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Pure Drug (pure + drug)
Selected AbstractsLong circulating nanoparticles of etoposide using PLGA-MPEG and PLGA-pluronic block copolymers: characterization, drug-release, blood-clearance, and biodistribution studiesDRUG DEVELOPMENT RESEARCH, Issue 4 2010Khushwant S. Yadav Abstract The anti-leukemic drug, etoposide (ETO), has variable oral bioavailability ranging from 24,74% with a short terminal half-life of 1.5,h i.v. necessitating continuous infusion for 24,34,h for the treatment of leukemia. In the present study, etoposide-loaded PLGA-based surface-modified nanoparticles (NPs) with long circulation were designed as an alternative to continuous i.v. administration. PLGA-mPEG and PLGA-PLURONIC copolymers were synthesised and used to prepared ETO-loaded NPs by high-pressure homogenization. The mean particle size of ETO-loaded PLGA-MPEG nanoparticles was 94.02±3.4,nm, with an Entrapment Efficiency (EE) of 71.2% and zeta potential value of ,6.9±1.3,mV. ETO-loaded PLGA-pluronic nanoparticles had a mean particle size of 148.0±2.1,nm, an EE of 73.12±2.7%, and zeta potential value of ,21.5±1.6,mV. In vitro release of the pure drug was complete within 4,h, but was sustained up to 7 days from PLGA-mPEG nanoparticles and for 5 days from PLGA-pluronic nanoparticles. Release was first order and followed non-Fickian diffusion kinetics in both instances. ETO and ETO-loaded PLGA nanoparticles labeled with 99mTc were used in blood clearance studies in rats where the two coated NPs, 99mTc- ETO-PLGA-PLU NP and 99mTc- ETO-PLGA-mPEG NP, were found to be available in higher concentrations in the circulation as compared to the pure drug. Biodistribution studies in mice showed that ETO-loaded PLGA-MPEG NP and PLGA-PLURONIC NP had reduced uptake by the RES due to their steric barrier properties and were present in the circulation for a longer time. Moreover, the NPs had greater uptake in bone and brain where concentration of the free drug, ETO, was negligible. Drug delivered from these NPs could result in a single i.v. injection that would release the drug for a number of days, which would be potentially beneficial and in better control of leukemia therapy. Drug Dev Res 71: 228,239, 2010. © 2010 Wiley-Liss, Inc. [source] Ultrasound-compacted indomethacin/polyvinylpyrrolidone systems: Effect of compaction process on particle morphology and dissolution behaviorJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2002Adamo Fini Abstract Indomethacin (IMC)/polyvinylpyrrolidone systems were prepared under different technological conditions, using co-evaporation, kneading, traditional, and ultrasound (US) compaction. The materials thus obtained were milled and sieved and the powders were analyzed by using scanning electron microscopy to evaluate the morphology of the final particles and the fractal dimension of the particle contour. In the case of US-treated particles, scanning electron micrographs suggest that IMC could have partially covered the excipient granule surface, which appears lustrous and smooth, whereas after co-evaporation, the particles display a stratified structure. The external color of the granules, the hot stage microscopy examination, and the absence of the melting peak of the drug in thermograms supports the idea that IMC converts into an amorphous form under US discharge. Each technological treatment performed on the binary mixtures increases the dissolution rate of the drug, with respect to the pure drug and the physical mixture, but to a lesser extent than US compaction. US compaction and co-evaporation produce comparable results in improving the release of the drug. Polyvinylpyrrolidone offers better results than ,-cyclodextrin in promoting the dissolution of IMC, when both systems are compacted under US. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1880,1890, 2002 [source] Improvement of dissolution and oral absorption of ER-34122, a poorly water-soluble dual 5-lipoxygenase/cyclooxygenase inhibitor with anti-inflammatory activity by preparing solid dispersionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2002Ikuo Kushida Abstract Several formulation approaches were attempted to improve the dissolution and the oral absorption of ER-34122, which is a novel dual 5-lipoxygenase/cyclooxygenase inhibitor with potent anti-inflammatory activity. The solid dispersion of ER-34122 with hydroxypropylmethylcellulose (TC-5RW), which is an inert solid carrier, resulted in a significant improvement in the dissolution rate of ER-34122. The solid dispersion was prepared by a solvent evaporation method using ethanol and water. The solid-state characteristics of the solid dispersion, the corresponding physical mixture, and ER-34122 alone were investigated by X-ray powder diffraction, Fourier transform infrared spectroscopy (FTIR), and an automated controlled-atmosphere microbalance. The X-ray powder diffraction patterns suggest that the solid dispersion exists in a totally amorphous state and the others exist in a crystalline state. The FTIR spectra results suggest that ER-34122 can interact with TC-5RW through intermolecular hydrogen bonding in the solid dispersion. This interaction may cause a stabilization of ER-34122 in the higher-energy, faster-dissolving amorphous state. The dissolution rate of ER-34122 from the solid dispersion was significantly greater than that from the physical mixture or the pure drug. Furthermore, when orally administrated to beagle dogs, ER-34122 showed about a 100-fold increase in both maximum concentration (Cmax) and area under the curve of concentration versus time (AUC) compared with the pure drug. Consequently, it was determined that the solid dispersion technique with TC-5RW provides a promising way to increase the dissolution rate and the oral absorption of poorly water-soluble drugs such as ER-34122. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:258,266, 2002 [source] An introduction to enantiomers in psychopharmacologyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S2 2001Brian E. Leonard Abstract There is growing scientific, clinical, commercial and regulatory recognition that enantiomers offer benefits over racemates in the management of psychiatric diseases as well as in clinical medicine generally. However, relatively few studies consider enantiomers' individual characteristics. This review considers some of the clinical benefits associated with using stereochemically pure drugs in psychiatric conditions other than depression. A review of the evidence shows that enantiomers offer four main benefits. Firstly, using a single enantiomer may allow a reduction in total dose, while maintaining or improving outcomes. For example, (+)-nefopam's antinociceptive activity is greater than that produced by both the racemate and (,)-nefopam, but with the same level of acute toxicity. Thus, a single enantiomer may offer greater efficacy, dose for dose, than the racemate. Secondly, assessing dose,response relationships is simpler. There is no reason to suppose that a racemate will necessarily contain the isomers' optimum therapeutic ratio, that one of the isomers will be inactive or that the enantiomers' dose,response curves will coincide. For example, the dose,response relationship for the induction of catalepsy in the rat by thioridazine suggested that the racemate was around 12 times more potent than (+)-thioridazine and three times more potent than (,)-thioridazine, when considering the actual concentrations in the striatum. Thirdly, using a single enantiomer may reduce pharmacokinetic and pharmacodynamic variability between patients. For example, the coefficients of variation for some of methadone's pharmacokinetic parameters may reach 70%, which might have clinical consequences. Finally, using a single enantiomer may reduce toxicity arising from the therapeutically inactive stereoisomer. For example, the single enantiomers of bupivacaine and ropivacaine are significantly less cardiotoxic than their respective racemates. This review illustrates why stereochemistry should be considered when assessing the toxicology, pharmacokinetics, metabolism and efficacy of a racemate. Indeed, the differences may be so marked that achiral analyses may be misleading, and clinicians should consider prescribing an enantiomer whenever possible. In many cases, prescribing a single enantiomer improves the benefit:risk ratio. Finally, there is no reason to suppose that a racemate's characteristics will apply to the constituent enantiomers. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||