International journal of pharmaceutics
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Comparative Study
Surface active drugs significantly alter the drug output rate from medical nebulizers.
Surface tension of aqueous solutions has a great impact on the resulting size of the produced aerosol droplets. Nevertheless, little attention has been drawn so far to the drug output of surface active substances during nebulization. ⋯ Following conclusions for an efficient nebulization delivery of drugs with surface activity with respect to optimal delivery device can be made. Generally, ultrasonic devices produce higher drug output rates within shorter periods of time as compared to jet and vibrating membrane nebulizers. Accordingly, prescription instructions have to be adjusted to these findings. The study also emphasizes that aqueous nebulizer solutions should preferably be prescribed in conjunction with a specific nebulizer which has been tested in vitro and been used in in vivo studies, rather than to let patients choose their delivery device themselves.
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Liposomes as one of the efficient drug carriers have some shortcomings such as their relatively short blood circulation time, fast clearance from human body by reticuloendothelial system (RES) and limited intracellular uptake to target cells. In this study, polyethylene glycol (PEG)-complexed cationic liposomes (PCL) were prepared by ionic complex of cationically charged liposomes with carboxylated polyethylene glycol (mPEG-COOH). The cationic liposomes had approximately 98.6+/-1.0 nm of mean particle diameter and 45.5+/-1.1 mV of zeta potential value. ⋯ In pharmacokinetic study in rats, PCL showed slightly lower plasma level of DOX than that of Doxil. In vivo antitumor activity of DOX-loaded PCL was comparable to that of Doxil against human SKOV-3 ovarian adenocarcinoma xenograft rat model. Consequently, the PCL, of which surface was complexed with PEG by ionic complex may be applicable as drug delivery carriers for increasing therapeutic efficacy of anticancer drugs.
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Comparative Study
CDs as solubilizers: effects of excipients and competing drugs.
In recent years cyclodextrins (CDs) have been acknowledged by the pharmaceutical industry as very useful enabling excipients for solubilization and stabilization of drugs in aqueous formulations. Their effect is however strongly influenced by other commonly used excipients. The purpose of this investigation was to examine the effects of excipients and drug combinations on the effects of CD solubilization of drugs and drug availability. ⋯ Drugs that have little affinity for CDs (e.g. amphotericin B) did in some cases improve the CD solubilization of dexamethasone. Flux diagrams obtained through semi-permeable cellophane membrane indicated that drug/CD complexes self-assemble to form aggregates, especially at CD concentrations above 5% (w/v). This aggregate formation was affected by the excipients and did influence drug availability from the formulations.
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The use of solubilizing agents to improve the solubility of poorly water-soluble drugs often results in an alteration of intestinal membrane barrier function and intestinal membrane damage. In this study, 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-labeled dextran (MW 4400, FD4) were used as model compounds to examine the effects of twelve common solubilizing agents, sodium taurocholate (NaTC), Labrasol, polyethylene glycol 400 (PEG 400), Transcutol P, propylene glycol, Gelucire 44/14, HCO-60, ethanol, Cremophor EL, Tween 80, 2 hydroxypropyl-beta-cyclodextrin (2HP-beta-CyD) and dimethylsulfoxide (DMSO), on intestinal membrane barrier function and membrane toxicity in rats. Intestinal transport and absorption of CF were examined using an in vitro diffusion chamber and an in situ closed-loop technique. ⋯ The LDH level was also increased in the presence of 10% (v/v) of Cremophor EL. These findings suggest that the solubilizing agents at these concentrations except for NaTC, Gelucire 44/14 and Cremophor EL are considered safe and do not cause intestinal membrane damage. In conclusion, this study provides a basic approach in screening and predicting the effects of solubilizing agents for intestinal absorption studies using drugs poorly soluble in water.
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Mathematical models are available which predict aerosol deposition in the respiratory system assuming that the aerosol concentration and size are constant during inhalation. In this study, we constructed a sinusoidal breathing model to calculate the aerosol concentration produced by a nebulizer as a function of inhalation time. The laser diffraction technique (Spraytec, Malvern Instruments Ltd., Malvern, UK) was used to validate this model as it allows the aerosol concentration and particle size to be measured in real time. ⋯ All of the nebulizers produced a relatively constant particle size distribution. Our findings confirm that the concentration observed during inhalation is often not constant over time. The laser diffraction method allows the concentration and size of particles for each unit volume of air inhaled to be measured and could therefore be used to predict the aerosol deposition pattern more precisely.