Interactions between drugs and polymers influencing hot melt extrusion

Abstract

Objectives Hot melt extrusion (HME) as a technique for producing amorphous solid dispersion (ASD) has been widely used in pharmaceutical research. The biggest challenge for the application of HME is the thermal degradation of drug, poor physical stability of ASD and precipitation of drug during dissolution. Interactions between drugs and polymers may play an important role in overcoming these barriers. In this review, influence of drug-polymer interactions on HME and the methods for characterizing the drug-polymer interactions were reviewed. Key findings Strong drug-polymer interactions, especially ionic interactions and hydrogen bonds, are helpful to improving the thermal stability of drug during HME, enhancing the physical stability of ASD during storage and maintaining supersaturated solution after dissolution in gastrointestinal tract. The interactions can be quantitatively and qualitatively characterized by many analysing methods. Conclusions As many factors collectively determine the properties of HME products, drug-polymer interactions play an extremely important role. However, the action mechanisms of drug-polymer interactions need intensive investigation to provide more useful information for optimizing the formulation and the process parameters of HME.

An investigation into the influence of drug–polymer interactions on the miscibility, processability and structure of polyvinylpyrrolidone-based hot melt extrusion formulations

“…It has been suggested that HME products need to be processed at an extrusion temperature (T ex ) approximately 30-60 o C higher than glass transition temperature (T g ) of the polymer to allow the polymer to have a viscosity low enough to allow extrusion (Chokshi et al, 2005;Li et al, 2014;McGinity et al, 2006). However, it is also necessary to consider the liquefaction of the drug within the processing apparatus, as the presence of a suspension would be expected to increase viscosity and hence impede processing.…”

“…The issue of minimizing processing temperature via molecular interactions, which is itself related to miscibility, so as to reduce the risk of degradation has been highlighted by Li et al (2014) who discussed the possibility of extrusion at temperatures below the melting point of the drug via judicious use of interacting systems. Here we examine the role of such interactions in reducing the extrusion temperature below the Tg of the polymer itself with a concomitant view to examining the capacity for forming molecular dispersions using interactive and (effectively) non-interactive systems.…”

“…The method involves application of mechanical mixing to a heated sample followed by extrusion and/or shaping in a single continuous process (Netchacovitch et al, 2015). The practical and economic feasibility of the approach, together with the favorable dissolution performance of the incorporated API, has attracted great interest within the pharmaceutical industry (Kanaujia et al, 2011;Li et al, 2014;Tian et al, 2013). In order to successfully extrude polymer-based amorphous dispersions, the extrusion temperature is typically set 30 to 60 o C higher than the T g (glass transition temperature) or T m (melting temperature) of the polymer to ensure good flowability of the mixture during the extrusion process (Chokshi et al, 2005;Li et al, 2014;McGinity et al, 2006).…”

“…The practical and economic feasibility of the approach, together with the favorable dissolution performance of the incorporated API, has attracted great interest within the pharmaceutical industry (Kanaujia et al, 2011;Li et al, 2014;Tian et al, 2013). In order to successfully extrude polymer-based amorphous dispersions, the extrusion temperature is typically set 30 to 60 o C higher than the T g (glass transition temperature) or T m (melting temperature) of the polymer to ensure good flowability of the mixture during the extrusion process (Chokshi et al, 2005;Li et al, 2014;McGinity et al, 2006). However, given that the choice of a high T g polymer is often preferred due to the physical stabilisation of the amorphous solid dispersions (Hancock and Zografi, 1997;Sathigari et al, 2012;Shah et al, 2013), the T g of many pharmaceutically acceptable polymers may be too high for the extrusion process for reasons of cost or heat-induced degradation; hence, a more moderate working temperature is required and there is therefore a balance between stabilization of the system and feasibility of manufacture.…”

Formulation development and systematic optimization of stabilized ziprasidone hydrochloride capsules devoid of any food effect

“…In the present formulation, it is imperative that the amalgamation of the polymers and the active substance happens to the best possible extent followed by melting of polymer blend and solubilization of drug substance [25][26][27] . Soluplus is a unique hydrophobic polymer with amphiphilic nature.…”