Methods and formulations for enhansing the absorption and gastro-intestinal bioavailability of hydrophobic drugs - Patents

Methods and formulations for enhansing the absorption and gastro-intestinal bioavailability of hydrophobic drugs
Agent: Mckee, Voorhees & Sease, P.L.C - Des Moines, IA, US
Inventor: Curtis A. Spilburg
Class: 424450000 (USPTO), A61K009/127 (Intl Class)
#20050244488
11/03/05
A hydrophobic drug delivery system that includes a plant derived sterol (stanol), lecithin or a sterol (stanol) derived ester, and an active, hydrophobic drug, all dissolved and then dried to form a liposome delivery system.
FIELD OF THE INVENTION
[0002] This invention relates to a general method for enhancing the bioavailability of hydrophobic drug active compounds, using naturally-occurring formulation ingredients that are present in the diet as a food grade emulsifier. Specifically, this invention is especially useful as a general formulation method for the delivery of drugs in dry form that heretofore have produced variable pharmacological responses, which are indicative of poor bioavailability.
SUMMARY OF THE INVENTION
[0014] A general method and delivery composition is provided for enhancing the bioavailability of hydrophobic, poorly water soluble compounds and drugs, using the following steps and materials:
[0015] (a) An amphiphile, such as lecithin or one of its derivatives, a sterol (preferably a plant-derived sterol and most preferably a reduced plant-derived sterol) and a selected drug are mixed in a non-polar solvent (preferably ethyl acetate or heptane) at its boiling point;
[0016] (b) a solid residue is collected after the solvent is driven off at elevated temperature to maintain the solubility of all the components;
[0017] (c) the solid residue is broken into small pieces and dispersed with vigorous stirring in water to form a milky solution at a temperature that is less than the decomposition temperature of any one of the components or the boiling point of water, whichever is lower;
[0018] (d) the milky solution is passed through a homogenizer, such as a Gaulin Dairy Homogenizer (or suitable equivalent) operating at maximum pressure; and thereafter
[0019] (e) a suitable drying aid is added (e.g. Maltrin, Capsule M or suitable equivalent and then the milky solution is spray dried or lyophilized to produce a solid that can be incorporated into tablets or capsules, providing the appropriate excipients are added.
[0020] In another alternative method, the amphiphile, plant sterols and active drug are mixed in the presence of an organic solvent such as hexane or ethyl acetate, the solvent removed and the solid compressed and extruded for the formulation of tablets and capsules.
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