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991.
银杏酮酯口服自微乳化给药系统的制备 总被引:1,自引:0,他引:1
研究制备银杏酮酯口服自微乳化给药系统。采用平衡溶解度方法筛选乳化剂与助乳化剂; 采用伪三元相图法制备微乳; 采用正交法优化处方组成; 并考察自微乳化制剂的乳化效率、溶出度、稳定性与药动学研究等。结果表明, 由肉豆蔻酸异丙酯IPM、聚氧乙烯蓖麻油Cremophor EL、丙二醇与银杏酮酯组成的自微乳化给药系统遇水可自发形成粒径为20~50 nm的稳定微乳。自微乳化给药系统的乳化效率与溶出快, 且制剂稳定性高, 能提高生物利用度。制备的银杏酮酯口服自微乳化给药系统稳定有效。 相似文献
992.
Wim Jiskoot Rianne M. F. van Schie Myrra G. Carstens Huub Schellekens 《Pharmaceutical research》2009,26(6):1303-1314
Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed
for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications
are associated with administration of DDS. These immunological events can compromise the efficacy and safety of these systems
by changing the pharmacokinetics, biodistribution and targeting capability of DDS, and by inducing hypersensitivity reactions.
Antibodies induced by administration of DDS can be directed against the carrier material, the drug and/or targeting ligands
associated with the DDS. Complement activation and opsonization of DDS, which may or may not be associated with antibody formation,
may lead to accelerated clearance, hypersensitivity reactions and formation of membrane attack complexes resulting in premature
release of the drug. Also platelets have been reported to play a role in DDS immunogenicity. Despite our curtailed understanding
of the relationships between physicochemical characteristics and immunogenicity of DDS, several risk factors have been identified.
Insight into these factors should be employed in the development of novel DDS with low immunological risk. 相似文献
993.
Jos Hureaux Frdric Lagarce Frdric Gagnadoux Laurent Vecellio Anne Clavreul Emilie Roger Marie Kempf Jean-Louis Racineux Patrice Diot Jean-Pierre Benoit Thierry Urban 《European journal of pharmaceutics and biopharmaceutics》2009,73(2):239-246
Aerosol drug delivery permits the development of dose-intensification strategies in severe, malignant lung diseases. The aim of the study was to demonstrate that the encapsulation of paclitaxel in lipid nanocapsules (LNCs), a novel drug nanocarrier for lipophilic components, allows one to provide pulmonary drug delivery of paclitaxel by nebulisation, thereby allowing preclinical and clinical studies. LNC dispersions are made into aerosols with commercial nebulisers. The structure, drug payload and cytotoxicity of nebulised LNCs were compared to fresh LNCs. The results demonstrated that LNC dispersions could be made into aerosols by using mesh nebulisers without altering the LNC structure. Only eFlow® rapid-produced aerosols are compatible with human use: the mean duration to nebulise 3 ml of LNC dispersion is less than 9 min, with an aerosol mass median aerodynamic diameter equal to 2.7 ± 0.1 μm and a fine-particle fraction (between 1.0 and 5.0 μm) of 81.5 ± 3.1%. No modifications of drug payload or cytotoxicity effects of paclitaxel-loaded LNC (PTX–LNC) were observed. In order to carry out preclinical studies, a scaled-up LNC formulation protocol was used. Chemical parameters, such as acidity and osmolarity, were optimised, and a storage procedure for PTX–LNC batches was set-up. Animal studies are now needed to determine the tolerance and therapeutic potential of LNC dispersion aerosols. 相似文献
994.
Vincent Malaterre Joerg Ogorka Robert Gurny 《European journal of pharmaceutics and biopharmaceutics》2009,73(3):311-323
The number of marketed oral osmotically driven systems (OODS) has doubled in the last 10 years. The main clinical benefits of OODS are their ability to improve treatment tolerability and patient compliance. These advantages are mainly driven by the capacity to deliver drugs in a sustained manner, independent of the drug chemical properties, of the patient’s physiological factors or concomitant food intake. However, access to these technologies has been restricted by the crowded patent landscape and manufacturing challenges. In this review article, we intend to give an overview of the OODS development in the last 30 years, detailing the technologies, specific products and their clinical use. General guidance on technology selection is described in light of the recent advances in the field. The clinical performance of these technologies is also discussed, with a focus on food effects and the in vivo-in vitro correlation. Special attention is paid to safety given the controversial case study of Osmosin®. Overall, oral osmotically driven systems appear to be a promising technology for product life-cycle strategies. 相似文献
995.
Katrin Moebus Roland Bodmeier 《European journal of pharmaceutics and biopharmaceutics》2009,72(1):42-53
Purpose: The aim of this study was to prepare and characterize novel hydrogel-based delivery systems allowing for the controlled release of drugs to mucosal surfaces. Methods: Terbutaline sulfate and bovine serum albumin (BSA)-loaded alginate-poloxamer microparticles were prepared by a w/o-emulsion- and external gelation method. The microparticles were characterized by optical and scanning electron microscopy, laser light diffraction, atomic absorption spectroscopy, energy-dispersive X-ray analysis, via complexation with 1,9-dimethyl methylene blue and using dialysis bags as well as modified Franz diffusion cells for in vitro drug-release measurements. Results: Using heptane as organic phase, homogeneous and almost spherical microparticles were obtained with a high-loading efficiency (>90%). The resulting drug-release patterns could effectively be adjusted by varying the “alginate:poloxamer” blend ratio. In addition, the particle size, morphology, calcium and chloride content as well as alginate-release rates could be altered. Erosion was the predominant release mechanism for BSA. Special attention needs to be paid to the microparticle recovery procedure, which can significantly affect key properties such as the resulting drug-release patterns. Conclusions: The novel hydrogel-based microparticles offering mild conditions for incorporated drugs (e.g., proteins) provide an interesting potential as controlled delivery systems for mucosal surfaces. 相似文献
996.
Sungwon Kim Oju Jeon Kinam Park 《European journal of pharmaceutics and biopharmaceutics》2009,71(3):420-430
Engineered polymers have been utilized for developing advanced drug delivery systems. The development of such polymers has caused advances in polymer chemistry, which, in turn, has resulted in smart polymers that can respond to changes in environmental condition such as temperature, pH, and biomolecules. The responses vary widely from swelling/deswelling to degradation. Drug-polymer conjugates and drug-containing nano/micro-particles have been used for drug targeting. Engineered polymers and polymeric systems have also been used in new areas, such as molecular imaging as well as in nanotechnology. This review examines the engineered polymers that have been used as traditional drug delivery systems and as more recent applications in nanotechnology. 相似文献
997.
Chiara Parlati Paolo Colombo Francesca Buttini Paul M. Young Handoko Adi Alaina J. Ammit Daniela Traini 《Pharmaceutical research》2009,26(5):1084-1092
Purpose Tobramycin microparticulate powders containing the hydrophobic adjunct sodium stearate were studied for their use as pulmonary
formulations in dry powder inhalers.
Methods Spray-dried powders were characterized in terms of particle size distribution, morphology, crystallinity, drug dissolution
rate, toxicity on epithelial lung cells and aerosol efficiency.
Results The presence of the sodium stearate had a direct influence on the aerosol performance of tobramycin spray-dried powders. Powders
containing 1% w/w sodium stearate had fine particle fraction FPF of 84.3 ± 2.0% compared to 27.1 ± 1.9% for powders containing no adjunct.
This was attributed to the accumulation of sodium stearate at the particle surface. Powders with higher sodium stearate concentrations
(2% w/w) showed significantly lower FPF (66.4 ± 0.9%) and less accumulation of sodium stearate at the particle surface. This was
attributed to the formation of adjunct micelles, which remained internalised in the particle structure due to their reduced
tropism toward the drying drop surface and molecular mobility. Preliminary analysis of the toxicity effect of sodium stearate
on A549 cell lines showed that the adjunct, in the concentration used, had no effect on cell viability over a 24-h period
compared to particles of pure tobramycin.
Conclusions Tobramycin pulmonary powders with low level of sodium stearate, presenting high respiration performances and no overt toxicity
on lung cells, could be used to improve therapeutic outcomes of patient with Cystic Fibrosis (CF). 相似文献
998.
Giorgia Pastorin 《Pharmaceutical research》2009,26(4):746-769
Amidst the myriad of Drug Delivery Systems able to enhance delivery, absorption and intracellular uptake of a bioactive molecule
while protecting it from deactivation, Carbon Nanotubes (CNTs) have emerged as a recent and promising option especially in
cancer therapy. This is mainly due to their unique properties, which render them extremely versatile through the incorporation
of several functional groups and targeting molecules at the same time, while their natural shape allows them to selectively
penetrate across biological barriers in a non-invasive way. In this expert review we aim to evaluate whether this innovative
material, once chemically-modified with suitable functionalizations, can be considered as a valuable system in comparison
to the already existing nanodevices. This will include the estimation of the most recent advances in the field of nanotechnology,
together with a cautious evaluation of potential risks and hazards associated with the extensive use of this fascinating,
but still unknown, nanomaterial. 相似文献
999.
Sherry Y. Wu Lisa N. Putral Mingtao Liang Hsin-I. Chang Nigel M. Davies Nigel A. J. McMillan 《Pharmaceutical research》2009,26(3):512-522
Purpose A simple yet novel method was developed to prepare stable PEGylated siRNA-loaded lipid particles which are suitable for in vivo use.
Methods PEGylated siRNA-loaded lipid particles were formulated by hydration of a freeze-dried matrix. The effect of various formulation
parameters on the size and homogeneity of resulting particles was studied. Particles prepared using this method were compared
to those prepared using an established post-insertion procedure for the entrapment efficiency, stability, in vitro biological activity as well as in vivo biodistribution.
Results Using this hydration method, a particle size of less than 200 nm can be obtained with high siRNA entrapment efficiency (>90%)
and high gene-silencing efficiency. Following intravenous administration into mice, these particles achieved a similar degree
of accumulation in subcutaneous tumours but displayed less liver uptake compared to the post-insertion formulations. Importantly,
in contrast to post-insertion preparations, particles made by hydration method retained 100% of their gene-silencing efficiency
after storage at room temperature for 1 month.
Conclusions This paper describes a simple method of formulating PEGylated siRNA-loaded lipid particles. Given the ease of preparation,
long term stability and favourable characteristics for in vivo delivery, our work represents an advance in lipid formulation of siRNA for in vivo use. 相似文献
1000.
Anthony S. Ham Marilyn R. Cost Alexandra B. Sassi Charlene S. Dezzutti Lisa Cencia Rohan 《Pharmaceutical research》2009,26(3):502-511
Purpose Nanoparticles formulated from the biodegradable co-polymer poly(lactic-co-glycolic acid) (PLGA), were investigated as a drug
delivery system to enhance tissue uptake, permeation, and targeting for PSC-RANTES anti-HIV-1 activity.
Materials and Methods PSC-RANTES nanoparticles formulated via a double emulsion process and characterized in both in vitro and ex vivo systems to determine PSC-RANTES release rate, nanoparticle tissue permeation, and anti-HIV bioactivity.
Results Spherical, monodisperse (PDI = 0.098 ± 0.054) PSC-RANTES nanoparticles (d = 256.58 ± 19.57 nm) with an encapsulation efficiency of 82.23 ± 8.35% were manufactured. In vitro release studies demonstrated a controlled release profile of PSC-RANTES (71.48 ± 5.25% release). PSC-RANTES nanoparticle
maintained comparable anti-HIV activity with unformulated PSC-RANTES in a HeLa cell-based system with an IC50 of approximately 1pM. In an ex vivo cervical tissue model, PSC-RANTES nanoparticles displayed a fivefold increase in tissue uptake, enhanced tissue permeation,
and significant localization at the basal layers of the epithelium over unformulated PSC-RANTES.
Conclusions These results indicate that PSC-RANTES can readily be encapsulated into a PLGA nanoparticle drug delivery system, retain its
anti-HIV-1 activity, and deliver PSC-RANTES to the target tissue. This is crucial for the success of this drug candidate as
a topical microbicide product. 相似文献