Formulation and In-vitro Evaluation of Macitentan Solid Dispersions

Radhika Padarthy¹, Dr. M. Venkata Ramana^2
1Research Scholar, Department of Pharmaceutics, JNTU Hyderabad, Telangana
²Principal, Gurram Balanarasaiah Institute of Pharmacy, Ghatkesar, Ranga Reddy–501301.

ABSTRACT
Cyclodextrin inclusion complexation is one of the promising approaches to enhance the drug dissolution rate and solubility. As the drug is included in the hydrophilic cavity of cyclodextrins, the solubility and dissolution rate of poorly soluble drug can be expected to be improved.  The main objective of the present investigation was to improve the dissolution rate and solubility of an antihypertensive drug Macitentan using cyclodextrin inclusion complexation and followed by converting to orally administerable tablets using a super disintegrates. Cyclodextrin Drug Inclusion complexes (1:1, 1:3 and 1:5) of macitentan were prepared by solvent evaporation method using different cyclodextrins such as α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), Hydroxy Propyl β-cyclodextrin (HP-β-CD), Methylated  β-cyclodextrin (M-β-CD) and γ-Cyclodextrin (γ-CD). Prepared inclusion complexes were evaluated for their solubility and in vitro drug release. It was observed that formulations prepared with HP-β-CD at 1:5 ratio (MCD9) has shown faster drug release and higher solubility than other formulations. As drug release of this is higher than other formulations, it was further converted to oral tablet using various superdisintegrants such as crosscaramellose sodium, sodium starch glycollate and soluplus. Similarly tablets were prepared using pure drug as such and keeping other excipients at same level. Comparative evaluation of prepared tablets was done. From in vitro dissolution data of tablets, it was observed that the cyclodextrin tablet formulation (MCDT3) prepared with soluplus has shown faster drug release than marketed formulation and pure drug formulation (MPDT3). Hence, it can be concluded that the cyclodextrin inclusion complexation and further conversion to tablet using superdisintegrants is a promising approach to improve the solubility and dissolution rate of poorly soluble drug like macitentan.
Keywords: Macitentan, Cyclodextrins, α-cyclodextrin, glycollate, HP-β-CD