Abstract
The commercially available parenteral dosage forms of cyclophosphamide (Endoxan®, Cycloblastine®) are manufactured by an aseptic dry-filling technique and exhibit a slow dissolution rate. A novel dosage form has been developed by one of the manufacturers based on the technique of freeze drying. Dissolution rates of both types of formulations were determined and it was shown that the freeze-dried formulation dissolves more rapidly, within 20 seconds, while it takes at least three minutes to dissolve the dry-filled formulation. The chemical stabilities of the cyclophosphamide solutions, obtained after reconstitution and/or dilution of both formulations. have been investigated and tested as a function of drug concentration (20 and 1 mg/mL). solvent (water. 0.9% sodium chloride, 5% dextrose), container material (glass and polyvinyl chloride (pvc)), light conditions (normal room fluorescent light/dark) and temperature (4°, 20,22° and 37°C). The test solutions were analyzed by a stability-indicating reverse phase high performance liquid chromatographic method with ultraviolet detection at 214 nm. Cyclophosphamide solutions (solvent: water; drug concentration: 20 mg/mL) are stable when stored for seven days at 4°C in the dark. At higher temperatures degradation occurred during the test period with 10% loss after seven days at 37°C ambient temperature and 50% loss after seven days storage at 37?C. Similar data were found in admixtures with 5% dextrose and 0.9% sodium chloride and initial drug concentration of 1mg/mL. There are no significant differences in chemical stability between the solutions obtained from reconstitution and dilution of the dry-filled and lyophilized formulations. The type of container materials tested (glass and PVC) HAVE NO INFLUENCE ON the overall chemical stability of cyclophosphamide (concentration: 20 mg/mL) in the dark On the other hand, in diluted solutions (drug concentration: 1 mglmL in 0.9% sodium chloride) exposed to normal room fluorescent light in a day-night cycle at ambient temperature, cyclophosphamide is stable in PVC (less than 5% degradation after seven days storage) but shows 10% degradation in glass. In pvc minibags containing 0.9% sodium chloride. cyclophosphamide (1 mg/mL) shows > 5% degradation when stored for seven days at ambient temperature in the dark. When exposed to normal fluorescent light at ambient temperature the drug (1 mg/mL) degrades for approximate 5% in both glass and PVC containers.
- Received November 4, 1991.
- Accepted February 20, 1992.
- Copyright © Parenteral Drug Association. All rights reserved.
PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.
If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing.
Full issue PDFs are for PDA members only.
Note to pda.org users
The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.