A bilayer vaginal tablet for the localized delivery of disulfiram and 5-fluorouracil to the cervix
Abidin, Ismin Zainol
Fehrenbach, Gustavo Waltzer
Murphy, Emma J.
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This study was performed to develop an adjuvant therapy in the form of a self-administered vaginal tablet regimen for the localized delivery of chemotherapeutic drugs. This therapy will help to reduce relapse by eradicating cancerous cells in the margin of cervical tumors. The vaginal tablet is a very common formulation that is easy to manufacture, easy to place in the vagina, and has a low cost of manufacture, making them ideal for use in developing countries. A combination of disulfiram and 5-fluorouracil, which are both o -patent drugs and provide di erent modes of action, were evaluated. The tablets developed were evaluated for weight variation, thickness, hardness, friability, swelling index, di erential scanning calorimetry (DSC), particle morphology, in vitro drug release, and cytotoxicity on Ca-Ski cells. Both layers were designed to release both drugs concurrently for a synergistic e ect. The polymer–polymer interaction between the layers was able to reduce the loss of formulation due to chitosan. While the bilayer tablet had satisfactory performance in the physicochemical tests, in vitro cell culture with Ca-Ski also showed a synergistic e ect using a combination of drugs at a low dose. However, the formulation only had 24-h dose release before degradation. Further drug combinations should be evaluated in subsequent studies.
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