Pharmaceutical Technology: Controlled Drug Release, Volume 2

CH. 7] A NEW IBUPROFEN PULSED RELEASE ORAL DOSAGE FORM 83
Fig. 1—Schematic representation of the prepared pulsed release system: a, layer containing the immediately available
dose of drug (first dose); b, barrier of swellable polymeric material; c, layer containing the second dose of drug; d
impermeable film container.
(iv) the dissolution rate of the remaining dose.
In vivo experiments
A preliminary study involving two healthy adult volunteers was carried out. Each subject received
a single oral administration of the following dosage forms:
(a) conventional marketed plain tablets (300 mg of Ibuprofen);
(b) Conventional plain tablets prepared with granulate A (300 mg of Ibuprofen); two preparations
differing in particle size distribution of the active principle;
(c) pulsed release system (2×300 mg of Ibuprofen).
Collection of blood samples (10 ml) was effected over 12 h following dosing. Plasma was
separated by centrifugation and stored at −20°C until analysed. ibuprofen concentration was
determined by HPLC using the method described in ref. 14.
RESULTS AND DISCUSSION
The system prepared is presented in Fig. 1.
Structural characteristics of the systems
In vitro testing
The system works as follows: on contact with the dissolution medium, the uncoated layer (a)
rapidly disintegrates, leaving the remaining part of the system intact. The dissolution medium will
then come into contact with the barrier (b), slowly interacting with it. The barrier delays the
interaction between the dissolution medium and the second dose layer (c) for a time depending on
its composition and thickness. As a result of medium-polymer interaction, the barrier slowly
becomes viscous and its mechanical resistance decreases. When a sufficient amount of water
crosses the barrier, the disintegrants present in layer c swell, thus developing a disintegrating