Development of solidified self-microemulsifying delivery systems with enhanced stability of sirolimus and extended release

- The stability of SRL in SMEDDS was influenced by the pH of the media.
- Addition of citric acid successfully promoted the stability of SRL in SMEDDS.
- The SRL-SMEDDS was solidified by preparing tablets with HPMC.
- The formulation of SRL-SMEDDS-tablets was optimized to achieve a sustained release for 12 h.

The application of sirolimus (SRL) as immunosuppressive agent is hampered by its poor water solubility and narrow therapeutic range. The self-microemulsifying drug delivery system (SMEDDS) succeeded in improving the solubility of SRL in our previous work. In this study, the formulation of the SMEDDS was further optimized by investigating the influence of the excipients including the media, antioxidant and organic acid. It was demonstrated that addition of 0.20% of citric acid in SMEDDS most efficiently promoted the stability of SRL under high temperature (40 ± 2 °C), high humidity (relative humidity 90 ± 5%) or strong light irradiation (4500 ± 500 lx). SMEDDS absorbed by microcrystalline cellulose (MCC) was mixed with hydroxypropyl methylcellulose (HPMC) to prepare tablets. The optimal formulation composed of 15% of HPMC 100 LV with hardness of 120 N, which had a sustained release of 12 h. Results of X-ray powder diffraction and differential scanning calorimetry demonstrated that SRL in the tablets was in amorphous or molecularly dispersed state. The SMEDDS-tablets presented as promising substrates for water insoluble drugs with enhanced stability and extended release.

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