Jack Cooper

Oral Prolonged Action Medicaments: Their Pharmaceutical Control and Therapeutic Aspects

THE successful introduction of oral prolonged action substances has stimulated interest in the physical and chemical means of extending the therapeutic activity of a drug administered by this route. Only in the past few years have clinical reports on such formulations appeared in the medical literature. Concomitantly, questions have been raised concerning in vitro and in vivo measurements of the release rate of the active ingredient in preparations of this kind. The technique used for measuring the release of active substance from sugar or enteric coated tablets does not necessarily apply to these new forms, and modifications may be necessary. A critical review of sustained action medication, with particular emphasis on the measurement of pharmacological and therapeutic effects, appears appropriate at this time. Various expressions have been used to describe oral sustained release preparations. Extended action, sustained release, sustained action, oral repository, timed disintegration, timed release, oral depot therapy, prolonged action, prolonged release, controlled release and protracted release are examples of terms in current usage. At a recent meeting of representatives of the major pharmaceutical manufacturing firms in the United States, various suggestions were made for a definitive term other than timed releasel. In this review article, the terms prolonged action and sustained release will be used interchangeably. Several definitions have been offered in the literature for prolonged action medication. Lang2 used the designation “prolonged action” for formulations in which adequate measures provide a longer duration of therapeutic effect of the drug substance than is usually achieved with classical preparations. Theoretically, there would be an equilibrium in the body between the continuous administration and the inactivation and elimination of the active substance within the therepeutically optimal range of concentration. Abrahams and LinnelP have stated that ideally an orally administered drug should be in such form that a single dose would be continuously absorbed over an extended period of time thereby maintaining a uniform optimal level in the tissues and avoiding unnecessarily high peak concentrations as well as wasteful depressions. Blythe4 describes oral sustained release preparations as those which “provide a sustained therapeutic effect by first releasing a therapeutic dose, then gradually and continually releasing medication over a prolonged period.”