Abbvie Inc.

Abbvie Deutschland Gmbh and Co Kg

Wisconsin Alumni Research Foundation

Abbott Gmbh & Co Kg

Barrier Therapeutics, Inc.

Markus Maegerlein

Geoff G Zhang

Bernd Liepold

Matthias Degenhardt

Joerg Rosenberg

Gunther Berndl

Thomas Kessler

Yuchuan Gong

Lian Yu

Gerrit Dispersyn

Jing Tao

Ye Sun

G Z Geoff

This invention relates to novel crystalline lopinavir/surfactant adducts, methods for their preparation, therapeutic uses of those crystalline lopinavir/surfactant adducts, and pharmaceutical compositions containing them or made from them.

Crystalline lopinavir/surfactant adducts

A solid dispersion product comprising an effective amount of one or more active ingredients and an effective amount of one or more hydroxypropyl methylcellulose(s), which satisfies the Formula 0.35&#x3e;&#x394;H(1) (wherein AHrepresents the endotherm (J/g) accompanying a transition at about 240&#xb0; C.). The solid dispersion product is used for the manufacture of a dosage form having improved bioavailability of said one or more active ingredients by oral administration to a patient in need thereof.

Dosage forms with improved bioavailability

A viable strategy to enhance the bioavailability of poorly soluble drugs is to use amorphous solids in place of the more commonly used crystalline solids in pharmaceutical formulations. However, amorphous solids are physically meta-stable and tend to revert back to their crystalline counterpart. An effective approach to stabilizing an amorphous drug against crystallization is to disperse it in a polymer matrix. The drug's solubility in the chosen polymer defines the upper limit of drug loading without any risk of crystallization. Measuring the solubility of a drug in a polymer has been a scientific and technological challenge because the high viscosity of polymers makes achieving solubility equilibrium difficult and because pharmaceutically important drug/polymer dispersions are glasses, which undergo structural relaxation over time. The invention provides a method based on Differential Scanning calorimetry (DSC) for measuring the solubility of crystalline drugs in polymeric matrices. The method relies on the detection of the dissolution endpoint of a drug/polymer mixture prepared by cryomilling.

Method for evaluating the solubility of a crystalline substance in a polymer

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Mannheim, Germany

Markus Maegerlein