TY - JOUR
T1 - In vitro release from oil injectabels for intra-articular administration
T2 - importance of interfacial area, diffusivity and partitioning
AU - Thing, Mette Agergaard
AU - Larsen, Claus Selch
AU - Østergaard, Jesper
AU - Jensen, Henrik
AU - Larsen, Susan Weng
PY - 2012/2/14
Y1 - 2012/2/14
N2 - Most in vitro methods for evaluating parenteral oil based depots are focusing on intramuscular or subcutaneous injection. For intra-articular injection other mechanisms may control the overall drug release rate due to a relatively smaller interfacial area and longer transport distance of the drug substance in the oil to the oil-synovial fluid interface. In the current work, an in vitro model for testing drug release from oil solutions intended for intra-articular injection was evaluated. The release of the model drugs naproxen, piroxicam and ropivaciane from a well-defined surface area of the lipophilic solutions were followed using an in vitro model based on a modified USP II paddle apparatus with modest agitation (50 rpm) of the oil formulation. By alteration of the viscosity of the oil, the oil-water interfacial area, the oil volume and the stirring efficiency of the release medium, it was shown that the drug release rate was dependent on the drug diffusivity in the oil and the degree of agitation generated in the oil vehicle. In addition, the partitioning of the drug between the oil vehicle and the release media was found to influence the release rate. In combination with an improved understanding of in vivo drug release and distribution, the present work may form a promising foundation for future in vivo in vitro correlations.
AB - Most in vitro methods for evaluating parenteral oil based depots are focusing on intramuscular or subcutaneous injection. For intra-articular injection other mechanisms may control the overall drug release rate due to a relatively smaller interfacial area and longer transport distance of the drug substance in the oil to the oil-synovial fluid interface. In the current work, an in vitro model for testing drug release from oil solutions intended for intra-articular injection was evaluated. The release of the model drugs naproxen, piroxicam and ropivaciane from a well-defined surface area of the lipophilic solutions were followed using an in vitro model based on a modified USP II paddle apparatus with modest agitation (50 rpm) of the oil formulation. By alteration of the viscosity of the oil, the oil-water interfacial area, the oil volume and the stirring efficiency of the release medium, it was shown that the drug release rate was dependent on the drug diffusivity in the oil and the degree of agitation generated in the oil vehicle. In addition, the partitioning of the drug between the oil vehicle and the release media was found to influence the release rate. In combination with an improved understanding of in vivo drug release and distribution, the present work may form a promising foundation for future in vivo in vitro correlations.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1016/j.ejps.2011.12.006
DO - 10.1016/j.ejps.2011.12.006
M3 - Journal article
C2 - 22178293
SN - 0928-0987
VL - 45
SP - 351
EP - 357
JO - Norvegica Pharmaceutica Acta
JF - Norvegica Pharmaceutica Acta
IS - 3
ER -