Jacques Timmermans

The Bilayer Floating Capsule - a Stomach-directed Drug Delivery System for Misoprostol

A bilayer floating dosage unit is proposed to achieve local delivery of misoprostol, a prostaglandin E1 analogue, at the gastric mucosa level. The system is a capsule consisting of a floating layer maintaining the dosage unit buoyant upon the gastric content and a drug layer formulated to act as a sustained-delivery system. The differential design of the two layers allows the optimization of both floating capability and drug release profile. The layers are both composed of a hydrophilic matrix based upon hydroxypropylmethyl cellulose (HPMC). Parameters influencing the release profiles are described. The use of a large capsule increases the gastric residence time (GRT), as it impedes passage through the pylorus opening. γ-Scintigraphic studies were performed to visualize cohesion of the two layers in vivo and to determine GRT as a function of meal regimen. The average GRTs were 199 ± 69 min after a single meal (breakfast) and 618 ± 208 min after a succession of meals.

How well do floating dosage forms float

Abstract Peroral floating dosage forms have up to now been used and prescribed without having achieved any determination of their real floating capabilities versus time. Using a novel in vitro resultant-weight measuring system, the authors present different examples of floating-force kinetics obtained from polymeric matrix floating forms, amongst which several are marketed products and others have undergone in vivo experiments conducted on human volunteers. The floating curves are showing that the bulk density of a dosage form is not the most appropriate parameter for describing its buoyancy capabilities. These capabilities are, however, perfectly represented and monitored by resultant-weight measurements. Results also indicate that the magnitude of floating strength may vary as a function of time and usually decreases after immersion of the dosage form into the fluid consequently to the evolution of its hydrodynamical equilibrium. To prevent drawbacks of unforeseeable floating capability variations during in vivo studies, the authors suggest optimization of dosage form formulations to be realised with respect to the significance level, the stability and durability of the floating forces produced.

Conception and in vivo investigation of peroral sustained release floating dosage forms with enhanced gastrointestinal transit

Abstract Previous published works have shown that hydrodynamically balanced systems (HBS) — i.e. sustained release oral dosage forms with a specific gravity lower than 1 and remaining buoyant on the gastric juice of the stomach — can have an enhanced gastrointestinal transit time. For this investigation, a double-layer sustained release compressed hydrophilic matrix was formulated in order to achieve a foreseeable and reproducible flotation of the tablet. A carbon dioxide generating blend was, for this purpose, added to one of the layers, this gas being entrapped in the gelified hydrocolloid as liberated by the action of the gastric medium. The in vivo behaviour of this floating tablet was then compared to a classical HBS capsule and to a similar but non-floating double-layer hydrophilic matrix on subjects alternatively in fasted or fed state. As these three dosage forms contain a riboflavin (RF) soluble derivative, it was possible to measure the RF urinary excretion rates and, consequently, to conclude that in vivo buoyancy is preponderant over bioadhesion for both floating capsules and tablets. These dosage forms also significantly increase the gastric residence time when compared to the non-floating dosage form. Compared to the classical HBS capsule, the floating tablet is showing in vivo equivalent floating properties when administered after a light meal and higher RF urinary excretion rates when administered to fasted subjects.

Intragastric positioning of two concurrently ingested pharmaceutical matrix dosage forms

A triple nuclide scintigraphic technique is presented for the precise and lasting intragastric monitoring in man of two concurrently ingested hydrophilic matrix pharmaceutical forms. After in vitro testing of various labels, ion exchange resin-coupled 201T1- and 111In-oxinate were selected for their release characteristics. 99mTc-pertechnetate oral solution was used to selectively delineate the stomach. This technique was validated on healthy volunteers. It allowed measurement of the effects on gastric residence time of galenic parameters (size, density of matrices), as well as of physiological parameters such as subject posture.