The objective of our study was to exploit the principles of quality by design (QbD) to assist the formulation development. QbD helped identify the variables causing potential risk to the quality attributes namely, particle size and entrapment efficiency. The factors causing high risk to the quality attributes were further studied using an experimental design in order to improve the product quality. The application of QbD aided the development of stable formulations of enhanced quality. The optimized PEGylated mixed micelles of meloxicam (M-PMM) had a high percent entrapment efficiency of 73.6% ± 0.72% and mean particle size of 132 nm ± 67nm. The cytotoxicity of M-PMM was much higher (GI 50 <10µg/mL) than free meloxicam (MLX) and conventional mixed micelles (GI 50 >80µg/mL). This was achieved essentially due to the presence of PEG corona which enhanced the cellular association with the HT-29 cell lines. The PEG corona also enhanced the stability of the mixed micelles formulation as observed in the zeta potential data. The M-PMM had a zeta potential of -31mv. It was observed that M-PMM was capable of releasing MLX in a slow and sustained manner; releasing 62.7% ± 0.37% drug in 24h. The formation of ellipsoidal mixed micelles was confirmed by small angle neutron scattering (SANS) analysis. The shape and size of the M-PMM was further corroborated by transmission electron microscopy (TEM). The differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD) results justified that MLX was entrapped inside the PEGylated mixed micelles and was stabilized in the amorphous form. A long term stability study indicated that the formulation was stable for three months. As a result, it was concluded that PEGylated mixed micelles can be considered to be a promising system for the delivery of MLX. Furthermore, the in vitro cytotoxicity results affirmed that M-PMM could serve as a better alternative for treating and preventing human colorectal cancer.
