Stability of Extemporaneous Oral Tramadol, Fluoxetine, and Doxycycline Suspensions in SyrSpend SF pH4.

Extemporaneous compounding in veterinary practice sometimes represents the only possibility for treating animals in the absence of appropriate commercial formulations, especially for particular species. This method involves manipulating pharmaceutical active ingredients to a suitable dosage and formulation for administration to humans or animals. However, veterinarians and pharmacists should focus on the risk of potential incompatibilities and instability of their preparations. To help practitioners in drug compounding, we investigated the stability of oral suspensions of tramadol, fluoxetine, and doxycycline in a commercial ready-to-use vehicle (SyrSpend). A validated high-performance liquid chromatography method was developed to assay these active pharmaceutical ingredients. The oral suspensions were prepared at two concentration ranges and were stored in amber glass bottles under refrigerated conditions and at room temperature. After 90 days, the average recovery rates were between 90% and 110% for tramadol (5 mg/mL to 30 mg/mL) and doxycycline  (2 mg/mL to 10 mg/mL) without organoleptic modification. For fluoxetine, only the formulation at 2 mg/mL was stable; at higher concentrations, the uniformity of the suspension was compromised.

ABCC1, ABCC2 and ABCC3 are implicated in the transepithelial transport of the myco-estrogen zearalenone and its major metabolites.

The myco-estrogene zearalenone (ZEA) is a worldwide cereal contaminant, implicated in reproductive disorders in animals and humans. Intestinal cells constitute a first barrier to mycotoxins exposure, since they express membrane ABC transporters that may affect the bioavailability of food xenobiotics. In this study, we investigated the mechanisms involved in the transepithelial transfer of ZEA and its major metabolites alpha- and beta-zearalenols (ZOLs), first using human intestinal Caco-2 cells. When exposed to ZEA, alpha-ZOL or beta-ZOL either in the apical (AP) or basolateral (BL) compartment, cells showed asymmetry in the AP-BL and BL-AP transfer of mycotoxins. Metabolic inhibitors increased ZEA, alpha-ZOL and beta-ZOL intracellular accumulation. Caco-2 cells apically exposed to ZEA produced metabolites (ZOLs and glucuronides) whose distribution between AP, BL and intracellular compartments was significantly modified by ABCCs inhibitor MK571. ABCB1-, ABCC1-, ABCC2 and ABCC3-transfected cells were used for studies of intracellular accumulation of ZEA, alpha-ZOL and beta-ZOL with or without specific inhibitors, and for competitive studies using fluorescent substrates. The results showed that ZEA, alpha-ZOL and beta-ZOL were substrates for ABCC2. ABCC1 was also involved in ZEA and alpha-ZOL transport, whereas ABCC3 only interacted with beta-ZOL. These specific interactions suggest a role for ABCC1-3 transport proteins in zearalenone exposure and its resulting risk for human health.