制粒技术在药物掩味方面的研究进展
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摘要
在常用的口服固体制剂中,口感不良会导致患者对药物的依从性差,进而使得该药物的市场竞争力降低。药物制剂的掩味问题一直是制剂学面临的重要问题之一,随着人们对药物口感的要求日渐提升,近几年掩盖药物不良口味的方法也逐渐增加。通过对掩盖药物不良口味的相关文献进行总结,常用的掩味技术有添加掩味剂、包合技术、微球/微囊技术、固体分散技术、离子交换技术等。然而,除以上掩味技术之外,在固体制剂的制造过程中,制粒技术也可以实现对药物不良口味的遮蔽,且制粒技术方法简单,能够很好地达到掩盖药物不良口味的效果,该文系统介绍了制粒技术在药物掩味方面的研究进展,以期为药物掩味技术的选择提供参考。随着人们对药物口感的需求逐渐提高,药物掩味技术越来越受到广大制剂工作者的重视,但目前仍然存在一些问题,如口感评价体系不完善、方法特异性较低等,这一系列的问题均有待于相关药学工作者进一步研究和解决。
In commonly used oral solid preparations,poor mouthfeel results in poor patient compliance with the drug,which in turn reduces the market competitiveness of the drug. The problem of taste masking of pharmaceutical preparations has always been one of the important problems faced by pharmaceutics. With the increasing demand for the taste of drugs,the methods of masking bad taste of drugs have gradually increased in recent years. By summarizing the relevant literature covering the bad taste of drugs,the commonly used taste masking techniques include the addition of taste masking agents,inclusion techniques,microsphere/microcapsule technology,solid dispersion technology,ion exchange technology and the like. However,in addition to the above taste masking techniques,in the manufacturing process of the solid preparation,the granulation technique also can achieve the shielding of the bad taste of the medicine,and the granulation technique is simple,and can well achieve the effect of masking the bad taste of the medicine. This paper systematically introduces the research progress of granulation technology in drug taste masking,in order to provide reference for the selection of drug taste masking technology. With the increasing demand for drug taste,drug masking technology has been paid more and more attention by the majority of preparation workers,however,there are still some problems,such as imperfect taste evaluation system and low specificity of methods. This series of problems need to be further studied and solved by relevant pharmaceutical researchers.
In commonly used oral solid preparations,poor mouthfeel results in poor patient compliance with the drug,which in turn reduces the market competitiveness of the drug. The problem of taste masking of pharmaceutical preparations has always been one of the important problems faced by pharmaceutics. With the increasing demand for the taste of drugs,the methods of masking bad taste of drugs have gradually increased in recent years. By summarizing the relevant literature covering the bad taste of drugs,the commonly used taste masking techniques include the addition of taste masking agents,inclusion techniques,microsphere/microcapsule technology,solid dispersion technology,ion exchange technology and the like. However,in addition to the above taste masking techniques,in the manufacturing process of the solid preparation,the granulation technique also can achieve the shielding of the bad taste of the medicine,and the granulation technique is simple,and can well achieve the effect of masking the bad taste of the medicine. This paper systematically introduces the research progress of granulation technology in drug taste masking,in order to provide reference for the selection of drug taste masking technology. With the increasing demand for drug taste,drug masking technology has been paid more and more attention by the majority of preparation workers,however,there are still some problems,such as imperfect taste evaluation system and low specificity of methods. This series of problems need to be further studied and solved by relevant pharmaceutical researchers.
引文
[1]李学林,王盼盼,刘瑞新,等. 3种掩味剂单独或联合应用对黄柏的掩味作用探究及掩味前后化学成分的比较[J].中国实验方剂学杂志,2017,23(2):7-11.
[2]范建伟,刘武占,李艳芳,等.制剂用水蛭原粉掩味前后主要腥臭异味物质的变化分析[J].中国实验方剂学杂志,2018,24(6):22-25.
[3] WANG Y,FENG Y,WU Y,et al. Sensory evaluation of the taste of berberine hydrochloride using an Electronic Tongue[J]. Fitoterapia,2013,86:137-143.
[4] Faisal W,Farag F,Abdellatif A A H,et al. Taste masking approaches for medicines[J]. Curr Drug Deliv,2018,15(2):167-185.
[5] Dashevskiy A,Mohylyuk V,Ahmed A R,et al.Micropellets coated with Kollicoat Smartseal 30D for taste masking in liquid oral dosage forms[J]. Drug Dev Ind Pharm,2017,43(9):1548-1556.
[6]刘斌斌,简晖,田佳明,等.中药矫味与掩味技术的研究进展及问题分析[J].中国实验方剂学杂志,2016,22(16):229-234.
[7]于飞千,刘臻,潘卫三.药物制剂中苦味掩盖方法的研究进展[J].中国新药杂志,2007,16(15):1171-1174.
[8]吴飞,赵春草,冯怡,等.中药口服制剂矫味研究的探讨[J].中国新药杂志,2015,24(8):893-899.
[9]赵昌军,高新贞.掩盖药物苦味技术的新进展[J].齐鲁药事,2009,28(12):741-744.
[10] SHANG R,LIU C,QUAN P,et al. Effect of drug-ion exchange resin complex in betahistine hydrochloride orodispersible film on sustained release,taste masking and hygroscopicity reduction[J]. Int J Pharm,2018,545(1/2):163-169.
[11] LIU Y L,LI P,QIAN R,et al. A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate[J]. Drug Dev Ind Pharm,2018,44(8):1317-1327.
[12] Malaquias L F B,Sá-Barreto L C L,Freire D O,et al.Taste masking and rheology improvement of drug complexed withβ-cyclodextrin and hydroxypropyl-β-cyclodextrin by hot-melt extrusion[J]. Carbohydr Polym,2018,185:19-26.
[13] Münster M,Schoch C,Schmidt C,et al. Multiparticulate system combining taste masking and immediate release properties for the aversive compound praziquantel[J].Eur J Pharm Sci,2017,109:446-454.
[14] Ali B E,Al-Shedfat R I,Fayed M H,et al. New methodology for development of orodispersible tablets using high-shear granulation process[J]. Acta Pol Pharm,2017,74(3):969-981.
[15]吴司琪,伍振峰,岳鹏飞,等.中药制粒工艺及其设备的研究概况[J].中国医药工业杂志,2016,47(3):341-346.
[16] Bar D,Debus H,Brzenczek S,et al. Determining particle size and water content by near-infrared spectroscopy in the granulation of naproxen sodium[J]. J Pharm Biomed Anal,2018,151:209-218.
[17]陈吼.高速剪切湿法制粒工艺制备氯沙坦钾片[J].沈阳药科大学学报,2017,34(6):461-466.
[18]王蕊,孙学志.高剪切制粒与传统湿法制粒在骨架片制粒工艺中的应用比较[J].医药,2016(9):311-312.
[19] TAO J,Pandey P,Bindra D S,et al. Evaluating scale-up rules of a high-shear wet granulation process[J]. J Pharm Sci,2015,104(7):2323-2333.
[20] MENG W,Kotamarthy L,Panikar S,et al. Statistical analysis and comparison of a continuous high shear granulator with a twin screw granulator:effect of process parameters on critical granule attributes and granulation mechanisms[J]. Int J Pharm,2016,513(1/2):357-375.
[21] Shirai Y,Sogo K,Yamamoto K,et al. A novel fine granule system for masking bitter taste[J]. Biol Pharm Bull,1993,16(2):172-177.
[22] Mojet J,Heidema J,Christ-Hazelhof E. Taste perception with age:generic or specific losses in supra-threshold intensities of five taste qualities[J]. Chem Senses,2003,28(5):397-413.
[23]许谙,孙丹青.熔融制粒法制备盐酸二甲双胍缓释片[J].中国现代应用药学,2013,30(7):758-762.
[24] LIU M X,YIN D P,FU H L,et al. Double-coated enrofloxacin microparticles with chitosan and alginate:preparation,characterization and taste-masking effect study[J]. Carbohydr Polym,2017,170:247-253.
[25] Yajima T,Umeki N,Itai S. Optimum spray congealing conditions for masking the bitter taste of clarithromycin in wax matrix[J]. Chem Pharm Bull(Tokyo),1999,47(2):220-225.
[26] Yajima T,Nogata A,Demachi M,et al. Particle design for taste-masking using a spray-congealing technique[J]. Chem Pharm Bull(Tokyo),1996,44(1):187-191.
[27] Amrutkar P P,Patil S B,Todarwal A N,et al. Design and evaluation of taste masked chewable dispersible tablet of lamotrigine by melt granulation[J]. Int J Drug Deliv,2011,2(2):188-196.
[28] Eckert C,Pein M,Breitkreutz J. Lean production of taste improved lipidic sodium benzoate formulations[J]. Eur J Pharm Biopharm,2014,88(2):455-461.
[29] Ahire S B,Gaikwad P D,Bankar V H,et al. Taste masking of metoclopramide hydrochloride by novel melt granulation[J]. Int J Drug Deliv,2012,4(2):89-94.
[30] Aloorkar N H,Bhatia M S. Rapidly disintegrating tablets of metoclopramide hydrochloride using novel chemically modified cellulose[J]. Ars Pharm,2011,52(3):26-34.
[31] Rodriguez L,Cavallari C,Passerini N,et al. Preparation and characterization by morphological analysis of diclofenac/PEG 4000 granules obtained using three different techniques[J]. Int J Pharm,2002,242(1/2):285-289.
[32] Albertini B, Cavallari C, Passerini N, et al.Characterization and taste-masking evaluation of acetaminophen granules:comparison between different preparation methods in a high-shear mixer[J]. Eur J Pharm Sci,2004,21(2/3):295-303.
[33] Khan A,Iqbal Z,Ibrahim M,et al. Prediction of the effect of taste masking on disintegration behavior,mechanical strength and rheological characteristics of highly water soluble drug(itopride HCl); an application of Se De M-ODT expert system[J]. Powder Technol,2015,284:411-417.
[34] Shanmugam S. Granulation techniques and technologies:recent progresses[J]. Bioimpacts,2015,5(1):55-63.
[35]谈华明,罗莉,徐瑞超,等. Plackett-Burman合BoxBehnken设计法优选杏苏止咳颗粒流化床制粒工艺研究[J].亚太传统医药,2017,13(12):25-28.
[36]郭良然,孙佩男,潘卫三.流化床制粒特点及影响因素[J].中国药剂学杂志:网络版,2005(6):346-351.
[37]丁平,黄敏.多功能流化床制罗红霉素颗粒剂的研究[J].药品评价,2006,3(6):423-425.
[38]郭廓.固体制剂流化床喷雾剂制粒工艺技术研究[J].黑龙江科学,2015,6(2):33,35.
[39]王海刚,邱桂芝,叶佳敏,等.流化床颗粒制备过程层析成像测量和优化控制[J].工程热物理学报,2015,36(5):1015-1018.
[40]曹韩韩,杜若飞,冯怡,等.干法制粒技术在中药研究中的应用进展[J].中草药,2013,44(19):2772-2776.
[41]丁亚丽.干法制粒与节能降耗[J].现代制造,2010(2):39-41.
[42]黄生武,汤波,朱立华.五味安神颗粒干法制粒工艺优化研究[J].湖南中医杂志,2018,34(9):173-175.
[43] Kawano Y,Ito A,Sasatsu M,et al. Preparation of orally disintegrating tablets with taste-masking function:masking effect in granules prepared with correctives using the dry granulation method and evaluation of tablets prepared using the taste-masked granules[J].Yakugaku Zasshi,2010,130(1):81-86.
[44] Silva A F,Vercruysse J,Vervaet C et al. Process monitoring and evaluation of a continuous pharmaceutical twin-screw granulation and drying process using multivariate data analysis[J]. Eur J Pharm Biopharm,2018,128:36-47.
[45] Karolewicz B. A review of polymers as multifunctional excipients in drug dosage form technology[J]. Saudi Pharm J,2016,24(5):525-536.
[46] Petrovick G F,Breitkreutz J,Pein-Hackelbusch M. Tastemasking properties of solid lipid based micropellets obtained by cold extrusion-spheronization[J]. Int J Pharm,2016,506(1/2):361-370.
[47] Onofre F,Macleod G,Muley V,et al. An investigation into taste masking of paracetamol using AquacoatECD applied via different granulation processes[J]. Int J Pharm,2016,511(2):1145-1146.
[2]范建伟,刘武占,李艳芳,等.制剂用水蛭原粉掩味前后主要腥臭异味物质的变化分析[J].中国实验方剂学杂志,2018,24(6):22-25.
[3] WANG Y,FENG Y,WU Y,et al. Sensory evaluation of the taste of berberine hydrochloride using an Electronic Tongue[J]. Fitoterapia,2013,86:137-143.
[4] Faisal W,Farag F,Abdellatif A A H,et al. Taste masking approaches for medicines[J]. Curr Drug Deliv,2018,15(2):167-185.
[5] Dashevskiy A,Mohylyuk V,Ahmed A R,et al.Micropellets coated with Kollicoat Smartseal 30D for taste masking in liquid oral dosage forms[J]. Drug Dev Ind Pharm,2017,43(9):1548-1556.
[6]刘斌斌,简晖,田佳明,等.中药矫味与掩味技术的研究进展及问题分析[J].中国实验方剂学杂志,2016,22(16):229-234.
[7]于飞千,刘臻,潘卫三.药物制剂中苦味掩盖方法的研究进展[J].中国新药杂志,2007,16(15):1171-1174.
[8]吴飞,赵春草,冯怡,等.中药口服制剂矫味研究的探讨[J].中国新药杂志,2015,24(8):893-899.
[9]赵昌军,高新贞.掩盖药物苦味技术的新进展[J].齐鲁药事,2009,28(12):741-744.
[10] SHANG R,LIU C,QUAN P,et al. Effect of drug-ion exchange resin complex in betahistine hydrochloride orodispersible film on sustained release,taste masking and hygroscopicity reduction[J]. Int J Pharm,2018,545(1/2):163-169.
[11] LIU Y L,LI P,QIAN R,et al. A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate[J]. Drug Dev Ind Pharm,2018,44(8):1317-1327.
[12] Malaquias L F B,Sá-Barreto L C L,Freire D O,et al.Taste masking and rheology improvement of drug complexed withβ-cyclodextrin and hydroxypropyl-β-cyclodextrin by hot-melt extrusion[J]. Carbohydr Polym,2018,185:19-26.
[13] Münster M,Schoch C,Schmidt C,et al. Multiparticulate system combining taste masking and immediate release properties for the aversive compound praziquantel[J].Eur J Pharm Sci,2017,109:446-454.
[14] Ali B E,Al-Shedfat R I,Fayed M H,et al. New methodology for development of orodispersible tablets using high-shear granulation process[J]. Acta Pol Pharm,2017,74(3):969-981.
[15]吴司琪,伍振峰,岳鹏飞,等.中药制粒工艺及其设备的研究概况[J].中国医药工业杂志,2016,47(3):341-346.
[16] Bar D,Debus H,Brzenczek S,et al. Determining particle size and water content by near-infrared spectroscopy in the granulation of naproxen sodium[J]. J Pharm Biomed Anal,2018,151:209-218.
[17]陈吼.高速剪切湿法制粒工艺制备氯沙坦钾片[J].沈阳药科大学学报,2017,34(6):461-466.
[18]王蕊,孙学志.高剪切制粒与传统湿法制粒在骨架片制粒工艺中的应用比较[J].医药,2016(9):311-312.
[19] TAO J,Pandey P,Bindra D S,et al. Evaluating scale-up rules of a high-shear wet granulation process[J]. J Pharm Sci,2015,104(7):2323-2333.
[20] MENG W,Kotamarthy L,Panikar S,et al. Statistical analysis and comparison of a continuous high shear granulator with a twin screw granulator:effect of process parameters on critical granule attributes and granulation mechanisms[J]. Int J Pharm,2016,513(1/2):357-375.
[21] Shirai Y,Sogo K,Yamamoto K,et al. A novel fine granule system for masking bitter taste[J]. Biol Pharm Bull,1993,16(2):172-177.
[22] Mojet J,Heidema J,Christ-Hazelhof E. Taste perception with age:generic or specific losses in supra-threshold intensities of five taste qualities[J]. Chem Senses,2003,28(5):397-413.
[23]许谙,孙丹青.熔融制粒法制备盐酸二甲双胍缓释片[J].中国现代应用药学,2013,30(7):758-762.
[24] LIU M X,YIN D P,FU H L,et al. Double-coated enrofloxacin microparticles with chitosan and alginate:preparation,characterization and taste-masking effect study[J]. Carbohydr Polym,2017,170:247-253.
[25] Yajima T,Umeki N,Itai S. Optimum spray congealing conditions for masking the bitter taste of clarithromycin in wax matrix[J]. Chem Pharm Bull(Tokyo),1999,47(2):220-225.
[26] Yajima T,Nogata A,Demachi M,et al. Particle design for taste-masking using a spray-congealing technique[J]. Chem Pharm Bull(Tokyo),1996,44(1):187-191.
[27] Amrutkar P P,Patil S B,Todarwal A N,et al. Design and evaluation of taste masked chewable dispersible tablet of lamotrigine by melt granulation[J]. Int J Drug Deliv,2011,2(2):188-196.
[28] Eckert C,Pein M,Breitkreutz J. Lean production of taste improved lipidic sodium benzoate formulations[J]. Eur J Pharm Biopharm,2014,88(2):455-461.
[29] Ahire S B,Gaikwad P D,Bankar V H,et al. Taste masking of metoclopramide hydrochloride by novel melt granulation[J]. Int J Drug Deliv,2012,4(2):89-94.
[30] Aloorkar N H,Bhatia M S. Rapidly disintegrating tablets of metoclopramide hydrochloride using novel chemically modified cellulose[J]. Ars Pharm,2011,52(3):26-34.
[31] Rodriguez L,Cavallari C,Passerini N,et al. Preparation and characterization by morphological analysis of diclofenac/PEG 4000 granules obtained using three different techniques[J]. Int J Pharm,2002,242(1/2):285-289.
[32] Albertini B, Cavallari C, Passerini N, et al.Characterization and taste-masking evaluation of acetaminophen granules:comparison between different preparation methods in a high-shear mixer[J]. Eur J Pharm Sci,2004,21(2/3):295-303.
[33] Khan A,Iqbal Z,Ibrahim M,et al. Prediction of the effect of taste masking on disintegration behavior,mechanical strength and rheological characteristics of highly water soluble drug(itopride HCl); an application of Se De M-ODT expert system[J]. Powder Technol,2015,284:411-417.
[34] Shanmugam S. Granulation techniques and technologies:recent progresses[J]. Bioimpacts,2015,5(1):55-63.
[35]谈华明,罗莉,徐瑞超,等. Plackett-Burman合BoxBehnken设计法优选杏苏止咳颗粒流化床制粒工艺研究[J].亚太传统医药,2017,13(12):25-28.
[36]郭良然,孙佩男,潘卫三.流化床制粒特点及影响因素[J].中国药剂学杂志:网络版,2005(6):346-351.
[37]丁平,黄敏.多功能流化床制罗红霉素颗粒剂的研究[J].药品评价,2006,3(6):423-425.
[38]郭廓.固体制剂流化床喷雾剂制粒工艺技术研究[J].黑龙江科学,2015,6(2):33,35.
[39]王海刚,邱桂芝,叶佳敏,等.流化床颗粒制备过程层析成像测量和优化控制[J].工程热物理学报,2015,36(5):1015-1018.
[40]曹韩韩,杜若飞,冯怡,等.干法制粒技术在中药研究中的应用进展[J].中草药,2013,44(19):2772-2776.
[41]丁亚丽.干法制粒与节能降耗[J].现代制造,2010(2):39-41.
[42]黄生武,汤波,朱立华.五味安神颗粒干法制粒工艺优化研究[J].湖南中医杂志,2018,34(9):173-175.
[43] Kawano Y,Ito A,Sasatsu M,et al. Preparation of orally disintegrating tablets with taste-masking function:masking effect in granules prepared with correctives using the dry granulation method and evaluation of tablets prepared using the taste-masked granules[J].Yakugaku Zasshi,2010,130(1):81-86.
[44] Silva A F,Vercruysse J,Vervaet C et al. Process monitoring and evaluation of a continuous pharmaceutical twin-screw granulation and drying process using multivariate data analysis[J]. Eur J Pharm Biopharm,2018,128:36-47.
[45] Karolewicz B. A review of polymers as multifunctional excipients in drug dosage form technology[J]. Saudi Pharm J,2016,24(5):525-536.
[46] Petrovick G F,Breitkreutz J,Pein-Hackelbusch M. Tastemasking properties of solid lipid based micropellets obtained by cold extrusion-spheronization[J]. Int J Pharm,2016,506(1/2):361-370.
[47] Onofre F,Macleod G,Muley V,et al. An investigation into taste masking of paracetamol using AquacoatECD applied via different granulation processes[J]. Int J Pharm,2016,511(2):1145-1146.