International Journal of Pharmaceutics 230 (2001) 67 – 75 Determination of the disappearance rate of iodine-125 labelled oils from the injection site after intramuscular and subcutaneous administration to pigs Susan Weng Larsen a, *, Elise Rinvar a , Ove Svendsen b , Jens Lykkesfeldt b , Gitte Juel Friis a , Claus Larsen a a Department of Analytical and Pharmaceutical Chemistry, The Royal Danish School of Pharmacy, Uniersitetsparken 2, DK-2100, Copenhagen, Denmark b Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural Uniersity, Ridebaneej, DK-1870, Frederiksberg, Denmark Received 4 June 2001; received in revised form 17 August 2001; accepted 21 August 2001 Abstract The rate of disappearance of clinically used vegetable oils, Viscoleo, sesame oil, castor oil and isopropyl myristate, from the injection site after intramuscular (i.m.) or subcutaneous (s.c.) administration to pigs were determined by using a non-invasive gamma-scintigraphy method. All the oil vehicles were spiked with 2.5% (v/v) 125 I-triolein and six injections of 1.9 ml were given to each of 12 pigs. No significant difference (ANOVA) in disappearance rate of each individual oil vehicle from the different injection sites was observed after administration of the oils: i.m. in the lower back, s.c. in the neck and s.c. in the mid-back. Likewise, no inter-individual difference between the pigs was observed. The half-life of 14 days for Viscoleo was significantly smaller than those of the other oil vehicles (P 0.0001), i.e. 23, 20, 20 days for sesame oil, castor oil and isopropyl myristate, respectively. Due to the spreading effect of the oils and reflux of the oils through the injection canal, the half-lives were calculated omitting the data for the first sampling day. © 2001 Elsevier Science B.V. All rights reserved. Keywords: Parenteral depots; Disapperance rates; Pig; I.m administration; S.c. administration; Gamma-scintigraphy www.elsevier.com/locate/ijpharm 1. Introduction Many long-acting injectables are formulated in the form of lipophilic prodrugs dissolved in oil vehicles. The drug release rate has been suggested to be controlled by the partition coefficient of drug between the oil vehicle and the tissue fluid (Chien, 1981; Hirano et al., 1982). However, recently we have suggested that for highly lipophilic compounds, the duration of ac- tion may not solely be explained by drug parti- tioning into the tissue fluid (Larsen et al., 2001a). To this end, several mechanisms may contribute to the absorption of a drug substance from an oil * Corresponding author. Tel.: +45-3530-6198; fax: +45- 3530-6010. E-mail address: swe@dfh.dk (S.W. Larsen). 0378-5173/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved. PII:S0378-5173(01)00860-2