Drug development and industrial pharmacy
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The purpose of this study was to investigate the degradation kinetics of teniposide in lipid emulsion and aqueous solution. The chemical stability of teniposide in lipid emulsion and aqueous solution at various pH values and temperatures was monitored by high-performance liquid chromatography. In addition, the viscosities of emulsion at different temperatures were investigated. ⋯ Furthermore, there was a difference between the shelf life of TLE actually measured (29 days) at 10 degrees C and the one deduced (15 days) from the degradation data of high temperatures by Arrhenius equation. It could be hypothesized that the difference was due to a slower diffusion of teniposide from oil phase to aqueous phase at the lower temperatures, which would be a speed-limited process in the degradation of TLE. The results of viscosity test confirmed the presumption.
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Review
Advanced formulation design: improving drug therapies for the management of severe and chronic pain.
Chronic pain is a condition affecting a vast patient population and resulting in billions of dollars in associated health care costs annually. Sufferers from severe chronic pain often require [correction of requite] twenty-four hour drug treatment through intrusive means and/or repeated oral dosing. Although the oral route of administration is most preferred, conventional immediate release oral dosage forms lead to inconvenient and suboptimal drug therapies for the treatment of chronic pain. ⋯ Ideally, these advanced delivery systems provide efficacious pain therapy with minimal side effects via a simple and convenient dosing regime. In this article, currently commercialized and developing drug products for pain management are reviewed with respect to dosage form design as well as clinical efficacy. The drug delivery systems reviewed herein represent advanced formulation designs that are substantially improving analgesic drug therapies.
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This contribution focused on the solubility improvement of the poorly water-soluble steroid hormone progesterone which, in its natural state, presents a reduced oral bioavailability. In the first part of this study, two simple, reproducible methods that were candidates for use in the preparation of inclusion complexes with cyclodextrins were investigated. Solubility capacities of the progesterone complex with hydroxypropyl-beta-CD (HPbeta-CD), hydoxypropyl-gamma-CD (HPgamma-CD), permethyl-beta-CD (PMbeta-CD), and sulfobutylether-beta-CD (SBEbeta-CD), prepared by the freeze-drying and precipitation methods, were evaluated by Higuchi phase solubility studies. ⋯ The interaction of progesterone with the cyclodextrins of interest on the form of the binary physical mixtures, complexes, or ternary complexes were investigated by differential scanning calorimetry (DSC) and Fourier transformed-infrared spectroscopy (FT-IR). The results proved that progesterone was diffused into the cyclodextrin cavity, replacing the water molecules and, in case of ternary systems, that the progesterone beta-cyclodextrin was well dispersed into PEG, thus improving progesterone bioavailability for subsequent oral delivery in the same way as derivatized cyclodextrins. The present work proves that ternary complexes are promising systems for drug encapsulation.
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Comparative Study
Inclusion complexation of lorazepam with different cyclodextrins suitable for parenteral use.
The development of a parenteral lorazepam formulation, using cyclodextrins (CDs) as inclusion complexation agents, was investigated. CDs suitable for parenteral injection, i.e., hydroxypropyl-beta-cyclodextrin (HP-beta-CD), hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), sulfobutylether-7-beta-cyclodextrin (SBE-7-beta-CD), and maltosyl-beta-cyclodextrin (malt-beta-CD) were studied for the possibility to increase the solubility of lorazepam. Lorazepam interacted with all tested CD derivatives and 1:1 complexes are formed. ⋯ The stability of the preparations was investigated in aqueous medium. During the first month, in all solutions more than 90% of lorazepam remained; after 3 months, less than 60% of lorazepam remained in the solutions with 15% (w/v) HP-beta-CD and around 65-70% in the solutions with 30% (w/v) of CDs. Because of this short stability time, the preparations need to be lyophilized.
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Loperamide is a peripherally acting antidiarrheal opioid with some affinity for P-glycoprotein (P-gp). One of the main reasons for its lack of central nervous system (CNS) activity is a combination first-pass metabolism and P-gp-mediated efflux preventing brain penetration. It was assumed that P-gp would also have a similar effect at the intestinal tract, limiting loperamide systemic absorption. However, previous in vitro studies had not determined loperamide flux using pH gradients present in the intestinal tract. Hence, our aim was to determine the influence of pH gradient conditions on the gastrointestinal uptake of loperamide, including any changes to its P-gp-mediated efflux. ⋯ P-gp-mediated efflux of loperamide is supplemented under pH gradient conditions. Hence, drugs used to decrease acid secretion in the stomach could result in higher plasma loperamide levels based on our in vitro system reflecting the in vivo environment. The addition of a P-gp inhibitor could potentially further increase the gastrointestinal absorption of loperamide.