ZLR-8喷雾干燥乳剂的制备及高效液相色谱法含量测定

目的:制备水极难溶性的一氧化氮供体药物ZLR-8喷雾干燥乳剂并测定干乳剂中ZLR-8含量。方法:采用喷雾干燥法制备ZLR-8喷雾干燥乳剂,建立高效液相色谱(HPLC)法测定ZLR-8在喷雾干燥乳剂中的含量。结果:ZLR-8在10.2~35.8mg.L-1范围内线性良好,r=0.999 8;低、中、高3种剂量的回收率分别为100.4%,99.75%,100.7%;RSD分别为0.21%,0.01%,0.66%。3批样品中ZLR-8的平均含量为100.2%,RSD为0.46%。结论:ZLR-8喷雾干燥乳剂的制备方法可行,HPLC法专属性好,能快速、准确测定喷雾干燥乳剂中ZLR-8的含量。     

口服喷雾干燥乳剂处方筛选

目的优化喷雾干燥乳剂处方。方法联用羟丙甲纤维素（HPMC）和蔗糖作固体载体,椰子油作油相,采用喷雾干燥工艺制备O/W型干乳剂。结果根据乳化性能及喷雾可操作性筛选出适于采用喷雾干燥法制备干乳剂的处方。即固体载体HPMC适宜黏度为3mPa.s,浓度为8%。结论HPMC的黏度和浓度对液体O/W乳剂的稳定性及经喷雾干燥制成干乳剂有一定影响,含高黏度HPMC的液体O/W乳剂不容易雾化,易堵塞雾化器的喷嘴。低黏度HPMC是一种有用的固体载体,并起到一定的乳化作用。     

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.     

药物干乳剂的研究进展

目的探讨药物干乳剂的研究现状。方法查阅近几十年的中外文献，对药物千乳剂的制备方法辅料种类及用量的选择进行了概述。并简述了药物干乳剂的质量评价项目和评价方法。结果不同的制备方法对药物干乳剂质量有一定的影响，质量可以从含量测定、包裹率测定、结晶度测定、再分散后性质指标测定来评价。结论药物干乳剂作为一种新剂型，还有待于进一步的研究和开发。     

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。     

含药干乳的研究概况

介绍近年来国内外有关含药干乳的研究概况，综述干乳的若干制备方法（包括喷雾干燥法、冷冻干燥法、减压蒸馏法和吸干法）、稳定性影响因索及应用前景，为干乳这种新型药物传递系统的研究提供参考。     

浅谈固体自乳化药物传递系统固体化技术（续）

3SSEDDS的剂型选择 3．1干燥乳剂 干燥乳剂由包含同体载体（乳糖、糊精、麦芽糖）的油／水乳化剂组成。常用制备方法为喷雾干燥法、冷冻干燥法和旋转蒸发法等。Mvers和Shivelv用重矿物油和蔗糖通过旋转蒸发以干泡沫形式获得固态的乳化玻璃。这些乳化的玻璃具有不需要表面活性剂的优点。冷冻干燥过程中，缓慢冷却和添加无定形的冷冻保护剂会产生最佳的稳定效应，而融化之前进行热处理则会降低稳定效应。     

喷雾与减压干燥的秦香止泻干膏粉吸湿性及流动性比较

目的比较喷雾干燥法与减压干燥法对秦香止泻干浸膏粉吸湿性及流动性的影响,为确定秦香止泻浓缩液（或稠浸膏）合理的干燥方法提供依据。方法通过测定秦香止泻干浸膏粉的吸湿速度,吸湿量达2％时的相对湿度（relative humidit,RH）,建立其动力学模型,提取吸湿速度参数并比较大小;通过测定秦香止泻干浸膏粉的休止角比较流动性优劣。结果两种干燥方法制成的干浸膏粉吸湿动力学模型皆符合对数正态分布模型,减压干燥比啧雾干燥吸湿速度快,吸湿量随RH变化的函数关系,喷雾干燥粉符合逻辑斯蒂模型;减压干燥粉符合修正指数函数曲线,吸湿量达2％时的RH,喷雾干燥粉为90．12％;减压干燥85．81％,减压干燥法比喷雾干燥法制成的干浸膏粉休止角大,流动性差。结论喷雾干燥制成的干浸膏粉不易吸湿,稳定性好,流动性好。     

尼莫地平干乳胶囊的制备及质量控制

<正>乳剂作为一种药物传递系统,口服可以改善难溶性药物的吸收,提高药物生物利用度;但作为一种热力学不稳定体系,乳剂易发生分层、絮凝甚至破乳等物理不稳定现象,给生产、贮存、运输和应用带来了极大不便,而将液态乳转变为干乳则是改善这些问题的一种有效途径[1]。干乳中的乳     

水难溶性药物的新型载体-干乳的研究进展

通过分析、整理、归纳近几年的国内外文献,分析乳剂、微乳等脂质处方促进水难溶性药物体内吸收的原因,介绍干乳常用制备工艺及相应干乳物性研究、促进药物体外溶出和饭内吸收的情况。     

Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.

A physically stabilized dry emulsion dosage form reforming the original emulsion after rehydration was developed by spray-drying a liquid oil-in-water emulsion containing maltodextrin as carrier and sodium caseinate as emulsifying agent. Several oil:water as well as maltodextrin:water ratios were tested, the homogenization and spray-drying processes and the reconstitution properties were investigated and an optimum formulation was selected for poorly soluble drug incorporation, having an identical oil:water and carrier:water ratio of 10% (w/w) and a load of solid material of 20% (w/w). Lipophilic 5-phenyl-1,2-dithiole-3-thione (5-PDTT) was selected as a model drug. 5-PDTT release from the solid state emulsion was studied using an in vitro two-phase stirred model and the relative bioavailability of 5-PDTT in the dry emulsion was obtained in the rabbit after oral administration of the reconstituted emulsion, compared to a 5-PDTT-sulfobutyl ether 7 beta-cyclodextrin complex in solution. Incorporation of 5-PDTT in the oil phase neither affects the surface morphology of the powder nor the reconstitution, the droplet size or the drug releasing properties and, furthermore, allows a 3-fold improvement of 5-PDTT relative bioavailability in rabbit after oral administration. These results indicate that dry emulsions may be considered as relevant dosage forms to improve bioavailability of poorly absorbable lipophilic drugs.     

复乳研究进展

复乳具有多层液体膜结构,是一种复杂的液体分散体系。复乳可作为缓控释给药系统与靶向给药系统的药物载体;亦可作为多肽、蛋白质类药物的载体避免药物口服后受胃肠液的破坏;同时有利于药物进入淋巴系统,因此复乳广泛的应用于药学领域。本文对复乳的定义、分类、特点、制备方法、常见问题及对策等方面进行综述。     

Biopharmaceutical powders: particle formation and formulation considerations

It is well known that protein/peptide-based drug formulations are more stable in the solid state than in the liquid state, thereby offering stability advantages in ambient temperature storage, product shipping/distribution, and long-term shelf life. Novel powder-based drug delivery systems recently emerging for applications in sustained release, inhalation, intradermal delivery, etc, add more value to protein solid dosage forms. Despite great research interests in understanding the drying effects on protein stability and a large collection of publications focusing on this area, systematic accounts of powder formation techniques are lacking. This review is to summarize a number of methods currently available for protein powder preparation. Some are common methods such as lyophilization, spray drying, pulverization, and precipitation, and some methods are more recently developed such as supercritical fluid precipitation, spray-freeze drying, fluidized-bed spray coating and emulsion precipitation. In addition to examining the individual process effect on protein stability that is always the focus of formulation scientists, this review also likes to evaluate each method from a more practical sense in terms of process versatility and scalability. The conclusion is that each method has its own advantages and the use of a method is formulation and application specific. With the understanding of the principles and advantages of these methods, it can benefit our choice on selecting appropriate techniques for preparing a desired protein powder formulation for specific applications.     

Pickering w/o emulsions: drug release and topical delivery

The skin absorption from Pickering emulsions as a new dosage form was investigated for the first time. Pickering emulsions are stabilized by adsorbed solid particles instead of emulsifier molecules. They are promising dosage forms that significantly differ from classical emulsions within several features. The skin permeation of a hydrophilic model penetrant (caffeine) was investigated from a w/o Pickering emulsion and compared to a w/o classical emulsion stabilized with an emulsifier. Both emulsions had the same composition and physicochemical properties in order to focus on the effect of the interfacial layer on the drug release and skin absorption processes. The highest permeation rates were obtained from the Pickering emulsion with a pseudo-steady state flux of 25 microg cm(-2)h(-1), threefold higher than from a classical emulsion (9.7 microg cm(-2)h(-1)). After 24h exposure, caffeine was mostly in the receptor fluid and in the dermis; cumulated amounts of caffeine were higher for the Pickering emulsion. Several physicochemical phenomena were investigated for clearing up the mechanisms of enhanced permeation from the Pickering emulsion. Among them, higher adhesion of Pickering emulsion droplets to skin surface was disclosed. The transport of caffeine adsorbed on silica particles was also considered relevant since skin stripping showed that aggregates of silica particles entered deeply the stratum corneum.     

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.     

Release of 5-fluorouracil from intramuscular w/o/w multiple emulsions

Comparative in vivo studies of aqueous solution, multiple w/o/w, and w/o emulsions showed that formulating 5-fluorouracil in emulsion systems significantly sustained the release of the drug from intramuscular injection sites in the rat. Intramuscular injection of the drug in both w/o and w/o/w emulsion systems produced sustained blood concentrations with a later blood level peak than observed following intramuscular injection of aqueous solutions of the drug. The multiple w/o/w emulsion exhibited a more rapid release of drug from the injection site than the w/o emulsion because of partitioning of the drug to the external aqueous phase during secondary emulsification. The fate of the oil phase following intramuscular injection of a water/hexadecane/water multiple emulsion spiked with 1-14C-hexadecane has been studied in rats as a function of stabilizer concentrations. Increasing the lipophilic surfactant (Span 80) concentration facilitated the clearance of the oily vehicle from the injection site, by mechanisms which remain to be elucidated.     

Enhanced oral bioavailability of dexibuprofen by a novel solid Self-emulsifying drug delivery system (SEDDS)

The main objective of this study was to prepare a solid form of lipid-based self-emulsifying drug delivery system (SEDDS) by spray drying liquid SEDDS with an inert solid carrier Aerosil 200 to improve the oral bioavailability of poorly water-soluble drug dexibuprofen. The liquid SEDDS was a system that consisted of dexibuprofen, Labrasol, Capryol 90 and Labrafil M 1944 CS. The particle size analysis revealed no difference in the z-average particle diameter of the reconstituted emulsion between liquid and solid SEDDS. The solid SEDDS was characterized by SEM, DSC and XRD studies. In vivo results of solid SEDDS and dexibuprofen powder in rats at the dose of 10 mg/kg showed that the initial plasma concentrations of drug in solid SEDDS were significantly higher than those of dexibuprofen powder (P < 0.05). The solid SEDDS gave significantly higher AUC and Cmax than did dexibuprofen powder (P < 0.05). In particular, the AUC of solid SEDDS was about twofold higher than that of dexibuprofen powder. Our results suggested that this solid SEDDS could be used as an effective oral solid dosage form to improve the bioavailability of poorly water-soluble drug dexibuprofen.     

Stability of pediatric liquid dosage forms of ethacrynic acid, indomethacin, methyldopate hydrochloride, prednisone and spironolactone

The stability of liquid dosage forms of ethacrynic acid (1 mg/ml), indomethacin (2 mg/ml), methyldopate hydrochloride (25 mg/ml), prednisone (0.5 mg/ml) and spironolactone (2 mg/ml), which often are compounded extemporaneously, was studied. One or two liquid dosage forms of each of the five drugs was prepared with the pure drug or the powder from a commercial dosage form using aqueous sorbitol or simple syrup alone or with a 10% (v/v) solution of alcohol in water. The dosage forms were stored at 24 C in amber-colored bottles for 21-224 days and assayed by various methods. All solutions studied were stable for at least 84 days. A solution was considered stable if it retained 90% of its drug concentration. Except for the prednisone solution, all solutions were stable for at least 164 days; however, the solution of methyldopate hydrochloride prepared from the pure drug became discolored after 98 days. The liquid dosage forms studied have limited stability but can be used by the pharmacist when extemporaneous oral solutions of these drugs are needed.     

Liquid spray formulations of xibornol by using self-microemulsifying drug delivery systems

Xibornol is a lipophilic drug mainly used in Italy and Spain in spray dosage forms for the local treatment of infection and inflammation of the throat. Its poor water solubility makes difficult the development of aqueous formulations of the drug, thus giving rise to a limited number of stable and pharmaceutically accepted preparations. In fact, xibornol is actually marketed only as spray aqueous suspension. The aim of this work was to evaluate the possibility of developing a stable liquid formulation of the drug intended for oral spray administration using a self-microemulsifying drug delivery system (SMEDDS). These systems are able to adequately improve the drug solubility, allowing the introduction of relatively high concentration of drugs in the form of solution. Labrafil M1944, Labrafil M2125 and Labrafac CC were screened as oil phases, Labrasol and Labrafac PG as surfactants and Transcutol as co-surfactant. Pseudo-ternary phase diagrams were constructed, by titration with the aqueous phase of different oil phases and surfactant/co-surfactant mixtures in order to identify the self-microemulsification region and the optimal micro-emulsion composition. Then, complete pharmaceutical formulations were prepared and evaluated for stability and viscosity properties. The final selected formulations, containing Labrafil M1944, Transcutol, Labrafac PG and a hydrophilic co-solvent (propylene glycol or PEG 200) allowed complete solubilization of the required xibornol concentration (3%, w/v) and showed physical good stability up to 2 months at 25 and 4 °C, suitable viscosity and organoleptic properties.