马来酸卡比沙明药物树脂复合物的制备优化及评价
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摘要
目的制备马来酸卡比沙明药物树脂复合物,筛选最佳制备条件,并考察其理化性质、药物释放及掩味效果。方法动态法制备复合物,响应面法优化筛选药液流速、质量浓度及洗脱时间对药物利用率(DA)和树脂载药量(DL)的影响。用差示扫描量热法(DSC)及傅里叶变换红外光谱(FTIR)分析其形成机理,并考察其释放及掩味效果。结果通过Box-Behnken响应面法进行优化后选择药液质量浓度为7.97mg·mL-1,药液流速为1.35mL·min-1,洗脱时间为114.38min,得到实际药物利用率为85.75%,树脂载药量为1.035g·g-1。经DSC与FTIR进行理化性质分析表明复合物为无定型态。模拟胃肠道释放实验证明其仅在消化道离子丰富的环境中释放,且苦味实验证明其掩味效果明显。结论动态法制备药物树脂复合物能够满足实际生产中高药物利用率和高载药量的要求,同时优化的药物树脂复合物掩味效果明显,能提高药物顺应性。
Objective To optimize the process variables in the preparation of carbinomaxine maleate drug resin complex and to evaluate the physicochemical properties,drug release and in vivo taste masking effect.Methods Drug resin complex was prepared using column process.The experimental design was conducted to study the effect of drug concentration,drug flow rate and elution time on drug availability(DA)and drug loading efficiency(DL).Physicochemical characterization studies were proceeded including differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR).Results The optimal reaction conditions included 7.97 mg·mL-1 drug concentration and 1.35 mL·min-1 drug flow rate and 114.38 min elution time which led to the optimum DA of 85.75% and DL of 1.035 g·g-1.Physicochemical characterization of DSC and FTIR showed amorphous nature of resinates.Drug release profiles manifested that resinates only got released in an ion-rich environment(stomach or intestine)when taken into the body.In vivo taste evaluation demonstrated a sound taste-masking effect.Conclusion The optimized column process successfully improved the drug availability and the drug loading efficiency.Drug resin complex effectively masked unpleasant taste and improved the patient compliance.
Objective To optimize the process variables in the preparation of carbinomaxine maleate drug resin complex and to evaluate the physicochemical properties,drug release and in vivo taste masking effect.Methods Drug resin complex was prepared using column process.The experimental design was conducted to study the effect of drug concentration,drug flow rate and elution time on drug availability(DA)and drug loading efficiency(DL).Physicochemical characterization studies were proceeded including differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR).Results The optimal reaction conditions included 7.97 mg·mL-1 drug concentration and 1.35 mL·min-1 drug flow rate and 114.38 min elution time which led to the optimum DA of 85.75% and DL of 1.035 g·g-1.Physicochemical characterization of DSC and FTIR showed amorphous nature of resinates.Drug release profiles manifested that resinates only got released in an ion-rich environment(stomach or intestine)when taken into the body.In vivo taste evaluation demonstrated a sound taste-masking effect.Conclusion The optimized column process successfully improved the drug availability and the drug loading efficiency.Drug resin complex effectively masked unpleasant taste and improved the patient compliance.
引文
[1]孙艳冬,张然然,赵源,等.离子交换树脂作为药物载体的应用进展[J].中国医药工业杂志,2016,47(6):802-806.
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[12]刘玮,丁慧,朱宇涵,等.左旋多巴/盐酸苄丝肼复方药物树脂制备[J].实用药物与临床,2015,18(11):1346-1350.
[13]陈丽丽,安杉杉,陈燕忠,等.雷贝拉唑钠树脂复合物的制备及评价[J].西北药学杂志,2016,31(3):297-301.
[14]付茜,王勤辉,孙璐,等.响应面法优化超声提取灯心草中去氢厄弗酚的工艺[J].西北药学杂志,2015,30(4):331-334.
[15]刘宏飞,师双双,赵欣,等.阿昔洛韦药物树脂复合物体外释药动力学的研究[J].中国新药杂志,2012,21(18):2205-2208.
[16]曾环想,王孟,黄凯,等.可待因树脂复合物的表征及其药物释放[J].沈阳药科大学学报,2010,27(4):273-278.
[17]Hu X,Li Y,Zhang E,et al.Preparation and evaluation of orally disintegrating tablets containing taste-masked microcapsules of berberine hydrochloride[J].AAPS Pharm Sci Tech,2015,14(1):29-37.
[18]Daihom B,Alayoubi A,Ma D,et al.Development and physicochemical characterization of clindamycin resinate for taste masking in pediatrics[J].Drug Dev Ind Pharm,2016,42(10):1600-1633.
[19]鲍光明,刘宝生,王小莺,等.氧氟沙星掩味微囊的制备及优化筛选[J].中国兽医学报,2017,37(1):92-96.
[20]Preis M,Grother L,Axe P,et al.In-vitro and in-vivo evaluation of taste-masked cetirizine hydrochloride formulated in oral lyophilisates[J].Int J Pharm,2015,491(1/2):8-17.
[2]Alayoubi A,Daihom B,Adhikari H,et al.Development of a taste-masked oral suspension of clindamycin HCl using ion exchange resin Amberlite IRP 69for use in pediatrics[J].Drug Dev Ind Pharm,2016,(10):1579-1589.
[3]孙运栋,生依灵,李红菊,等.枸橼酸莫沙必利掩味树脂复合物的制备及评价[J].中国药剂学杂志,2013,11(5):100-106.
[4]Ramadan A A,Mandil H,Genco T.Determination of carbinoxamine maleate in pharmaceuticals by direct and differential pulse polarography[J].Asian J Chem,2009,21(9):7387-7397.
[5]Palabiyik I M,Onur F.Simultaneous spectrophotometric and liquid chromatographic determination of dextromethorphan hydrobromide,phenylephrine hydrochloride,and carbinoxamine maleate in pharmaceutical preparations[J].J Anal Chem,2012,67(1):56-63.
[6]向志芸,李小芳,朱宁,等.龙胆总苷提取物掩味树脂复合物的制备[J].中成药,2016,38(4):785-790.
[7]Samprasit W,Rojanarata T,Akkaramongkolporn P,et al.Reused cyclodextrin as a new way to deliver and enhance drug loading onto ion exchange resin[J].Pharm Dev Technol,2014,10(7):1-12.
[8]Samprasit W,Raojanrata T,Akkaramongkolporn P,et al.Improvement of drug loading onto ion exchange resin by cyclodextrin inclusion complex[J].Drug Dev Ind Pharm,2013,39(11):1672-1680.
[9]Jeong S H,Park K.Drug loading and release properties of ion-exchange resin complexes as a drug delivery matrix[J].Int J Pharm,2008,361(1/2):26-32.
[10]Akkaramongkolporn P,Kulvanich P,Pathipvanich M.Preparation and in vitro release of dual-drug resinates containing equivalent content dextromethorphan and diphenhydramine[J].Drug Dev Ind Pharm,2006,32(4):483-496.
[11]关皎,魏敏,姚慧敏,等.卡络磺钠树脂复合物的制备及静态交换特性[J].沈阳药科大学学报,2010,27(3):163-167.
[12]刘玮,丁慧,朱宇涵,等.左旋多巴/盐酸苄丝肼复方药物树脂制备[J].实用药物与临床,2015,18(11):1346-1350.
[13]陈丽丽,安杉杉,陈燕忠,等.雷贝拉唑钠树脂复合物的制备及评价[J].西北药学杂志,2016,31(3):297-301.
[14]付茜,王勤辉,孙璐,等.响应面法优化超声提取灯心草中去氢厄弗酚的工艺[J].西北药学杂志,2015,30(4):331-334.
[15]刘宏飞,师双双,赵欣,等.阿昔洛韦药物树脂复合物体外释药动力学的研究[J].中国新药杂志,2012,21(18):2205-2208.
[16]曾环想,王孟,黄凯,等.可待因树脂复合物的表征及其药物释放[J].沈阳药科大学学报,2010,27(4):273-278.
[17]Hu X,Li Y,Zhang E,et al.Preparation and evaluation of orally disintegrating tablets containing taste-masked microcapsules of berberine hydrochloride[J].AAPS Pharm Sci Tech,2015,14(1):29-37.
[18]Daihom B,Alayoubi A,Ma D,et al.Development and physicochemical characterization of clindamycin resinate for taste masking in pediatrics[J].Drug Dev Ind Pharm,2016,42(10):1600-1633.
[19]鲍光明,刘宝生,王小莺,等.氧氟沙星掩味微囊的制备及优化筛选[J].中国兽医学报,2017,37(1):92-96.
[20]Preis M,Grother L,Axe P,et al.In-vitro and in-vivo evaluation of taste-masked cetirizine hydrochloride formulated in oral lyophilisates[J].Int J Pharm,2015,491(1/2):8-17.