Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble anticancer drugs

• Published in: Pharmaceutical research Vol. 13; no. 2; pp. 272 - 278
• Main Authors: MERISKO-LIVERSIDGE, E, SARPOTDAR, P, JONES, J, CORBETT, T, COOPER, E, LIVERSIDGE, G. G, BRUNO, J, HAJII, S, WEI, L, PELTIER, N, RAKE, J, SHAW, J. M, PUGH, S, POLIN, L
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-02-1996
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Chemical Phenomena; Chemistry, Pharmaceutical - methods; Chemistry, Physical; Crystallization; Drug Delivery Systems; Drug Screening Assays, Antitumor; Female; General aspects; Mammary Neoplasms, Experimental - drug therapy; Medical sciences; Mice; Mice, Inbred C3H; Particle Size; Pharmacology. Drug treatments; Solubility; Suspensions; Antineoplastic agent; Pharmaceutical technology; Preparation; Dosage form; Water solubility; Insolubilization; Particle suspension; Nanocrystal
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/a:1016051316815

Determine if wet milling technology could be used to formulate water insoluble antitumor agents as stabilized nanocrystalline drug suspensions that retain biological effectiveness following intravenous injection.
The versatility of the approach is demonstrated by evaluation of four poorly water soluble chemotherapeutic agents that exhibit diverse chemistries and mechanisms of action. The compounds selected were: piposulfan (alkylating agent), etoposide (topoisomerase II inhibitor), camptothecin (topoisomerase I inhibitor) and paclitaxel (antimitotic agent). The agents were wet milled as a 2% w/v solids suspension containing 1% w/v surfactant stabilizer using a low energy ball mill. The size, physical stability and efficacy of the nanocrystalline suspensions were evaluated.
The data show the feasibility of formulating poorly water soluble anticancer agents as physically stable aqueous nanocrystalline suspensions. The suspensions are physically stable and efficacious following intravenous injection.
Wet milling technology is a feasible approach for formulating poorly water soluble chemotherapeutic agents that may offer a number of advantages over a more classical approach.