A nanohybrid system for taste masking of sildenafil

Abstract

A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT), for taste masking of sildenafil (SDN). To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN–MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN–MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 ± 0.53%), suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN–MMT and Viagra^®, an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN–MMT during the first 2 hours while almost 100% of drug was released from Viagra^®. However, an in vivo experiment showed that the AEA-coated SDN–MMT exhibited higher drug exposure than Viagra^®. For the AEA-coated SDN–MMT, the area under the plasma concentration– time curve from 0 hours to infinity (AUC_0-∞) and maximum concentration (C_max) were 78.8 ± 2.32 μg · hour/mL and 12.4 ± 0.673 μg/mL, respectively, both of which were larger than those obtained with Viagra^® (AUC_0-∞ = 69.2 ± 3.19 μg · hour/mL; C_max = 10.5 ± 0.641 μg/mL). Therefore, we concluded that the MMT-based nanohybrid is a promising delivery system for taste masking of SDN with possibly improved drug exposure.

Keywords:

• montmorillonite
• nanohybrids
• polyvinylacetal diethylaminoacetate
• sildenafil citrate
• taste masking

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) (SRC program: 2012-0000650, and WCU program: R31-2008-000-10010-0), the Ministry of Knowledge Economy (10030036) and partly by the Ewha Global Top 5 Grant 2011 of Ewha Womans University.

Disclosures

Some authors are inventors of a relevant patent.⁵⁰ The authors declare no other conflicts of interest in this work.

Supplementary information

Table S1 Accuracy and precision of SDN analyses in plasma samples

Table S2 Recovery of SDN spiked into plasma samples

Table S3 In vitro drug dissolution profiles under a simulated buccal and gastric fluid condition

Table S4 Release profiles of sildenafil from (A) SDN–MMT, (B) AEA-coated SDN–MMT, (C) Viagra^®, and (D) sildenafil citrate. The release experiments were performed at pH = 1.2

Figure S1 Fourier transform infrared spectra of (A) sildenafil citrate, (B) montmorillonite (MMT), (C) sildenafil–montmorillonite (SDN–MMT), and (D) polyvinylacetal diethylaminoacetate (AEA)-coated SDN–MMT.

Notes: The circles (●) and the dashed vertical lines show the characteristic peaks seen with intact SDN and MMT.

Figure S2 The particle size distribution of (A) sildenafil–montmorillonite (SDN–MMT) and (B) polyvinylacetal diethylaminoacetate (AEA)-coated SDN–MMT.

Figure S3 Typical electrospray ionization mass spectrometry/mass spectrometry spectra of authentic sildenafil.

Figure S4 Representative chromatograms of (A) sildenafil detected in a plasma sample collected for 2 hours after sildenafil administration, and (B) blank plasma sample collected just before sildenafil administration.

Abbreviations: ES, electrospray; MRM, multiple reaction monitoring; TIC, total ion count.