重酒石酸卡巴拉汀可溶性微针的制备及透皮性能的考察
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摘要
目的以透明质酸为基质材料,制备载重酒石酸卡巴拉汀(RHT)的可溶性微针并对其经皮渗透性能进行考察。方法以透明质酸(HA)为材料,采用模具浇注法制备RHT可溶性微针,采用穿刺试验考察微针的机械强度和穿刺性能,显微照相考察微针在大鼠皮肤中的溶解性能,体外经皮吸收试验考察微针对RHT经皮吸收的促进作用。结果所制备的RHT可溶性微针贴片为圆形,直径为2 cm,针体形态完整均匀,针长为500μm;微针能有效穿透铝箔,并可在大鼠皮肤上形成与微针相一致的点状阵列;微针在大鼠皮肤内的溶解时间为1 h;体外经皮试验中,1%RHT溶液、RHT可溶性微针及RHT可溶性微针穿刺后给予1%RHT溶液的稳态透皮速率常数分别为3.08、8.04、18.5μg/(cm~2·h)。结论 RHT可溶性微针具有较强的机械性能,良好的皮肤穿刺性和溶解性;可溶性微针能增加RHT透皮给药的累积渗透量,或可成为一种新型的经皮给药方式。
Objective To prepare dissolving microneedles of hyaluronic acid loaded with rivastigmine hydrogen tartrate( RHT) and investigate its transdermal permeation properties. Methods Drug loaded dissolving microneedles was prepared by using the method of mould casting,aluminum foil and in vitro rat skin puncture experiment were carried out to estimate the mechanical strength of microneedles; Micrograph was employed to examine the insertion ability and dissolving properties of microneedles in rat skin. The in vitro transdermal delivery of rivastigmine hydrogen tartrate from microneedle arrays was measured by using the Franz diffusion cell. Results The prepared microneedle patch was 2 cm in diameter and was composed of uniform microneedles with length 500 μm. The microneedles could effectively penetrate the aluminum foil,and form dot array consistent with microneedles formation in rat skin. Dissolving time of microneedles in the skin of rats was about 1 h. In the in vitro transdermal experiments,the permeation rate constants J_S of 1% RHT solution,drug loaded microneedles and 1% RHT solution treated with microneedles were 3.08,8.04 and 18. 5 μg/( cm~2·h) respectively. Conclusion RHT dissolving microneedles have good mechanical properties,good skin penetration and solubility,which can increase cumulative permeation amount of the drug,and may be a new transdermal drug delivery system.
Objective To prepare dissolving microneedles of hyaluronic acid loaded with rivastigmine hydrogen tartrate( RHT) and investigate its transdermal permeation properties. Methods Drug loaded dissolving microneedles was prepared by using the method of mould casting,aluminum foil and in vitro rat skin puncture experiment were carried out to estimate the mechanical strength of microneedles; Micrograph was employed to examine the insertion ability and dissolving properties of microneedles in rat skin. The in vitro transdermal delivery of rivastigmine hydrogen tartrate from microneedle arrays was measured by using the Franz diffusion cell. Results The prepared microneedle patch was 2 cm in diameter and was composed of uniform microneedles with length 500 μm. The microneedles could effectively penetrate the aluminum foil,and form dot array consistent with microneedles formation in rat skin. Dissolving time of microneedles in the skin of rats was about 1 h. In the in vitro transdermal experiments,the permeation rate constants J_S of 1% RHT solution,drug loaded microneedles and 1% RHT solution treated with microneedles were 3.08,8.04 and 18. 5 μg/( cm~2·h) respectively. Conclusion RHT dissolving microneedles have good mechanical properties,good skin penetration and solubility,which can increase cumulative permeation amount of the drug,and may be a new transdermal drug delivery system.
引文
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[9]刘姝,权英淑,神山文男,等.新型经皮传递胰岛素透明质酸微针制剂的制备及性能考察[J].沈阳药科大学学报,2010,27(1):6-10.
[10]陈磊,桂双英,钱珊珊,等.复合物微针的制备及其对盐酸青藤碱透皮性能的影响[J].中国医院药学杂志,2014,34(4):255-259.
[11]刘艳玲,罗永煌,田朋鑫,等.反相HPLC法测定重酒石酸卡巴拉汀胶囊的含量及有关物质[J].药物分析杂志,2011,31(4):721-724.
[12]梁哲,梁漪,俞振伟,等.低频超声波促进重酒石酸卡巴拉汀经皮渗透的研究[J].中国现代应用药学,2015,32(4):455-459.
[13]DILLON S.Rivastigmine transdermal patch[J].Drugs,2011,71(9):1209-1231.
[2]解建国,薛艺东,屈文英,等.重酒石酸卡巴拉汀与盐酸多奈哌齐对阿尔兹海默症患者认知功能及血清缓激肽水平的影响[J].现代生物医学进展,2016,16(33):6460-6462.
[3]MOHAMMAD H,STANFORD S J,THOMAS S,et al.Estimation of the absolute bioavailability of rivastigmine in patients with mild to moderate dementia of the Alzheimers type[J].Clin Pharmacokinet,2002,41:225-234.
[4]利陪红,郭代红.利斯的明的临床研究与安全性评价[J].药物不良反应杂志,2004,1(3):170-173.
[5]KURZ A,FARLOW M,LEFEVRE G.Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer's disease:a review[J].Int J Clin Pract,2009,63(5):799-805.
[6]LEE J W,PARK J H,PRAUSNITZ M R.Dissolving Microneedles for Transdermal Drug Delivery[J].Biomaterials,2008,29(13):2113-2124.
[7]周友军,杨云珂,桂双英.生物可降解微针的研究进展[J].中国新药杂志,2013,22(2):177-182.
[8]LING M H,CHEN M C.Dissolving polymer microneedle patches for rapid and efficient transdermal delivery of insulin to diabetic rats[J].Acta Biomater,2013,9(11):8952-8961.
[9]刘姝,权英淑,神山文男,等.新型经皮传递胰岛素透明质酸微针制剂的制备及性能考察[J].沈阳药科大学学报,2010,27(1):6-10.
[10]陈磊,桂双英,钱珊珊,等.复合物微针的制备及其对盐酸青藤碱透皮性能的影响[J].中国医院药学杂志,2014,34(4):255-259.
[11]刘艳玲,罗永煌,田朋鑫,等.反相HPLC法测定重酒石酸卡巴拉汀胶囊的含量及有关物质[J].药物分析杂志,2011,31(4):721-724.
[12]梁哲,梁漪,俞振伟,等.低频超声波促进重酒石酸卡巴拉汀经皮渗透的研究[J].中国现代应用药学,2015,32(4):455-459.
[13]DILLON S.Rivastigmine transdermal patch[J].Drugs,2011,71(9):1209-1231.