A formulation comparison between micro- and nanosuspensions: the importance of particle size for absorption of a model compound, following repeated oral administration to rats during early development

Drug Development and Industrial Pharmacy
Kalle SigfridssonAnders Lindahl

Abstract

The aim of this study was to maximize the exposure of a model compound (MC) for forthcoming high-dose toxicological studies with the physical form of the original compound unaffected. The two evaluated formulation approaches for the present poorly water-soluble compound were micro- and nanosuspensions. The particle size was about 280 nm for the nanosuspensions and about 4 μm for the microsuspensions. The crystallinity and the crystalline form of the ground samples were conserved. The physical and the chemical stabilities of the two kinds of suspensions were unaffected during the investigated time period. The in vivo results of the study showed that the pharmacokinetic parameters investigated were comparable at the low-dose level (6 μmol/kg) for both formulations after single administration. However, at the two higher doses (60 and 300 μmol/kg), a significant difference in exposure was observed between the two suspensions with an improved exposure for smaller particles. After Day 7 of repeated administration, a significant difference in exposure was observed at all dose levels. The overall exposures were higher on Day 7, compared to the exposures on Day 1 (most significant for nanoparticles), due to an accumulation of compound i...Continue Reading

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Citations

Dec 24, 2013·Colloids and Surfaces. B, Biointerfaces·Lihua CaoHongliang Jiang
Nov 19, 2011·Drug Development and Industrial Pharmacy·Cheng-Dong HouHong Zhao
Apr 6, 2013·Drug Development and Industrial Pharmacy·Kalle SigfridssonMarie Strimfors
Aug 20, 2011·Drug Development and Industrial Pharmacy·Weijia ZhengSudhakar Garad
Jun 29, 2011·Drug Development and Industrial Pharmacy·Kalle SigfridssonKristina Ohlson
Aug 31, 2013·Drug Development and Industrial Pharmacy·Jardin Leleux, Robert O Williams
Aug 21, 2012·Drug Development and Industrial Pharmacy·Deni RahmatAndreas Bernkop Schnürch
Dec 18, 2012·Drug Development and Industrial Pharmacy·Kalle SigfridssonMarie Strimfors
Aug 8, 2014·Journal of Pharmaceutical Sciences·William Wei Lim ChinRajeev Gokhale
Jan 23, 2016·Advances in Colloid and Interface Science·Waseem Kaialy, Maen Al Shafiee
Sep 25, 2012·International Journal of Pharmaceutics·Jan P Möschwitzer
Apr 3, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lei GaoXiang Li
Feb 11, 2015·Clinical Pharmacokinetics·Kamla Pathak, Smita Raghuvanshi
Feb 7, 2013·Pharmacological Reviews·Hywel D WilliamsChristopher J H Porter
Aug 9, 2017·ACS Applied Materials & Interfaces·Rudolf KupcikJan M Macak

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