PLGA microparticles with zero-order release of the labile anti-Parkinson drug apomorphine.
Identifieur interne : 000736 ( PubMed/Curation ); précédent : 000735; suivant : 000737PLGA microparticles with zero-order release of the labile anti-Parkinson drug apomorphine.
Auteurs : C. Regnier-Delplace [France] ; O. Thillaye Du Boullay ; F. Siepmann ; B. Martin-Vaca ; N. Degrave ; P. Demonchaux ; O. Jentzer ; D. Bourissou ; J. SiepmannSource :
- International journal of pharmaceutics [ 1873-3476 ] ; 2013.
English descriptors
- KwdEn :
- Antiparkinson Agents (administration & dosage), Antiparkinson Agents (chemistry), Apomorphine (administration & dosage), Apomorphine (chemistry), Calorimetry, Differential Scanning, Drug Carriers (chemistry), Drug Compounding, Drug Stability, Freeze Drying, Hydrogen-Ion Concentration, Lactic Acid (chemistry), Microscopy, Electron, Scanning, Particle Size, Polyglycolic Acid (chemistry), Solubility, Surface Properties, X-Ray Diffraction.
- MESH :
- chemical , administration & dosage : Antiparkinson Agents, Apomorphine.
- chemical , chemistry : Antiparkinson Agents, Apomorphine, Drug Carriers, Lactic Acid, Polyglycolic Acid.
- Calorimetry, Differential Scanning, Drug Compounding, Drug Stability, Freeze Drying, Hydrogen-Ion Concentration, Microscopy, Electron, Scanning, Particle Size, Solubility, Surface Properties, X-Ray Diffraction.
Abstract
The treatment of patients suffering from advanced Parkinson's disease is highly challenging, because the efficacy of the "gold standard" levodopa declines with time. Co-administration of the dopamine receptor agonist apomorphine is beneficial, but difficult due to the poor oral bioavailability and short half-life of this drug. In order to overcome these restrictions, PLGA-based microparticles allowing for controlled parenteral delivery of this morphine derivative were prepared using (solid-in-)oil-in-water extraction/evaporation techniques. Particular attention was paid to minimize spontaneous oxidation of the labile drug and to optimize the key features of the microparticles, including encapsulation efficiency, initial burst release and particle size. Various formulation and processing parameters were adjusted in this respect. The systems were thoroughly characterized using SEM, EDX, DSC, laser diffraction, headspace-GC as well as in vitro drug release measurements in agitated flasks and flow-through cells. Importantly, apomorphine could effectively be protected against degradation during microparticle preparation and within the delivery systems upon exposure to phosphate buffer pH 7.4 (containing 0.2% ascorbic acid) at 37 °C: 90% intact drug was released at a constant rate during about 10d.
DOI: 10.1016/j.ijpharm.2013.01.008
PubMed: 23313920
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pubmed:23313920Le document en format XML
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<term>Calorimetry, Differential Scanning</term>
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<term>Lactic Acid (chemistry)</term>
<term>Microscopy, Electron, Scanning</term>
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<term>Hydrogen-Ion Concentration</term>
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<front><div type="abstract" xml:lang="en">The treatment of patients suffering from advanced Parkinson's disease is highly challenging, because the efficacy of the "gold standard" levodopa declines with time. Co-administration of the dopamine receptor agonist apomorphine is beneficial, but difficult due to the poor oral bioavailability and short half-life of this drug. In order to overcome these restrictions, PLGA-based microparticles allowing for controlled parenteral delivery of this morphine derivative were prepared using (solid-in-)oil-in-water extraction/evaporation techniques. Particular attention was paid to minimize spontaneous oxidation of the labile drug and to optimize the key features of the microparticles, including encapsulation efficiency, initial burst release and particle size. Various formulation and processing parameters were adjusted in this respect. The systems were thoroughly characterized using SEM, EDX, DSC, laser diffraction, headspace-GC as well as in vitro drug release measurements in agitated flasks and flow-through cells. Importantly, apomorphine could effectively be protected against degradation during microparticle preparation and within the delivery systems upon exposure to phosphate buffer pH 7.4 (containing 0.2% ascorbic acid) at 37 °C: 90% intact drug was released at a constant rate during about 10d.</div>
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