Acta Pharm. 62 (2012) 411-432
Original research paper
An in
vitro and in vivo comparative study of directly compressed solid
dispersions and freeze dried sildenafil citrate
sublingual tablets for management of pulmonary arterial
hypertension
REHAM ZAYED, AMANY O. KAMEL, MARWA SHUKR and ABD EL-HAMID
EL-SHAMY
1
Department
of Pharmaceutics, National Organization for Drug Control and Research, Cairo,
Egypt
2
Department
of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams
University, Cairo, Egypt
Accepted May 30, 2012
Sildenafil citrate (SILD) orodispersable sublingual tablets (ODSTs) have been developed using two comparative techniques for improving their oral disintegration, dissolution and bioavailability in order to manage acute attacks of pulmonary arterial hypertension (PAH). The techniques employed were direct compression of SILD-poloxamer 188 solid dispersions (SDs) and freeze drying using various excipients. The physicochemical and solid-state properties, as well as the dissolution behavior of the tablets were evaluated. Moreover, SILD bioavailability in human volunteers from the prepared ODSTs was compared to that of the conventional oral tablet. Incorporation of SD of poloxamer188 in sublingual tablets together with Pharmaburst using the direct compression technique enhanced the extent and dissolution rate of SILD with 100 % of drug being dissolved after 7 minutes. However, the lyophilization process was superior in enhancing dissolution and 100 % of SILD was dissolved after only one minute. Moreover, the in vivo study showed that the AUC0-12 of lyophilized tablets was significantly higher than that of directly compressed tablets, with bioavailability values of 159.81 and 140.85 %, respectively,compared to the commercial oral product.
Keywords: sildenafil, orodispersable sublingual tablets, pulmonary arterial hypertension, poloxamer 188, solid
dispersions, direct compression, freeze drying