Sorbents for Toxic-Metal Removal in Pharmaceutical Development and Manufacture

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$150,000.00
Award Year:
2011
Program:
SBIR
Phase:
Phase I
Contract:
1R43FD004079-01
Award Id:
n/a
Agency Tracking Number:
R43FD004079
Solicitation Year:
2011
Solicitation Topic Code:
FDA
Solicitation Number:
PA10-050
Small Business Information
TDA RESEARCH, INC., 12345 W 52ND AVE, WHEAT RIDGE, CO, 80033-1916
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
181947730
Principal Investigator:
GIRISH SRINIVAS
(303) 940-2321
gsrinivas@tda.com
Business Contact:
GIRISH SRINIVAS
(303) 940-2300
jdwright@tda.com
Research Institute:
Stub




Abstract
DESCRIPTION (provided by applicant): Sorbents for Toxic-Metal Removal in Pharmaceutical Development and Manufacture SBIR Phase I Application P.I.: Girish Srinivas, TDA Research, Inc. The overall project goal is to minimize toxic impurities in pharmaceuticals that arise during drug synthesis. Toxic contaminants include the metals used as catalysts during drug synthesis and undesired organic side-products produced by metal catalysts remaining in solution between synthetic steps. Sorbents are being developed to lower concentrations of catalytic metals, Pd, Pt, Rh, Ru and Ir to below 500 parts per billion by mass, the recommended maximum for intravenous injection. Homogeneous catalysts using Pt-group metals, and especially Pd, have revolutionized drug development and synthesis. However, many coordination compounds of the Pt-group metals have been found to be extremely toxic, producing effects similar to mercury and lead. This is well established from the known neurotoxicity and cytotoxicity of the anti- cancer agents, cis-platinum, cis-palladium and their analogues, which bind strongly to DNA and block transcription of critical neural enzymes and also bind, for example, to sulfhydryl groups at active sites of enzymes that are critical for energy metabolism in thenervous system. Moreover, homogeneous catalysts used in drug synthesis are often designed with lipophilic ligands, which allow rapid transport through lipid membranes analogous to transport of methyl mercury and tetraethyl lead. Modern drug synthesis may involve three or more catalytic steps. If metal catalysts used in early steps are not removed, they may catalyze formation of toxic organic side- products, not easily separated from drug molecules. Homogeneous catalysts may degrade, forming cluster compounds and nano-suspensions, which, if not removed between synthesis steps, catalyze additional side-reactions. To remove the entire range of toxic-metal particles under 10 nm, which are not easily removed by filtration or by centrifugation, carbon sorbents arebeing developed. The porous carbons, specifically designed for the pharmaceutical industry, will remove the entire range of toxic metal species, without significantly adsorbing drug product. PUBLIC HEALTH RELEVANCE: Sorbents for Toxic-Metal Removalin Pharmaceutical Development and Manufacture SBIR Phase I Application P.I.: Girish Srinivas, TDA Research, Inc. Public Health Relevance Statement: Many pharmaceuticals prescribed to millions of patients are contaminated with toxic impurities originatingfrom metal catalysts used during drug synthesis. The toxic metals accumulate in the nervous system causing damage similar to that of mercury and lead. Improved purification of medications will reduce many toxic side-effects.

* information listed above is at the time of submission.

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