International Journal of Pharmaceutics 323 (2006) 86–92 In vitro and in vivo evaluation of floating riboflavin pellets developed using the melt pelletization process J. Hamdani, J. Goole, A.J. Mo¨ es, K. Amighi ∗ Laboratoire de Pharmacie Gal´ enique et Biopharmacie, Universit´ e Libre de Bruxelles, Campus Plaine, CP 207, Boulevard du Triomphe, 1050 Brussels, Belgium Received 8 January 2006; received in revised form 18 May 2006; accepted 24 May 2006 Available online 2 June 2006 Abstract Floating pellets were prepared using the melt pelletization process in a Mi-Pro ® high shear mixer (Pro-C-epT, Belgium). Formulations were based on a mixture of Compritol ® and Precirol ® as meltable binders and on the use of sodium bicarbonate and tartaric acid as gas-generating agents. Good floating abilities were obtained by using the gas-generating agents in both the inner matrix and the outer coating layer of the pellets. In vitro evaluation of floating capability was performed both by using the resultant weight apparatus and by counting floating pellets at the surface of beakers containing 0.1N HCl solution, in vivo evaluation of floating pellets capabilities was also performed. Riboflavin-containing floating pellets (FRF) were administered orally to nine healthy volunteers versus non-floating pellets (NFRF). Volunteers were divided in two groups, fasted group (n = 4) 729 kcal and fed group (n = 5) 1634 kcal as the total calorie intake on the testing day. An increase of urinary excretion of riboflavin was observed when the volunteers were dosed with the floating pellets, especially after feeding. As riboflavin has a narrow window of absorption in the upper part of small intestine, this phenomenon could be attributable to the gastric retention of floating pellets. © 2006 Elsevier B.V. All rights reserved. Keywords: Melt pelletization; Controlled-release; Floating pellets; Riboflavin; Urinary excretion 1. Introduction Oral floating dosage forms are developed in order to be retained in the stomach and the upper part of small intestine, assuring a slow delivery of drug above the absorption site. Gastro-retentive devices may be useful for the delivery of many different kind of drugs, especially for optimum delivery of drugs that act locally in the stomach, e.g. misoprostol (Oth et al., 1992), and for stomach-specific antibiotic drug delivery used in the treatment of Helicobacter pylori (Burton et al., 1995; Patel and Amiji, 1996; Whitehead et al., 2000). In this regard, the present work aims to assess the intragastric behaviour in humans of a new multiple unit system produced by the melt pelletization process (Hamdani et al., in press). Riboflavin (RF) was therefore chosen as the drug tracer because its absorption occurs mainly in the proximal small intestine. Moreover, it undergoes very little metabolism and its pharma- ∗ Corresponding author. Tel.: +32 2 650 52 52; fax: +32 2 650 52 69. E-mail address: kamighi@ulb.ac.be (K. Amighi). cokinetics can be investigated by analysis of the urinary excre- tion following oral administration in humans (Sato et al., 2003, 2004). In this evaluation, riboflavin was used in its sodium salt form: sodium riboflavin 5 ′ -phosphate (RF5 ′ PNa). This Vitamin B 2 derivative is more water-soluble than riboflavin itself but is subject to the same absorption and transport mechanisms. Fur- thermore, it is excreted in the urine as RF and also has absorption sites mainly limited to the upper region of the small intestine. This allows indirect demonstration of an increase in the resi- dence time of the dosage form above the absorption area: any increase in the gastric transit time of the dosage form increases the quantities of absorbed and eliminated riboflavin (Ingani et al., 1987b). A previous investigation that included formulation, dissolu- tion and buoyancy tests had shown good in vitro floating capa- bilities for comparable placebo, tetracycline and theophylline formulations (Hamdani et al., in press). But in order to evaluate the real floating capabilities of floating RF5 ′ PNa pellets on the gastric content and their usefulness in achieving an extended gastric transit, these pellets were compared with non-floating RF5 ′ PNa pellets (control). The in vivo behaviour of RF5 ′ PNa 0378-5173/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2006.05.056