止痛贴膏剂的制备工艺及质量标准研究
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摘要
目的:
以新型水溶性高分子材料--部分被中和的聚丙烯酸(NP700)为基质,优选止痛贴膏剂的制备工艺,研究贴膏剂的体外透皮释药规律,并初步制定贴膏剂质量标准。
方法:
(1)川芎白芷的提取工艺研究:以欧前胡素和异欧前胡素的提取量为评价指标,考察了不同提取方法对提取的影响;以乙醇浓度、浸泡时间、溶剂倍量为因素,采用星点设计,优选川芎白芷的最佳提取工艺。
(2)花椒细辛提取工艺研究:以挥发油提取量和水溶性成分的出膏率为指标,分别考察了加水量、药材浸泡与否对提取挥油量和水溶性成分出膏率的影响,优选花椒细辛最佳提取工艺。
(3)止痛贴膏剂成型工艺的研究:①以感官指标为评价指标,采用单因素研究空白基质配比,初步筛选出各组成成分的用量范围;②以感官指标和剥离强度为评价指标,采用单因素和正交试验优选止痛贴膏剂最佳配比。
(4)止痛贴膏剂透皮吸收的研究:①以欧前胡素的透过量为指标,考察了不同接受液对促透效果的影响;②考察了不同促渗剂种类和用量对促透效果的影响;③以24h累积释药量为指标,考察了体外透皮给药的释药规律。
(5)止痛贴膏剂质量标准的研究:遵照相关规定,制定了本贴膏剂药物的薄层鉴别方法;建立了贴膏剂中欧前胡素的含量测定方法。
结果:
(1)确定了川芎白芷的最佳提取工艺为:以渗漉法为提取方法,采用86%乙醇、浸泡30h、溶媒用量30倍提取。
(2)确定花椒细辛最佳提取工艺为:采用不浸泡药材直接用8倍于药材的加水量,4个小时提取挥发油及水溶性成分。
(3)确定了处方中主要影响贴膏剂质量的组分的最佳配比为:NP700:甘油:酒石酸:交联剂(Alcl3:Al(OH)3)=2:7.5:0.012:(0.010:0.007);贴剂制备的溶剂为20%乙醇和45%乙醇。
(4)确定了最佳制备工艺:将A(NP700、甘油、氢氧化铝)用磁力搅拌均匀后超声脱气,将D(冰片、氮酮、N甲基砒咯烷酮、挥发油)相加入A相搅拌均匀。将C(川芎白芷提取物、花椒细辛水提物)相混合均匀后,加入A和D相搅拌均匀,超声脱气泡。将B(酒石酸、氯化铝)相混匀后,加入A、D、C相,搅至适当粘度后铺于无纺布上,70℃干燥2小时放冷后,加盖上防粘纸即可。
(5)确定了最佳促渗剂种类和用量为氮酮:N-甲基砒咯烷酮=1:1,用量为处方量的5%。体外释药行为符合威布尔分布函数方程:Q=1.0907t+4.8052r=0.991。
(6)确定了止痛贴膏剂的检查、定性鉴别、含量测定的质量标准草案,每片按欧前胡素计应不低于2mg。
结论:
止痛贴膏剂的制剂工艺可行,质量稳定可靠。NP700适合作为贴膏剂制备的粘合剂。本研究达到了课题设计的预期目的
Objectives
The part of polyacrylic acid (NP700) of the nature and characteristics arestudied as a paste on the new water-soluble polymer materials . To Optimizeextraction and preparation technology for the paste.To study the vitropermeation behavior,and draft quality standards.
Methods
(1)To study Chuanxiong and Baizhi of Extraction of Process: isoimperatorin andpeulustrin of the extraction of indicators as the evaluation to study ofdifferent extraction of methods on the extraction;The Central composite designis used to optimize Chuanxiong and Baizhi’s the best process by usingethanol’s concentration, soaking‘s time, times of solvent as a factors
(2)To study Zanthoxylum and Asarum of Extraction technique : The evaluationof extraction of volatile oil and water-soluble components of the index ratewere used as index to investigate water’s consumption,soak drug or no soak drug forconforming the matter which is water-soluble and volatile oil whether it isaffected. to optimize Zanthoxylum and Asarum of Extraction technique.
(3)To study Paste’s Process of technology:①the total evaluation of senseorgan index was used as index obserbation and single factor observation wasused to screen out the change ranges of main matrix.②The orthogonal designwas applied to optimize the best technology of preparation.
(4)To study of Paste’s percutaneous of absorption:①To use peulustrin in theamount of the indicators studied different acceptation of liquid to affectpermeability②inspected the different infiltration of the amount ofpenetration’senhancement effection③to study of the in vitro release oftransdermal drug delivery by 24h cumulative release of indicators.
(5)To study paste’s quality standards: 2005 edition Pharmacopoeia and relatedliterature is standard to establish this paste’s TLC and Paste method for thedetermination.
Results:
(1) Chuanxiong and Baizhi were extracted by using 86% ethanol of 30 times tosoak 30 h.
(2)The Asarum and the Zanthoxylum were distilled together for volatile oilswith 8-fold water for 4hours.
(3)The best matrix proportion of zhitong Emplastrum showed as polyacry acid(NP700,neutrualized partly)to glycerin to tartaric acid to linking agent(AlCl_3:Al(OH)_3)was 2.1 to 15 to 0.023 to (0.019 to 0.013).
(4)The best paste of preparation was use A ,which was NP700, glycerol, aluminum hydroxide, with uniform magnetic stirring after ultrasound degassing,thenmixed with D which was borneol, Azone,volatile oil,and mixed with C which isChuanxiong,Baizhi extracted,and mixed with B which is tartaric acid andaluminum chloride,then stirred to the appropriate viscosity after resurfacingin the non-woven fabrics, dry 70 degrees after 2 hours Leng,and can be theAnti-Burn Paper.
(5)The equation for in-vitro permeation was Q= 1.0907t+4.8052(r=0.991).
(6) Quality evaluation was performed in line with paste as designated in ChinesePharmacopoeia;besides,qualitative and quantitative method was establishedbased on which a quality standard proposal was drafted(≥2mg peulustrin/perpaste).
Conclusion
The process technology is feasible and stable . NP700 for Paste as a pasteprepared adhesive. Therefor ,the study is successful in achieving itsobjectives.
以新型水溶性高分子材料--部分被中和的聚丙烯酸(NP700)为基质,优选止痛贴膏剂的制备工艺,研究贴膏剂的体外透皮释药规律,并初步制定贴膏剂质量标准。
方法:
(1)川芎白芷的提取工艺研究:以欧前胡素和异欧前胡素的提取量为评价指标,考察了不同提取方法对提取的影响;以乙醇浓度、浸泡时间、溶剂倍量为因素,采用星点设计,优选川芎白芷的最佳提取工艺。
(2)花椒细辛提取工艺研究:以挥发油提取量和水溶性成分的出膏率为指标,分别考察了加水量、药材浸泡与否对提取挥油量和水溶性成分出膏率的影响,优选花椒细辛最佳提取工艺。
(3)止痛贴膏剂成型工艺的研究:①以感官指标为评价指标,采用单因素研究空白基质配比,初步筛选出各组成成分的用量范围;②以感官指标和剥离强度为评价指标,采用单因素和正交试验优选止痛贴膏剂最佳配比。
(4)止痛贴膏剂透皮吸收的研究:①以欧前胡素的透过量为指标,考察了不同接受液对促透效果的影响;②考察了不同促渗剂种类和用量对促透效果的影响;③以24h累积释药量为指标,考察了体外透皮给药的释药规律。
(5)止痛贴膏剂质量标准的研究:遵照相关规定,制定了本贴膏剂药物的薄层鉴别方法;建立了贴膏剂中欧前胡素的含量测定方法。
结果:
(1)确定了川芎白芷的最佳提取工艺为:以渗漉法为提取方法,采用86%乙醇、浸泡30h、溶媒用量30倍提取。
(2)确定花椒细辛最佳提取工艺为:采用不浸泡药材直接用8倍于药材的加水量,4个小时提取挥发油及水溶性成分。
(3)确定了处方中主要影响贴膏剂质量的组分的最佳配比为:NP700:甘油:酒石酸:交联剂(Alcl3:Al(OH)3)=2:7.5:0.012:(0.010:0.007);贴剂制备的溶剂为20%乙醇和45%乙醇。
(4)确定了最佳制备工艺:将A(NP700、甘油、氢氧化铝)用磁力搅拌均匀后超声脱气,将D(冰片、氮酮、N甲基砒咯烷酮、挥发油)相加入A相搅拌均匀。将C(川芎白芷提取物、花椒细辛水提物)相混合均匀后,加入A和D相搅拌均匀,超声脱气泡。将B(酒石酸、氯化铝)相混匀后,加入A、D、C相,搅至适当粘度后铺于无纺布上,70℃干燥2小时放冷后,加盖上防粘纸即可。
(5)确定了最佳促渗剂种类和用量为氮酮:N-甲基砒咯烷酮=1:1,用量为处方量的5%。体外释药行为符合威布尔分布函数方程:Q=1.0907t+4.8052r=0.991。
(6)确定了止痛贴膏剂的检查、定性鉴别、含量测定的质量标准草案,每片按欧前胡素计应不低于2mg。
结论:
止痛贴膏剂的制剂工艺可行,质量稳定可靠。NP700适合作为贴膏剂制备的粘合剂。本研究达到了课题设计的预期目的
Objectives
The part of polyacrylic acid (NP700) of the nature and characteristics arestudied as a paste on the new water-soluble polymer materials . To Optimizeextraction and preparation technology for the paste.To study the vitropermeation behavior,and draft quality standards.
Methods
(1)To study Chuanxiong and Baizhi of Extraction of Process: isoimperatorin andpeulustrin of the extraction of indicators as the evaluation to study ofdifferent extraction of methods on the extraction;The Central composite designis used to optimize Chuanxiong and Baizhi’s the best process by usingethanol’s concentration, soaking‘s time, times of solvent as a factors
(2)To study Zanthoxylum and Asarum of Extraction technique : The evaluationof extraction of volatile oil and water-soluble components of the index ratewere used as index to investigate water’s consumption,soak drug or no soak drug forconforming the matter which is water-soluble and volatile oil whether it isaffected. to optimize Zanthoxylum and Asarum of Extraction technique.
(3)To study Paste’s Process of technology:①the total evaluation of senseorgan index was used as index obserbation and single factor observation wasused to screen out the change ranges of main matrix.②The orthogonal designwas applied to optimize the best technology of preparation.
(4)To study of Paste’s percutaneous of absorption:①To use peulustrin in theamount of the indicators studied different acceptation of liquid to affectpermeability②inspected the different infiltration of the amount ofpenetration’senhancement effection③to study of the in vitro release oftransdermal drug delivery by 24h cumulative release of indicators.
(5)To study paste’s quality standards: 2005 edition Pharmacopoeia and relatedliterature is standard to establish this paste’s TLC and Paste method for thedetermination.
Results:
(1) Chuanxiong and Baizhi were extracted by using 86% ethanol of 30 times tosoak 30 h.
(2)The Asarum and the Zanthoxylum were distilled together for volatile oilswith 8-fold water for 4hours.
(3)The best matrix proportion of zhitong Emplastrum showed as polyacry acid(NP700,neutrualized partly)to glycerin to tartaric acid to linking agent(AlCl_3:Al(OH)_3)was 2.1 to 15 to 0.023 to (0.019 to 0.013).
(4)The best paste of preparation was use A ,which was NP700, glycerol, aluminum hydroxide, with uniform magnetic stirring after ultrasound degassing,thenmixed with D which was borneol, Azone,volatile oil,and mixed with C which isChuanxiong,Baizhi extracted,and mixed with B which is tartaric acid andaluminum chloride,then stirred to the appropriate viscosity after resurfacingin the non-woven fabrics, dry 70 degrees after 2 hours Leng,and can be theAnti-Burn Paper.
(5)The equation for in-vitro permeation was Q= 1.0907t+4.8052(r=0.991).
(6) Quality evaluation was performed in line with paste as designated in ChinesePharmacopoeia;besides,qualitative and quantitative method was establishedbased on which a quality standard proposal was drafted(≥2mg peulustrin/perpaste).
Conclusion
The process technology is feasible and stable . NP700 for Paste as a pasteprepared adhesive. Therefor ,the study is successful in achieving itsobjectives.
引文
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