Verapamil is an ionic calcium influx inhibitor more commonly known as a calcium channel blocking agent. The principal pharmacologic and physiologic action of verapamil is to inhibit the transmembrane influx of extracellular calcium ions across the membrane of myocardial cells and vascular smooth muscle cells. By inhibiting calcium influx, verapamil inhibits the contractile processes of cardiac and vascular smooth muscles, thereby dilating the main coronary and systemic arteries. The drug is indicated and approved by the Food and Drug Administration for the management of unstable or chronic stable angina pectoris for the treatment of supraventricular tachyarrhythmias, and for the temporary control of rapid ventricular rate in arterial flutter or atril fibrillation.
Verapamil is administered generally as its pharmaceutically acceptable addition salt. Orally administered verapamil is absorbed from the gastrointestinal tract. The prior art administers verapamil orally for the indicated cardiovascular indications in tablet form. Currently, verapamil is administered orally as tablets three or four times daily. While these conventional tablet forms are used for the indicated therapy, a fundamental limitation common to tablets is their temporal pattern of drug delivery. That is, they give up their drug to surrounding tissues and fluids at varying rates that are highest initially and then declines continually thereafter. For a therapeutically important cardiovascular drug such as verapamil, this sawtooth pattern of delivery of high-dose, low-dose variation of the needed drug presents drug to the tissues and then denies drug to the tissues, leading to unacceptable therapy. Also, within the intervals between doses, and with longer intervals between doses, there is a greater amplitude of the dosage cycle leading to irregularity of drug bioavailability and uncontrolled therapy.
It is apparent from the above presentation to a person having ordinary skill in the art to which the present subject matter pertains, that an urgent need exists for a dosage form for administering verapamil at a programmed rate for a prescribed period of time. The need exists for a dosage form that delivers verapamil at a controlled rate over a prolonged period of time for substantially eliminating the disadvantages known to the prior art.
USPTO Backgrounds
USPTO Backgrounds