Novel nanoparticles formulation for cassette dosing via intravenous injection in rats for high throughput pharmacokinetic screening and potential applications
In recent years, one of the biggest challenges for pharmaceutical industry is to increase the speed of finding new medicines while at the same time controlling the ever rising cost of drug discovery and development. In order to increase the speed at which drug candidates are identified, high through...
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Published in | Journal of nanoscience and nanotechnology Vol. 12; no. 10; p. 7993 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.10.2012
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Abstract | In recent years, one of the biggest challenges for pharmaceutical industry is to increase the speed of finding new medicines while at the same time controlling the ever rising cost of drug discovery and development. In order to increase the speed at which drug candidates are identified, high throughput assays (HTS) have been developed and have been widely implemented in the pharmaceutical industry. Cassette (or N-in-1) dosing for pharmacokinetic (PK) evaluation is the process of generating in vivo PK data in a higher throughput manner by dosing multiple compounds to individual animals. However, due to generally poor solubility of compounds being tested, high percentages of organic solvents are often used in the formulation vehicle in order to solubilize compounds for cassette studies. Utilization of high organic content in formulation vehicles can result in unwanted side effects and animal tolerability issues. The current study evaluates the suitability of using nanoparticles in an aqueous suspension for cassette IV dosing. Nanoparticles of 10 poorly soluble marketed drugs covering a wide range of clearances were prepared using an electrospray device and evaluated. PXRD, TGA and particle size data were obtained in order to ensure the quality for in vivo evaluation. Phosphate buffered saline (PBS) was used as the vehicle in IV cassette study using nanoparticles and pharmacokinetic estimates from this study were comparable to those from a traditional high organic formulation approach. The use of nanoparticles in an aqueous suspension formulation was demonstrated to be appropriate for cassette dosing. |
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AbstractList | In recent years, one of the biggest challenges for pharmaceutical industry is to increase the speed of finding new medicines while at the same time controlling the ever rising cost of drug discovery and development. In order to increase the speed at which drug candidates are identified, high throughput assays (HTS) have been developed and have been widely implemented in the pharmaceutical industry. Cassette (or N-in-1) dosing for pharmacokinetic (PK) evaluation is the process of generating in vivo PK data in a higher throughput manner by dosing multiple compounds to individual animals. However, due to generally poor solubility of compounds being tested, high percentages of organic solvents are often used in the formulation vehicle in order to solubilize compounds for cassette studies. Utilization of high organic content in formulation vehicles can result in unwanted side effects and animal tolerability issues. The current study evaluates the suitability of using nanoparticles in an aqueous suspension for cassette IV dosing. Nanoparticles of 10 poorly soluble marketed drugs covering a wide range of clearances were prepared using an electrospray device and evaluated. PXRD, TGA and particle size data were obtained in order to ensure the quality for in vivo evaluation. Phosphate buffered saline (PBS) was used as the vehicle in IV cassette study using nanoparticles and pharmacokinetic estimates from this study were comparable to those from a traditional high organic formulation approach. The use of nanoparticles in an aqueous suspension formulation was demonstrated to be appropriate for cassette dosing. |
Author | Chiang, Po-Chang Ubhayaka, Savita Wong, Harvey Deng, Yuzhong Cui, Yong Ran, Yingqing Chou, Kang-Jye La, Hank |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23421169$$D View this record in MEDLINE/PubMed |
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SubjectTerms | Animals Chromatography, Liquid Injections, Intravenous Male Nanoparticles Particle Size Pharmacokinetics Rats Rats, Sprague-Dawley Solubility Tandem Mass Spectrometry Thermogravimetry X-Ray Diffraction |
Title | Novel nanoparticles formulation for cassette dosing via intravenous injection in rats for high throughput pharmacokinetic screening and potential applications |
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