CN104434852B - Famciclovir vertical compression piece and preparation method thereof - Google Patents
Famciclovir vertical compression piece and preparation method thereof Download PDFInfo
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Abstract
The present invention provides a kind of famciclovir vertical compression pieces and preparation method thereof.With the total weight of the vertical compression piece, the famciclovir vertical compression piece include 70%~80% famciclovir, 10%~20% lactose, 5%~15% microcrystalline cellulose, 0.5%~1% colloidal silicon dioxide, 0.5%~1% magnesium stearate.
Description
Technical field
The invention belongs to pharmaceutical technology field, it is related to a kind of famciclovir vertical compression piece and preparation method thereof.
Background technique
Famciclovir (famciclovir, FCV) is purine nucleosides antiviral drugs of new generation, the entitled 6- deoxidation of chemistry
Penciclovir diacetate is the Penciclovir developed in the structure basis of Penciclovir (pencidlovir, PCV)
Pro-drug is listed by Smithkline Beecham company of Britain in exploitation in 1994, and FCV has broad-spectrum disease resistance toxic action,
It is active to herpesviral, hepatitis B, cytomegalovirus, Epstein-Barr virus etc., clinically it is mainly used for herpes simplex, band-like
The treatment 1 of bleb, genital herpes, hepatitis B).
Since famciclovir is crystalline powder, compressibility is poor and ratio is higher in prescription, and when direct tablet compressing can go out
Existing sliver and sticking phenomenon, thus direct compression method is caused to be constantly subjected to many restrictions in the application for preparing Famciclovir Tablet.
The preparation method of Famciclovir Tablet mostly uses one or many wet granulation technologies at present.CN101904825 provides a kind of general
VACV dispersible tablet.The Falacyclovir dispersion piece includes famciclovir, disintegrating agent, adhesive, lubricant.Famciclovir dispersion
Piece uses the preparation method of secondary granulation.CN101156856 discloses a kind of Falacyclovir dispersion piece, it is characterised in that following
The group of percentage composition is grouped as：40~55% famciclovir；One in 15~35% pregelatinized starch, microcrystalline cellulose and lactose
Kind or more than one；15~30% sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone and crosslinking
Carmethose；0.3~1% saccharin sodium or Aspartame；0.25~1% magnesium stearate；0.25~2% talcum powder or
Superfine silica gel powder, appropriate polyvinylpyrrolidone.The Falacyclovir dispersion piece uses the preparation method of wet granulation.The above invention is simultaneously
The improvement on quality controllability and product stability is not referred to.
And present inventor's discovery using Famciclovir Tablet made from direct compression method than general former times that wet granulation obtains
Lip river Wei piece has higher product stability.Therefore, it is necessary to improved direct compression methods to prepare Famciclovir Tablet, to simplify
Production technology saves cost and improves the stability of product.
Summary of the invention
It is an object of the present invention to provide a kind of famciclovir vertical compression pieces, and it includes the famciclovir as active constituent
And pharmaceutic adjuvant.In vertical compression piece of the invention, the content of famciclovir accounts for the 70%~80% of vertical compression piece total weight.Pharmaceutic adjuvant
It mainly include filler, disintegrating agent, glidant, lubricant and optional coating agent.Pharmaceutic adjuvant preferably has good stream
The auxiliary material of dynamic property and compressibility.
The filler is selected from lactose, pregelatinized starch, microcrystalline cellulose, mannitol and other tablets and commonly fills
One of agent is a variety of, preferably lactose, more preferably lactose Flowlac100.With vertical compression piece total weight, filler
Dosage is in the range of 10%~20%.
The glidant is selected generally from colloidal silicon dioxide, superfine silica gel powder and talcum powder, preferably colloidal silicon dioxide.With
Vertical compression piece total weight, the dosage of glidant is in the range of 0.5%~1%.
It is fine that the disintegrating agent is selected from microcrystalline cellulose, sodium carboxymethyl starch, crosslinked polyvinylpyrrolidone, cross-linked carboxymethyl
Tie up one of plain sodium, crosslinked carboxymethyl fecula sodium, modified starch and cellulosic polymer or a variety of, preferably microcrystalline cellulose
Element, more preferably microcrystalline cellulose 102.Commercially available 102 average grain diameter of microcrystalline cellulose is 90 μm, is suitble to direct tablet compressing.With vertical compression
Piece total weight, the dosage of disintegrating agent is in the range of 5%~15%.
The lubricant in magnesium stearate, odium stearate, enuatrol, sodium benzoate, sodium acetate and sodium chloride one
Kind is a variety of, preferably magnesium stearate.With vertical compression piece total weight, the dosage of lubricant is in the range of 0.5%~1%.
The coating agent is preferably Opadry Y-1-7000, with vertical compression piece total weight, the usage amount of coating agent 1%~
In the range of 3%.
In a preferred embodiment of the invention, with vertical compression piece total weight, a kind of famciclovir vertical compression piece includes
70%~80% famciclovir；10%~20% lactose；5%~15% microcrystalline cellulose；0.5%~1% colloidal silicon dioxide；
0.5%~1% magnesium stearate.
In a preferred embodiment of the invention, the ratio of lactose and microcrystalline cellulose is 1~3:1, preferably 1.5
~2.5:1.In a more preferred embodiment, lactose is selected from lactose Flowlac100, and microcrystalline cellulose is selected from microcrystalline cellulose
102。
Famciclovir vertical compression piece of the present invention can also optionally include 1%~3% coating agent, and the coating agent is excellent
It is selected as Opadry Y-1-7000.
It is a further object to provide a kind of preparation methods of famciclovir vertical compression piece, and the preparation method is using straight
Tablet forming technique is connect, i.e., directly the mixture of famciclovir bulk pharmaceutical chemicals and pharmaceutic adjuvant is carried out without pelletization the work of tabletting
Skill.
In one embodiment, preparation method of the invention includes the following steps：
1) it will be uniformly mixed after famciclovir bulk pharmaceutical chemicals and filler sieving；
2) it will be sieved after glidant and disintegrant mixture, mixed with 1) middle gained mixture,；
3) lubricant gained mixture in 2) is added to be uniformly mixed；
4) direct tablet compressing.
In preparation method of the present invention, the filler, disintegrating agent, glidant and lubricant and optional packet
Clothing agent and its usage amount are all as described above.
In a preferred embodiment, preparation method of the invention includes the following steps：
1) it will be uniformly mixed after famciclovir bulk pharmaceutical chemicals and lactose sieving；
2) it is sieved after mixing colloidal silicon dioxide and microcrystalline cellulose, is mixed with 1) middle gained mixture；
3) magnesium stearate gained mixture in 2) is added to be uniformly mixed；
4) direct tablet compressing.
Famciclovir bulk pharmaceutical chemicals good water solubility, but poor compressibility, and it is big to account for recipe quantity, easy sticking and sliver.To ensure object
The mobility and compressibility of material, partial size accounts for the famciclovir raw material of 50% or more total weight 150 μm or more of part preferably wherein
Medicine.Further preferably particle shape is close to spherical shape, without needle-shaped and flake-shaped particles famciclovir bulk pharmaceutical chemicals.Such bulk pharmaceutical chemicals are more
It is suitably applied direct tablet compressing technique.
In the preparation method, after microcrystalline cellulose and lactose is added, material fluidity and compressibility are obviously changed
It is kind；And appropriate, preferably 0.5~1% colloidal silicon dioxide and 0.5~1% magnesium stearate is added, it is existing that sticking can be effectively improved
As.Wherein improve sticking based on colloidal silicon dioxide role, magnesium stearate also has certain effect.
In the preparation method, the ratio of lactose and microcrystalline cellulose is 1~3:1, preferably 1.5~2.5:When 1, it can show
It writes and improves material fluidity and compressibility.
In the preparation method, tablet hardness is controlled in 5~12kgf.In the hardness range, the dissolution of products obtained therefrom
Characteristic no significant difference.
In addition, preparation method of the invention can also include the following steps：Coating agent is dissolved in suitable solvent with
Coating solution is obtained, vertical compression piece obtained in step 4) is coated with the coating solution.The coating process can be with one or more
Conventional method carries out, and the method is, for example, pan coating method and fluidized bed coating.
Beneficial effect
1. preparation process is direct compression method, the wet process or dry granulation procedure in traditional handicraft are avoided, thus can be saved
Shi Jieneng, simplify technique, and the stability of product can be made to be improved.
2. improving the mobility and compressibility of material by the partial size of control raw material and auxiliary material.
3. the blend proportion of lactose and microcrystalline cellulose is 1~3 in auxiliary material:1, it significantly improves the mobility of material and can press
Property.
4. colloidal silica silicone content is when 0.5~1% and lubricant content are 0.5~1%, hence it is evident that gluing when reducing tabletting
Phenomenon is rushed, wherein based on colloidal silicon dioxide role.
Detailed description of the invention
Fig. 1 is the displaing micro picture (400 times of amplification) of the famciclovir bulk pharmaceutical chemicals of Zhejiang Chetou Pharmaceutical Co., Ltd.'s production.
Fig. 2 is the displaing micro picture (400 times of amplification) of the famciclovir bulk pharmaceutical chemicals of Changzhou Kangli Pharmaceutical Co., Ltd's production.
Specific embodiment
Famciclovir bulk pharmaceutical chemicals used in the present invention are purchased from Zhejiang Chetou Pharmaceutical Co., Ltd., and colloidal silicon dioxide is rich by card
Special company (Cabot Corporation) production, other auxiliary materials are commercial product.
Reference preparation used in the present invention is (Famciclovir Tablet, lot number B8076 are purchased from Novartis), tool
Body parameter is as follows：
| Reference preparation parameter | As a result |
| Dosage | 250mg |
| Manufacturer | Novartis Farmaceutica S.A |
| Lot number | B8076 |
| Failure period | 2014.06 |
| Character | White circular piece removes whitening color after clothing film |
| Shape | Circle, 10.12mm × 4.34mm |
| Hardness (Kp) | 22.53 |
| Color | White |
| It carves characters | It is on one side FV, another side is " 250 " |
| Slice weight (mg) | 338 |
| Coating | Film-coating |
| Labelled amount | Every 0.25g containing famciclovir |
| Packaging | Plastic-aluminum |
| Storage requirement | Sealing, dry, 30 DEG C or less storages |
The following example is only used for the purpose of illustration certain aspects of the invention and embodiment, does not limit in any way
The scope of the present invention processed.
Embodiment 1：The selection of famciclovir bulk pharmaceutical chemicals
Famciclovir good water solubility, it is big to account for recipe quantity, it is therefore desirable to the particle shape and granularity of bulk pharmaceutical chemicals investigated,
Mobility and compressibility to ensure bulk pharmaceutical chemicals is preferable, is suitble to direct tablet compressing technique.To Zhejiang headstock pharmacy joint-stock company and often
The famciclovir bulk pharmaceutical chemicals of Zhou Kangli pharmaceutical Co. Ltd production are compared.
Amplify 400 times of observations under the microscope, as shown in Figure 1, the famciclovir of Zhejiang Chetou Pharmaceutical Co., Ltd.'s production
The partial size of bulk pharmaceutical chemicals is larger, and shape is close to spherical shape, without needle-shaped and flake-shaped particles.As shown in Fig. 2, Changzhou Kang Li pharmacy is limited
The partial size of the famciclovir bulk pharmaceutical chemicals of company's production is smaller, there is more slender rod shaped particle.Screened method measurement, Zhejiang headstock system
Partial size accounts for 50% or more of total weight 150 μm or more of part in the famciclovir raw material of medicine Co., Ltd production；Changzhou Kang Li
The famciclovir bulk pharmaceutical chemicals partial size of pharmaceutical Co. Ltd's production is at 150 μm or more partially below the 10% of total weight.
It is tested through tabletting, the famciclovir bulk pharmaceutical chemicals of Zhejiang Charioteer Pharmaceutical Co., Ltd.'s production, grain shape rule,
Partial size is larger, good fluidity, is more suitable for direct tablet compressing technique, and the raw material fine powder of Changzhou Kangli Pharmaceutical Co., Ltd's production is more, can
Pressure property poor, easy sticking and sliver.
Therefore, wherein partial size 150 μm or more of part accounts for 50% or more of total weight for selection, and particle shape is close to spherical shape,
There is no needle-shaped and flake-shaped particles famciclovir bulk pharmaceutical chemicals for direct tablet compressing technique.
Embodiment 2：The investigation of direct tablet compressing technological feasibility
Direct powder compression is respectively adopted, wet granulation technology prepares Famciclovir Tablet, prescription is shown in Table 1：
1 Famciclovir Tablet craft screening prescription of table (every 1000 contain, g)
| Supplementary material | 1/ direct tablet compressing of prescription | 1/ wet granulation of prescription |
| Famciclovir | 125.0 | 125.0 |
| Lactose | 29.0 | 29.0 |
| Hydroxypropylcellulose | 3.0 | 3.0 |
| Sodium carboxymethyl starch | 2.0 | 2.0 |
| Magnesium stearate | 1.0 | 1.0 |
Preparation process
(1) direct tablet compressing technique
Famciclovir, lactose, hydroxypropylcellulose and sodium carboxymethyl starch are uniformly mixed, magnesium stearate is eventually adding, is mixed
Close uniform tabletting (DPG-30 single-punch tablet press, Beijing Gylongli Sci.&Tech. Co., Ltd., manual tabletting).
(2) wet granulation technology
1) famciclovir, lactose and sodium carboxymethyl starch cross 26 meshes, are uniformly mixed, spare.
2) hydroxypropylcellulose adds water and stirs dissolution, and the binder solution of compound concentration 3% is added in 1) gained mixture, 26
Mesh granulation, 50 DEG C of dryings, 26 mesh sieves, additional magnesium stearate mix.
3) tabletting (DPG-30 single-punch tablet press, Beijing Gylongli Sci.&Tech. Co., Ltd., manual tabletting).
Sample and reference preparation prepared by direct tablet compressing and wet granulation technology is placed 3 days in 60 DEG C, test sample has
Close the situation of change of substance.
Famciclovir is carried out in relation to substance according to the description in United States Pharmacopeia Famciclovir Tablet, and method and condition is mainly as follows
It is described：
1) chromatographic condition
Mobile phase：Methanol-buffer salt (6.8g/L potassium dihydrogen phosphate, pH3.0) (30:70)
Chromatographic column：Octadecylsilane chemically bonded silica column
Detection wavelength：UV310nm
Flow velocity：1.0ml/min
Sample volume：10μl
Column temperature：35℃
2) preparation of test solution
To respectively be taken using sample prepared by wet granulation technology and direct tablet compressing 5 it is finely ground in mortar, weigh appropriate thin
In powder to volumetric flask, with buffer salt solution (6.8g/L potassium dihydrogen phosphate, pH3.0) ultrasonic dissolution, famciclovir in sample solution
Concentration is 75 μ g/ml, sample introduction after 0.45 μm of membrane filtration.
3) prepared by reference substance solution
Precision measures above-mentioned test solution 1ml, is placed in 100ml volumetric flask, is diluted to quarter with above-mentioned buffer salt solution
Degree, shakes up, as reference substance solution.
Each 10 μ l of above-mentioned test solution and control solution is taken respectively, is injected liquid chromatograph (Hitachi L2400), record
Chromatogram calculates the content in relation to substance in test solution.
4) measurement result：The results are shown in Table 2.
Table 2 is in relation to substance testing result
The above testing result shows that direct tablet compressing technique is more advantageous to the stabilization of raw material than wet granulation technology, therefore right
It is feasible that this product, which carries out production using direct tablet compressing technique,.
Embodiment 3
According to following prescription, tablet is made using direct tablet compressing method, prescription is shown in Table 3.
3 Famciclovir Tablet craft screening prescription of table (every 1000 contain, g)
| Supplementary material | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 |
| Famciclovir | 125 | 125 | 125 | 125 |
| Lactose (Flowlac100) | 34.5 | 29.5 | 24.5 | 22.5 |
| Microcrystalline cellulose (102) | 0 | 5 | 10 | 15 |
| Colloidal silicon dioxide | 0.5 | 0.5 | 0.5 | 0.5 |
| Magnesium stearate | 1 | 1 | 1 | 1 |
Preparation process：
1) famciclovir and lactose (Flowlac100) are uniformly mixed after crossing 26 meshes respectively
2) 26 meshes are crossed after colloidal silicon dioxide is mixed with microcrystalline cellulose (102), are mixed with 1) middle gained mixture
3) it takes recipe quantity magnesium stearate to be added in 2) to be uniformly mixed in gained mixture
4) tabletting (DPG-30 single-punch tablet press, Beijing Gylongli Sci.&Tech. Co., Ltd.).
As a result as described in Table 4.
4 Famciclovir Tablet prescription screening result of table
| Investigation project | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 |
| Angle of repose (°) | 40 | 38 | 37 | 37 |
| Piece appearance character | Without sliver | Without sliver | Without sliver | Without sliver |
| It carves characters situation | Clearly | Clearly | Clearly | Clearly |
| Tableting processes | Slight sticking | Slight sticking | Slight sticking | Slight sticking |
* angle of repose measuring method：Fixed funnel method measures angle of repose, and wherein fixed funnel method refers to material from admittedly
The funnel set flows down to form cone, then measures the height and bottom surface radius of cone, then stopped with the calculating of arc tangent formula
Angle.
The results show that lactose Flowlac100 and 102 partial size of microcrystalline cellulose are big, mobility and compressibility are all good, piece
Not sliver, but still have slight sticking phenomenon.Continuing to investigate the compressibility of the above prescription on high speed tablet press, (GZPK3045 type is high
Fast tablet press machine, 45 punchings, Shanghai Tianxiang Jian Tai pharmaceutical Co. Ltd, pressure 4.5KN, revolving speed 15RPM, water-drop-shaped punching), as a result such as table
Shown in 5.
5 high speed tablet press tabletting result of table
| Investigation project | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 |
| Piece appearance character | Sliver | Sliver | Without sliver | Without sliver |
| It carves characters situation | - | - | Clearly | Clearly |
| Tableting processes | - | - | Slight sticking | Slight sticking |
The compressibility of prescription 4 and prescription 5 meets the requirement of high speed tablet press, can after appropriate microcrystalline cellulose (102) are added
Pressure property is obviously improved, and does not have sliver phenomenon.Microcrystalline cellulose 102 and lactose Flow100 are used in combination, when the two ratio exists
1~3:High-content Famciclovir tablet poor compressibility can be effectively solved the problems, such as when 1.
Embodiment 4
Famciclovir tablet is prepared using direct compression method according to prescription 6, prescription is shown in Table 6.
6 Famciclovir Tablet craft screening prescription of table (every 1000 contain, g)
1) famciclovir of recipe quantity and lactose (Flowlac100) are crossed into 26 meshes respectively, then by colloidal silicon dioxide
26 meshes are crossed after mixing with microcrystalline cellulose (102), are uniformly mixed with famciclovir and lactose.
2) double-cone mixer (W100 double-cone mixer, Shanghai Zhen Chun powder equipment factory) is added in the material after above-mentioned sieving
Mixing 60 minutes.
3) recipe quantity magnesium stearate is taken, is added in double-cone mixer and carries out total mix, mix to uniform.
4) above-mentioned total mix material is taken, carrying out direct tablet compressing, (GZPK3045 type high speed tablet press, 45 punchings, Shanghai Tianxiang are good for platform
Pharmaceutical Co. Ltd, revolving speed 15RPM, water-drop-shaped punching), tablet hardness is controlled in 5~12kgf.
During direct tablet compressing, sliver and sticking phenomenon are not observed.Show to increase colloidal silicon dioxide and stearic acid
The dosage of magnesium can overcome sticking phenomenon.
Embodiment 5
Coating agent and purified water are added on the basis of prescription 6, famciclovir coating tablet, place are prepared using direct compression method
Fang Jianbiao 7.
7 Famciclovir Tablet craft screening prescription of table (every 1000 contain, g)
1) famciclovir of recipe quantity and lactose (Flowlac100) are crossed into 26 meshes respectively, then by colloidal silicon dioxide
26 meshes are crossed after mixing with microcrystalline cellulose (102), are uniformly mixed with famciclovir and lactose.
2) double-cone mixer (W100 double-cone mixer, Shanghai Zhen Chun powder equipment factory) is added in the material after above-mentioned sieving
Mixing 60 minutes.
3) recipe quantity magnesium stearate is taken, is added in double-cone mixer and carries out total mix, mix to uniform.
4) above-mentioned total mix material is taken, carrying out direct tablet compressing, (GZPK3045 type high speed tablet press, 45 punchings, Shanghai Tianxiang are good for platform
Pharmaceutical Co. Ltd, revolving speed 15RPM, water-drop-shaped punching), tablet hardness is controlled in 5~12kgf.
5) it takes Opadry Y-1-7000 and purified water to be added in rustless steel container, stirs to being completely dispersed, be configured to contain admittedly
The dispersion liquid of amount about 10.0%, it is spare as coating solution.Gained plain piece above is incited somebody to action, coating pan (BGB-150D type efficient packet is added to
Clothing machine, Pharmaceutical Equipment Factory, Wenzhou City) in be coated, preheat：Pot revolving speed 2rpm, temperature of outgoing air≤45 DEG C；Hydrojet：Pot revolving speed 4
~8rpm, 35~45 DEG C of temperature of outgoing air；It is dry：Pot revolving speed 2rpm, temperature of outgoing air≤45 DEG C, drying time 30 minutes.Coating increases
It weighs about as 1-3%.
Embodiment 6
Coating sample and reference preparation obtained by Example 5 carry out dissolution rate comparative study, molten with pH1.0 hydrochloric acid respectively
Liquid, pH4.0 acetate buffer, pH6.8 phosphate buffer and water are dissolution medium, investigate made products and reference preparation exists
The difference of dissolved corrosion in different dissolution mediums.
Dissolution Rate Testing method is as described below：
(1) leaching condition：
Dissolution medium：
PH1.0 hydrochloric acid solution：9ml hydrochloric acid, is diluted with water to 1000ml, shake up to get.
PH6.8 phosphate buffer：6.8g potassium dihydrogen phosphate and 0.9583g sodium hydroxide, are dissolved in water and are diluted to
1000ml, shake up to get.
PH4.0 acetate buffer：0.738g anhydrous sodium acetate is dissolved in water and is diluted to 1000ml, with glacial acetic acid tune
Section pH to 4.0 shake up to get.
Medium volume：900ml
Device：Paddle method (two the second methods of annex X C of Chinese Pharmacopoeia version in 2010)
Revolving speed：50 turns
Medium temperature：37℃
Sample time：5,10,15,20,30min
(2) dissolution determination condition
Mobile phase：Methanol-buffer salt (6.8g/L potassium dihydrogen phosphate, pH3.0) (30:70)
Chromatographic column：Octadecylsilane chemically bonded silica column
Detection wavelength：UV310nm
Flow velocity：1.0ml/min
Sample volume：10μl
Column temperature：35℃
(3) dissolution results
The results are shown in Table 8.
Test result shows：By draft the pilot sample of formulation and technology preparation in 4 kinds of different dissolution mediums with reference system
The dissolved corrosion of agent is almost the same, and the prescription that this research is drafted is reasonable.
The dissolution curve of the Famciclovir Tablet in 4 kinds of media of table 8 compares
Embodiment 7
According to the preparation process of embodiment 4, using prescription 6, if other conditions are the same, prepared with different pressures
Sample investigates influence of the different hardness to famciclovir dissolution rate in tablet, the results are shown in Table 9.
9 different hardness Famciclovir Tablet dissolution data of table
"-" indicates that no data, self-control sample only check dissolution in 15 minutes.
As the result is shown：Sample preparation product are pushed in different hardness, dissolution characteristic no significant difference shows in 5~12kgf hardness model
In enclosing, hardness is on Dissolution of Tablet without influence.
Embodiment 8
By 4 prescription of embodiment amplification production three batches, batch 100,000, after aluminum-plastic packaged, respectively 30 ± 2 DEG C, RH65 ±
5% and 25 ± 2 DEG C, stability test is carried out under the conditions of RH60 ± 10%, different time points check that data are shown in Table 10 and table 11 respectively.
10 Famciclovir Tablet long term test data (25 ± 2 DEG C, RH60 ± 10%) of table
11 Famciclovir Tablet intermediate experiment data (30 ± 2 DEG C, RH65 ± 5%) of table
From stability data in December it is found that this product uses direct compression method, technique can be simplified, and the stability of product can be made
Improved.
Bibliography
1）A kind of quick novel antiviral drug famciclovir [J] medicine clinical research of fragrant, 2002;19(2):1421
2）Chen Xinyue, Wang Juntao.Therapeutic effect [J] gastroenterology and hepatopathy of the famciclovir to chronic hepatitis B
Magazine, 2002;9(1):77-781
3）Chen Xinyue, Wang Jun sheath or bow case anti-hepatitis B virus new drug-famciclovir [J] Chinese Journal of Hepatology, 1999;7
(supplementary issue):70-721
4）The multi-center clinical trial of Chen Xiangsheng, Cui's packing domestic famciclovir and Aciclovir in Treatment on Herpes Zoster
[J] Chinese journal of dermatology, 2000;33(1):65-661
5）Xu Huizhen, Mao Linge wait famciclovir and the research of Aciclovir in Treatment on Herpes Zoster Comparison of therapeutic [J] clinical
Dermatology's magazine, 2001;29(5):288-2891
6）Ji Suzhen, Yang Haizhen wait famciclovir (famciclovir) Randomized controlled test shingles zoster multicenter to face
Bed test [J] The Chinese Journal of Clinical Pharmacology 2000;16(4):269-2701
Claims (12)
1. a kind of famciclovir vertical compression piece, which is characterized in that with the total weight of the vertical compression piece, the vertical compression piece includes 70%
~80% famciclovir, 10%~20% lactose, 5%~15% microcrystalline cellulose, 0.5%~1% colloidal state dioxy
SiClx, 0.5%~1% magnesium stearate.
2. famciclovir vertical compression piece according to claim 1, which is characterized in that the ratio of lactose and microcrystalline cellulose is 1
~3:1.
3. famciclovir vertical compression piece according to claim 1, which is characterized in that the ratio of lactose and microcrystalline cellulose is
1.5~2.5:1.
4. famciclovir vertical compression piece according to any one of claim 1 to 3, which is characterized in that the lactose is selected from cream
Sugared Flowlac100, the microcrystalline cellulose are selected from microcrystalline cellulose 102.
5. famciclovir vertical compression piece according to any one of claim 1 to 3, which is characterized in that with the vertical compression piece
Total weight, the vertical compression piece also include 1%~3% coating agent.
6. famciclovir vertical compression piece according to claim 5, which is characterized in that the coating agent is Opadry Y-1-
7000。
7. such as the preparation method of famciclovir vertical compression piece as claimed in any one of claims 1 to 6, which is characterized in that the preparation
Method includes the following steps：
1) it will be uniformly mixed after famciclovir bulk pharmaceutical chemicals and lactose sieving；
2) it is sieved after mixing colloidal silicon dioxide with microcrystalline cellulose, is mixed with 1) gained mixture；
3) magnesium stearate is added in 2) gained mixture and is uniformly mixed；
4) direct tablet compressing.
8. preparation method according to claim 7, which is characterized in that partial size is at 150 μm in the famciclovir bulk pharmaceutical chemicals
Above part accounts for 50% of total weight or more.
9. preparation method according to claim 7 or 8, which is characterized in that the ratio of lactose and microcrystalline cellulose is 1~3:
1。
10. preparation method according to claim 7 or 8, which is characterized in that the ratio of lactose and microcrystalline cellulose is 1.5
~2.5:1.
11. preparation method according to claim 7 or 8, which is characterized in that the vertical compression sheet hardness is in 5~12kgf.
12. preparation method according to claim 7 or 8, which is characterized in that the method also includes obtaining in step 4)
To vertical compression piece be coated.
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| CN106511286B (en) * | 2016-10-27 | 2019-12-20 | 四川省百草生物药业有限公司 | Famciclovir tablet with high stability and preparation method thereof |
| CN112587491B (en) * | 2021-01-03 | 2022-08-23 | 迪沙药业集团有限公司 | Famciclovir tablet composition |
| CN114306619B (en) * | 2022-01-29 | 2022-10-21 | 杭州沐源生物医药科技有限公司 | High-stability famciclovir composition and preparation method thereof |
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| GB9600847D0 (en) * | 1996-01-16 | 1996-03-20 | Smithkline Beecham Plc | Pharmaceuticals |
| CN1626089A (en) * | 2003-12-11 | 2005-06-15 | 江苏晨牌药业有限公司 | Valaciclovir oral desintegration tablet and preparation method |
| CN1562210A (en) * | 2004-04-12 | 2005-01-12 | 成都圣诺科技发展有限公司 | Burnet disintegration tablet of mouth and preparation method |
| CN1698644A (en) * | 2004-05-17 | 2005-11-23 | 北京扬新科技有限公司 | Ribavirin orally disintegrating tablet and preparation method thereof |
| MX2007014068A (en) * | 2005-05-10 | 2008-02-07 | Novartis Ag | Modified release famciclovir pharmaceutical compositions. |
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