酸性染料比色法测定复方岩白菜素片中马来酸氯苯那敏的含量

目的：测定复方岩白菜素片中马来酸氯苯那敏的含量,为该药提供质量控制方法。方法：应用酸性染料比色法测定复方岩白菜素片中马来酸氯苯那敏的含量。结果：马来酸氯苯那敏的平均回收率为１００．１％,ＲＳＤ为１．０４％（ｎ＝６）。结论：方法简便,快速,准确,可作为该药的质量控制方法。     

复方马来酸氯苯那敏凝胶剂的制备及质量控制

目的 :制备以马来酸氯苯那敏和盐酸麻黄碱组成的复方凝胶剂。方法 :以卡波姆 -940为乳化剂 ,三乙醇胺调节 pH ,丙二醇作防腐剂 ,制备水溶性透明凝胶。采用一阶导数光谱法和双波长分光光度法分别测定复方凝胶剂中马来酸氯苯那敏和盐酸麻黄碱的含量。结果 :制得的凝胶剂质地均匀、细腻 ,粘稠度适中。马来酸氯苯那敏含量为101 0 % ,平均回收率为100 4 % ,RSD为0 99 % ;盐酸麻黄碱的含量为100 4 % ,平均回收率为101 3 % ,RSD为1 7 %。结论 :该制剂性质稳定 ,无刺激性 ,是治疗过敏性鼻炎的理想新剂型     

正交函数分光光度法测定马来酸氯苯那敏乳膏含量

为建立一种快速而准确的马来酸氯苯那敏乳膏含量测定方法，采用正交函数分光光度法，不经分离直接测定马来酸氯苯那敏乳膏，应用计算机程序辅助筛选测定波长。结果表明，平均回收率为１００．４０％，ＲＳＤ＝０．７３％。用计算机辅助正交函数分光光度法精确简便，可排除尼泊金和基质的干扰。该法可作为马来酸氯苯那敏乳膏的质量控制方法     

高效液相法测定康乐鼻炎片的马来酸氯苯那敏含量

目的：建立测定康乐鼻炎片的马来酸氯苯那敏含量的方法。方法：采用高效液相色谱法。结果：马来酸氯苯那敏与其它成分分离效果好,具有良好线性关系（r=0．9998,y=849．58x-2.0171）,平均回收率为99．1％,RSD为0.3％。结论：用高效液相检测马来酸氯苯那敏含量的方法方便而且准确,该质量标准可以很有效的控制康乐鼻炎片的质量。     

维C银翘片中马来酸氯苯那敏含量测定方法的优化

目的：优化维c银翘片中马来酸氯苯那敏含量测定方法。方法：采用反复萃取（药典法）和直接超声两种提取方法,比较马来酸氯苯那敏的含量测定结果。结果：反复萃取法步骤繁琐,污染环境,其回收率仅为91．4％,含量为116％;直接提取法简单,环境友好,其回收率为100．3％,含量为131％。二极管阵列检测结果表明优化后的方法色谱峰纯度符合要求。结论：优化方法适用于控制维c银翘片中马来酸氯苯那敏的质量,实验数据提示,维C银翘片的质量问题需要密切关注。     

复方马来酸氯苯那敏酊的制备及疗效观察

目的研制复方马来酸氯苯那敏酊的制备方法,观察其临床疗效。方法以马来酸氯苯那敏、氢化可的松为主药,以75％乙醇为溶媒,用常规方法制备。对瘙痒症、神经性皮炎各80例病人进行疗效观察。结果制剂稳定性好,治疗有效率为91．25％、90％。结论复方马来酸氯苯那敏酊安全、有效。     

锌试剂络合分光光度法测定咳特灵胶囊中马来酸氯苯那敏的含量

本文采用锌试剂结合分光光度法，测定了咳特灵胶囊中马来酸氯苯那敏的含量。在ｐＨ４．５的条件下，马来酸氯苯那敏与锌试剂形成１：１的络合物，用氯仿提取，在５３５ｎｍ波长处测定吸收度。马来酸氯苯那敏浓度在３～１５μｇ／ｍｌ范围内符合比耳定律。方法回收率为９９．０％（ｎ＝９）ＲＳＤ＜１．５％。     

HPLC法测定咳特灵颗粒中马来酸氯苯那敏的含量

目的建直咳特灵颗粒的含量测定标准以控制产品质量。方法采用高效液相色谱法测定制剂中马来酸氯苯那敏的含量，高效液相色谱条件：Hypersil柱（4．6mm×250mm，5μl）、流动相为乙腈-0．3％十二烷基硫酸钠溶液-磷酸（65：35：0．02）：检测波长为262nm。结果高效液相法测定马来酸氯苯那敏，重复性好，精度高。结论该方法可用于咳特灵颗粒中的马来酸氯苯那敏的含量。     

锌试剂络合分光光度法测定咳特灵胶囊中马来酸氯苯那敏的…

本文采用锌试剂络合分光光度法，测定了咳特灵胶囊中马来酸氯苯那敏的含量，在ｐＨ４．５的条件下，马来酸氯苯那敏与锌试剂形成１：１的络合物，用氯仿提取，在５３５ｎｍ波长处测定吸收度，马来酸氯苯那敏度在３～１５μｇ／ｍｌ范围内符合比耳定律，方法回收率为９９．０％（ｎ＝９）ＲＳＤ〈１．５％。     

氨酚伪麻那敏胶囊中马来酸氯苯那敏和盐酸伪麻黄碱含量测定方法的改进

目的：建立氨酚伪麻那敏胶囊中马来酸氯苯那敏和盐酸伪麻黄碱的含量测定方法。方法：采用HPLC法测定，C18柱（4.6mm×200mm，5μm），以乙腈-0.5％十二烷基硫酸钠-磷酸（57：43：0.02）为流动相，流速为1mL·min^-1，检测波长为221nm，进样量：20μL。结果：马来酸氯苯那敏和盐酸伪麻黄碱线性范围分别为0.2044～1．0220和2．134～10．670μg；平均回收率（n=9）分别为100.4％（RSD为1，1％）和99.7％（RSD为0.7％）。结论：方法简便、准确，可为评价氨酚伪麻那敏胶囊中马来酸氯苯那敏盐酸伪麻黄碱的含量提供依据。     

川陈皮素温敏型鼻用原位凝胶体外释药行为研究

分别采用扩散池法、无膜溶出法以及渗析池法考察川陈皮素温敏型鼻用原位凝胶的体外释药特性与机制.结果表明,川陈皮素原位凝胶通过扩散释放的药物量较少,150 min仅为1.4%;通过无膜溶出法药物释放完全,120 min时药物基本释放完全,且药物的释放量与溶蚀量具有良好的相关性.渗析池法药物的释放量较扩散池法多,120min可释放8%的药物.因此,本实验室研制的川陈皮素温敏型鼻用原位凝胶可能主要通过溶蚀方式释药.     

Development of in situ gel for nasal delivery: design,optimization, in vitro and in vivo evaluation

Abstract

Context: The mucoadhesive gel formulations are helpful to prolong the residence time at the nasal absorption site and thereby facilitate the uptake of drug. Sumatriptan succinate has oral bioavailability of 15% and undergoes hepatic metabolism, hence it is suitable for nasal administration.

Objective: The objective of the investigation was to develop a mucoadhesive in situ gel to improve the bioavailability of the sumatriptan succinate.

Materials and methods: Deacetylated gellan gum was used as gelling agent. In situ gel was formulated by ion activation mechanism in simulated nasal fluid. A 3² factorial design was found suitable to optimize batch. In vivo study was carried out in Spraugue-Dawley rats, and drug was estimated in plasma by UPLC-MS.

Result: The optimized batch showed drug release of 98.57% within 5?h followed by Peppas model of drug release. Ex vivo studies on sheep nasal mucosa showed 93.33% within 5?h. In histopathological study, optimized batch was found to be safe and stable in accelerated stability study for three months. Optimized formulation, F7 has shown absolute bioavailability, which was found to be 164.70%. Drug targeting index for brain tissues was found to be 1.866.

Discussion: Concentration of the gelling polymer was compromised for satisfactory gel strength and an acceptable viscosity. The release depended on viscosity of formulation. Drug targeting index indicates sumatriptan can reach to brain via olfactory pathway.

Conclusion: In situ gel proved to be suitable for administration of sumatriptan succinate through nasal route. The ease of administration coupled with less frequent administration enhances patient compliance.     

银杏叶鼻用原位凝胶的制备及体外吸收研究

目的制备银杏叶鼻用原位凝胶剂,并考察促渗剂对银杏叶透黏膜吸收作用。方法以卡波姆934、HPMC为凝胶基质制备pH敏感型鼻用原位凝胶剂,对粘度、粘附性及药物离体透黏膜吸收进行研究。结果0.8%卡波姆934和1.5%HPMC可制备原位凝胶。3种促渗剂黏膜渗透速率为：1%氮酮〉1%吐温〉0.5%冰片。随氮酮浓度的增大,药物黏膜吸收逐渐增加,吸收过程符合Weibull动力学方程。结论本银杏叶鼻用原位凝胶剂制备工艺可行,氮酮能有效地促进银杏叶的鼻腔吸收。     

Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties

The prolonged residence of drug formulation in the nasal cavity is of utmost importance for intranasal drug delivery. The objective of the present investigation was to develop a mucoadhesive in situ gel with reduced nasal mucociliary clearance in order to improve the bioavailability of the antiemetic drug, metoclopramide hydrochloride (MCP HCl). The in situ gelation upon contact with nasal mucosa was conferred via the use of the thermogelling poloxamer 407 whereas mucoadhesion and drug release enhancement were modulated via the use of mucoadhesive and polyethylene glycol (PEG) polymers respectively. The results revealed that the different mucoadhesives augmented the gel viscosity but reduced its sol–gel transition temperatures (T_sol–gel) and the drug release. The inclusion of PEG counteracted the effect of the mucoadhesive polymers whereby it decreased the gel consistency and increased the T_sol–gel as well as the in vitro drug release. The formulations with favorable sol–gel transition temperatures (25–32 °C) and high in vitro drug release (100% release in 60 min) were also rheologically stable upon storage. The mucoadhesiveness test was performed in vivo in rats, results showed that the carbopol-containing in situ gel prolonged the mucociliary transport time from 10 min (control solution) to 52 min (mucoadhesive gel) and maintained nasal mucosal integrity after 14-days application. The bioavailability study in rabbits revealed that the absolute bioavailability of MCP HCl was significantly increased from 51.7% in case of the oral drug solution to 69.1% in case of the nasal in situ gel. The study point to the potential of mucoadhesive nasal in situ gel in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved drug bioavailability.     

Nasal delivery of insulin using bioadhesive chitosan gels

Recently nasal delivery of insulin has gained considerable attention. Some limitations of this route include rapid mucociliary clearance of the drug from the site of deposition resulting in short time span available for absorption and low permeability of the nasal membrane for peptides. The objective of the present study was development of a chitosan bioadhesive gel for nasal delivery of insulin. A nasal perfusion test was used to study the toxicity of 4 absorption enhancers: saponin, sodium deoxycholate, ethylendiamine tetra-Acetic Acid (EDTA) and lecithin. The gels contained 4000 Iu/dl insulin, 2 or 4% of low and medium molecular weight of chitosan, and lecithin or EDTA. Drug release was studied by a membraneless diffusion method and bioadhesion by a modified tensiometry test. The optimized gel was administered nasally in diabetic rats. The serum insulin levels were analyzed by an insulin enzyme immunoassay kit and serum glucose by glucose oxidase method kits. Formulations containing 2% of low molecular weight of chitosan with EDTA had higher release percentage and dissolution efficiency (DE)_2.5%, lower T_50% (Time required to release 50% of the drug), mean dissolution time, and bioadhesion than gels containing 4% of medium molecular weight of chitosan with lecithin. Insulin was released by a zero-order kinetic from the gels. The gel of 2% medium molecular weight of chitosan with EDTA caused increase in insulin absorption and reduction the glucose level by as much as 46% of the intravenous route. Considering our in vitro and in vivo studies, the proposed gel formulation could be a useful preparation for controlled delivery of insulin through the nasal route.     

盐酸恩丹西酮鼻用凝胶剂的制备与质量控制

目的设计盐酸恩丹西酮鼻用凝胶剂处方,并建立其质量控制方法.方法以卡波姆-940和甘油作为凝胶基质和主要辅料,用三乙醇胺调节pH值,制备盐酸恩丹西酮鼻用凝胶剂,采用紫外分光光度法对凝胶剂中盐酸恩丹西酮的含量进行测定.结果所得凝胶剂质量稳定,含量准确,盐酸恩丹西酮平均回收率为100.15%.结论该制剂制备工艺简便、稳定性好,质量控制方法简便、快速、准确.     

Acyclovir Liposomes for Intranasal Systemic Delivery: Development and Pharmacokinetics Evaluation

Intranasal route is one of the most attractive routes for distributing drugs to systemic circulation. Liposomes are used as biocompatible carriers to improve delivery properties across nasal mucosa. The objective of the present study was to formulate acyclovir liposomes and partition into poly-N-vinyl-2-pyrrolidone. Entrapment efficiency showed that multilamellar and unilamellar liposomes were 43.2% ± 0.83 and 21% ± 1.01, respectively. The bioavailability of acyclovir from nasal mucoadhesive gel was 60.72% compared with intravenous route. The use of liposomes acyclovir and mucoadhesive gel not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity, but also facilitated direct absorption through the nasal mucosa.     

泰麻鼻用凝胶的制备与质量控制

目的 设计泰麻鼻用凝胶处方,并进行质量控制.方法 以卡波姆-940、甘油为主要辅料,三乙醇胺调节pH值,制备泰麻鼻用凝胶,分别采用紫外分光光度法和旋光法对凝胶中氧氟沙星和盐酸麻黄碱的含量进行测定.结果 所得凝胶质量稳定,含量准确,氧氟沙星的平均回收率为100.87%,RSD 0.85%(n=6);盐酸麻黄碱平均回收率为100.74%,RSD=1.96%(n=6).结论 该制剂处方简单,质量可控,为一种理想的医院制剂.     

Acyclovir liposomes for intranasal systemic delivery: development and pharmacokinetics evaluation

Intranasal route is one of the most attractive routes for distributing drugs to systemic circulation. Liposomes are used as biocompatible carriers to improve delivery properties across nasal mucosa. The objective of the present study was to formulate acyclovir liposomes and partition into poly-N-vinyl-2-pyrrolidone. Entrapment efficiency showed that multilamellar and unilamellar liposomes were 43.2% +/- 0.83 and 21% +/- 1.01, respectively. The bioavailability of acyclovir from nasal mucoadhesive gel was 60.72% compared with intravenous route. The use of liposomes acyclovir and mucoadhesive gel not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity, but also facilitated direct absorption through the nasal mucosa.     

Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeting and study their effects on rats

The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC–MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9–98.6%), (82.4–98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that C_max and AUC_0–6?h in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.