A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix

Abstract

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 off-patent drugs and provide different modes of action, were evaluated. The tablets developed were evaluated for weight variation, thickness, hardness, friability, swelling index, differential 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 effect. 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 effect 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.

A systematic review of mucoadhesive vaginal tablet testing

“…Tablets are usually prepared by direct compression, which is an easy, rapid, and cheap method (35). Similar to tablets intended for other administrative routes, vaginal tablets also have advantages including portability, avoidance or antimicrobial agents for preservation, and ease of storage and handling (11,18). Furthermore, the application is convenient, with no applicators or supervision needed, giving the user an added advantage of discretion (18,34).…”

“…However, recent research has started using smaller sized tablets. Tablets kept at a smaller size offer a more efficient drug release ability, reduce the risk of an inhomogeneous blend or non-uniform drug content in finished tablets, and can also improve patient comfort and thus compliance (18).…”

“…Tablet formulations are evaluated to comply to specific pharmacopoeia requirements, including precompression (e.g. tabletability, flowability), tablet uniformity, friability, disintegration time, tablet ejection force, and dissolution performance and any other relevant evaluations (18). If any of these requirements are not met, the formulation should be excluded and new formulation is designed and re-evaluated to address identified deficiencies (18).…”

“…Bulk and tapped densities are commonly reported together, as it measures the volume occupied by the powder (of known mass), g/mL, in a graduated cylinder mounted onto a tapping platform. The volume occupied before tapping is reported as the bulk density and after a range of 250-1,000 taps, the volume obtained is reported as the tapped density (18). Both these densities are used to calculate CI and HR to characterize flowability.…”

“…Even with major advancement in the gel (hydrogel) and film formulations, moderate vaginal leakage was still observed and daily administration was required (16). Therefore, vaginal tablets still often represent the typically acceptable dosage form with stability-related advantages and an economical choice for both manufacturers and users (17,18), thus advocating its role and relevance in the vaginal drug delivery system. So, it won't be obsolete just yet.…”