188,889 research outputs found
Accelerated polymer biodegradation of risperidone poly(D, L-lactide-co-glycolide) microspheres
No full textThe influence of a tertiary amine, namely risperidone (pKa = 7.9) on the degradation of poly(D, L lactide-co-glycolide) (PLGA) microspheres was elucidated. Risperidone and blank microspheres were fabricated at two lactide/glycolide ratios, 65:35 and 85:15. The microspheres were characterized for drug loading by high-performance liquid chromatography, particle size by laser diffractometry, and surface morphology by scanning electron microscopy. Polymer degradation studies were carried out with drug-loaded microspheres and blank microspheres in presence of free risperidone in 0.02 M PBS containing 0.02% Tween®80 at 37°C. Molecular weight was monitored by gel permeation chromatography. Risperidone and blank microspheres had similar size distribution and were spherical with a relatively nonporous smooth surface. The presence of risperidone within the microspheres enhanced the hydrolytic degradation in both polymeric matrices with faster degradation occurring in 65:35 PLGA. The molecular weight decreased according to pseudo-first-order kinetics for all the formulations. During the degradation study, the surface morphology of drug-loaded microspheres was affected by the presence of risperidone and resulted in shriveled microspheres in which there appeared to be an intrabatch variation with the larger microspheres being less shriveled than the smaller ones. When blank microspheres were incubated in free risperidone solutions, a concentration-dependent effect on the development of surface porosity could be observed. Risperidone accelerates the hydrolytic degradation of PLGA, presumably within the microenvironment of the drug-loaded particles, and this phenomenon must be taken into consideration in designing PLGA dosage forms of tertiary amine drugs
Accelerated polymer biodegradation of risperidone poly(d, l-lactide-co-glycolide) microspheres
No full textThe influence of a tertiary amine, namely risperidone (pKa=7.9) on the degradation of poly(D, L lactide-co-glycolide) (PLGA) microspheres was elucidated. Risperidone and blank microspheres were fabricated at two lactide/glycolide ratios, 65:35 and 85:15. The microspheres were characterized for drug loading by high-performance liquid chromatography, particle size by laser diffractometry, and surface morphology by scanning electron microscopy. Polymer degradation studies were carried out with drug-loaded microspheres and blank microspheres in presence of free risperidone in 0.02 M PBS containing 0.02% Tween (R) 80 at 37 degrees C. Molecular weight was monitored by gel permeation chromatography. Risperidone and blank microspheres had similar size distribution and were spherical with a relatively nonporous smooth surface. The presence of risperidone within the microspheres enhanced the hydrolytic degradation in both polymeric matrices with faster degradation occurring in 65:35 PLGA. The molecular weight decreased according to pseudo-first-order kinetics for all the formulations. During the degradation study, the surface morphology of drug-loaded microspheres was affected by the presence of risperidone and resulted in shriveled microspheres in which there appeared to be an intrabatch variation with the larger microspheres being less shriveled than the smaller ones. When blank microspheres were incubated in free risperidone solutions, a concentration-dependent effect on the development of surface porosity could be observed. Risperidone accelerates the hydrolytic degradation of PLGA, presumably within the microenvironment of the drug-loaded particles, and this phenomenon must be taken into consideration in designing PLGA dosage forms of tertiary amine drugs
Effect of agitation regimen on the in vitro release of leuprolide from poly(lactic-co-glycolic) acid microparticles
No full textBecause of the importance of in vitro release tests in establishing batch-to-batch reproducibility and in vitroin vivo correlation, this study investigated the influence of agitation regimen on the in vitro release behavior of leuprolide from poly(lactic-co-glycolic) acid microparticles. Leuprolide-loaded microspheres were prepared using Resomer (R) RG502H and RG503H as polymers. Leuprolide in vitro release was performed in phosphate buffer solution under continuous or once-a-week agitation. At predetermined intervals, leuprolide release, polymer mass loss, and degree of hydration were investigated. Leuprolide release and polymer mass loss were higher under continuous agitation with respect to that under intermittent agitation. Using a modified version of Koizumi equation, it was possible to fit leuprolide release profiles. Similarity factor comparison showed a high level of similarity between experimental and modeled data in the case of once-a-week agitation regimen. This work highlights the importance of the in vitro release conditions on peptide release behavior from polyester microparticles. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:12121220, 201
Limb ataxia and proximal intracranial territory brain infarcts: clinical and topographical correlations
No full textBACKGROUND: Limb ataxia is classically attributed to cerebellar hemispheric lesions, although isolated lesions of the inferior cerebellar peduncle (ICP) in the medulla may also cause this sign. It is still unclear why only some patients with acute cerebellar infarcts in the posterior inferior cerebellar artery (PICA) territory present with limb ataxia. The proximal intracranial posterior circulation (P-PC) territory includes structures fed by the intracranial vertebral arteries (ICVAs): the medulla, supplied by small ICVAs branches, and posterior inferior portion of the cerebellum, fed by PICA. ICP and PICA territory cerebellar infarcts most often occur independently but occasionally occur together. OBJECTIVE: To identify structures responsible for limb ataxia in acute P-PC brain infarcts, correlating clinical and topographical findings. METHODS: Sixteen patients (8 women) were included, aged 30-82 years (mean 62 years), with isolated acute strokes in the P-PC territory. RESULTS: The cases reported here indicate that limb ataxia in acute P-PC territory infarcts may be associated with damage to the ICP in the dorsolateral medulla, regardless of a hemispheric cerebellar lesion. In fact, among the nine patients with PICA stroke, limb ataxia was observed only in the two patients who also presented damage to the dorsolateral medulla involving the ICP. Of the seven patients with isolated dorsolateral medullary infarct, only five patients with ICP damage had limb ataxia. CONCLUSIONS: When correlating limb ataxia and acute P-PC infarcts, it is important to take into account the entire ICVA territory
Effect of Hydration on Physicochemical Properties of End-Capped PLGA
No full textThe objective of this study was to assess the physicochemical effects of hydrating a hydrophobic end-capped poly(lactide-coglycolide)(PLGA)polymerintheliquidandvaporstate.PLGARG503polymerwasincubatedat37∘Cin0.5%polyvinylalcohol (PVA)solutionandat90%RH.Sampleswerewithdrawnatpredeterminedintervalsandchangestopolymerpropertieslikeglass transition temperature (Tg), moisture uptake, molecular weight change, and % acid number were determined using differential scanningcalorimetry,KarlFishertitrimetry,gelpermeationchromatography,andacidbasetitrimetry,respectively.Studyresults showed that Tg was depressed instantaneously upon hydration, indicating that bulk water acted as a plasticizer of hydrophobic end-cappedPLGA.Tg valuesdecreasedtolevelsbelowtheincubationtemperaturewhenhydratedin0.5%PVAsolutionbutnotin 90%RH.ThedropinTg exhibitedalinearrelationship(2 > 0.99)totheamountofwateruptakebythepolymer;highermoisture uptakewasnotedwithliquidwater.RemovalofmoisturefromthepolymermatrixresultedinrecoveryofTg,onlyuptoaperiod of14days.Presenceofwaterinliquidorvaporformcausedareductioninmolecularweightofthepolymerandacorresponding increasein%acidnumberoverthedurationofthestudy
Effect of agitation regimen on the in vitro release of leuprolide from poly(lactic-co-glycolic) acid microparticles
No full textBecause of the importance of in vitro release tests in establishing batch-to-batch reproducibility and in vitro-in vivo correlation, this study investigated the influence of agitation regimen on the in vitro release behavior of leuprolide from poly(lactic-co-glycolic) acid microparticles. Leuprolide-loaded microspheres were prepared using Resomer(®) RG502H and RG503H as polymers. Leuprolide in vitro release was performed in phosphate buffer solution under continuous or once-a-week agitation. At predetermined intervals, leuprolide release, polymer mass loss, and degree of hydration were investigated. Leuprolide release and polymer mass loss were higher under continuous agitation with respect to that under intermittent agitation. Using a modified version of Koizumi equation, it was possible to fit leuprolide release profiles. Similarity factor comparison showed a high level of similarity between experimental and modeled data in the case of once-a-week agitation regimen. This work highlights the importance of the in vitro release conditions on peptide release behavior from polyester microparticles
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