<Emphasis Type="Italic">In Vivo</Emphasis> Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen |
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Authors: | Pawel Stasiak Malgorzata Sznitowska Carsten Ehrhardt Maria Luczyk-Juzwa Pawel Grieb |
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Institution: | (1) Department of Pharmaceutical Technology, Medical University of Gdansk, ul. Hallera 107, 80-416 Gdansk, Poland;(2) School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland;(3) Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Zabrze, Poland;(4) Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland; |
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Abstract: | Polymer-drug conjugates have gained significant attention as pro-drugs releasing an active substance as a result of enzymatic
hydrolysis in physiological environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a carboxylic acid
group-bearing model drug (ibuprofen) was evaluated in vivo as a potential pro-drug for parenteral administration. Two different formulations, an oily solution and an o/w emulsion were
prepared and administered intramuscularly (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The concentration
of ibuprofen in blood plasma was analysed by HPLC, following solid–phase extraction and using indometacin as internal standard
(detection limit, 0.05 μg/ml). No significant differences in the pharmacokinetic parameters (C
max, T
max, AUC) were observed between the two tested formulations of the 3-hydroxybutyric acid conjugate. In comparison to the non-conjugated
drug in oily solution, the relative bioavailability of ibuprofen conjugates from oily solution, and o/w emulsion was reduced
to 17% and 10%, respectively. The 3-hydroxybutyric acid formulations released the active substance over a significantly extended
period of time with ibuprofen still being detectable 24 h post-injection, whereas the free compound was almost completely
eliminated as early as 6 h after administration. The conjugates remained in a muscle tissue for a prolonged time and can hence
be considered as sustained release systems for carboxylic acid derivatives. |
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Keywords: | |
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