Biomaterial Database

Stereoselective disposition of suspensions of conventional and wax-matrix sustained release ibuprofen microspheres in rats. 1997

C M Adeyeye, and F F Chen

Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282, USA. adeyeyechri@duq3.cc.duq.edu

OBJECTIVE The aim of the study is to evaluate stereoselective in vivo disposition of suspensions of conventional and wax-matrix sustained release ibuprofen microspheres in rats. METHODS Male wistar rats were dosed i.v. with 20 mg/kg, or orally with conventional suspension, and three suspension formulations of sustained release microspheres (having three different particle sizes) of racemic ibuprofen. Blood samples were analyzed stereoselectively by reverse phase HPLC. RESULTS The mean Cmax for (S)- and (R)-ibuprofen decreased with increased particle size of the drug or microspheres in the suspension dosage forms, while the Tmax increased with increased particle size. The mean S/R ratio (AUC0-48) of the suspensions decreased with increase in particle size of the drug or microspheres and these ratios (for both conventional and sustained formulations) were higher than that of the i.v., an indication of presystemic inversion. Decrease in the ratios with increased particle size is suggestive of formulation dependent inversion. The plasma concentration-time data of the sustained release formulations showed bimodal profiles, irrespective of the particle size of the microspheres. The second peak observed after 8 hours is indicative of colonic absorption. CONCLUSIONS Stereoselective disposition of ibuprofen microspheres showed higher bioavailability compared to the conventional suspension. Bimodal disposition is influenced by dosage form while presystemic inversion is both site-specific, and dosage form dependent.

UI	MeSH Term	Description	Entries
D007052	Ibuprofen	A non-steroidal anti-inflammatory agent with analgesic, antipyretic, and anti-inflammatory properties	Advil,Benzeneacetic Acid, alpha-methyl-4-(2-methylpropyl)- trimethylsilyl ester,Brufen,Ibumetin,Ibuprofen, (+-)-Isomer,Ibuprofen, (R)-Isomer,Ibuprofen, (S)-Isomer,Ibuprofen, Aluminum Salt,Ibuprofen, Calcium Salt,Ibuprofen, Copper (2+) Salt,Ibuprofen, Magnesium Salt,Ibuprofen, Potassium Salt,Ibuprofen, Sodium Salt,Ibuprofen, Zinc Salt,Ibuprofen-Zinc,Motrin,Nuprin,Rufen,Salprofen,Trauma-Dolgit Gel,alpha-Methyl-4-(2-methylpropyl)benzeneacetic Acid,Ibuprofen Zinc,Trauma Dolgit Gel
D008297	Male		Males
D008863	Microspheres	Small uniformly-sized spherical particles, of micrometer dimensions, frequently labeled with radioisotopes or various reagents acting as tags or markers.	Latex Beads,Latex Particles,Latex Spheres,Microbeads,Bead, Latex,Beads, Latex,Latex Bead,Latex Particle,Latex Sphere,Microbead,Microsphere,Particle, Latex,Particles, Latex,Sphere, Latex,Spheres, Latex
D010316	Particle Size	Relating to the size of solids.	Particle Sizes,Size, Particle,Sizes, Particle
D003692	Delayed-Action Preparations	Dosage forms of a drug that act over a period of time by controlled-release processes or technology.	Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D017208	Rats, Wistar	A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.	Wistar Rat,Rat, Wistar,Wistar Rats