Enhanced oral bioavailability of paclitaxel by solid dispersion granulation

Autor:	Jong Soo Woo, Yong-Il Kim, Eun-Seok Park, Ho Taek Im, Young Taek Sohn, Srinivasan Shanmugam, Jae-Hyun Park
Rok vydání:	2015
Předmět:	Male Paclitaxel Chemistry Pharmaceutical Pharmaceutical Science Administration Oral Biological Availability Tetrazoles Beagle chemistry.chemical_compound Granulation Dogs Drug Discovery Animals Technology Pharmaceutical Benzopyrans ATP Binding Cassette Transporter Subfamily B Member 1 Dissolution Pharmacology Chromatography Organic Chemistry Isoquinolines Antineoplastic Agents Phytogenic Bioavailability Drug Liberation chemistry Solubility Fluidized bed Spray drying Dispersion (chemistry) Tablets
Zdroj:	Drug development and industrial pharmacy. 41(11)
ISSN:	1520-5762
Popis:	The main objective of this study was to develop novel orally administrable tablets containing solid dispersion granules (SDG) of amorphous paclitaxel (PTX) prepared by fluid bed technology, and to evaluate its in vitro dissolution and in vivo pharmacokinetics (PK) in beagle dogs. The SDG were prepared using optimized composition by fluid bed technology, and characterized for solid-state properties. The release study of SDG tablet (SDG-T) in simulated gastric fluid showed a rapid release of PTX, reaching maximum dissolution within 20 min. Finally, the PK profile of SDG-T and a reference formulation Oraxol™ (oral solution formulation used in Phase I clinical study) at a dose of 60 mg orally with co-administration of P-gp inhibitor HM38101, and Taxol® at a dose of 10 mg intravenously (i.v.) was investigated in beagle dogs. The mean absolute BA% of PTX following SDG-T and Oraxol™ solution was 8.23 and 6.22% in comparison to i.v. administration of Taxol®. The relative BA% of PTX from SDG-T in comparison to Oraxol™ solution was 132.25% at a dose of 60 mg following oral administration. In conclusion, we have successfully prepared PTX tablets with solid dispersion granules (SDG) of amorphous PTX using fluid bed technology that could provide plasma PTX concentration in the range of 10-150 ng/mL for a period of 24 h following oral administration in dogs with a P-gp inhibitor. Hence, this could be a promising formulation for PTX oral delivery and could be used in our intended clinical studies following pre-clinical efficacy studies.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::18a5349f481f675ed60cbde10a07cec6 https://pubmed.ncbi.nlm.nih.gov/25775012 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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