Opportunities for Successful Stabilization of Poor Glass-Forming Drugs: A Stability-Based Comparison of Mesoporous Silica Versus Hot Melt Extrusion Technologies

Abstract

Amorphous formulation technologies to improve oral absorption of poorly soluble active pharmaceutical ingredients (APIs) have become increasingly prevalent. Currently, polymer-based amorphous formulations manufactured by spray drying, hot melt extrusion (HME), or co-precipitation are most common. However, these technologies have challenges in terms of the successful stabilization of poor glass former compounds in the amorphous form. An alternative approach is mesoporous silica, which stabilizes APIs in non-crystalline form via molecular adsorption inside nano-scale pores. In line with these considerations, two poor glass formers, haloperidol and carbamazepine, were formulated as polymer-based solid dispersion via HME and with mesoporous silica, and their stability was compared under accelerated conditions. Changes were monitored over three months with respect to solid-state form and dissolution. The results were supported by solid-state nuclear magnetic resonance spectroscopy (SS-NMR) and scanning electron microscopy (SEM). It was demonstrated that mesoporous silica was more successful than HME in the stabilization of the selected poor glass formers. While both drugs remained non-crystalline during the study using mesoporous silica, polymer-based HME formulations showed recrystallization after one week. Thus, mesoporous silica represents an attractive technology to extend the formulation toolbox to poorly soluble poor glass formers.

Ternary Amorphous Solid Dispersions Containing a High-Viscosity Polymer and Mesoporous Silica Enhance Dissolution Performance

“…Concerning the stabilization of amorphous API into MPC pores, Ditzinger et al have reported that a mesoporous silica formulation was superior to polymer-based hot melt extrusion (HME) formulations in stabilizing noncrystalline API after one week of storage. 6 The loading of drug into/onto MPC can be done by several methods, which include organic solvent methods such as immersion 7 and spray drying, 8−10 or solvent-free methods including ball milling 11 and HME. 12 ASD research is also expanding beyond conventional binary API/carrier systems to include ternary systems, which have been formulated as API/polymer/polymer, 13−15 API/polymer/ surfactant, 16−18 API/polymer/oligomer, 19−21 and API/polymer/MPC systems, 22−26 with the aim of improving bioavailability and stabilizing the amorphous drug.…”

“…Recently, it has been reported that the use of mesoporous carriers (MPCs), which have a high number of nano-scale pores, as an alternative to polymer carriers in ASD formulations can improve the solubility, dissolution rate, and stability of amorphous API. Concerning the stabilization of amorphous API into MPC pores, Ditzinger et al have reported that a mesoporous silica formulation was superior to polymer-based hot melt extrusion (HME) formulations in stabilizing noncrystalline API after one week of storage . The loading of drug into/onto MPC can be done by several methods, which include organic solvent methods such as immersion and spray drying, − or solvent-free methods including ball milling and HME .…”

Tuning the Physical State of Aripiprazole by Mesoporous Silica

“…It requires a lot of work and time and, frequently, it turns out that the conditions needed for its formation may be difficult to repeat, resulting in problems in manufacturing procedures. 22,23 In this paper, the impact of mesoporous silica (MS) on the physical state of aripiprazole (ARP) will be presented. The use of ARP, an atypical antipsychotic employed in treating various mood and psychotic disorders, as a model drug was essential.…”

Effect of Span 20 Feeding Zone in the Twin Screw Extruder on the Properties of Amorphous Solid Dispersion of Ritonavir

“…Polymer-based ASDs can satisfy two requirements: suspending the drug in an amorphous form and inhibiting precipitation from supersaturated states [ 8 ]. It has been reported that various pharmaceutical polymers can be used as precipitation inhibitors (PIs) in ASDs, such as PVPVA, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMC-AS), and Eudragit [ 9 ].…”