Biomaterial Database

Pharmaceutical development of a parenteral lyophilized formulation of the investigational polymer-conjugated platinum anticancer agent AP 5280. 2003

M Bouma, and B Nuijen, and R Harms, and J R Rice, and D P Nowotnik, and D R Stewart, and B A J Jansen, and S van Zutphen, and J Reedijk, and M J van Steenbergen, and H Talsma, and A Bult, and J H Beijnen

Department of Pharmacy and Pharmacology, Slotervaart Hospital/ The Netherlands Cancer Institute, Amsterdam, The Netherlands. m.bouma@wza.nl

AP 5280 is a novel polymer-conjugated platinum anticancer agent showing promising in vitro and in vivo activity against solid tumors. The aim of this study was to develop a parenteral pharmaceutical dosage form for phase I clinical trials. AP 5280 drug substance was characterized by using a wide range of analytical techniques and showed excellent solubility in water. However, as aqueous solutions of AP 5280 proved to be labile upon sterilization by moist heat, it was decided to develop a lyophilized dosage form. Initially, glass vials were used as primary packaging, but this led to a high breakage rate, which could be completely prevented by the use of CZ resin vials. Stability studies to date show that the lyophilized product in glass vials is stable for at least 12 months when stored at 2-8 degrees C in the dark and the lyophilized product in CZ resin vials is stable for at least 6 months under these conditions. Photostability testing revealed photolability of AP 5280 drug substance and lyophilized product in both types of primary container, necessitating storage in the dark. The first clinical experiences indicate that the proposed formulation is fully applicable for use in the clinical setting.

UI	MeSH Term	Description	Entries
D007263	Infusions, Parenteral	The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.	Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D009944	Organoplatinum Compounds	Organic compounds which contain platinum as an integral part of the molecule.	Compounds, Organoplatinum
D002626	Chemistry, Pharmaceutical	Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.	Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D005612	Freeze Drying	Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products.	Lyophilization,Drying, Freeze,Dryings, Freeze,Freeze Dryings,Lyophilizations
D000178	Acrylamides	Colorless, odorless crystals that are used extensively in research laboratories for the preparation of polyacrylamide gels for electrophoresis and in organic synthesis, and polymerization. Some of its polymers are used in sewage and wastewater treatment, permanent press fabrics, and as soil conditioning agents.
D000970	Antineoplastic Agents	Substances that inhibit or prevent the proliferation of NEOPLASMS.	Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013678	Technology, Pharmaceutical	The application of scientific knowledge or technology to pharmacy and the pharmaceutical industry. It includes methods, techniques, and instrumentation in the manufacture, preparation, compounding, dispensing, packaging, and storing of drugs and other preparations used in diagnostic and determinative procedures, and in the treatment of patients.	Technology, Pharmacy,Pharmaceutic Technology,Pharmaceutical Technology,Pharmacy Technology,Technology, Pharmaceutic
D015507	Drugs, Investigational	Drugs which have received FDA approval for human testing but have yet to be approved for commercial marketing. This includes drugs used for treatment while they still are undergoing clinical trials (Treatment IND). The main heading includes drugs under investigation in foreign countries.	Investigational Drug,Investigational New Drug,Investigational New Drugs,Investigational Drugs,Drug, Investigational,Drug, Investigational New,Drugs, Investigational New,New Drug, Investigational,New Drugs, Investigational
D017671	Platinum Compounds	Inorganic compounds which contain platinum as the central atom.	Platinum Compound,Platinum Compounds, Inorganic,Platinum-Containing Compound,Platinum-Containing Compounds,Compound, Platinum,Compound, Platinum-Containing,Compounds, Inorganic Platinum,Compounds, Platinum,Compounds, Platinum-Containing,Inorganic Platinum Compounds,Platinum Containing Compound,Platinum Containing Compounds