The Journal of pharmacy and pharmacology · 2014
Disulfiram-loaded immediate and extended release vaginal tablets for the localised treatment of cervical cancer.
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Baffoe Clara S, Nguyen Nhi, Boyd Peter, Wang Weiguang, Morris Mark, McConville Christopher
Аннотация
OBJECTIVES: To develop and manufacture both immediate and sustained release vaginal tablets containing the anticancer drug disulfiram, which has the potential to be used as a non-invasive treatment for cervical cancer.
METHODS: Disulfiram-loaded vaginal tablets were manufactured at pilot scale using the direct compression method. These tablets were tested in accordance with the European Pharmacopeia testing of solid dosage form guidelines. They were also tested using a biorelevant dissolution method as well as a dual-chambered release model designed to better mimic the dynamic nature of the vaginal vault.
KEY FINDINGS: We have developed both immediate and sustained release vaginal tablets, which when manufactured at pilot scale are within the limits set by the European Pharmacopeia for the testing of solid dosage forms. Furthermore, these tablets are capable of releasing disulfiram in vitro using the dual-chambered release model at levels 25,000 times and 35,000 times greater than its IC50 concentration for the HeLa cervical cancer cell line.
CONCLUSIONS: The successful pilot manufacture and testing of both the immediate and sustained release disulfiram-loaded vaginal tablets warrant further investigation, using an in-vivo model, to assess their potential for use as a non-invasive treatment option for cervical cancer.
METHODS: Disulfiram-loaded vaginal tablets were manufactured at pilot scale using the direct compression method. These tablets were tested in accordance with the European Pharmacopeia testing of solid dosage form guidelines. They were also tested using a biorelevant dissolution method as well as a dual-chambered release model designed to better mimic the dynamic nature of the vaginal vault.
KEY FINDINGS: We have developed both immediate and sustained release vaginal tablets, which when manufactured at pilot scale are within the limits set by the European Pharmacopeia for the testing of solid dosage forms. Furthermore, these tablets are capable of releasing disulfiram in vitro using the dual-chambered release model at levels 25,000 times and 35,000 times greater than its IC50 concentration for the HeLa cervical cancer cell line.
CONCLUSIONS: The successful pilot manufacture and testing of both the immediate and sustained release disulfiram-loaded vaginal tablets warrant further investigation, using an in-vivo model, to assess their potential for use as a non-invasive treatment option for cervical cancer.