Abstract

Advanced drug delivery formulations have been allowing more and more complex therapeutic goals to be accomplished mainly through a control of the rate, time and/or site of release. In this particular area of pharmaceutics, pulsatile delivery systems are generally meant as non-conventional dosage forms able to release the conveyed bioactive compound when required after a lag phase (1-3). The onset of release may either be triggered by changes in the external environment (e.g., chemical, thermal, or magnetic stimuli) or, alternatively, be governed by mechanisms inherent in the formulation itself regardless of major physiological variables such as pH, ionic strength and temperature (4). In the latter case, drug delivery would be subject to a merely temporal control and, therefore, is frequently defined as delayed or time-controlled pulsatile release. These terms, however, are non-fully compendial compliant since dosage forms with such release patterns have specifically not been addressed by the European and US pharmacopoeias so far (3). Indeed, despite a widespread use in the scientific literature, “pulsatile” appears in the European Pharmacopoeia only, although the meaning provided is not exactly the same as mentioned above. On the other hand, “delayed” is reported in both the Eur. Ph. 7th Ed. and USP 34 but it includes enteric-coated units, which yield non-programmable lag times dictated by gastric residence. Due to the lack of updated and harmonized pharmacopoeial references, “pulsatile,” intended as a short form for “time-controlled pulsatile,” and “delayed” will hereinafter be employed as synonyms in accordance with their prevalent usage.