Nifedipine formulation

Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A. Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation. Pharmazie 1994 49(7) 522-524. 

Polyacrylate (Eudragit retard) microspheres for oral controlled release of nifedipine Formulation design and... 

Schug BS, Brendel E, Wonnemann M, Wolf D, Wargenau M, Dingier A, Blume HH. Dosage form-related food interaction observed in a marketed once-daUy nifedipine formulation after a high-fat American breakfast. Eur J Clin Pharmacol 2002 58(2) 119-25. 

Nifedipine XL 30 qd 90 mg bid 10% 100% 100% 100% Avoid short-acting nifedipine formulation... 

Cramer JA, Robbins B, Barbeito R, Bedman TC, Dreisbach A, Meligeni lA. Lamisil interaction study with a sustained release nifedipine formulation. PharmRes (1996) 13 (9 Siq>pl), S436,... 

Procardia XL. Procardia XL extended-release capsules, marketed by Pfizer Labs Division of Pfizer, Inc., contain nifedipine [21829-25-4] a calcium channel blocker of mol wt 346.3. The extended release tablet is formulated as a once-a-day controlled release capsule for oral adrninistration dehvering either 30, 60, or 90 mg nifedipine. Procardia XL is indicated for use in the management of vasospastic angina, chronic stable angina, and hypertension (see Cardiovascularagents). 

Fast DHP-induced lowering of blood pressure results in compensatory sympathetic activation and a subsequent increase in heart rate and cardiac oxygen demand. This unfavorable effect has been mainly associated with the use of short-acting DHPs, such as nonretarded formulations of nifedipine, nitrendipine, or... 

Short-acting nifedipine may rarely cause an increase in the frequency, intensity, and duration of angina in association with acute hypotension. This effect may be obviated by using sustained-released formulations of nifedipine or other dihydropyridines. Other side effects of dihydropyridines include dizziness, flushing, headache, gingival hyperplasia, and peripheral edema. Side effects due to vasodilation such as dizziness, flushing, head-... 

Nifedipine is a calcium-channel blocker of the dihydropyridine group. It relaxes smooth muscle and dilates both coronary and peripheral arteries by interfering with the inward displacement of calcium-channel ions through the active cell membrane. Unlike verapamil, nifedipine can be given with beta-blockers. Long-acting formulations of nifedipine are preferred in the long-term treatment of hypertension. 

Amlodipine and nifedipine are dihydropyridine calcium-channel blockers. Amlodipine differs from nifedipine in that it has a longer duration of action and can therefore be given once daily, unlike nifedipine. Both are indicated in hypertension and angina and tend to cause ankle oedema that does not respond to diuretic therapy. Neither amlodipine nor nifedipine are available as spray formulations. 

Angina patients maintained on the nifedipine capsule formulation may be switched to the sustained release tablet at the nearest equivalent total daily dose. Experience with doses more than 90 mg in angina is limited. 

As mentioned before, nifedipine was the first marketed dihydropyridine CCB. Initially, the drug indication was exclusively for angina, but the more recently developed extended release (ER) formulations are used off-label primarily for hypertension (Bayer, 2004). The extended-release tablets use a cellulose coat that extends their release time. The half-life of the ER formulation is reported as 7 h, whereas the immediate-release formulation has a half-life of 2 h (Bayer). 

Answer Nifedipine, unless formulated for slow, sustained release, is characterized by relatively rapid onset of vasodUatory effects. This man s side effects reflect the rapid and intense fall in blood pressure and consequent reflex increases in sympathetic tone. The increase in anginal episodes also is a result of drug-induced periodic increases in heart rate. 

Nifedipine has a rapid onset of action and a short elimination half-life. A slow-release formulation allows a single daily dose to be prescribed and prevents reflex tachycardia. Newer, second- and third-generation dihydropyridines, have a slower onset and a longer elimination half-life. This makes special pharmaceutical formulations unnecessary. 

Verapamil, diltiazem, and the dihydropyridine family (amlodipine, felodipine, isradipine, nicardipine, nifedipine, and nisoldipine) are all equally effective in lowering blood pressure, and many formulations are currently approved for this use in the USA. Clevidipine is a newer member of this group that is formulated for intravenous use only. 

Save, T., et al. 1994. Comparative study of buccoadhesive formulations and sublingual capsules of nifedipine. J Pharm Pharmacol 46 192. 

Nifedipine (Fig. 7.1) is the lead compound which was first introduced for the treatment of coronary angina. However, its use in the treatment of hypertension was blunted by a short plasma half-life (in the range of 1.5-2 h) this led to the need for multiple daily administration, and consequently blood pressure control and patient compliance were not fully achieved. However, slow-release formulations - for example, the once-daily Nifedipine Oros - made possible the wide use of nifedipine in cardiovascular therapy. 

Nisoldipine (Fig. 7.7) is an analogue of nifedipine, but it is at least five to ten times more potent than nifedipine on arterial smooth muscle, without affecting myocardial contractility. It also possesses a very potent and selective relaxation activity on small arteries, and therefore it can be used for the treatment of hypertension. Since its duration is limited by a massive hepatic first-pass effect, it is currently used as an extended-release formulation for once-daily administration. 

Schug BS, Brendel E, Chantraine E et al. (2002) The effect of food on the pharmacokinetics of nifedipine in two slow release formulations pronounced lag-time after a high fat breakfast. Br J Clin Pharmacol 53 582-588 Stoepel K, Heise A, Kazda S (1981) Pharmacological studies of the antihypertensive effect of nitrendipine. Arzneimit-tel Forsch 31 2056-2061... 

Thoma s interests included methods of testing (76-78), the influence of excipients and formulations on the photostability of products (71,79-83) and methods of photoprotection via packaging (67,71,84-88) or formulation (67,89-91). Several of his papers dealt with specific photostability problems such as antibiotics (92) antimitotics (93-96), adrenaline (97), molsidomin (98), phenothiazines (99), quinolines (100) and nifedipine (101-107). 

Thoma K, Klimek R. The photoinstabiUty of nifedipine. Part 3. PhotostabUization of nifedipine in pharmaceutical formulations. Pharm Ind 1991 53(4) 388-396. 

The impact of the surface area can also be shown by the fact that once a formulation is pressed into tablets, little difference between the particle sizes of the drug compound is evident, as then the surface area of the tablet becomes more important. Figure 7 shows the comparison of two different sizes of nifedipine active and tablets produced using these materials. This comparison also reveals a decrease in the photodegradation rate, which can be attributed to the decrease in the drug surface exposed to incident radiation. Similar results were obtained with molsidomine (Thoma K, Aman W. In preparation) (4). 

Kaminsky EE, Cohn RM, McGuire JL, Carstensen JT. Light stability of norethindrone and ethinyl estradiol formulated with FD C colorants. J Pharm Sci 1979 68(3) 368-370. Desai DS, Abdebiasser MA, Rubitski BA, Varia SA. Photostabilization of uncoated tablets of sorivudine and nifedipine by incorporation of synthetic iron oxides. Int J Pharm 1994 103 69-76. 

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