In VivoScreening Model for Excipients and Vehicles Used in Subcutaneous Injections

Abstract

Incorporation of an insoluble drug in Subcutaneous (SC) dosage form requires addition of a cosolvent. The use of a cosolvent may result in burning sensation and/or severe skin inflammation response after the injection. In this investigation the inflammation response of rat skin after SC administration of excipients and vehicles was demonstrated by a simple and effective in vivo technique. Four hours after SC injection, of each vehicle with or without excipients, the skin fold thickness of rat skin was measured. Among the oils tested, Planters' peanut oil showed a higher increase in skin fold thickness (25%). In the mean time, the SC injection of MCT Estasan GT 80 oil resulted in an insignificant increase (< 15%). A group of cosolvents prepared in sesame oil was tested in rats after SC injections. The magnitudes of the percentage increase in skin fold thickness of 10% benzyl alcohol, 10% ethyl oleate, 15% phospholipon 100, 4% ethyl alcohol, and 0.2% triethanolamine were 172, 45, 38, 31, and 31, respectively. The rest of excipients evaluated showed minor inflammation responses. Different concentrations of benzyl alcohol (1, 2, 5 and 10% v/v) in sesame oil were injected. Only the 1% benzyl alcohol produced an insignificant increase in skin fold thickness.