PRODAS®
Programmable Oral Drug Absorption System is a multiparticulate technology, which is unique in that it combines the benefits of tabletting technology within a capsule.
 | PRODAS is presented as a number of minitablets combined in a hard gelatin capsule. PRODAS is a very flexible technology, which can be used to pre-program the release rate of a drug. It is possible to incorporate many different minitablets, each one formulated individually and programmed to release drug at different sites within the gastro-intestinal tract. It is also possible to incorporate minitablets of different sizes so that high drug loading is possible. |
In its most basic form, PRODAS involves direct compression of an immediate release granulate to produce individual minitablets. These minitablets are subsequently packaged into hard gelatin capsules, which represent the final dosage form. A more beneficial use of the technology, however, is in the production of controlled release formulations. In this case the incorporation of various polymer combinations within the granulate delays the release rate of drug from each of the individual minitablets. These minitablets may subsequently be coated with controlled release polymer solutions to provide additional delayed release properties.
PRODAS technology can:
- Achieve equivalent bioavailability to reference multiple dose product in a once daily formulation
- Show minimum peak to trough ratio at steady state
- Show minimal food impact
- Facilitate pulsed / programmed release to different sites in the GI tract
PRODAS technology, by incorporating minitablets with different release rates, can display the characteristics of a number of different conventional dosage forms:
- Immediate release component will mimic the conventional formulation ensuring that the once daily formulation is as fast acting
- Delayed release can provide site / regional release and food resistance
- Sustained release component provides additional controlled release / protection
Case Study
In collaboration with a multi-national pharmaceutical firm Elan employed PRODAS technology to orchestrate precise control of an agent, which is conventionally dosed four times daily, to facilitate once daily dosing. Elan developed the controlled release dosage form despite a number of significant technical challenges, and a full dossier for regulatory submission was prepared. However, due to the emergence of significant clinical implications with the drug itself, the commercial viability of the product was suddenly reduced, and the PRODAS formulation was not submitted for regulatory approval.
Typical equipment involves multi-tip tableting, tablet coating and multi-station capsule filling. PRODAS is an advanced technology with full scale-up and manufacturing capability available at Elan’s Athlone site.
A number of biostudies were carried out over the course of the development work, which clearly illustrate the attributes of the PRODAS dosage form.
(i) Sustained Plasma Profile
PRODAS; smooth sustained plasma levels
(ii) Food Effect
PRODAS is not affected by the presence of food in the GI tract. This is a patient friendly dosage form, leading to increased compliance as the dose can be administered irrespective of the fed or fasting state.
PRODAS effect of food, fed vs. Fasted state
As can be seen from the above data, the effect of food on the plasma profile is minimal. Individual steady state data, as below, clearly illustrates the predictability and reliability of the dosage form.
Reliability
