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Duragesic is a transdermal patch containing the opioid pain killer fentanyl and it was developed by Alza. The patch has a form-fill-and-seal drug reservoir and an ethylene-vinyl acetate membrane for the controlled delivery of the opioid [145]. The reservoir contains the drug in an aqueous ethanolic solution that has the dual purpose of enhancing the permeation of ethanol through skin and reducing the amount of fentanyl in the reservoir by limiting its solubility [146]. The later fact is significant because fentanyl is an abusable substance. |
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Duragesic was introduced in the marketplace by Janssen Pharmaceutica, Inc. in April 1991 for the control of chronic pain. It has a duration of activity of 72 hours and is removed from the skin 24 hours after application. The patch remains effective for 72 hours because fentanyl has a skin depot effect [147]. During its first year, Duragesic had sales of $25 million, more than doubling total fentanyl sales. In 1992 and 1993 the sales were $45 and $67 million respectively. As mentioned above, Duragesic has been approved for use in chronic pain but it has been investigated and found to be effective in the treatment of post-operative pain [148,149] as well. With over 40 million surgical procedures per year, the market for Duragesic is conservatively estimated at $500 million. |
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Procardia XL extended release capsules were designed for once-a-day oral delivery of Nifedipine. Nifedipine belongs to a class of calcium channel blockers that interfere with the normal transmembrane flux of extracellular calcium on which vascular tissue depends for contraction and impulse generation [150] and it is used for the long term management of angina and hypertension [151]. |
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Procardia XL was introduced in September 1989 by Pfizer to replace Procardia, an immediate release formulation designed to release 30, 60, or 90 mg Nifedipine T.I.D. By the time the patent expired in 1991 Pfizer had switched all its patients to Procardia XL. Procardia XL was designed by Alza and it is based on an osmotic push-pull pump system especially useful in delivering insoluble drugs, such as Nifedipine, in suspension [152]. |
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Procardia XL is a bilayer tablet with the top layer containing the drug and the bottom layer containing a hydrophilic polymer, polyethylene oxide [153]. The bilayer is coated with a cellulosic semipermeable membrane and a hole is drilled by a laser beam on the drug side to allow for the release of the drug. In operation, water is osmotically imbibed in both layers, dispersing the drug and swelling the polyethylene oxide polymer, which pushes the dispersed drug through the laser-drilled orifice. This provides a predictable 24-hour zero-order release of Nifedipine with one-to-one correspondence between in vivo and in vitro results [152]. |
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The success of the new formulation was such that even with strong generic competition Pfizer sales of Nifedipine increased from $700 million in 1989 to |
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