Abstract
Purpose: :
To evaluate effect of different methods and process variables on nanoparticulate based formulation of a water soluble prodrug of dexamethasone.
Methods: :
We have synthesized dipeptide conjugated prodrug of dexamethasone in our laboratory (Val-Val-dexamethasone). Because of higher aqueous solubility, developments of a nanoparticulate based formulation with higher entrapment efficiency possess a major challenge. We have formulated nanoparticulate based formulation utilizing single emulsion method, double emulsion method and solid in oil in water (S/O/W) method. We prepared hydrophobic ion pairing (HIP) complex of prodrug with dextran sulphate and used that complex to make nanoparticles using S/O/W method. PLGA 85:15 was employed for the preparation of nanoparticles. Prepared nanoparticles were studied for their entrapment efficiency, size and surface morphology.
Results: :
The entrapment efficiency of nanoparticles was highly dependent on the method of preparation. Nature of polymer and stabilizer concentration did not affect entrapment efficiency of the nanoparticles in single emulsion method. pH of internal phase and ratio of aqueous to organic phase has moderately enhanced the entrapment efficiency in double emulsion method. But still maximum entrapment was just 12-15% in optimized formulation. S/O/W method utilized to prepare nanoparticles of HIP complex was highly dependent on process parameters. The size of the nanoparticles was around 200nm in all the cases. Maximum entrapment of the val-val-dexamethasone was obtained up to around 40% in case S/O/W.
Conclusions: :
Development of a nanoparticulate formulation of a water soluble drug is significant challenge. Different methods of preparation and process variables have shown higher impact on the entrapment of prodrug inside the nanoparticles. Nanoparticle preparation by S/O/W method utilizing HIP complex has shown promising result (maximum entrapment around 40%).
Keywords: corticosteroids • retina • pH