Temperature- and volume-dependent dissolution of amifostine 500 mg reconstituted for subcutaneous injection in normal saline or sterile water for injection

Abstract

3207 Background: Because the dissolution of amifostine (Ethyol) 500 mg in 0.9% normal saline (NaCl) or sterile water for injection (SWI) for subcutaneous administration is temperature- and volume-dependent, studies were performed to evaluate amifostine dissolution using three different volumes of the two diluents at four temperatures. Methods: Amifostine 500 mg was reconstituted in 2.0, 2.5, or 2.9 mL NaCl or SWI at 15, 20, 25, and 30°C with gentle rotation in controlled water bath. Dissolution times were determined visually. Reconstituted vials were subsequently held in a water bath at 22°C for 5 hr or 4°C for 8 hr. The stability of the amifostine solution was assessed by HPLC analysis of WR-1065, the primary hydrolysis product. Results: The final volume after reconstitution of amifostine 500 mg in 2.5 mL NaCl was 2.88 ± 0.04 mL, and in 2.9 mL NaCl the final volume was 3.34 ± 0.05 mL. Mean levels of WR-1065 in 2.9 mL NaCl were 0.6% ± 0.1% after 5 hr at 22°C and 0.4% ± 0.1% after 8 hr at 4°C, well below the lot-release specification of 1.3%. Dissolution times are summarized in Table 1. Conclusions: Dissolution of amifostine for subcutaneous injection is volume- and temperature-dependent. Reconstitution of lyophilized amifostine powder (500 mg) with 2.9 mL NaCl or SWI (final volume, 3.3–3.4 mL) at 20–25° C, (68–77° F) results in complete dissolution within minutes. Reconstitution in smaller volumes such as 2.0 mL or 2.5 mL is feasible, but requires more time, and/or warmer temperature. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune MedImmune MedImmune MedImmune