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1.
Eur J Pharm Biopharm ; 163: 158-170, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33848628

RESUMO

The purpose of this work was to evaluate solid lipid nanoparticles (SLNs) as a long acting injectable drug delivery platform for intramuscular and subcutaneous administration. SLNs were developed with a low (unsaturated) and high (supersaturated) drug concentration at equivalent lipid doses. The impact of the drug loading as well as the administration route for the SLNs using two model compounds with different physicochemical properties were explored for their in vitro and in vivo performance. Results revealed that drug concentration had an influence on the particle size and entrapment efficiency of the SLNs and, therefore, indirectly an influence on the Cmax/dose and AUC/dose after administration to rats. Furthermore, the in vitro drug release was compound specific, and linked to the affinity of the drug compounds towards the lipid matrix and release medium. The pharmacokinetic parameters resulted in an increased tmax, t1/2 and mean residence time (MRT) for all formulations after intramuscular and subcutaneous dosing, when compared to intravenous administration. Whereas, the subcutaneous injections performed better for those parameters than the intramuscular injections, because of the higher blood perfusion in the muscles compared with the subcutaneous tissues. In conclusion, SLNs extend drug release, need to be optimized for each drug, and are appropriate carriers for the delivery of drugs that require a short-term sustained release in a timely manner.

2.
Bioanalysis ; 6(3): 293-306, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24471951

RESUMO

BACKGROUND: Capillary microsampling (CMS) of blood with subsequent blood analysis offers a potential strategy to deal with increased demand to reduce blood sample volumes in animal discovery and preclinical studies. RESULTS: A generic approach is presented allowing PK analysis in 15 µl blood samples. CMS blood exposure data were compared with the traditional plasma exposure results in rats and dogs. Blood PK profiles obtained for two different compounds were in agreement with profiles obtained in plasma. From these studies ex vivo blood to plasma ratios were also obtained. In a mouse study, blood PK profiles that were obtained following automatic sampling overlay with the blood PK profiles obtained with CMS. CONCLUSION: CMS in 15 µl glass capillaries allows collection and handling of small and exact volumes of blood. Although CMS can also be applied for plasma collection, the full benefit is only achieved with blood collection and analysis.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Animais , Coleta de Amostras Sanguíneas/instrumentação , Calibragem , Cães , Camundongos , Controle de Qualidade , Ratos
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