Abstract: The invention relates generally to combination therapies comprising an endothelin A receptor (ETA) antagonist and a phosphodiesterase 5 (PDE5) inhibitor, pharmaceutical compositions comprising ETA antagonist and PDE5 inhibitor and methods of treating various disorders comprising administering an ETA antagonist and a PDE5 inhibitor. In particular, the combination therapies and pharmaceutical compositions are useful for the treatment and/or prevention of cardiac disorders such as pulmonary arterial hypertension (PAH).

Abstract: The invention relates to a novel pharmaceutical sustained release formulation of guaifenesin and at least one additional drug ingredient. The formulation may comprise a hydrophilic polymer, preferably a hydroxypropyl methylcellulose, and a water-insoluble polymer, preferably an acrylic resin, in a ratio range of about one-to-one (1:1) to about nine-to-one (9:1), more preferably a range of about three-to-two (3:2) to about six-to-one (6:1), and most preferably in a range of about two-to-one (2:1) to about four-to-one (4:1) by weight. This formulation capable of providing therapeutically effective bioavailability of guaifenesin for at least twelve hours after dosing in a human subject. The invention also relates to a modified release product which has two portions: a first portion having an immediate release formulation of guaifenesin and a second portion having a sustained release formulation of guaifenesin, wherein one or both portions has at least one additional drug ingredient.