双层口腔溃疡膜的制备工艺及释放度研究

目的 制备中药黄柏提取物双层口腔溃疡膜,并考察其体外释放情况.方法 采用流延法制备双层膜,以海藻酸钠浓度(A)、海藻酸钠/氯化钙比例(B)、壳聚糖用量(C)为因素进行正交试验优选保护层处方,采用HPLC法测定盐酸小檗碱含量,并计算体外释放度.结果 所制膜性状良好,保护层处方确定A为2.0%,B为1∶2,C为10mL.盐酸小檗碱浓度线性范围为0.2~2.2μg·mL-1,平均回收率为100.41%,RSD值为0.85%.双层膜可持续释药6h,3h体外累积释放度83.42%.双层膜可持续释药6h,3h体外累积释放度83.42%.结论 所制膜剂设计合理,工艺简单可行,具有一定应用价值.     

口腔溃疡双层膜的研制及质量控制

目的通过口腔溃疡双层膜的制备工艺设计和研究，建立口腔溃疡双层膜的制备及质量控制的方法。方法以盐酸地卡因、硫酸新霉素、倍他米松为主药，以聚乙烯醇、羧甲基纤维素钠按适当比例为基质制成一定厚度的膜剂，采用紫外分光光度法在310nm波长处对盐酸地卡因含量进行测定来控制质量。结果制成的膜剂塑性、色泽良好，以紫外扫描地卡因在310nm处有明显的吸收峰，且无干扰，线性关系良好r=0．9993，平均回收率为99．8％，RSD=0．95％。结论该制剂符合膜剂项下的有关规定，紫外分光光度法测口腔溃疡双层膜中地卡因含量简便、快速、准确；可作为医院制剂的质量控制方法。     

麦滋林-S口腔溃疡膜的处方优选及临床疗效

目的：选择麦滋林口腔溃疡膜的最佳处方,并观察临床疗效.方法：采用正交试验法,以药膜外观、粘性、溶解性为指标进行评分.将108例患者随机分为2组,治疗组58例,用麦滋林口腔溃疡膜治疗;对照组50例,用洗必泰口腔含漱液治疗.结果：本膜剂成膜最佳处方聚乙烯醇PVA1750：PVA17-88：羧甲基纤维素钠（CMC-Na）为1%：3%：4%.治疗组有效率 89.7%,对照组有效率52%（P＜0.05）.结论：本膜剂配方合理,疗效确切.     

橘红总黄酮凝胶剂的制备工艺研究

目的：研究橘红总黄酮凝胶剂最优制备工艺。方法：以凝胶剂的涂展性和光泽度等为指标,通过正交实验法考察卡波姆940、氮酮、丙二醇、甘油的用量,优选橘红总黄酮凝胶剂的制备工艺。结果：橘红总黄酮凝胶剂的最优工艺处方为：橘红总黄酮/卡波姆940/氮酮/丙二醇/甘油=1.3%/0.8%/2%/15%/10%。结论：经过试验研究得出的制备工艺简单、稳定、可行,为橘红总黄酮凝胶剂的实际生产提供参考。     

复方奥硝唑口腔溃疡复合膜的制备及质量控制

目的：制备复方奥硝唑口腔溃疡复合膜,为临床提供更适合治疗口腔溃疡的理想药物制剂。方法：先以8％聚乙烯醇。、5％甘油为成膜液制成空白隔离层,40℃烘干。再以奥硝唑为主药,壳聚糖、明胶、甘油为辅料制成药物层成膜液,均匀涂布于空白隔离层上制成复合膜。用紫外分光光度法测定主药奥硝唑含量,测定波长为312nm。结果：该膜剂外观性状良好且具良好的生物相容性、柔韧性。奥硝唑检测浓度在6．64～19．92μg.ml^-1范围内线性关系良好（r=0．9999）,平均回收率101．12％（RSD=1．59％,n=9）。结论：该膜剂制备工艺简单、含量测定准确、质量可控,是临床治疗口腔溃疡理想的新制剂。     

龙血竭总黄酮纳米粒的制备工艺研究及其表征

目的：制备龙血竭总黄酮纳米粒（Dragon's blood total flavonoid nanoparticles,DBF-NPs）,并优化其处方和制备工艺。方法：结合HPLC与葡聚糖凝胶柱层析法,构建样品包封率测定方法;以包封率,粒径及外观为综合指标,在单因素试验的基础上进行正交试验设计确定最佳处方及工艺。结果：所优选葡聚糖凝胶柱层析条件为：柱规格10 mm×450 mm,洗脱剂为去离子水,上样量1 mL（含龙血竭总黄酮1 mg）,流速（6±1）mL·h^-1;薄膜超声法为最佳制备方法;最优处方为：有机相与水相体积比1：1,Tween 80浓度为1%,PDLLACOOR 0.7%,龙血竭总黄酮 0.1%;制得纳米粒包封率和平均粒径分别为81%±2.6%、（203±12）nm。结论：通过工艺优化,制得DBF-NPs包封率较高,粒径合适,稳定性良好。     

帕利哌酮缓释片的制备及体内外评价

目的：制备帕利哌酮缓释片,并对其在Beagle犬体内的药动学进行评价。方法：首先制备含有帕利哌酮的缓释片芯,再将其通过压制包衣的手段包埋在同样含有帕利哌酮的缓释材料中,压片制得。采用单因素试验和星点设计-效应面法,以自研缓释片和原研制剂（芮达^®）在pH 6.8磷酸盐缓冲液（PBS）中释放行为的相似性为评价指标,优化自制缓释片的处方;以Beagle犬为模型,考察了自制缓释片和原研制剂的体内药动学行为,采用液-质联用（LC-MS/MS）法测定血浆中帕利哌酮浓度,并采用非房室模型计算两制剂的药动学参数。结果：优化后的自制缓释片与原研制剂在pH 6.8磷酸盐缓冲液中的释放行为相似（相似因子大于50）,自研缓释片与原研制剂的C_max为（76.79±67.88）ng·mL^-1和（76.86±59.80）ng·mL^-1,AUC_{（0→∞）}为（1 643.92 ±1 307.79）ng·mL^-1·h和（1 652.33±1 249.45）ng·mL^-1·h,提示两制剂相似。结论：通过压制包衣制备帕利哌酮缓释片可实现与原研制剂（芮达^®）达到一致的目的。     

富马酸喹硫平口腔崩解片的研制及质量控制初探

目的：研制富马酸喹硫平口腔崩解片并评价其质量。方法：以富马酸喹硫平为主药,采用粉末直接压片法制备口腔崩解片,以外观、口感及体外崩解时间为考察指标设计L₉（3⁴）正交试验,并对其硬度、溶出度及含量进行测定。结果：微晶纤维素20%,甘露醇50%,交联聚维酮6%,矫味剂为阿斯巴甜/草莓香精,按2：1的比例占处方量的6%时所制备的处方表面光滑,口感良好,体内外崩解时间均在30 s内;采用高效液相色谱法测得富马酸喹硫平平均回收率为98.56%,平均RSD为1.85%,日内和日间精密度RSD均小于15%。结论：处方设计合理,制备工艺可行,符合用药要求;建立的高效液相色谱法重现性好、专属性强,测定准确快速,产品质量可控。     

口腔溃疡散Ⅱ号双层膜的研制及药效学研究

目的：研制一种单向缓释口腔溃疡散Ⅱ号双层膜，延长口腔溃疡散作用时间。方法：用聚乙烯醇、羧甲基纤维素钠作成膜材料，将口腔溃疡散Ⅱ号制成双层膜，观察其口腔粘附时间和对实验性口腔溃疡的治疗作用。结果：口腔溃疡散Ⅱ号双层膜的口腔粘附时间长，对实验性口腔溃疡有较好的治疗作用。结论：口腔溃疡散Ⅱ号双层膜克服了口腔溃疡散Ⅱ号作用时间短的不足，有较好的临床应用前景。     

功能化载药黑磷纳米片的制备表征及抗骨肉瘤活性评价

目的：制备可稳定分散的载药纳米黑磷,并将其用于光热/化疗协同的纳米制剂。方法：采用液相剥离法,以N-甲基吡咯烷酮（NMP）为剥离剂,聚乙二醇二胺（H₂N-PEG-NH₂）、壳聚糖（CS）及A型明胶（Gel）为修饰剂,筛选并载带化疗药物盐酸阿霉素（DOX）制备出分散性良好的载药黑磷纳米片。通过透射电镜、傅立叶变换红外光谱仪及流式细胞仪等仪器,进行形貌结构表征及体外细胞学评价。结果：剥离方法筛选试验表明BPNSs最佳制备工艺为：水浴超声300 W,10 h,探头超声180 W,6 h,温度<30℃,表现出外观形貌均一;修饰剂筛选试验表明H₂N-PEG-NH₂/BPNSs质量比为10：1,BPNSs/DOX质量比为1：1,表现出良好的稳定性及负载率;体外释放试验表明,DOX在弱酸性条件下结合近红外光照（NIR）释放迅速,展现出光控释药特性;体外细胞学试验表明PEG-BPNSs-DOX具有良好的抗骨肉瘤活性。结论：PEG-BPNSs-DOX可稳定分散,制备简单,具有NIR光控释药特性及良好的光热性能,有利于光热/化疗协同治疗骨肉瘤,在纳米递送系统中具有广阔应用前景。     

进口血竭药材与国产血竭指纹图谱的比较研究

目的研究比较进口血竭药材与国产血竭药材的指纹图谱。为血竭药材质量控制提供有效的方法。方法利用HPLC指纹图谱技术研究、比较两者之间指纹图谱差别。结果测定了6批国产血竭及1批进口血竭的指纹图谱,两者指纹图谱差别明显。结论建立HPLC法测定血竭药材的指纹图谱,为血竭药材质量控制提供依据。     

HPLC测定龙血竭中龙血素A和龙血素B的含量

目的建立龙血竭中龙血素A和龙血素B的含量测定方法。方法采用HPLC法,用C18柱,乙腈-1%冰醋酸溶液(37∶63)为流动相,检测波长275nm,柱温30℃。结果方法线性关系良好,平均加样回收率龙血素A为100.25%,RSD=1.2%(n=6);龙血素B为101.32%,RSD=1.7%(n=6)。结论所用方法简便易行,结果准确,可用于龙血竭药材的质量控制。     

龙血竭胶囊治疗老年患者压疮的效果观察

目的探讨龙血竭胶囊治疗老年患者压疮的效果。方法将36例(56处)老年并发压疮患者随机分成观察组和对照组,观察组18例(30处),予适量龙血竭粉与黄酒调为糊状,均匀外敷创面;对照组26(处),予以氟哌酸粉外敷。结果观察组换药次数较对照组明显减少、愈合时间缩短,有效率观察组为98.2%,对照组为82.6%,两组比较有显著差异性(P<0.05)。结论龙血竭胶囊治疗老年患者压疮起效快,安全有效,且价格低廉,使用方便。     

Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies

A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced. Films from the optimum formulation were 0.427?±?0.015?mm thick, weighed 55.89?±?0.79?mg, and had a surface pH of 6.34?±?0.01. The drug content of the optimum formulation approximated the theoretical value with good uniformity (2.959?±?0.106?mg/cm² for OD and 0.877?±?0.031?mg/cm² for DEX). The formulation showed favorable swelling characteristics and both drugs were released at >95% after 4?h. Moreover, the compound film had a statistically significant effect on mucosal repair and reduced ulcer inflammation without stimulating the human oral mucosa. C_max of OD in saliva was 37.04?μg/ml and that of DEX was 9.737?μg/ml. Given promising therapeutic effects, the compound film developed here could become a local drug delivery device for treating oral ulcers.     

野菊花总黄酮口腔生物黏附双层贴片成型工艺优化

目的:研究野菊花总黄酮口腔生物黏附双层片的成型工艺。方法:采用Franz扩散法优选可阻止有效成分渗透的保护层;以黏附力和释放度为指标,采用单因素试验筛选生物黏附材料,以正交试验优选载药量、黏附材料的比例及填充剂用量。结果:该贴片的黏附层为卡波普934P和羟丙基纤维素1:2混合物,占75.8%,总黄酮20%,乳糖4%,微粉硅胶0.2%,以乙基纤维素作为黏附片的保护层。结论:该成型处方制成的野菊花生物黏附双层片具有较好的生物黏附性,背衬层可阻滞药物释放。     

Formulation of biphasic release tablets containing slightly soluble drugs.

A new biphasic release system for slightly soluble drugs has been proposed. To enhance the dissolution rate, the drug was milled with a superdisintegrant. Then, double-layer tablets were prepared. One layer was formulated to release the drug in a very short time (fast-release). The other consisted of an extended-release hydroxypropylmethylcellulose (HPMC) matrix. Different HPMC concentrations (10, 16 and 22%) and viscosity grades (Methocel K4, K15 and K100M) were used to obtain different release rates of the drug from the extended-release layer, ketoprofen and praziquantel were used as slightly soluble model drugs.The in vitro dissolution tests of the prepared double-layer systems, showed the desired biphasic behaviour: the drug contained in the fast releasing layer dissolved within the first 15 min, while the drug contained in the prolonged-release layer was released at different times, depending on the formulation of the hydrophilic matrix. In particular, an increase in the percentage and viscosity grade of HPMC, in the extended release layer, leads to a decrease in the drug delivery rate and produces a wide range of different release rates from only a few hours up to 24 h.     

复方口腔溃疡散的制备与临床应用

目的介绍自制复方口腔溃疡散的制备方法与临床疗效。方法制备复方口腔溃疡散,按中国药典2000年版一部有关方法对该制剂主药进行鉴别,并对326例患者分组进行临床疗效观察。结果该制剂制备工艺可行,质量控制合理;治疗组(172例)总有效率为95.9%,对照组(154例)总有效率为76.6%(P<0.01)。结论该制剂对各种口腔溃疡疾病疗效满意,稳定性好,可供临床应用。     

制霉菌素口腔双层贴膜在口腔内释药动态研究

目的：测定自制的制霉菌素口腔双层贴膜在口腔内释药过程。方法：采用剩余量法测定制霉菌素口腔双层贴膜在口腔内释药情况,测定制霉菌素口腔双层贴膜体外释放度,并比较体内外释放的相关性。结果：体外释放方程：ln（100-Q）=-0.089t＋4.998,r=0.997 0,口腔内释药方程为ln（100-P）=-0.022t＋5.014,r=0.993 5。以体内平均释放百分率（Y,%）对体外平均释放百分率（X,%）回归,得方程Y=0.990X＋0.372,r=0.998 0。结论：体内外释放度具有良好的相关性,可以用体外释放度来预测药物的释放。     

Formulation and evaluation of mucoadhesive buccal films impregnated with carvedilol nanosuspension: a potential approach for delivery of drugs having high first-pass metabolism

Abstract

Context: Mucoadhesive buccal films containing three layers (mucoadhesive layer, nanosuspension containing layer and backing membrane) were incorporated with carvedilol nanosuspension.

Objective: Formulation and evaluation of nanosuspension incorporated mucoadhesive buccal films of carvedilol for bioavailability enhancement by avoiding first-pass metabolism.

Methods: Carvedilol-loaded nanosuspension was prepared by a precipitation–ultrasonication method with varying concentrations of the polymer. The formulation was analyzed for size, size distribution, surface charge and morphology. Optimized nanosuspension was incorporated into drug gel layer which was sandwiched between a mucoadhesive layer and a backing layer to form tri-layered buccal films. They were evaluated for their physical, mechanical and bioadhesive parameters followed by in vitro and in vivo studies.

Results and discussion: Nanosuspension showed a negative zeta potential (?17.21?mV) with a diameter of around 495 nm and a polydispersity index of 0.203. Nanosuspension incorporated drug gel layer (62.4% drug loading) was optimized to contain 3% HPMC and 50?mg Carbopol 934P. The mucoadhesive layer and the backing layer were optimized to contain 3% HPMC and 1% ethyl cellulose, respectively. In vitro drug release was 69% and 62.4% in 9?h across synthetic membrane and porcine buccal mucosa, respectively. In vivo studies conducted in rabbit model showed 916% increase in the relative bioavailability in comparison to marketed oral tablet formulation. The C_max and T_max of the prepared formulation increased due to increased surface area of drug and also by-passing hepatic metabolism.

Conclusion: The drug delivery system has been designed as a novel platform for potential buccal delivery of drugs having high first-pass metabolism.