Category: Formulation and Quality
Purpose: Lipid based drug delivery systems are effective tool for solubility and bioavailability enhancement of poorly water soluble drugs i.e. BCS class II and IV molecules. Ticagrelor (TGR) is an orally active antiplatelet agent, indicated to reduce the rate of thrombotic cardiovascular events. It belongs to BCS Class-IV and having low Log P value 2. Gelucire 48/16® is a PEG 32 mono and diesters of stearic and palmitic acid, with an HLB of 16 and CMC of 153±31 mg/L, which helps to increase solubility of hydrophobic and lipophobic molecules. Being a solid at ambient temperature with a melting point of 48°C, makes it robust and suitable solid solubilizer for melt processes.
The objective of the present study was to prepare lipidic formulations of TGR with Gelucire 48/16® in combination with other lipidic co surfactant and co solvent by hot melt technique to improve solubility and bioavailability of TGR followed by filling of the melt into hard gelatin capsules.
Methods: Gelucire 48/16® based lipidic formulations were fabricated and evaluated to improve solubility and dissolution of TGR. To evaluate the suitability of Gelucire 48/16® for TGR formulations it was melted at 70oC and TGR was dissolved in the molten mass. Solubility studies of TGR and Gelucire 48/16® dispersions in the ratios of 1:0.5, 1:1, 1:2, 1:3, 1:4 and 1:5 were performed in water at 37±0.2oC. Solubility of TGR in other components of formulation was also determined to choose right excipients for solubilization. Three variants of TGR 90 mg capsule formulations with different total fill weights viz. 550 mg, 600 mg and 900 mg were prepared by dispersing TGR in suitable blend of co surfactant and co solvent and adding to molten Gelucire® 48/16. The blend was allowed to homogenize before capsule filling. Developed formulations were evaluated for following parameters:
Ketkee Deshmukh– Technical Manager, Gattefosse India Pvt. Ltd., Mumbai, Maharashtra, India
Sunil Bambarkar– Mumbai, Maharashtra, India
Nabil Farah– Global Technical Director, Gattefosse SAS, Saint Priest, Lyon, Rhone-Alpes, France
Kavita Singh– Mumbai, Maharashtra, India