Issues in contemporary drug delivery. Part VI: Advanced cardiac drug formulations.
OBJECTIVE
To identify and discuss the clinical utility of new delivery systems and formulations of cardiac drugs.


METHODS
Studies describing or evaluating new drug delivery systems for cardiac drugs were identified through a MEDLINE literature search.


METHODS
All studies describing or evaluating new delivery systems for cardiac drugs were reviewed.


METHODS
Data were abstracted and evaluated by each author independently.


RESULTS
The most common oral sustained-release formulations include the wax-matrix system, the gastrointestinal therapeutic system (GITS), and the spheroidal oral drug absorption system (SODAS). The wax-matrix delivery system is limited by the occurrence of "dose-dumping." In a low-pH setting, the wax-matrix formulation may dissolve too rapidly, liberating the entire dose in a short period of time. The clinical relevance of this phenomenon is unknown. The GITS and SODAS formulations are less likely to be affected by pH and food. Nitroglycerin is available by many routes of administration. The topical patch forms are convenient to use, but are associated with the development of tolerance. A buccal formulation incorporates a relatively short onset of effect with a three- or four-times-daily dosing regimen. Although tolerance is less of a problem with buccal nitroglycerin than with topical nitrates, this formulation is less convenient to use because of buccal irritation and interference with eating and talking. A new spray formulation of nitroglycerin offers longer shelf-life storage stability and an easier mode of administration. The spray canister is stable for three years compared with 12 weeks for an opened bottle of sublingual nitroglycerin tablets. Sublingual administration of oral cardiac drugs offers the potential for a more rapid onset of effects. Although nifedipine is often given sublingually, objective data indicate that it is not absorbed buccally but rather in the stomach. It appears that the chew-and-swallow route is most appropriate for nifedipine. Captopril is absorbed sublingually but its efficacy has not been demonstrated. Transdermal clonidine improves compliance and is associated with fewer adverse effects than oral clonidine. Transdermal formulations of beta-blockers are currently being evaluated.


CONCLUSIONS
Further advancements in the development of novel delivery systems for cardiac drugs are expected in the future.
Hilleman
D E
DE
Creighton University, School of Pharmacy and Allied Health Professions, Omaha, NE.
Banakar
U V
UV
D000279:Administration, Cutaneous; D000284:Administration, Oral; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000592:standards* / Q000639:trends; D005069:Evaluation Studies as Topic; D005544:Forecasting; D006801:Humans; D014481:United States