美洛昔康干乳的制备及其稳定性考察

目的:对水不溶性的可选择性抑制环氧化簪2型非甾体类抗炎药美洛昔康喷雾干燥乳剂(O/W)处方、质量检测方法进行研究,并考察其稳定性.方法:根据美洛昔康的溶解性筛选油及非水溶剂,选用乳化性能好的的固体载体,使用喷雾干燥法制备美洛昔康干乳,采用高效液相法测定美洛昔康含量,影响因素试验、长期试验考察其稳定性.结果:以Labrafac CC(HLB为1)作油相,麦芽糖糊精作固体栽体,制得的干乳溶于纯化水后的平均粒径是喷雾干燥前匀质化乳剂平均粒径的1.4倍.恒温试验120d,UV照射对比试验24h(93.7%～35.5%),含量及粒径大小未见明显改变.结论:制得的非甾体抗炎药美洛昔康喷干乳质量可控,稳定性良好,与传统口服乳剂相比具有更多优势.     

固体脂质纳米粒的制备和载体结构的研究进展及其应用

目的:从固体脂质纳米载体的制备和结构特征方面介绍其研究进展.方法:以国内外大量有代表性的论文为依据进行分析、归纳整理.结果:固体脂质纳米粒的多种制备方法各有优缺点,其中以高压乳化法和微乳化法被推崇.以固体和液体的混合脂质为基材,制备出O/F/W结构的纳米粒,不但能够有较好的载药能力,还可以拥有优异的缓控释功能.结论:固体脂质纳米粒是一种性能优异、有发展前景的新型给药系统.     

硫酸长春碱乳酸-羟基醋酸共聚物微球的处方和制备工艺研究

目的：制备硫酸长春碱生物可降解注射微球，考察处方和制备工艺对微球包封率及释放度的影响。方法：以乳酸-羟基醋酸共聚物（PLGA）为载体材料，分别采用O／O型和W／O／W乳化溶剂挥发法制备微球。结果：采用O／O型乳化溶剂挥发法制备的微球表面光滑无孔洞，内部结构致密；W／O／W型微球表面有较多皱褶，内部结构多孔。采用O／O型乳化溶剂挥发法制备的微球包封率在70％左右，明显高于W／O／W型乳化溶剂挥发法制备的微球，释药速度明显低于第2种方法制备的微球。采用O／O型乳化溶剂挥发法，以PLGA（50：50．10000）制备的微球在体外可持续释药21d以上。结论：硫酸长春碱PLGA微球的制备工艺可行，缓释特征明显，无突释效应。     

星点设计效应面法优选穿琥宁固体脂质微粒处方

目的:应用星点设计效应面法优选穿琥宁固体脂质微粒的处方。方法:以乳化-溶剂挥发法制备穿琥宁固体脂质微粒,以包封率、平均粒径为评价指标,考察内水相与油相体积比(W1/O)、脂质比(SA/SPC,m/m)、外水相表面活性剂(即泊洛沙姆)质量分数对处方的影响,对结果分别进行多元线性与二项式方程拟合,采用效应面预测最佳处方。结果:最佳处方为W1/O为0.2∶0.2,SA/SPC为8∶1(m/m),泊洛沙姆质量分数为1.0%。二项式拟合方程优于多元线性回归方程,但相关性较差。此条件下,包封率为54.90%、平均粒径为(6.27±0.08)μm。结论:所选处方制备的穿琥宁固体脂质微粒质量合格、重现性好,可为该制剂的进一步研发提供参考。     

延胡索乙素固体脂质纳米粒缓释片制备及工艺优化

目的：制备延胡索乙素固体脂质纳米粒缓释片，并研究延胡索乙素固体脂质纳米粒缓释片的释药模型和释药机理。方法：乳化-溶剂挥发法制备延胡索乙素固体脂质纳米粒，以乳糖作为冻干剂，羟丙基甲基纤维素（HPMC）为缓释材料进一步制备缓释片。在单因素考察的基础上，设计正交试验优化延胡索乙素固体脂质纳米粒缓释片处方，并对缓释片体外释药模型和释药机理进行探讨。结果：延胡索乙素固体脂质纳米粒缓释片最佳处方为缓释材料HPMC K4M和HPMC K15M比例为1：1，用量为40 mg，PEG 4000的用量为20 mg，硬脂酸镁用量为片芯质量的0.5%。延胡索乙素固体脂质纳米粒缓释片最佳处方的体外释放行为符合Higuchi释药模型，释药方程为：Mt/M_∞=0.286 8 t^1/2-0.073 8（r=0.990 8），12 h内累积释放度为93.56%，缓释片释药机理为扩散和溶蚀共存。结论：制备的延胡索乙素固体脂质纳米粒缓释片，工艺重复性较好，其释药行为符合Higuchi释药模型。     

姜黄素二元载体固体分散体的制备及其评价

目的:将姜黄素制备成固体分散体以提高其溶出度。方法:以聚乙烯吡咯烷酮(polyvinylpyrrolidone K30,PVP K30)和羟丙基甲基纤维素(hydroxypropylmethyl, HPMC)为载体，采用溶剂蒸发法，制备姜黄素固体分散体。经正交试验设计，以溶出度为指标进行处方筛选，制备双载体固体分散体。利用差示扫描量热分析、显微扫描电镜、X射线粉末衍射、傅立叶红外变换光谱进行物相表征，同时考察制剂的稳定性。结果:应用正交试验设计方法确定最终制备处方工艺为：药物与双载体比例1∶6,PVP K30和HPMC的比例为4∶1,溶解搅拌时间3 h,旋蒸水浴温度60℃。物相表征结果表明药物以非结晶状态存在，制剂应保存在避光干燥的条件下。结论:以PVP K30和HPMC两种载体联用制备固体分散体，溶出度能达到80%,相比于原料药提升40%,能够显著提升姜黄素的溶出度。     

环孢菌素A自乳化半固体骨架胶囊的制备

目的考察环孢菌素A自乳化半固体骨架胶囊的处方。方法制备药物的饱和溶液用以测定药物在不同油相中的溶解度;采用伪三元相图法考察不同乳化剂形成微乳的能力和区域,绘制不同处方组成的相图;采用体外乳化实验筛选处方,并制备环孢菌素A自乳化半固体骨架胶囊。结果该胶囊中的乳化剂为Tween 80-聚氧乙烯(40)氢化蓖麻油(质量比为1∶1),助乳化剂为聚乙二醇-8-甘油辛酸/葵酸脂(labrasol),油相为辛酸/癸酸三甘油酯,半固体载体为泊洛沙姆188-硬脂酸聚烃氧(40)酯(质量比为1∶1)。该处方所形成的微乳平均粒径为40 nm。结论按优化处方制得的环孢菌素A自乳化半固体骨架胶囊能够提高环孢菌素A在水中的溶出度。     

乳化溶剂挥发法在微球制备中的应用

微球(microspheres)是药物溶解或分散于高分子材料中形成的微小球状实体,一般制备成混悬剂供注射或口服用。用于制备缓控释微球的可生物降解高分子材料中,以聚乳酸(polylactic acid,PLA)及其共聚物为代表的羟基酸聚合物应用最广。制备药物缓释微球的方法很多,包括乳化溶剂挥发法、相分离法、乳化溶剂萃取法、喷雾干燥法、熔融法等,其中乳化溶剂挥发法最为常用。笔者对乳化溶剂挥发法制备微球的方法及制备过程中影响微球质量的因素进行综述。1乳化溶剂挥发法主要包括O/W乳化法、O1/O2乳化法、复乳-液中干燥法。O/W乳化法适合脂溶性药物微…     

长春西汀固体过饱和自乳化释药系统的研制

目的:制备长春西汀(VIN)固体过饱和自乳化释药系统(VIN-S-sSEDDS),并对其体内、外特性进行研究。方法:以羟丙基甲基纤维素(HPMC)为促过饱和物质、右旋糖苷-40为固体载体,采用喷雾干燥法制备VIN-S-sSEDDS。以常规长春西汀自乳化释药系统(VIN-SEDDS)为对照,比较二者在粒径、体外溶出度和大鼠灌胃给药后体内生物利用度上的不同。结果:与VIN-SEDDS比较,VIN-S-sSEDDS粒径降低(65.12 nm vs.58.78 nm)、累积溶出百分率(2 h)增加(58.2%vs.88.7%)、大鼠体内相对生物利用度增加(1.63 vs.2.30)。结论:所制备的VIN-S-sSEDDS可提高VIN的溶出度和生物利用度,比常规自乳化制剂更具有优势。     

达托霉素透皮制剂的制备及效果评价

目的 制备达托霉素软膏,并对其进行制剂学和药效学初步评价.方法 采用乳化法制备O/W型和W/O型两种达托霉素软膏.通过考察物理性状、体外透皮渗透率、体内外药效学及抗细菌生物被膜,确定较优处方并初步建立达托霉素软膏剂透皮实验方法.结果 O/W型达托霉素软膏的累积渗透率在8h时达53.35％,透皮渗透量为78.30μg/cm2.与W/O型达托霉素软膏相比具有更强的抑菌作用.结论 O/W型达托霉素软膏制备工艺简单,制剂稳定性好,抑菌快速强效.     

Preparation of redispersible dry emulsions by spray drying

Development of stable dry emulsions being able to reform the original o/w-emulsion by reconstitution in water is presented. Dry emulsions were prepared by spray drying liquid o/w-emulsions in a laboratory spray dryer. Three hydroxypropylmethylcellulose (HPMC) types were applied as solid carrier and emulsifier. The lipid phase was fractionated coconut oil. The ratio of solid carrier to lipid phase influenced the reconstitution properties. It was possible to prepare redispersible dry emulsions of a lipid content up to 40% dry powder mass. The different HPMC types had no noticeable effect on the reconstitution properties, but too viscous liquid o/w-emulsions were difficult to atomise. The type of rotary atomizer, or the rate of rotation did not affect the technical properties of the dry emulsions containing 40% lipid. It was concluded that low viscosity HPMC was a useful solid carrier. The dry emulsions remained physically stable for at least 6 months.     

Technical optimisation of redispersible dry emulsions

Preparation of dry emulsions suitable for tablet processing was examined in this study. Liquid o/w-emulsions were spray dried in a laboratory spray dryer applying hydroxypropylmethylcellulose (HPMC) as a solid carrier and emulsifier. As the lipid phase, fractionated coconut oil was used. The ability of various excipients to increase the density of dry emulsions was investigated. Adding sucrose to the formulation, redispersible dry emulsions with higher density were obtained. The type of rotary atomizer did not affect the dry emulsions containing sucrose nor the rate of rotation of the atomizer applied in the spray drying process. By wet granulation, using ethanol as a binder, free-flowing and compactable dry emulsions were obtained and simultaneously the reconstitution properties were preserved. It was concluded that dry emulsions could be optimised for tablet processing by wet granulation. Tablets having a lipid content up to 20% had proper tablet properties.     

In vivo evaluation of tablets and capsules containing spray-dried o/w-emulsions for oral delivery of poorly soluble drugs

It is recognised that poorly soluble drugs may show an increased oral bioavailability when incorporated in o/w-emulsions. Encapsulating the emulsion lipid droplets in hydroxypropyl methylcellulose (HPMC) by spray drying has been demonstrated to preserve an improved bioavailability releasing lipid droplets from the powder in vivo. However, the spray-dried powder is cohesive and bulky requiring additional processing to improve handling. This was resolved in previous work where a directly compressible dry emulsion formulation was described. The purpose of the present study is to investigate the oral bioavailability resulting from administration of a directly compressible dry emulsion as a tablet and compare it with a HPMC dry emulsion powder and a simple lipid solution. Four female Beagle dogs received a single dose of each formulation containing the same amount of medium-chain triglycerides (MCT) and a model drug, Lu 28-179. Cyclodextrin solutions administered orally and intravenously were used as references. The absolute bioavailability decreased in the order cyclodextrin solution (0.14), HPMC dry emulsion (0.11), technically improved dry emulsion (0.10) and MCT solution (0.06). The directly compressible dry emulsion tablets were concluded to be comparable to a HPMC dry emulsion powder in terms of bioavailability. The lack of statistically significant differences relative to a MCT solution was ascribed to a low and variable absolute oral bioavailability of the model drug.     

口服干乳剂研究进展

干乳剂是新型的药物载体传递系统，理化稳定性好，再分散性好，能显著改善难溶性药物的溶出，增加体外释放，促进肠吸收，提高口服生物利用度。对近年来国外文献以喷雾干燥法制备干乳剂的最新研究进展，该文做了主要概述，表明喷雾干燥乳剂作为一种含油的粉末制剂，其应用前景广阔。     

Preparation of an enteric-soluble solid-state emulsion using oily drugs

To improve the patient's compliance and enhance the stability of oily drugs in the gastric fluid, an enteric-soluble solid-state emulsion (ESE), was developed. The ESE was prepared by spreading liquid o/w-emulsions on a flat glass and drying at the oven maintained at 40 degrees C. Aerosil 200 was applied as solid carrier and emulsifier. And Eudragit L30D-55 was used as enteric coating material. The influence of various preparation parameters on the residual volatile oil and the release behavior was investigated. Droplet size distribution of the primary emulsions and the emulsion after reconstitution of zedoary turmeric oil (ZTO) ESE in the phosphate buffer were also measured. When ZTO ESE was immersed into phosphate buffer (pH 6.8), the stable emulsion was formed in 20min, but the release was obviously suppressed when it was exposed to the gastric fluid. It was concluded that preparation of enteric-soluble solid-state emulsion by the present method for oral oily drug was feasible.     

Physical stability of redispersible dry emulsions containing amorphous sucrose.

The objective of the present study was to estimate the stability of redispersible dry emulsions containing amorphous sucrose. Dry emulsions were prepared by spray drying liquid o/w-emulsions in a laboratory spray dryer. The effect of hydroxypropyl methylcellulose (HPMC) on the glass transition temperature T(g) of spray dried sucrose-HPMC mixtures, relative to the T(g) of amorphous sucrose, was investigated. For the sucrose-HPMC mixtures the values of T(g) followed the ideal Gordon-Taylor equation up to 30% HPMC. For dry emulsions containing 40% HPMC, 30% lipid and 30% sucrose, the T(g) was increased by 12 degrees C relative to the T(g) of amorphous sucrose. The stability of the dry emulsions was investigated by a conventional stability study and by an enthalpy relaxation study. The measured enthalpy recovery of amorphous sucrose below T(g) was used to calculate molecular relaxation time parameters based on the Williams-Watts equation. The molecular mobility of amorphous sucrose at temperatures 50 degrees C below T(g) was low and negligible with respect to the shelf life stability. It was concluded that the dry emulsions are physically stable with respect to the lifetime of a pharmaceutical product when stored in dry condition and at temperatures up to 28 degrees C.     

Preparation of scopolamine hydrobromide nanoparticles-in-microsphere system

This study is to prepare scopolamine hydrobromide nanoparticles-in-microsphere system (SH-NiMS) and evaluate its drug release characteristics in vitro. SH nanoparticles were prepared by ionic crosslinking method with tripolyphosphate (TPP) as crosslinker and chitosan as carrier. Orthogonal design was used to optimize the formulation of SH nanoparticles, which took the property of encapsulation efficiency and drug loading as evaluation parameters. With HPMC as carrier, adjusted the parameters of spray drying technique and sprayed the SH nanoparticles in microspheres encaposulated by HPMC was formed and which is called nanoparticles-in-microsphere system (NiMS). SH-NiMS appearances were observed by SEM, structure was obsearved by FT-IR and the release characteristics in vitro were evaluated. The optimized formulation of SH nanoparticles was TPP/CS 1:3 (w/w), HPMC 0.3%, SH 0.2%. The solution peristaltic speed of the spray drying technique was adjusted to 15%, and the temperature of inlet was 110 degrees C. The encapsulation product yeild, drug loading and particle sizes of SH-NiMS were 94.2%, 20.4%, and 1256.5 nm, respectively. The appearances and the structure of SH-NiMS were good. The preparation method of SH-NiMS is stable and reliable to use, which provide a new way to develop new dosage form.     

喷雾干燥技术在蛋白、多肽类药物微球制备中的应用

按照不同的常用载体材料（聚乳酸类和壳聚糖类），分类综述应用喷雾干燥技术制备蛋白、多肽类药物微球的研究进展，主要介绍和比较了溶液，喷雾干燥、乳剂，喷雾干燥、喷雾冷冻干燥、喷雾液中冷冻及低温喷雾提取等制备工艺的特点。     

不同干燥条件大黄水提物的外观及理化性质比较研究

目的研究不同干燥方式对大黄水提物外观及理化性质的影响。方法分别采用真空、常压、喷雾、微波和冷冻干燥等5种不同干燥方式对大黄水提物进行干燥,测定并比较各样品的外观质地、pH及相对临界湿度（CRH）的差异。结果不同干燥方式样品的外观性状差异较大,pH差异不大;CRH由大到小依次为常压干燥、微波干燥、真空干燥、冷冻干燥、喷雾干燥样品,其中喷雾干燥样品最小且与常压干燥样品有显著差异（P〈0．05）。结论干燥方式对样品的外观及理化性质影响明显。喷雾干燥样品的吸湿性增大,对产品的稳定性有一定影响。