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The supplementary material waits for in dispersion piece research further thoroughly
    公布工夫:2006-11-18    浏览次数:1109

1st, dispersion piece prescription research

    After the request dispersion piece meets the water, breaks up as soon as possible the finely ground particles, and forms the even suspension, therefore it and ordinary piece biggest not consubstantiality now in prescription design. 

   1.1 disintegration medicinal preparations

    The disintegration medicinal preparation's type and the amount used to the dispersion piece's disintegration, dissolve the effect to be very important, is factor which must first consider. Generally the request selects the disintegration medicinal preparation swelling capacity is bigger than 5ml/g, most commonly used has the ethyloic starch sodium (CMS-Na), the low substitution hydroxy third cellulose (L-HPC), the crossing linking suo armor cellulose sodium (cCMC-Na), crossing linking polyethylene pyrrolidone (PVPP) and so on. 
 

1.1.1 amounts used

   Should the paramount consideration disintegration medicinal preparation type to the tablet disintegration behavior influence, even if is the identical disintegration medicinal preparation, in the amount used difference possibly will also produce the poles apart to the dispersion piece disintegration behavior the effect. If MS-Na takes one kind of highly effective fast disintegration medicinal preparation, has the good hygroscopicity and the expansibility, after full inflation, the volume may increase 200 ~300 times. When controls its amount used when 7%, may play the best disintegration role, and will not form stickiness solution in the water to hinder the tablet to continue to break up is higher than 8% amounts used to cause CMS-Na the caking and forms the hydrated membrane in the water in the flat and thin piece surface, instead has prevented moisture content permeating, will slow down the tablet the disintegration. Jia Yan and so on discussed the CMS-Na amount used not to disperse the piece disintegration to the law for Ding the influence, the experiment indicated that the CMS-Na amount used was when 1%~2% broke up the influence to the tablet not to be obvious; when 3%~7% may speed up the disintegration obviously, 8%~10% instead retarded the disintegration. If in certain dispersion piece prescription the CMS-Na amount used is big, possibly affects the tablet to break up, then may consider that matches the mix disintegration medicinal preparation with other disintegration medicinal preparation by the appropriate proportion, both may meet the requirements the amount used, and can display CMS-Na the fast disintegration performance.

1.1.2 union applications or replace  

   When the disintegration medicinal preparation amount used is big or the cost is high, may consider several kind of disintegration medicinal preparation union application. If comes in handy PVPP and cCMC-Na according to the certain proportion the substitution to use only PVPP, may achieve good similarly fast collapses the effect. In addition may change to Vivastar (German JRS Corporation) to replace PVPP, its disintegration effect surpasses CMS-Na, L-HPC, but the price is only PVPP 1/4. 

1.1.3 optimized method choice

    Because the medicine physics and chemistry nature is different, breaks up the medicinal preparation physical properties and so on granular mass which, flat and thin piece outward appearance, absorption of moisture forms with it mix also to have the very big difference, to achieve the best prescription combination, often take disperses the piece the disintegration time, to mix hangs the nature either the uniformity, dissolves and so on to use the orthogonal as the inspection target, even and so on design methods to screen disintegration medicinal preparation the type and the best allocated proportion or the amount used. If the primary election disintegration medicinal preparation's amount used scope or several kind of disintegration medicinal preparation's proportional region is small time may select the testing sequence few orthogonal design; If the amount used, the proportion are not very explicit time, may select the homogeneous design; If the factor relatedness is big time, selects optimizations suitably and so on pattern identification mode. Lu Zhufen and so on take breaks up the time, the dispersion uniformity to test the primary election as the target to leave swelling capacity supplementary material and the disintegration medicinal preparation type, and based on this, take broke up the time to determine as the target Nepali US Shurly dispersed the piece the best prescription. Xiao Xuecheng and so on uses the orthogonal test to screen the cloth Luo river fragrance dispersion piece the prescription and the craft, take optimizes the tablet disintegration time which the craft system results in as 45.1s, disperses after the water can pass the 710mm mesh. Du Qing and so on uses the orthogonal test to screen yin duo US Xin Changrong to disperse the piece the prescription and the craft, its disintegration time for (33 ±3) s, dissolves the speed in the artificial intestinal juices to dissolve the piece and the capsule quickly obviously in the market intestines. 

    1.2 bond

   Certain medicines itself either after supplementary material mix lacks stickiness or stickiness is small, may use CMC, the polyethylene pyrrolidone (PVP) and HPMC and so on water affinity the polymer dilute alcohols or the peroxide solution is the bond, is most commonly used by PVP, very little uses the starch. Uses PVP to make the pellet surface water affinity which the bond system results to be big, after the sheeting, the moisture content easy to permeate the piece core to cause its fast disintegration to dissolve.

    Jia Yan and so on uses 5%PVP the different density ethyl alcohol solution not to disperse the piece for the bond preparation law for Ding, reduces along with the ethyl alcohol density, breaks up the time (absolute ethyl alcohol) to reduce from 6.2min to 0.8min (peroxide solution). The 10%PVP peroxide solution system results in the tablet the disintegration time is 5.2min, along with the PVP proportion's reduction, breaks up speeds up; during 1%~3% densities difference not remarkable (0.8 ~0.9min). Therefore when preparation should also consider that the bond the appropriate composition and the proportion, favor the dispersion piece the disintegration.  

  1.3 other supplementary materials

    At present applies many helps the class medicinal preparation is the fine powder silica gel, it not only may improve the powder, the pellet fluidity, and because of its silicon mellow base's strong polarity and the water affinity, is advantageous to the moisture content permeating tablet, can obviously enhance the infusibility medicine to dissolve the speed. Moreover, to further improve the medicine to dissolve the speed to auxiliary by the surface active agent, like lauryl sodium sulfate (SLS), sulfo group succinic acid two Xin Zhina (DS) and so on. The scattered piece one breaks up or the dispersion after the water takes, takes medicine the time gravel feeling for the reduction, often joins improvement feeling in the mouth and so on water-soluble good mannitol in the auxiliaries. Moreover, the appropriate auxiliaries may have the synergism to the disintegration medicinal preparation, often uses the swelling capacity good auxiliaries, like micrite cellulose (MCC), processing agar-agar and so on. Because, as soon as the identical auxiliaries the different model, the factory and so on will also have the influence which to the disintegration will decide. Fang Xiao Ling and so on selected MCC to make the auxiliaries to compare Japan to produce PH101, 102, 301 and domestically produced PH102 to the disintegration the influence. The result showed that 4 kind of MCC dissolves to the medicine has the remarkable difference, uses Japan to produce PH301 and in only the PH101 prescription, the medicine dissolves very quickly, dissolves the favorable balance of trade in 2min 95%; But uses domestically produced PH102 and the Japanese PH102 prescription degree of hardness is only bad, cannot achieve the anticipated degree of hardness (6g). 

2nd, dispersion piece preparation technical study

2.1 medicine pretreatments

    Many medicines have the bitter taste or the bad stink, makes dispersion piece Yi Rangren not to accept directly, therefore after may first wraps the medicine and the water dispersion bond or other coating material mix, mixes the uniform sheeting again with the diluent. Generally must pass through the first medicine micronizing processing, causes its particle size below 100mm. When compound prescription sulfanilamide armor wicked zuo dispersion piece preparation crushes the first medicine particle size 11.6mm the fine dust, the obtained tablet in 1min breaks up completely in the water, dissolves the time not to surpass 15min. Sometimes micronizing processing also will bring some questions, if will increase along with the tiny medicinal powder granule compared to the surface area, the granule will build up in the same place, will affect the medicine to dissolve. Does not dissolve in the water original medicine many crystal condition existence, the tablet breaks up after the water the medicine cannot dissolve the molecular state very quickly, affects dissolves and the absorption. If can not dissolve before the sheeting or the infusibility medicine and the water affinity supplementary material grinds together, may cause the crystal condition original medicine to transform the amorphous state, may also prevent the granule the accumulation, increases the granule surface the wettability, enhances the medicine to dissolve enormously. Not only the scattered piece the request breaks up quickly, dissolves similarly must be quick. Although many dispersion pieces break up very quickly, but dissolves slowly, even if joined surface active agent like SLS, DS, PEG6000 and so on still not to be able the very good improvement to dissolve. In this case, may consider that makes in advance the first original medicine the solid dispersing medium. Lu Dan and so on uses the solvent extraction dissolves the niter benzene plain medicine and PVP K30 according to 1 ∶1 ~1 ∶5 proportions in 95% ethyl alcohol, the preparation solid dispersing medium, in does not add under the highly effective disintegration medicinal preparation with the starch, the MCC mix sheeting, 20min dissolves then reaches 73.7%.

  2.2 powder direct sheeting

    After the original medicine and the supplementary material mix uniform, if the fluidity and the compressibility are good, or also after joining right amount helps the class medicinal preparation like fine powder silica gel, the talcum powder may obtain the good fluidity, should use the powder direct sheeting as far as possible. Because this law technological process is simple, the obtained dispersion piece's disintegration speed is quick. 

 2.3 aqueous method granulations

   Generally the request uses a wet legal system grain of obtained wet pellet in 1mm (18 items) below, the dry pellet in 0.6mm (30 items) below. If uses fluid bed one step system grain, may make the pellet the quality to enhance, presses the flat and thin piece greatly can break up well, dissolve.

2.4 degree of hardness

  The scattered piece should the disintegration and dissolves in as far as possible the short time, therefore tablet degree of hardness must be smaller than the ordinary piece, guaranteed that the flat and thin piece has the enough factor of porosity, but breaks up fast, but must be able to maintain the outward appearance, the improvement smooth finish and so on. Sometimes to avoid the scattered piece absorption of moisture, but must carry on thin film coating processing, this request tablet has the suitable degree of hardness. Therefore wants overall evaluation sheeting pressure and various supplementary materials allocated proportion, obtains the disintegration time and degree of hardness conforms to the request scattered piece. The Arab League base industry inspected the law not to disperse the piece for Ding degree of hardness the influence which and dissolved to the disintegration, the experiment indicated that degree of hardness in 3.0 ~7.5kg in the scope, and dissolved to the disintegration affects not obviously; When degree of hardness is big (9, 10. 5 kg), then breaks up reduces speed, dissolves reduces.

  3rd, quality specification

    The scattered piece besides must conform to the ordinary piece quality specification, may refer to the BPC request, when 19 ~2l ℃ water should in 3min break up completely. After simultaneously deals with the disintegration the uniformity or mixes hangs the nature to carry on the examination: Takes the dispersion piece 2 pieces, sets in 20 ℃ water l00ml, to breaks up the caster to pour completely on the 710mm aperture strainer, the scattered pellet can pass the strainer completely. 

  4th, conclusion

    The improvement infusibility medicine's biological exploitability, by the minimum dosage display maximum drug efficacy, reduces the medicine the poisonous side effect is develops the dispersion piece the goal. Our country studies the scattered piece variety are not many, enters the market to be less. The scattered piece's research also waits for further thoroughly. If uses the new disintegration medicinal preparation and the diluent according to fast collapses the preparation the design concept to prepare absorbs quickly, the biological exploitability high traditional Chinese medicine (quick release) the preparation, this will have the major impact on our country's traditional Chinese medicine research and the development.

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