Sustained Release Nifedipine Formulations

Abstract

Nifedipine antagonises influx of calcium through cell membrane slow channels, and sustained release formulations of the calcium channel blocker have been shown to be effective in the treatment of mild to moderate hypertension and both stable and variant angina pectoris. Preliminary findings also indicate that these formulations are effective in the treatment of Raynaud's phenomenon and hypertension in pregnancy, and that they reduce the frequency of ischaemic episodes in some patients with silent myocardial ischaemia. The exact mechanism of action of nifedipine in all of these disorders has not been defined. However, its potent peripheral and coronary arterial dilator properties, together with improvements in oxygen supply/demand, are of particular importance. A major goal of sustained release therapy is to permit reductions in the frequency of nifedipine administration, preferably to once daily, and thus improve patient compliance. Two new once-daily formulations--the nifedipine gastrointestinal therapeutic system (GITS) and a fixed combination capsule comprising sustained release nifedipine 20 mg and atenolol 50 mg--have exhibited marked antihypertensive efficacy. The GITS preparation has also been used effectively in the treatment of stable angina pectoris, and both formulations appear to be well tolerated. Sustained release nifedipine formulations are generally better tolerated than their conventionally formulated counterparts, particularly with regard to reflex tachycardia. Adverse effects seem to be dose related, are mainly associated with the drug's potent vasodilatory action, and include headache, flushing and dizziness. Generally, these effects are mild to moderate in severity and transient, usually diminishing with continued treatment. Thus, sustained release nifedipine formulations are useful and established cardiovascular therapeutic agents which have demonstrable efficacy in various forms of angina, mild to moderate hypertension and Raynaud's phenomenon. Further, promising results shown by the nifedipine GITS formulation, with its advantage of once daily administration suggest that it is likely to become one of the preferred nifedipine formulations for the treatment of hypertension and the various forms of angina.

Pharmacological aspects of calcium channel blockers

“…The GITS formulation of nifedipine has an oral bioavailability of 55-65% after a single dose and 75-85% at steady state. Plasma nifedipine concentrations begin to rise approximately 2 hours after oral administration and plateau approximately 6 hours later [4].…”

Development and characterization of ethylcellulose based microsphere for sustained release of nifedipine

“…Microspheres have been widely accepted as a means to achieve an oral and parenteral controlled release drug delivery system [7] . Microspheres are better tolerated in the form of sustained release of nifedipine for their conventional counterparts and dosage [8] . Nifedipine is a prototype dihydropyridine calcium channel blocker with a rapid onset and a short duration of action [9] .…”

Pharmacokinetics and Bioequivalence of 2 Nifedipine Controlled‐Release Tablets: A Randomized, Single‐Dose, 2‐Period Crossover Study in Healthy Chinese Volunteers Under Fasting and Fed Conditions

“…The dihydropyridine ring of nifedipine is first oxidized to the pyridine ring, which is the main metabolite, and then further converted to other acidic metabolites 15 . Eventually, 70%–80% of nifedipine is eliminated in the urine as metabolites, with the remaining metabolites being eliminated in the feces 16,17 . Several drug‐drug interaction studies have been reported, ketoconazole, ginkgo biloba leaf extract, and Shengmai‐San increased the maximum plasma concentration (C max ) and area under the plasma concentration–time curve (AUC) of nifedipine due to their inhibitory effect on CYP 18–20 .…”