Nifedipine modified release

Significant food interactions observed with a nifedipine modified-release... 

FIGURE 22.8 Steady-state plasma pro les of immediate-release nifedipine (Three times a day) and Procardia XL on day 5. (Adapted from V fong, P., et al.,Modified-Release Drug Delivery Technolp y. J. Rathbone, et al. (Ed.), Osmotically Controlled Tablets, Marcel Dekker, Inc., p. 107.)... 

Modified-release nifedipine 40 mg tds caused marked hjrpotension when used to delay preterm labor in a previously healthy 29-year-old woman who started contracting at 29 weeks the hypotension may have precipitated an uncomplicated non-Q-wave myocardial infarction (135). 

Modified-release formulations of nifedipine have been associated in case reports with the formation of bezoars, concretions of undigested material within the gastrointestinal tract, mostly in the stomach. An unusual case of tablet impaction in the duodenum, with gastric outlet obstruction, was discovered 1 year after the patient stopped taking a modified-release formulation of nifedipine (27). 

A 77-year-old woman developed constipation and weight loss. Esophagogastroduodenoscopy showed a deformed pylorus and an elongated duodenal bulb, with numerous impacted tablets and ulceration in the outlet. Since only a few tablets could be recovered by endoscopy, she underwent partial duodenal resection to remove the contents 25 intact tablets that were confirmed to be modified-release nifedipine. 

Wang, Z., Hirayama, R, Uekama, K. Design and in vitro evaluation of a modified-release oral dosage form of nifedipine by hybridization of hydroxypropyl-(3-cyclodextrin and hydroxypropyl-cellulose. J. Pharm. Pharmacol. 1993, 45, 942-946. 

CyD, HCO-60 and HPCs can serve as a modified-release carrier of nifedipine and can be applied to other poorly water-soluble drugs with short elimination half-lives. 

Cyclodextrin-based drug delivery systems The hydrophilic cyclodextrins have been extensively )plied to enhance the oral bioavailabilily of steroids, cardiac glycosides, nonsteroidal anti-inflammatory drugs, barbiturates, antiepileptics, benzodiazepines, antidiabetics, vasodilators, etc. Delayed and prolonged release of diltiazem and molsidormine was achieved by their complexation with CD derivatives, modified release of nifedipine can be achieved by its complexation with 2-HP-P-CD fiirosemide and piretanide (loop diuretics) release can be modified after complexation with DM-P-CD. Prednisolone dosage forms can be optimized also by complex-formation with 2-HP-P-CD. 

Nifedipine. In a small study in 18 patients, low-dose aspirin 100 mg daily for 2 weeks did not alter the blood pressure lowering effect of nifedipine 30 to 60 mg daily, given as a modified-release preparation. 

Some modified-release preparations of felodipine, nifedipine, and nisoldipine show markedly increased levels when given with food, particularly when high in fat. The bioavailability of lercanidipine is markedly increased by food, and it should therefore be given on an empty stomach. Manidipine should be given with food, as this improves its absorption. Food modestly decreases the rate and extent of absorption of nimodipine capsules. Food had no effect on the absorption of amlodipine, bepridil, diltiazem, isradipine, or verapamil in the studies cited. 

Colestyramine, sucralfate, modified-release formulations, guar gum, ion exchange resins [5-7] magnesium salts [8] nifedipine [9,10] psyllium [11] BUiary hthiasis or Atazanavir [12] ceftriaxone [13] ... 

Buccoadhesive-controlled release tablets for delivery of nifedipine were prepared by direct compression of carboxymethyl cellulose (CMC) with carbomer (CP) and compared to those prepared with PVP, PVA, HPMC, and acacia by a modified tensiometry method in vitro. It was found that the adhesion force was significantly affected by the mixing ratio of CP CMC in the tablets. CMC is necessary for controlling the release rate, whereas CP is important in providing bioadhesion. The tablets containing 15% CMC and 35% CP were found to have optimum drug release rate and bioadhesion [81]. 

Comparative pharmacokinetic profiles of nifedipine delivered from Procardia XL, an osmotic pressure-controlled drug delivery system, once-a-day versus that from Procardia, an immediate-release dosage form, taken on time 0, 8 and 16 in human volunteers. Modified from Y.W. Chien. Oral drug delivery and delivery systems. Y.W.Chien (ed.) (1992) Novel Drug Delivery Systems. Marcel Dekker, Inc. New York, pp. 139-196... 

---