
In a specific embodiment, in above-mentioned steps (5), use blister packaging machine to carry out hot synthetic type to capsule, technological parameter is as follows: compressed air 0.4～0.7MPa, 130～150 ℃ of upper plate temperatures, 130～150 ℃ of lower plate temperatures, 200～230 ℃ of heat-sealing temperatures, 190～210 ℃ of imprint temperature.Aluminum-plastic packaged capsule storage condition is shading, sealing, dry, and the storage time is no more than 12 days.
In a specific embodiment, in above-mentioned steps (6) according to batch packaging directive pack, mounted box, thermal contraction, vanning work.
Potassium v calcium capsule manufacturing process of the present invention is easy, with low cost, and does not need to add correctives, and end product quality is stable, is beneficial to suitability for industrialized production.
Accompanying drawing explanation
Fig. 1 potassium v calcium capsule manufacturing process flow diagram and region are divided.
The specific embodiment
Below by embodiment, further illustrate the present invention, but the present invention is not limited.The experimental technique of unreceipted actual conditions in the following example, conventionally according to normal condition, or the condition of advising according to manufacturer.Below the percent not specializing is mass percent.
Supplementary material title used and quantity are in Table 1.
Table 1
By packaging material title and quantity in Table 2.
Table 2
End product quality standard is in Table 3.
Table 3
Between each process operations and capital equipment respectively in Table 4 and table 5.
Table 4
Table 5
| Operation | Device name | Model |
| Total mixed | Mixers with Multi-direction Movement | HD-1500 |
| Filling | Capsule filler | NJP-2000 |
| Aluminum-plastic packaged | Blister packaging machine | DPT190 |
| Outsourcing | Pillow type packing machine | DZB-250 |
According to technological process shown in Fig. 1, manufacture potassium v calcium capsule.
1. supplementary material is prepared:
According to batch production ordering, from warehouse, get this batch of required raw and auxiliary material, slough after outer package with the towel of drinking water moistening inner bag wiped clean, then use 75% ethanol spray disinfectant, stick the appointed area, chamber of getting the raw materials ready between placing car after material state sign temporary.
2. weigh:
According to batch production ordering to each material weigh, labelling, electronic scale should check according to < < pharmaceutical workshop electronic balance, electronic scale rule of operation > > before using, and should observe < < and weigh process operations rules > > during weighing.
In every batch of medicine production process, monitor the character of supplementary material, and verification weighs instrument before weighing.
3. always mixed:
Load weighted former, adjuvant is added in HDA-1000 type Mixers with Multi-direction Movement by vacuum feeding successively, according to < < Mixers with Multi-direction Movement rule of operation > > M-MD01-00102, mix 5 minutes, as one, produce and criticize.Mixed medicated powder is contained in the bucket of inner lining plastic bag, carries out the status indication of material after weighing, hands over intermediate station to preserve.Qualified through pick test, can carry out filling.
Condition of storage: shading, sealing, preserves at dry place.
Storage time: 15 days.
4. filling:
Specification: press C
16h
18n
2o
5s calculates, 0.236g (40Wan unit)/grain
Content scope: 93.0%～107.0% of standard loading amount
The trial run stage: go to work every day and change while criticizing and should do test-run a machine work.According to < < NJP-2000 type fully-automatic capsule filling machine rule of operation > >, carry out the loading amount of installation, operation filling machine and the adjusting capsule of punch die, it is qualified in after QA personnel Signature Confirmation to debug, the commencement of commercial operation of can starting shooting.Technological parameter is in Table 6.
Table 6
During formal production run, within every 30 minutes, at least sample once, each appointing, is got 20, and the capsule after filling is stored in intermediate station and does honest material status indication.
Condition of storage: shading, sealing, preserves at dry place.
Storage time: 18 days.
The medicated powder and the test-run a machine substandard products that scatter on board are destroyed as garbage.
During every batch of sand off, should change in time and batch clear out a gathering place, clear out a gathering place and see the < < rule of management > > that clears out a gathering place, clearing out a gathering place can lower batch filling after qualified.
Process quality Standard of Monitoring in stowing operation and capsule quality of intermediate amount Standard of Monitoring are respectively in Table 7 and table 8.
Table 7
Table 8
5. aluminum-plastic packaged:
With blister packaging machine, capsule is carried out to hot synthetic type, according to batch packaging directive, choose corresponding mould (12/10 of every plates), press the operation of blister packaging machine rule of operation, heat-sealing should meet the control criterion after medicine plate hot synthetic type, after QA personnel sign confirmation, can formally produce.Heat-sealing should meet the control criterion after medicine plate hot synthetic type, after QA personnel sign confirmation, can formally produce.Device parameter is controlled in Table 9.
Table 9
| Project | Unit | Parameter area |
| Compressed air | MPa | 0.4～0.7 |
| Upper plate temperature | ℃ | 130～150 |
| Lower plate temperature | ℃ | 130～150 |
| Heat-sealing temperature | ℃ | 200～230 |
| Imprint temperature | ℃ | 190～210 |
After every batch of heat seal, clear out a gathering place in time, clearing out a gathering place can lower batch of production after qualified.
The substandard products that produce in every batch of production process should be processed according to related request in time.
Condition of storage: shading, sealing, preserves at dry place.
Storage time: 12 days.
Product quality monitoring standard in aluminum-plastic packaged process and process quality Standard of Monitoring are respectively in Table 10 and table 11.
Table 10
| Control point | Monitoring project | The frequency | Monitor staff |
| Interior packaging material | The name of an article, lot number, quantity, specification, outward appearance | Every batch once | Operator |
| Medicine plate | Lot number, valid until, outward appearance, sealing | Every batch is no less than five times | QA |
Table 11
6. outsourcing:
Packing specification:
(1) every plate is 10,2 bags, every box (every bag of 2 plates), and 1 description of every box, every 400 boxes are a case, 1 work certificate of every case.
(2) every plate is 12, every box 4 plates, and 1 description of every box, every 400 boxes are a case, 1 work certificate of every case.
(3) every plate is 12, every box 2 plates, and 1 description of every box, every 500 boxes are a case, 1 work certificate of every case.
(4) every plate is 10, every box 2 plates, and 1 description of every box, every 500 boxes are a case, 1 work certificate of every case.
(5) every plate is 10, every box 5 plates, and 1 description of every box, every 400 boxes are a case, 1 work certificate of every case.
According to batch packaging directive, to the lot number on capsule, work certificate and carton, valid until, date of manufacture, packing date test print, after QA personnel sign and confirm, can formally print.
According to batch packaging directive pack, mounted box, thermal contraction, vanning work.
After batch packing finishes, by the < < rule of management > > that clears out a gathering place, clear out a gathering place, clearing out a gathering place can lower batch of packing after qualified.
The labels class packaging material such as the useless capsule producing in production process, useless description, the waste quality certification, litter decoration, under QA supervision, tear to pieces processing.
Finished product proceeds to warehouse and fills in storage bill.
Production process quality monitoring standard in outer packet procedures and middle process quality Standard of Monitoring are respectively in Table 12 and table 13.
Table 12
| Control point | Monitoring project | The frequency | Monitor staff |
| Pack | Lot number, product code, outward appearance | At any time | QA/ operator |
| Coding | Date of manufacture, lot number, effect duration | At any time | QA/ operator |
| Mounted box | Quantity, lot number, valid until, description, job number | At any time | QA/ operator |
| Vanning | Quantity, lot number, valid until, date of manufacture, outward appearance | At any time | QA/ operator |
Table 13
According to said method, produce a collection of potassium v calcium capsule, each post yield and yield rate are in Table 14, and packaging material utilization rate is in Table 15.
Table 14
Table 15
| Title | Utilization rate account form | Utilization rate scope (%) |
| Capsule utilization rate (U1) % | Output/(amount of receiving-surplus) * 100% | 95.00<U1<100.00 |
| Description utilization rate (U2) % | Output/(amount of receiving-surplus) * 100% | 95.00<U2<100.00 |
| Work certificate utilization rate (U3) % | Output/(amount of receiving-surplus) * 100% | 95.00<U3<100.00 |
| Carton utilization rate (U4) % | Output/(amount of receiving-surplus) * 100% | 95.00<U4<100.00 |
| The large case code of supervision code utilization rate (U5) % | Output/(amount of receiving-surplus) * 100% | 95.00<U5<100.00 |
Claims (8)
1. a potassium v calcium capsule, comprises and is placed in the former medicine 0.236g of potassium v calcium (40Wan unit) of gelatine capsule and the adjuvant magnesium stearate of former medicine weight 1%, and the hard sheet of polrvinyl chloride solid medicinal and the drug packaging aluminium foil that cover outward.
2. the preparation method of potassium v calcium capsule claimed in claim 1, is characterized in that comprising the following steps:
(1) supplementary material is prepared;
(2) weigh;
(3) always mixed;
(4) filling;
(5) aluminum-plastic packaged;
(6) outsourcing.
3. preparation method according to claim 2, is characterized in that operating according to flow process shown in Fig. 1.
4. according to the preparation method described in claim 2 or 3, the operating procedure of described step (1) comprising: according to batch production ordering, get this batch of required raw and auxiliary material from warehouse, after sloughing outer package, use the towel of drinking water moistening by inner bag wiped clean, use again 75% ethanol spray disinfectant, stick the appointed area, chamber of getting the raw materials ready between placing car after material state sign temporary.
5. according to the preparation method described in claim 2 or 3, in described step (2) according to batch production ordering to each material weigh, labelling, every batch of 1,500,000 needs weigh the former medicine 404.57kg of potassium v calcium, magnesium stearate 4.05kg.
6. according to the preparation method described in claim 2 or 3, the operating procedure of described step (3) comprising: load weighted former, adjuvant is added in HDA-1000 type Mixers with Multi-direction Movement by vacuum feeding successively, mix 5 minutes, mixed medicated powder is contained in the bucket of inner lining plastic bag, after weighing, carry out the status indication of material, hand over intermediate station to preserve; The condition of storage of mixed medicated powder is shading, airtight, dry, and the storage time is no more than 15 days.
7. according to the preparation method described in claim 2 or 3, in described step (4), use NJP-2000 type fully-automatic capsule filling machine to carry out filling, technological parameter is as follows: powder disc thickness 14～16mm, 1500～2000/minute of filling velocities, vacuum 0.02～0.06MPa; Capsule after filling is stored in intermediate station and does honest material status indication; The condition of storage of the capsule after filling is shading, sealing, dry, and the storage time is no more than 18 days.
8. according to the preparation method described in claim 2 or 3, in described step (5), use blister packaging machine to carry out hot synthetic type to capsule, technological parameter is as follows: compressed air 0.4～0.7MPa, 130～150 ℃ of upper plate temperatures, 130～150 ℃ of lower plate temperatures, 200～230 ℃ of heat-sealing temperatures, 190～210 ℃ of imprint temperature; Aluminum-plastic packaged capsule storage condition is shading, sealing, dry, and the storage time is no more than 12 days.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410396192.2A CN104146985B (en) | 2014-08-13 | 2014-08-13 | The preparation method of potassium v calcium capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410396192.2A CN104146985B (en) | 2014-08-13 | 2014-08-13 | The preparation method of potassium v calcium capsule |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104146985A true CN104146985A (en) | 2014-11-19 |
| CN104146985B CN104146985B (en) | 2016-01-13 |
Family
ID=51872754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410396192.2A Active CN104146985B (en) | 2014-08-13 | 2014-08-13 | The preparation method of potassium v calcium capsule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104146985B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1939258A (en) * | 2005-09-26 | 2007-04-04 | 刘凤鸣 | Oral preparation containing penicillin V potassium and its making method |
-
2014
- 2014-08-13 CN CN201410396192.2A patent/CN104146985B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1939258A (en) * | 2005-09-26 | 2007-04-04 | 刘凤鸣 | Oral preparation containing penicillin V potassium and its making method |
Non-Patent Citations (3)
| Title |
|---|
| 任进民等: "国产青霉素V钾胶囊剂的药代动力学和生物利用度", 《中国临床药理学杂志》, vol. 16, no. 2, 31 March 2000 (2000-03-31), pages 132 - 134 * |
| 缪德骅主编: "《药品生产质量管理规范实施指南2001》", 31 August 2001, 化学工业出版社, article "片剂、胶囊剂", pages: 195-205 * |
| 肖洁玲: "成型药品泡罩透湿性能测试的必要性探讨", 《中国包装》, no. 9, 31 December 2013 (2013-12-31), pages 43 - 45 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104146985B (en) | 2016-01-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO20053796L (en) | Process for the production of particles | |
| CN102925426A (en) | Coated granular microbial agent and production method thereof | |
| CN107875136A (en) | A kind of Amoxicillin pharmaceutical preparation and preparation method thereof | |
| WO2007116371A2 (en) | Optimization and control of the freeze-drying process of pharmaceutical products | |
| CN102670563A (en) | Preparation method of soft capsule without gelatin | |
| CN105752365A (en) | Screening and packaging line production device for organic fertilizer | |
| CN207241178U (en) | A kind of capsule is carved characters equipment | |
| CN105769905B (en) | A kind of modified-release tablets of potassium chloride and preparation method thereof | |
| CN104146985B (en) | The preparation method of potassium v calcium capsule | |
| CN104146986A (en) | Control method of relative substance and polymer in phenoxymethylpenicillin potassium | |
| CN201251474Y (en) | Full-automatic weighing device | |
| CN202715043U (en) | Traditional Chinese medicine tablet production equipment | |
| CN104173340A (en) | Preparation method of amoxicillin sodium and clavulanate potassium for injection | |
| CN207015661U (en) | A kind of packaging facilities of paper diaper | |
| CN102824361B (en) | Composition containing glucose | |
| CN109018542A (en) | A kind of quantitative automatic packing apparatus of Chinese medicine | |
| CN208292136U (en) | A kind of packaging system of Couteat of Folic Acid | |
| CN103435390A (en) | Technology for producing organic fertilizer from pig manures | |
| CN107362149A (en) | A kind of preparation technology of amlodipine besylate tablets | |
| CN106176643A (en) | Clobazam sheet and preparation method | |
| CN106902706A (en) | For the device of organic fertilizer production | |
| BR0305252A (en) | Tablet Pressing Machine | |
| CN205293135U (en) | Multi -functional combined type feedway | |
| Butkevych et al. | Technological aspects of tablets creation based on Flammulina velutipes biomass dry powder | |
| CN103893150B (en) | A kind of micro-capsule of potassium v calcium and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |