Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs. 2006

Jun-ichi Jinno, and Naoki Kamada, and Masateru Miyake, and Keigo Yamada, and Tadashi Mukai, and Masaaki Odomi, and Hajime Toguchi, and Gary G Liversidge, and Kazutaka Higaki, and Toshikiro Kimura
Otsuka Pharmaceutical Co., Ltd., 224-18 Ebisuno Hiraishi Kawauchi-cho, Tokushima 771-0182, Japan.

The purpose of the present study was to investigate the effects of particle size on the dissolution and oral absorption of cilostazol. Three types of suspensions having different particle size distributions were prepared of the hammer-milled, the jet-milled cilostazol crystals and the NanoCrystal spray-dried powder of cilostazol. In vitro dissolution rate of cilostazol was significantly increased by reducing the particle size. The dissolution curves of the cilostazol suspensions were in good agreement with the simulation based on the Noyes-Whitney equation. The bioavailability of cilostazol after oral administration to dogs was increased with reducing the particle size. While positive food effect on the absorption was observed for the suspensions made of the hammer-milled and the jet-milled crystals, no significant food effect was found for the suspension made of the NanoCrystal cilostazol spray-dried powder. These results could be qualitatively predicted from the in vitro dissolution data using the bio-relevant media, FaSSIF and FeSSIF. In conclusion, the NanoCrystal technology is found to be efficient to improve the oral bioavailability of cilostazol and to avoid the food effect on the absorption.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D010975 Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D011208 Powders Substances made up of an aggregation of small particles, as that obtained by grinding or trituration of a solid drug. In pharmacy it is a form in which substances are administered. (From Dorland, 28th ed) Powder
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005215 Fasting Abstaining from FOOD. Hunger Strike,Hunger Strikes,Strike, Hunger,Strikes, Hunger
D000077407 Cilostazol A quinoline and tetrazole derivative that acts as a phosphodiesterase type 3 inhibitor, with anti-platelet and vasodilating activity. It is used in the treatment of PERIPHERAL VASCULAR DISEASES; ISCHEMIC HEART DISEASE; and in the prevention of stroke. 6-(4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy)-3,4-dihydro-2(1H)-quinolinone,OPC 13013,OPC-13013,Pletal
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

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