Investigation of drug-polymer miscibility and design of ternary solid dispersions for oral bioavailability enhancement by Hot Melt Extrusion

Muralidhar Pisay, Prerana D. Navti, Vinay Rao, Kunnatur Balasundara Koteshwara, Srinivas Mutalik

Research output: Contribution to journalArticlepeer-review

Abstract

The present investigation aimed to enhance the oral bioavailability of the poorly water-s Glibenclamide (GLB) using amorphous solid dispersions (ASD) with various polymers. The drug-polymer miscibility was predicted using in-silico molecular dynamics simulation, Hansen solubility parameter, Flory-Huggins theory, and Gibb's free energy calculation. To enhance the solubility further, the effervescence amorphous solid dispersions (ESD) technique was included. The solid dispersions (SDs) were initially prepared using the solvent evaporation method. The polymers that enhanced the solubility were optimized by the Design of Experiments (DoE) approach and Hot Melt Extruder (HME) technique. The optimized formulation were subjected to various solid and liquid state characterizations. The XRD and DSC study confirmed conversion into the amorphous form, and hydrogen bonding between the drug and polymer was confirmed by FTIR and 1H NMR. The morphology was assessed by SEM study. The optimized formulation showed enhanced solubility and dissolution data. The optimized formulation remained stable at the accelerated conditions for six months. The optimized formulation subjected to the pre-clinical pharmacokinetic and pharmacodynamics study showed a better pharmacokinetics profile of the drug and enhanced pharmacological activity. Introducing the effervescent technique to the conventional ASD technique helped to enhance the physicochemical properties with improved pharmacological action.

Original languageEnglish
Article number105107
JournalJournal of Drug Delivery Science and Technology
Volume90
DOIs
Publication statusPublished - 12-2023

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Investigation of drug-polymer miscibility and design of ternary solid dispersions for oral bioavailability enhancement by Hot Melt Extrusion'. Together they form a unique fingerprint.

Cite this