PT  - JOURNAL ARTICLE
AU  - R. J. Prankerd
AU  - S. G. Frank
AU  - V. J. Stella
TI  - 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
DP  - 1988 May 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 76--81
VI  - 42
IP  - 3
4099  - http://journal.pda.org/content/42/3/76.short
4100  - http://journal.pda.org/content/42/3/76.full
SO  - PDA J Pharm Sci Technol1988 May 01; 42
AB  - Penclomedine (NSC-338720) is a novel cytotoxic agent which has shown activity in several tumor model systems when screened as an aqueous suspension by National Cancer Institute. To more fully evaluate the cytotoxic activity of this practically water insoluble drug (≈ / μg/mL), a parenteral dosage form containing >5 mg/mL of penclomedine was desired. Therefore, the purpose of the present study was to evaluate the solubility characteristics of penclomedine in various solvents and to explore methods for the development of a safe parenteral dosage form for further testing purposes. A de novo emulsion formulation was developed. Solutions of penclomedine in soybean oil were emulsified with water using lecithin as the emulsifying agent. These emulsions had mean hydrodynamic panicle sizes (quasi-elastic laser light scattering) of 0.24–0.32 μm with a particle size distribution width of <0.2 μm. Penclomedine concentrations of up to 10 mg/mL could be prepared in the final emulsion, which was physically and chemically stable for at least one year under refrigeration conditions. Cytotoxicity testing of the de novo emulsion formulation of penclomedine was carried out in mice bearing i.p. implanted P38S leukemia cells. Intraperitoneal and intravenous administration of the emulsion formulation showed better cytotoxic activity when compared to an aqueous suspension of the solid bulk drug at comparable doses.