Supersaturable self-microemulsifying drug delivery system enhances dissolution and bioavailability of telmisartan

Abstract

To enhance the dissolution and oral bioavailability of telmisartan (TMS), a poorly water-soluble anti-hypertensive drug, a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) was developed. Amorphous alkalinized TMS (AAT) was formulated into a SMEDDS, composed of Capmul® MCM (oil), Cremophor^® RH40 (surfactant), and tetraglycol (co-surfactant). Although the SMEDDS was rapidly dissolved (>80% within 5 min) in a limited condition (500 mL, pH 6.8), drug precipitation was observed over time, resulting in a decrease in dissolution levels. The precipitation was due to drug recrystallization, as determined by differential scanning calorimetry and powder X-ray diffraction analyses. Several polymers, including Soluplus^® (SOL), were screened as precipitation inhibitors; ultimately, SuSMEDDS-SOL was prepared by admixing SOL and the SMEDDS at a 5:100 (w/w) ratio. SuSMEDDS-SOL was superior in terms of dissolution efficiency (>90% over 2 h) and dissolution-retaining time (no precipitation over 2 h). An in vivo pharmacokinetic study in rats revealed that the oral bioavailability of SuSMEDDS-SOL was 4.8-, 1.3-, and 1.2-fold greater than those of the TMS suspension, AAT solution, and SMEDDS, respectively. Therefore, SuSMEDDS-SOL is a promising candidate to enhance the dissolution and oral bioavailability of TMS.

Keywords:

• Telmisartan
• supersaturable self-microemulsifying drug delivery system (SuSMEDDS)
• precipitation inhibitor
• Soluplus
• dissolution
• bioavailability

Acknowledgments

The authors thank Editage (www.editage.co.kr) for English language editing (CAUNE_6103).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Chung-Ang University Graduate Research Scholarship in 2019. This work was also supported in part by a grant from the National Research Foundation of Korea (NRF) funded by the Korea government (MSIP) [No. 2019R1G1A1100173].