Abstract

This contractor is assigned difficult formulation problems by the NCI and is asked to develop a suitable parenteral dosage form. About two to four such problem compounds are assigned annually. Usually the compounds possess inadequate solubility and/or stability. The contractor is required to develop stability indicating assays for each compound and perform both solubility and stability studies leading to a pharmaceutical dosage form. The major effort involves developing suitable methods to improve drug solubility. Then the contractor is required to prepare 30 to 90 units of the dosage from for subsequent evaluation in an appropriate tumor model system. Solublity and stability behavior of the finished dosage form are evaluated under simulated use conditions: i.e. after constitution and further dilution with intravenous fluids.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Treatment (NCI)
Type
Research and Development Contracts (N01)
Project #
N01CM067912-003
Application #
3614446
Study Section
Project Start
1986-06-30
Project End
1989-06-29
Budget Start
1988-06-30
Budget End
1989-06-29
Support Year
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Kansas Lawrence
Department
Type
Schools of Pharmacy
DUNS #
072933393
City
Lawrence
State
KS
Country
United States
Zip Code
66045

  Publications

Rajewski, R A; Traiger, G; Bresnahan, J et al. (1995) Preliminary safety evaluation of parenterally administered sulfoalkyl ether beta-cyclodextrin derivatives. J Pharm Sci 84:927-32
Sisco, J M; Stella, V J (1992) Is ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] unusually reactive for an imide? Pharm Res 9:1076-82
Mathew, A E; Mejillano, M R; Nath, J P et al. (1992) Synthesis and evaluation of some water-soluble prodrugs and derivatives of taxol with antitumor activity. J Med Chem 35:145-51
Sisco, J M; Stella, V J (1992) An unexpected hydrolysis pH-rate profile, at pH values less than 7, of the labile imide, ICRF-187: (+)-1,2-bis-(3,5-dioxopiperazin-1-yl)propane. Pharm Res 9:1209-14
Waugh, W N; Trissel, L A; Stella, V J (1991) Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers. Am J Hosp Pharm 48:1520-4
Prankerd, R J; Stella, V J (1990) The use of oil-in-water emulsions as a vehicle for parenteral drug administration. J Parenter Sci Technol 44:139-49
al-Razzak, L A; Benedetti, A E; Waugh, W N et al. (1990) Chemical stability of pentostatin (NSC-218321), a cytotoxic and immunosuppressant agent. Pharm Res 7:452-60
Prankerd, R J; Frank, S G; Stella, V J (1988) Preliminary development and evaluation of a parenteral emulsion formulation of penclomedine (NSC-338720;3,5-dichloro-2,4-dimethoxy-6-trichloromethylpyridine): a novel, practically water insoluble cytotoxic agent. J Parenter Sci Technol 42:76-81
Paborji, M; Waugh, W N; Stella, V J (1987) Mechanistic investigation of the degradation of sulfamic acid 1,7-heptanediyl ester, an experimental cytotoxic agent, in water and 18oxygen-enriched water. J Pharm Sci 76:161-5