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。     

苦参止痒膏制备工艺研究

目的 优选并确立苦参止痒膏的最佳制备工艺。方法 采用水煎煮法,选择加水量、浸泡时间、煎煮时间为考察因素,以浸膏得率为评价指标,采用L₉(3⁴)正交试验优选提取条件;以油相用量、载药量、乳化剂用量为自变量,设计苦参止痒膏制备工艺的响应面试验,确定最佳制备条件。结果 苦参止痒膏最优提取工艺为10倍的水,浸泡处方4 h,煎煮2 h;乳膏最佳制备工艺为油相用量10%(g·g^-1),载药量2.5%(g·g^-1),乳化剂用量为5.0%(g·g^-1),所制得的乳膏质量和性状最好。结论 新的制备工艺简便、稳定可行,模型预测功能良好,可为中药新药的开发及工业化放大生产提供参考。     

愈溃生物黏附单向释药贴膜的质量标准研究

目的:建立愈溃生物黏附单向释药贴膜的质量标准。方法:采用薄层色谱(TLC)法对方中牡丹皮、青黛、冰片进行定性鉴别;用高效液相色谱法测定胡黄连中胡黄连苷Ⅰ和胡黄连苷Ⅱ的含量。结果:TLC斑点清晰、分离度好;胡黄连苷Ⅰ、胡黄连苷Ⅱ的检测浓度分别在0.08～0.40、0.12～0.60μg·mL-1(r均为0.9999)范围内与各自峰面积积分值呈良好线性关系,平均回收率分别为100.24%、99.61%,RSD分别为1.72%、1.76%(n均为9)。结论:所建标准可用于愈溃生物黏附贴膜的质量控制。     

阿托伐他汀钙纳米粒的制备与质量评价

目的:制备阿托伐他汀钙纳米粒新剂型,对其性质进行研究,优选最佳工艺条件。方法:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒溶液,通过对处方优化,以载体材料用量(X₁)、有机溶剂用量(X₂)、表面活性剂用量(X₃)为自变量,利用Box Behnken设计响应面法以纳米粒粒径(Y)为响应值,优化了阿托伐他汀钙纳米粒的处方。用Malvern激光粒度分析仪测定了粒径分布和纳米粒的Zeta电位,扫描电镜分析了其形态,用高速冷冻离心法和紫外分光光度法测定了包封率和载药量。结果:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒溶液是适合的。响应面优化最优值为阿托伐他汀钙20 mg、卵磷脂178 mg、乙酸乙酯15 mL、聚山梨酯80774 mg,所制备的阿托伐他汀钙纳米粒呈类球形,其平均粒径(71.99±13.62) nm,Zeta电位为(-31.48±2.46) mV,包封率为(91.27±1.7)%,载药量(9.58±0.22)%。结论:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒处方及工艺适合,相关性质检测方法可行。     

心痛宁滴丸增大载药量的工艺研究

目的优选出心痛宁滴丸增大载药量的最佳成型工艺。方法采用L9(3)4正交实验设计优选出增大滴丸载药量的成型工艺,并以圆整度、溶散时限、滴丸硬度作为检测指标。结果增大滴丸载药量的最佳制备工艺为:滴丸基质种类为PEG6000:S-40(8∶1);基质和药物比例为5∶1;滴制温度为70℃。结论滴丸制备工艺简便可行、稳定合理、参数可控、评分指标客观,为滴丸增大载药量的研究提供了实验依据。     

β-(3,4-二羟基苯基)-α-羟基丙酸异丙酯滴丸制剂处方优化

目的:优化β-(3,4-二羟基苯基)-α-羟基丙酸异丙酯(IDHP)滴丸的制剂处方。方法:采用Box-Behnken中心组合设计,以载药量、淀粉用量和羧甲基淀粉钠用量为自变量,总评归一化值(OD)为因变量,利用响应曲面法分析自变量对因变量的影响,确定滴丸剂较优处方并进行验证。结果:IDHP滴丸的最佳处方为:载药量为23.0%,淀粉用量为14.0%,CMS-Na用量为4.0%,PEG 6000用量为59.0%。结论:试验所得处方合理,IDHP滴丸的成型质量良好。     

正交试验优选壳聚糖阴道生物黏附膜处方

目的:优选壳聚糖阴道生物黏附膜的最佳处方.方法:通过自制黏附力测定装置以垂直黏附力和切向黏附力为考察指标,利用L9(34)正交试验对处方组成进行优选.结果:各因素的影响大小顺序为:酸性壳聚糖浓度(A)>甘油浓度(C)>药物含量(D)>明胶浓度(B),优选的最佳处方为A2B2C2D3,即酸性壳聚糖浓度为1.0%,明胶浓度为1.5%,甘油浓度为8.0%,药物含量为1.0%.结论:优选的处方具有较好的黏附力和体外释放度.     

芍药苷聚乳酸-羟基乙酸共聚物纳米粒制备工艺的优化及对心肌细胞的保护作用

目的:优化芍药苷聚乳酸-羟基乙酸共聚物(PLGA)纳米粒制备工艺,并探讨芍药苷PLGA纳米粒对H₂O₂诱导损伤的H9c2心肌细胞的保护作用。方法:首先使用复乳-溶剂挥发法制备芍药苷PLGA纳米粒,采用Plackett-Burman设计实验以及Box-Behnken响应面设计实验对其制备工艺进行优选,得出最佳处方,并对按最佳处方制备的芍药苷PLGA纳米粒进行表征分析、4℃储藏稳定性考察以及体外释放考察;最后通过H₂O₂诱导建立大鼠H9c2心肌细胞氧化损伤模型,考察芍药苷PLGA纳米粒对心肌细胞的保护作用,CCK-8法检测细胞存活率,试剂盒检测心肌细胞乳酸脱氢酶(LDH)漏出量、丙二醛(MDA)、超氧化物歧化酶(SOD)的含量。结果:最佳处方：泊洛沙姆浓度为0.4%,给药量为3.1 mg, PLGA为21.4 mg;所得芍药苷PLGA纳米粒包封率为(45.49±0.29)%,载药量为(4.52±0.05)%,粒径为(115.1±3.61) nm,多分散系数(polydiseperse index, PD...     

伊贝沙坦脉冲微丸的制备方法

目的：考察伊贝沙坦脉冲控释微丸的制备工艺。方法：采用流化床工艺,将伊贝沙坦原料黏附在空白丸芯上,制成含药微丸;以低取代羟丙基纤维素为包溶胀层材料,乙基纤维素水分散体为包控释层材料,采用同样的工艺包溶胀层和控释层,并通过正交试验优选最佳工艺条件。按最佳包衣工艺操作,以低取代羟丙基纤维素、吐温-80、乙基纤维素水分散体和葵二酸二丁酯为包衣材料,以释药时滞及时滞后的突释药量为指标,优选最佳处方。结果：最佳工艺条件为：上药、包溶胀层、包控释层工艺中使用的风量分别为20、30、40 m3.h-1;进风温度分别为45、50、50℃;喷雾压力均为0.2 MPa;喷液速度分别为8、9、9.gs-1。4种包衣材料在微丸中所占的最佳质量百分比分别为25%、1%、25%和0.5%,制得的脉冲控释微丸的平均时滞约为7小时,时滞后2小时突释量均大于70%。结论：在该工艺条件下制备的伊贝沙坦脉冲控释微丸的体外释放能够达到脉冲控释效果,制备工艺简单、可控。     

川芎嗪涂膜剂的制备及其体外经皮渗透特性研究

目的:初步优选川芎嗪涂膜剂的制备工艺,并研究其体外经皮渗透特性。方法:采用单因素试验,以聚乙烯醇(PVA-124)、无水乙醇、甘油、吐温80、氮酮的用量为因素,采用改良的评分标准对涂膜剂基质的成膜时间、成膜性、延展性、均匀度和有无气泡等指标进行评价,优选川芎嗪涂膜剂基质处方。在优选基质处方的基础上制备含不同载药量川芎嗪(300、250、200、150、100、50 mg/mL)的涂膜剂,并考察其最大载药量。采用高效液相色谱法测定川芎嗪含量,并进行方法学考察。取离体大鼠背部皮肤,对高、中、低载药量(100、75、50 mg/mL)川芎嗪涂膜剂进行体外经皮渗透试验,分别于第15、30、45、60、75、90、120、150、180min时取样测定,并计算川芎嗪的渗透速率。结果:PVA-124、无水乙醇、甘油、吐温80、氮酮的用量分别为2.5 g、7.0 mL、1.97 mL、0.07 mL、0.28 mL(以50 mL处方量计)时的川芎嗪涂膜剂基质处方为最优;川芎嗪的最大载药量为100 mg/mL。川芎嗪含量测定方法的线性范围为3.125～100μg/mL,其专属性、精密度、重复性、回收率、稳定性考察均符合要求(RSD均小于2%);高、中、低载药量川芎嗪涂膜剂的渗透速率分别为608.42、384.19、158.20μg/(cm~2·h)。结论:按优选处方制备的川芎嗪涂膜剂成膜时间短、质量稳定可靠,载药量可达100 mg/mL;75 mg/mL载药量的涂膜剂即可达到川芎嗪有效治疗血药浓度的渗透速率范围。     

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.     

正交试验优选复方银杏叶片的处方研究

目的:筛选复方银杏叶片的最佳处方。方法:采用正交设计试验,以多指标(片重差异、崩解度)综合评分法,筛选最佳处方(低取代羟丙基纤维素用量、原料药与填充剂的用量比例、微晶纤维素用量)。结果:最佳处方系低取代羟丙基纤维素用量为5%,原料药与填充剂的用量比例为1∶1,微晶纤维素用量为10%。结论:该片剂处方合理,且片剂成型质量好。     

紫草膜剂的制备及左旋紫草素的含量测定

目的:确定并优化紫草膜剂的处方工艺,建立稳定可靠的左旋紫草素含量测定方法,对紫草膜剂进行质量控制。方法:以紫草提取物为原料药,采用聚乙烯醇为成膜材料,加入甘油、羧甲基纤维素钠制备紫草膜剂。通过单因素实验与正交试验,以膜的机械性能为评价指标,筛选优化处方工艺。采用高效液相色谱法对膜剂中主要活性成分左旋紫草素的含量进行测定。结果:PVA的种类与用量,增塑剂甘油的用量及载药量均会明显影响膜剂的成型与机械性能。优化处方中成膜材料聚乙烯醇205S与540S的用量比为1∶3,甘油的用量为7.6%,聚乙烯醇:紫草提取物为9∶1。含量测定的HPLC方法日内、日间精密度分别为0.77%与0.74%,加样回收率为99.67%(n=9),重复性好。结论:所制备的紫草膜剂含量均匀,机械性能良好,符合膜剂质量要求。     

Development of three layered buccal compact containing metoprolol tartrate by statistical optimization technique

The objective of this work to evaluate the effect of formulation variables on release properties and bioadhesive strength in development of three layered buccal compact containing highly water-soluble drug metoprolol tartrate (MT) by statistical optimization technique. Formulations were prepared based on rotatable central composite design with peripheral polymer ratio (carbopol 934P: HPMC 4KM) and core polymer ratio (HPMC 4KM: sodium alginate) as two independent formulation variables. The three layered buccal compact comprises a peripheral layer, core layer and backing layer. Four dependent (response) variables were considered: bioadhesion force, percentage MT release at 8 h, T50% (time taken to release 50% of drug) and release exponent (n). The release profile data was subjected to curve fitting analysis for describing the release mechanism of MT from three layered buccal compact. The main effects and interaction terms was quantitatively evaluated by quadratic model. The decrease in MT release was observed with an increase in both the formulation variables and as the carbopol: HPMC ratio increases the bioadhesive strength also increases. The desirability function was used to optimize the response variables, each having a different target and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of three layered buccal compact containing highly water-soluble drug MT.     

Preparation of mucoadhesive oral patches containing tetracycline hydrochloride and carvacrol for treatment of local mouth bacterial infections and candidiasis

The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability.     

Drug release kinetics from polymeric films containing propranolol hydrochloride for transdermal use

Polymeric films containing propranolol hydrochloride (PPN) were formulated and evaluated with a view to select a suitable formulation for the development of transdermal drug delivery systems. Films containing different ratios of ethyl cellulose (EC), poly(vinylpyrrolidone) (PVP), and PPN were prepared by mercury substrate method. In vitro drug release and skin permeation studies were conducted using paddle over disk and modified Franz diffusion cell, respectively. The drug release profiles from the polymeric film indicated that the drug content in the film decreased at an apparent first-order rate, whereas the quantity of drug release was proportional to the square root of time. The release rate of PPN increased linearly with increasing drug concentration and PVP fraction in the film, but was found to be independent of film thickness. The increase in release rate may be due to leaching of hydrophilic fraction of the film former, which resulted in the formation of pores. It was also observed that the release of drug from the films followed the diffusion-controlled model at low drug concentration. A burst effect was observed initially, however, at high drug loading level, which may be due to rapid dissolution of the surface drug followed by the diffusion of the drug through the polymer network in the film. The in vitro skin permeation profiles displayed increased flux values with increase of initial drug concentration in the film, and also with the PVP content. From this study, it is concluded that the films composed of EC/PVP/PPN, 9:1:3, 8:2:2, and 8:2:3, should be selected for the development of transdermal drug delivery systems using a suitable adhesive layer and backing membrane for potential therapeutic applications.     

Dermal therapeutic systems permeable to water vapour

Dermal therapeutic systems (DTS) are self-adhesive patches that consist of a flexible backing layer and an adhesive controlled release matrix layer containing the drug. They are formulated to obtain a controlled release of drugs in order to treat topical skin pathologies. As permeability to water vapour is an important characteristic for DTS, the aim of this work was to develop systems with different predictable water vapour permeabilities (WVP), to be selected according to the therapeutic needs of the treated disease, and with good adhesive properties. In the present study, the WVP of 12 materials, usable as backing layers, were tested. In order to prepare DTS, the artificial silk was selected as a backing layer as it has good water vapour permeability, compatibility with the coating process and cohesion with the matrices. Two adhesive hydrophilic copolymers of dimethylaminoethyl methacrylate and neutral methacrylic esters (Plastoid® E 35 M–Plastoid® E 35 L) mixed with a non-adhesive hydrophobic copolymer of ethylacrylate and methylmethacrylate, supplied in suspension in two different concentrations (Eudragit® NE 30 D–Eudragit® NE 40 D), were used to prepare four series of DTS. Water vapour permeability and adhesion properties of the prepared DTS were evaluated. Adding 10–30% w/w of Eudragit® NE to Plastoid® E 35 permits the formulation of patches with higher water vapour permeability and good adhesive properties.     

正交试验优化尼索地平口腔黏附片处方

目的:优化尼索地平口腔黏附片制备处方。方法:采用正交试验设计,以含药层及保护层中卡波普与壳聚糖用量比例、乳糖含量、压片硬度为因素优化处方,并测定优化处方的生物黏附力和体外释放度。结果:优化的处方组成是含药层与保护层中卡波普与壳聚糖用量比例分别为22.5∶22.5、33.3∶16.7mg,乳糖为10mg,压片硬度为5kg;3批优化处方所制制剂平均生物黏附力为79.5g·cm-2,12h时平均体外累积释放度大于95%。结论:按照优化处方制备的尼索地平口腔黏附片具有理想的生物黏附力和缓释性。     

Novel biomaterial for transdermal application: in vitro and in vivo characterization

The objective of the present study was to evaluate a novel film forming biomaterial for its potential application in the preparation of unilaminate transdermal adhesive matrix systems. The biomaterial, Damar Batu (DB), was tried alone and in combination with Eudragit RL100 as a matrixing agent in the preparation of transdermal patches. Developed transdermal patches of Diltiazem hydrochloride (DH) were evaluated for thickness uniformity, weight uniformity, folding endurance and drug content. USP dissolution apparatus V was used for in vitro drug release studies. Modified Franz diffusion cell used for permeation study using excised human cadaver skin. Total 6 formulations were developed and on the basis of in vitro drug release and in vitro skin permeation profile F5 composed of DB: Eudragit RL100 (60:40) and carrying 20 %w/w DH was selected as an optimized formulation for in vivo study. The in vivo study results showed that F5 achieved the Cmax of about 269.76 ± 1.52 ng/mL in 6 h and sustained the release of the drug till 24 h. The skin irritation study results proved that the novel biomaterial is non-sensitizing and non-irritating. Drug-polymer interaction study carried out to check the compatibility of drug and polymer showed the intactness of the drug in the formulation proving the compatibility of the polymer. It can be proposed from the outcome of the present study that by applying suitable adhesive layer and backing membrane, DB: Eudragit RL100 (60:40) transdermal patches can be of potential therapeutic use.