Related Experiment Video
Updated: Oct 6, 2025

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
Creation of Hydrochlorothiazide Pharmaceutical Cocrystals Via Hot-Melt Extrusion for Enhanced Solubility and
Sagar Narala1, Dinesh Nyavanandi1, Abdullah Alzahrani1
1Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Oxford, Mississippi, 38677, USA.
Abstract:
Crystal engineering is an emerging tool for altering the physicochemical properties of drug candidates. The objective of the current investigation was to develop cocrystals of hydrochlorothiazide (HCT) with coformers such as nicotinamide (NIC), resorcinol (RSL), and catechol (CAT) using hot-melt extrusion (HME) technology. The liquid-assisted grinding (LAG) method was used to prepare cocrystals by grinding the drug and coformer in a definite molar ratio as a reference and to check the feasibility of cocrystal formation. Cocrystals were prepared using HME and evaluated with differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffractometry, and scanning electron microscopy and compared with LAG cocrystals. Barrel temperature was the critical process parameter for producing high-quality cocrystals in HME. All cocrystals exhibited improved solubility compared to the native drug, and HCT-NIC cocrystals showed a two-fold increase in solubility. Similarly, HCT-RSL and HCT-CAT showed higher solubility profiles and improved diffusion/permeability characteristics compared to that of the pure HCT due to the drug-coformer interactions in the cocrystals. In this study, the solubility of the coformer was the key factor determining cocrystal solubilization. However, hot-melt extrusion is an alternative technology for creating pharmaceutical cocrystals and has potential for industrial scale-up.
Related Concept Videos
Bioavailability Enhancement: Drug Solubility Enhancement
Bioavailability Enhancement: Drug Permeability Enhancement
Factors Influencing Drug Absorption: Pharmaceutical Parameters
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

