title: Controlled delivery of nanosuspensions from osmotic pumps: zero order and non-zero order kinetics.
abstract: Nanosuspensions have gained great interest in the last decade as a formulation tool for poorly soluble drugs. By decreasing particle sizes nanosuspensions enhance dissolution rate and bioavailability of the active pharmaceutical ingredient. Micro-osmotic pumps are widely used in experimental pharmacology and offer a tool of interest for the sustained release of nanosuspensions via the intraperitoneal or subcutaneous application site. The purpose of the present study was to investigate in-vitro the influence of (1) nanosuspension viscosity, (2) pump orifice position and (3) formulation osmolality on the delivery behavior of formulations in implantable osmotic systems. Therefore fenofibrate nanosuspension, methylene blue and fluorescein sodium solutions were chosen as model formulations. They were released in water or isotonic saline solution and drug/dye concentrations were determined by HPLC/UV. Release of nanosuspension particles in low viscous formulations resulted in a burst whereas increasing the viscosity led to the expected zero order delivery. Pumps with upward-positioned orifices released the nanosuspension in a zero order manner. Within the release of dyes, constant delivery could be ensured up to an osmolality of 486 mO sm/kg; above this value premature release of formulation was observed. The results indicate the requirement of in-vitro experiments prior to in-vivo animal testing for determining the release profiles of osmotic pumps.
authors.affiliation: Department of Pharmacy, Institute of Pharmaceutical Technology and Biopharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str 4, 06120 Halle/Saale, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hill
authors.forename: Simon
authors.initials: S
authors.lastname: Geissler
authors.forename: Markus
authors.initials: M
authors.lastname: Weigandt
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry; D002216:Captopril / Q000737:chemistry; D004396:Coloring Agents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D011345:Fenofibrate / Q000737:chemistry; D019793:Fluorescein / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000737:chemistry; D015918:Infusion Pumps, Implantable; D007700:Kinetics; D008751:Methylene Blue / Q000737:chemistry; D009995:Osmosis; D010316:Particle Size; D013535:Suspensions
chemical_list: D000959:Antihypertensive Agents; D004396:Coloring Agents; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D013535:Suspensions; D002216:Captopril; D008751:Methylene Blue; D019793:Fluorescein; D011345:Fenofibrate