Supersaturating drug delivery systems: The potential of co-amorphous drug formulations

Abstract

Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading to high dosage volumes and thereby challenges in the formulation of the final dosage form. As a response to the shortcomings of the ASDs, the so-called co-amorphous formulations, which are amorphous combinations of two or more low molecular weight components, have emerged as an alternative formulation strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition is needed. The current status of this research is reviewed in this paper. Furthermore, the potential of novel preparation methods for co-amorphous systems with respect to the current preparation methods are discussed.

Permeability of glibenclamide through a PAMPA membrane: The effect of co-amorphization

“…Thus, this study showed that detailed investigation of the supersaturation and its effects on drug permeability is needed for co-amorphous formulations, since the components of a co-amorphous mixture may also have unpredictable and unwanted effects on dissolution and absorption potential in vivo and thus potential for enhancing drug bioavailability [67].…”

Advances in coamorphous drug delivery systems

“…The “spring” is the higher energy amorphous API that facilitates dissolution and supersaturation of drugs when dissolves along with the other drugs or excipients. Here, supersaturation can be affected by multiple factors such as the exact nature of the dissolution media, the free energy difference between the crystalline and amorphous phases, and release rates of different components, etc 114 . The “parachute” is the co-former that delays nucleation and crystal growth of amorphous API to maintain or prolong the supersaturation over the desirable time period.…”

Solubilization of itraconazole by surfactants and phospholipid-surfactant mixtures: interplay of amphiphile structure, pH and electrostatic interactions

“…Itraconazole has been widely used as a model compound for development of advanced drug formulations. Considerable attention has been devoted to amorphous solid dispersions [1 4 -20], which aim at ensuring fast dissolution kinetics and drug supersaturation in the small intestine, hence leading to increased absorption and bioavailability [21][22][23]. Liposomes have also been considered as potential vehicles for itraconazole delivery by combining phospholipids with polymers, such as chitosan [24], or with bile salts [25] and cholesterol [26].…”