Absorption and tissue tolerance of ricobendazole in the presence of hydroxypropyl-beta-cyclodextrin following subcutaneous injection in sheep

International Journal of Pharmaceutics
Zimei WuNatalie J Medlicott

Abstract

Post-injection precipitation may cause poor and erratic drug absorption and tissue irritation at the injection site. Tissue tolerance and pharmacokinetics of a low pH ricobendazole (RBZ) injectable containing 20% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were simultaneously investigated after subcutaneous injection in sheep compared to a reference formulation without HP-beta-CD. Each animal received a RBZ containing formulation on one side of the back and the respective vehicle on the contralateral side. The HP-beta-CD vehicle showed good tissue tolerance and the acidic solution caused minimal injection site reactions. Both RBZ containing formulations caused pain on injection and tissue histological changes in some animals. Lack of elevation of plasma creatine kinase indicated that none of the formulations caused significant damage to the underlying muscle tissue. Compared to the reference formulation, AUC and C(max) of the HP-beta-CD formulation were 1.6 and 2.2 times higher, respectively, whereas t(max), MRT and t(1/2) were significantly shorter suggesting faster and greater absorption of RBZ in the presence of HP-beta-CD. This was attributed to the effect of inhibition of post-injection drug precipitation and drug absorpt...Continue Reading

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Citations

May 18, 2013·International Journal of Pharmaceutics·Sen Xu, Wei-Guo Dai
Feb 24, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wenli ZhangZimei Wu
Apr 28, 2016·International Journal for Parasitology. Drugs and Drug Resistance·L CeballosC Lanusse
Aug 18, 2018·Biomedical Chromatography : BMC·Miao WangChunjie Zhao
Apr 23, 2020·Pharmaceutics·Heejun ParkMin-Soo Kim
May 31, 2018·AAPS PharmSciTech·Daniel RealClaudio J Salomon

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