TY - JOUR

T1 - In vitro release studies of insulin from lipid implants in solution and in a hydrogel matrix mimicking the subcutis

AU - Jensen, Sabrine S

AU - Jensen, Henrik

AU - Møller, Eva H

AU - Cornett, Claus

AU - Siepmann, Florence

AU - Siepmann, Jürgen

AU - Østergaard, Jesper

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Widely accepted in vitro methodologies for sustained release parenteral drug formulations remain to be established. Hydrogels have been proposed as a release matrix more closely resembling the in vivo conditions for formulations intended for subcutaneous administration. The perspective of the current work was to investigate the feasibility of developing UV imaging-based in vitro methods enabling visualization and characterization of drug release and transport of protein therapeutics intended for subcutaneous administration. Specifically, the objectives were to prepare lipid implants providing sustained release of the model protein insulin and investigate the release into 0.5% (w/v) agarose hydrogels, pH7.40, using UV imaging- and a gel sampling-based release testing method. These results were compared to insulin release into well agitated buffer solution. Irrespective of the applied in vitro release method, the insulin release from Sterotex implants with a drug load of 20% (w/w) was faster as compared to the release from implants with a load of 10% (w/w), most likely due to the higher porosity of the implants with increasing drug load. Insulin release from 10% (w/w) implants into agitated solution was faster as compared to release into agarose hydrogel. This was ascribed to the additional mass transfer resistance provided by the agarose hydrogel. Interestingly, the release profiles of insulin from implants with an initial drug load of 20% (w/w) obtained by the three in vitro methods were relatively similar. The gel-based methods, in particular UV imaging, enable monitoring local drug concentrations in the vicinity of the implant over time thereby facilitating assessment of, e.g., sink conditions. The study highlights that the selection of the in vitro release method should take into account various factors including mass transport, drug stability, data analysis and simplicity of the methodology.

AB - Widely accepted in vitro methodologies for sustained release parenteral drug formulations remain to be established. Hydrogels have been proposed as a release matrix more closely resembling the in vivo conditions for formulations intended for subcutaneous administration. The perspective of the current work was to investigate the feasibility of developing UV imaging-based in vitro methods enabling visualization and characterization of drug release and transport of protein therapeutics intended for subcutaneous administration. Specifically, the objectives were to prepare lipid implants providing sustained release of the model protein insulin and investigate the release into 0.5% (w/v) agarose hydrogels, pH7.40, using UV imaging- and a gel sampling-based release testing method. These results were compared to insulin release into well agitated buffer solution. Irrespective of the applied in vitro release method, the insulin release from Sterotex implants with a drug load of 20% (w/w) was faster as compared to the release from implants with a load of 10% (w/w), most likely due to the higher porosity of the implants with increasing drug load. Insulin release from 10% (w/w) implants into agitated solution was faster as compared to release into agarose hydrogel. This was ascribed to the additional mass transfer resistance provided by the agarose hydrogel. Interestingly, the release profiles of insulin from implants with an initial drug load of 20% (w/w) obtained by the three in vitro methods were relatively similar. The gel-based methods, in particular UV imaging, enable monitoring local drug concentrations in the vicinity of the implant over time thereby facilitating assessment of, e.g., sink conditions. The study highlights that the selection of the in vitro release method should take into account various factors including mass transport, drug stability, data analysis and simplicity of the methodology.

KW - Delayed-Action Preparations

KW - Drug Implants

KW - Drug Liberation

KW - Hydrogels

KW - Hydrogen-Ion Concentration

KW - Insulin

KW - Lipids

KW - Models, Theoretical

KW - Solutions

KW - Subcutaneous Tissue

KW - Journal Article

U2 - 10.1016/j.ejps.2015.10.011

DO - 10.1016/j.ejps.2015.10.011

M3 - Journal article

C2 - 26478185

VL - 81

SP - 103

EP - 112

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

ER -