Diltiazem modified-release preparations

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. 

The exception to this is the case of some sustained-release preparations where the release properties of different brands may vary (for example modified-release diltiazem or theophylline preparations). In these cases, it is usual for patients to be maintained on one particular brand to prevent fluctuations in plasma concentration. See the British National Formulary for further details. 

Diltiazem. In a placebo-controlled study in 12 healthy subjects diltiazem 60 mg three times daily was given to 12 healthy subjects for 7 days, with ranolazine 240 mg three times daily on days 4 to 7. Ranolazine did not alter the pharmacokinetics of diltiazem, but diltiazem increased the AUC and maximum plasma level of ranolazine by 85% and twofold, respectively. A further study using modified-release diltiazem 180 mg, 240 mg, and 360 mg once daily, and a slow-release preparation of ranolazine 1 g twice daily, resulted in increases in the AUC of ranolazine of 52%, 93%, and 139%, respectively. ... 

Zentner and coworkers [24,26] utilized this information in their development of a system that releases this drug over a 24 hr period. The use of NaCl to modulate the release of diltiazem presents an interesting problem in that the concentration of the solubility modifier must be maintained within certain limits and below its saturation solubility within the device. To solve this problem, core formulations were developed that contained both free and encapsulated NaCl. The encapsulated NaCl was prepared by placing a microporous coating of cellulose acetate butyrate containing 20 wt% sorbitol onto sieved NaCl crystals. The coated granules released NaCl over 12-14 hr period via an osmotic mechanism into either water or the core tablet formulation. The in vitro release profile for tablets (core I devices) containing 360 mg of diltiazem HC1 and 100 mg of NaCl equally divided between the immediate release and controlled release fractions... 

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