Oral lipid-based formulations.

Poor drug solubility remains a significant and frequently encountered problem for pharmaceutical scientists. The ability of lipid-based formulations to facilitate gastrointestinal absorption of many poorly soluble drug candidates has been thoroughly documented in the published literature. However, a considerable gap exists between our knowledge of this technology and the know-how required for its application. This commentary provides a comprehensive summary of the development, characterization, and utilization of oral lipid-based formulations, from both physicochemical and biopharmaceutical perspectives. The characteristics of currently available lipid excipients are reviewed in context of their application to the basic lipid-based formulation modalities. The fundamental concepts of in vitro and in vivo evaluation of lipid-based formulations are summarized followed by a forward-looking summary of unrealized opportunities and potential limitations to more widespread use of this technology.

Chronic Collection of Mesenteric Lymph From Conscious, Tethered Rats.

Previously reported methods for collecting lymph from the rat require total restraint of the animal and fluid replacement, by intravenous or intraduodenal infusion, to maintain lymph output. We developed a rat model to allow collection of mesenteric lymph for several days from conscious, minimally restrained animals. This model obviates the need for total restraint or general anesthesia, both of which are known to influence intestinal lymphatic transport of test compounds in unpredictable ways. Animals are provided free access to an electrolyte solution, which they consume in sufficient quantity to maintain excellent lymph output without the need for the previously required infusions for fluid replacement. Intestinal lymph flow rate during the first 24 hours after surgery averaged 2.23 (61.01) mL/hr, increasing to 4.89 (61.64) mL/hr thereafter. This flow rate is considerably greater than that previously described for methods requiring anesthesia or restraint of the animals. Using our model, we have successfully maintained lymph collection from cannulated rats for up to 5 days, with fully patent cannulae and no gross signs of physical distress.