The efficient development of a sildenafil orally disintegrating tablet using a material sparing and expedited approach.

Abstract

The purpose of this work is to develop an orally disintegrating tablet (ODT) of sildenafil (SIL) using a materials sparing and expedited development approach, enabled by the materials science tetrahedron principle and predictive technologies. To overcome the problem of bitter taste of SIL, an artificial sweetener, acesulfame (Acs), was used to form a sweet SIL salt (SIL-Acs) using an effective reaction crystallization process to prepare phase pure bulk SIL-Acs with a high yield. The SIL-Acs salt shows excellent thermal stability (Tm=200.2°C), low hygroscopicity, and acceptable dissolution rate. Formulation and process parameters were optimized based on powder flowability, tabletability, tablet disintegration time, and expedited friability. A particle engineering approach, i.e., nanocoating, was employed to attain adequate flowability of the SIL-Acs ODT formulation required for the direct compression process. The wide range of compression forces for making tablets exhibiting both fast disintegration time (≤30s) and low friability (≤0.8%) suggested excellent flexibility in manufacturing SIL-Acs ODT. The development of a sildenafil ODT formulation, including solid form selection and characterization, crystallization method development, formulation development, and DC process optimization, only required 5g of SIL citrate and 2weeks of time.