Preparation and Evaluation of 5 Fluorouracil solid dispersion formulations for therapeutic management of colorectal cancer (CRC)

Yinka Oyeniyi, Nemeka D Nnamani

Abstract


Background

A solid dispersion formulation (SD) involves dispersion of poor water soluble active pharmaceutical ingredients (API) in a solubility enhancing polymer with the uttermost goal of improving the oral bioavailability of the API.

Objective

This study is aimed at production and evaluation of 5- Fluorouracil (5- FU) SD formulations for colon delivery using the hot met technique.

Method

The solid dispersions of 5-FU were prepared by hot melting method; The  SD formulations were characterized using a scanning electron microscopy, USP dissolution apparatus type 2, and  MTT assay.

Results

The SEM revealed that all SD formulations particles were in amorphous state, they rod like shaped with size ranging between 98 -112µm. The FTIR spectral show no chemical interactions between the excipients and 5 FU.  The yield (PY), drug entrapment efficiency (DEE) and the drug loading (DL) values were high enough to support commercial scale up of the technique.

SD2 had the highest DEE, cumulative drug released and DL values. This may be responsive for its improved cytotoxicity against HT115 cells. The releases of 5 FU in all the formulations follow both Fickian´s and non-Fickian´s kinetics which are also pH responsive with no sign of dose dumping.

Conclusion

This study demonstrated successful production of pH responsive 5 FU solid dispersions, by hot melt technique. The release follows Korymeyer –Peppas kinetic models and selectively delivered 5 FU to the colon which improved cytotoxicity activity against CRC.


Keywords


Solid dispersion, colorectal cancer and 5-Fluorouracil

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