A COMPARATIVE STUDY OF LEDIPASVIR SOLID DISPERSION TECHNIQUE USING SPRAY DRYING AND HOT-MELT EXTRUSIONAbstract
Ledipasvir is an inhibitor of the HCV NS5A protein, which is required for viral replication used in the treatment of hepatitis C. Ledipasvir is practically insoluble (less than 0.1 mg/mL) across the pH range of 3.0-7.5 Due to low solubility, it results into poor bioavailability after oral administration. Therefore, solid dispersions (SDs) of Ledipasvir were prepared by two methods, i.e. spray drying technique and hot-melt extrusion by using various carriers like polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (soluplus), hypromellose 5 cPs and copovidone (kollidonVA64) to increase its aqueous solubility. Faster and high drug release was found in the SDs which was prepared by spray drying technique (SDT) with co-povidone in the ratio of 1:2 as compared with hot melt extrusion (HME) using drug substance and soluplus in the ratio of 1:2. There are 5 folds increases in the solubility of Ledipasvir prepared by SDT and HME compared with plain drug substance. FSD3 and FHM9 are finalized as optimized formulations prepared by SDT and HME based on their solubility, drug substance content and in-vitro drug dissolution studies. FT-IR, XRD and DSC of SDs by SDT and HME showed a change in crystalline structure toward an amorphous form of Ledipasvir. The obtained results suggested that developed Ledipasvir SDs by SDT and HMT has potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of Ledipasvir.
P. C. R. Guntaka * and S. Lankalapalli
GITAM Institute of Pharmacy, GITAM University, Rushikonda, Visakhapatnam, Andhra Pradesh, India.
02 April, 2018
03 June, 2018
26 June, 2018
01 December, 2018