热熔胶贴膏质量评价研究
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摘要
本文以临床常用的外用制剂“关节止痛膏”为研究对象,以热熔胶基质为载体,制成热熔胶关节止痛膏经皮给药制剂,并对其质量进行相关评价。
论文对制备的热熔胶贴膏进行了质量控制和评价。首先对本制剂的性状、含膏量、耐热性、透气性、粘附性等项目进行了规定；建立了关节止痛膏中辣椒流浸膏和颠茄流浸膏的薄层色谱鉴别法；建立了盐酸苯海拉明HPLC含量测定方法、樟脑、薄荷脑、水杨酸甲酯GC含量测定方法；并进行了稳定性研究。结果显示：本品为棕黄色片状热熔胶贴膏,气芳香,质地均匀、平整柔软,黏性适宜；暂定本贴膏含膏量为每100 cm2不得少于2.4 g；耐热性符合标准；湿气透过量在500-600 g/m2·24h之间；粘附性能适中,暂定本贴膏初粘性可黏住24号钢球,持粘性为26.31 h,剥离强度为2.55 KN/m；暂定本贴膏盐酸苯海拉明的含量限度每片不得少于2.754 mg,樟脑(C10H16O)每片不得少于67.95 mg,含薄荷脑(C10H20O)每片不得少于5.21 mg,含水杨酸甲酯(C8H803)每片不得少于22.78 mg。
采用药典的方法比较了热熔胶贴膏与橡胶膏的体外释药性能；采用FRANZ池法比较了热熔胶贴膏与橡胶膏的经皮渗透性能。体外释放研究结果表明,与橡胶膏基质相比,热熔胶基质的关节止痛膏无论是亲水性成分盐酸苯海拉明,还是疏水性成分挥发油类(樟脑、薄荷脑、水杨酸甲酯),均具有较高的释药性；体外渗透研究结果显示,盐酸苯海拉明在热熔胶基质中的渗透速率可达至(?)0.76 (μg/cm2·h),24h的累积透皮渗透量可达到38.02%。挥发油成分樟脑、薄荷脑、水杨酸甲酯在热熔胶基质中的渗透速率分别为21.17、1.91、9.53 (μg/cm2·h),其24h的累积透皮渗透量可分别达到33.18%、56.78%、47.60%,比在橡胶膏基质中具有较高的体外经皮渗透性。
稳定性研究显示,室温及加速条件下6个月内稳定,暂定有效期为24个月。
本文为热熔胶贴膏质量标准的研究提供了实验依据和方法借鉴,为建立一个系统的、完整的热熔胶贴膏质量评价体系奠定基础。
Guanjiezhitonggao is a classic external preparation in a clinical use. To increases therapeutic effect, hot melt pressure sensitive adhesive was used as a carrier of Guanjiezhitonggao preparation.
The quality of Guanjiezhitonggao with hot melt pressure sensitive adhesive was evaluated. The characters of preparation that including properties, anointed quantity, heat resistance, permeability and adhesion were definite. Thin Layer Chromatography (TLC) was used to investigate the pepper extracts and belladonna flow extracts in Guanjiezhitonggao. HPLC method was used to test the content of diphenhydramine hydrochloride. Camphor, menthol and gaultherolin was tested by GC. And the stability of the hot melt pressure sensitive adhesive was evaluated. The results showed that hot melt pressure sensitive adhesive was yellowish-brown flake hot melt adhesive with fragrance, soft quality, suitable viscosity. Per 100 cm2 at least had 2.4 g adhesive. Heat resistance conformed to the standards. Moisture quantity was 500-600 g/m2 in 24 h. The initial adhesion of Hot Melt Pressure Sensitive Adhesive could stick to No.24 steel ball, and the viscosity was 26.31 h, peel strength was 2.55 KN/m. Each tablet contain at least 2.754 mg diphenhydramine hydrochloride as hydrophilic composition,67.95 mg camphor (C10H16O) 5.21 mg menthol (C10H20O) and 22.78 mg gaultherolin (C8H8O3) as hydrophobic naphtha compositions.
The vitro medicinal release properties and percutaneous permeability were compared between hot melt pressure sensitive adhesive and rubber paste by the method in Pharmacopoeia and FRANZ method. Compared with rubber adhesive, hot melt pressure sensitive adhesive has a higher vitro medicinal properties both in its hydrophilic composition (diphenhydramine hydrochloride) and its hydrophobic composition (camphor, menthol and gaultherolin). The vitro penetration results showed that the penetration rate of diphenhydramine hydrochloride in hot melt adhesive was 0.76 (μg/cm2·h), and its permeability in 24h was 38.02%. The penetration rate of camphor, menthol and gaultherolin in hot melt adhesive were 21.17,1.917 and 9.537 (μg/cm2·h), and their permeabilities in 24h were 33.18%,56.78% and 47.60%. Hot melt pressure sensitive adhesive has a higher vitro penetration than rubber adhesive.
The stability of Guanjiezhitonggao with hot melt pressure sensitive adhesive was detected with acceleration stability test and room temperature test, the result showed an excellent stability between 0 and 6 months. So we interim its period of validity was 24 months.
This article have provided a quality standard and evaluation system for the research of hot melt pressure sensitive adhesive hot melt adhesive.
论文对制备的热熔胶贴膏进行了质量控制和评价。首先对本制剂的性状、含膏量、耐热性、透气性、粘附性等项目进行了规定；建立了关节止痛膏中辣椒流浸膏和颠茄流浸膏的薄层色谱鉴别法；建立了盐酸苯海拉明HPLC含量测定方法、樟脑、薄荷脑、水杨酸甲酯GC含量测定方法；并进行了稳定性研究。结果显示：本品为棕黄色片状热熔胶贴膏,气芳香,质地均匀、平整柔软,黏性适宜；暂定本贴膏含膏量为每100 cm2不得少于2.4 g；耐热性符合标准；湿气透过量在500-600 g/m2·24h之间；粘附性能适中,暂定本贴膏初粘性可黏住24号钢球,持粘性为26.31 h,剥离强度为2.55 KN/m；暂定本贴膏盐酸苯海拉明的含量限度每片不得少于2.754 mg,樟脑(C10H16O)每片不得少于67.95 mg,含薄荷脑(C10H20O)每片不得少于5.21 mg,含水杨酸甲酯(C8H803)每片不得少于22.78 mg。
采用药典的方法比较了热熔胶贴膏与橡胶膏的体外释药性能；采用FRANZ池法比较了热熔胶贴膏与橡胶膏的经皮渗透性能。体外释放研究结果表明,与橡胶膏基质相比,热熔胶基质的关节止痛膏无论是亲水性成分盐酸苯海拉明,还是疏水性成分挥发油类(樟脑、薄荷脑、水杨酸甲酯),均具有较高的释药性；体外渗透研究结果显示,盐酸苯海拉明在热熔胶基质中的渗透速率可达至(?)0.76 (μg/cm2·h),24h的累积透皮渗透量可达到38.02%。挥发油成分樟脑、薄荷脑、水杨酸甲酯在热熔胶基质中的渗透速率分别为21.17、1.91、9.53 (μg/cm2·h),其24h的累积透皮渗透量可分别达到33.18%、56.78%、47.60%,比在橡胶膏基质中具有较高的体外经皮渗透性。
稳定性研究显示,室温及加速条件下6个月内稳定,暂定有效期为24个月。
本文为热熔胶贴膏质量标准的研究提供了实验依据和方法借鉴,为建立一个系统的、完整的热熔胶贴膏质量评价体系奠定基础。
Guanjiezhitonggao is a classic external preparation in a clinical use. To increases therapeutic effect, hot melt pressure sensitive adhesive was used as a carrier of Guanjiezhitonggao preparation.
The quality of Guanjiezhitonggao with hot melt pressure sensitive adhesive was evaluated. The characters of preparation that including properties, anointed quantity, heat resistance, permeability and adhesion were definite. Thin Layer Chromatography (TLC) was used to investigate the pepper extracts and belladonna flow extracts in Guanjiezhitonggao. HPLC method was used to test the content of diphenhydramine hydrochloride. Camphor, menthol and gaultherolin was tested by GC. And the stability of the hot melt pressure sensitive adhesive was evaluated. The results showed that hot melt pressure sensitive adhesive was yellowish-brown flake hot melt adhesive with fragrance, soft quality, suitable viscosity. Per 100 cm2 at least had 2.4 g adhesive. Heat resistance conformed to the standards. Moisture quantity was 500-600 g/m2 in 24 h. The initial adhesion of Hot Melt Pressure Sensitive Adhesive could stick to No.24 steel ball, and the viscosity was 26.31 h, peel strength was 2.55 KN/m. Each tablet contain at least 2.754 mg diphenhydramine hydrochloride as hydrophilic composition,67.95 mg camphor (C10H16O) 5.21 mg menthol (C10H20O) and 22.78 mg gaultherolin (C8H8O3) as hydrophobic naphtha compositions.
The vitro medicinal release properties and percutaneous permeability were compared between hot melt pressure sensitive adhesive and rubber paste by the method in Pharmacopoeia and FRANZ method. Compared with rubber adhesive, hot melt pressure sensitive adhesive has a higher vitro medicinal properties both in its hydrophilic composition (diphenhydramine hydrochloride) and its hydrophobic composition (camphor, menthol and gaultherolin). The vitro penetration results showed that the penetration rate of diphenhydramine hydrochloride in hot melt adhesive was 0.76 (μg/cm2·h), and its permeability in 24h was 38.02%. The penetration rate of camphor, menthol and gaultherolin in hot melt adhesive were 21.17,1.917 and 9.537 (μg/cm2·h), and their permeabilities in 24h were 33.18%,56.78% and 47.60%. Hot melt pressure sensitive adhesive has a higher vitro penetration than rubber adhesive.
The stability of Guanjiezhitonggao with hot melt pressure sensitive adhesive was detected with acceleration stability test and room temperature test, the result showed an excellent stability between 0 and 6 months. So we interim its period of validity was 24 months.
This article have provided a quality standard and evaluation system for the research of hot melt pressure sensitive adhesive hot melt adhesive.
引文
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