Crystallisation Behaviour of Pharmaceutical Compounds Confined within Mesoporous Silicon

Abstract

The poor aqueous solubility of new and existing drug compounds represents a significant challenge in pharmaceutical development, with numerous strategies currently being pursued to address this issue. Amorphous solids lack the repeating array of atoms in the structure and present greater free energy than their crystalline counterparts, which in turn enhances the solubility of the compound. The loading of drug compounds into porous materials has been described as a promising approach for the stabilisation of the amorphous state but is dependent on many factors, including pore size and surface chemistry of the substrate material. This review looks at the applications of mesoporous materials in the confinement of pharmaceutical compounds to increase their dissolution rate or modify their release and the influence of varying pore size to crystallise metastable polymorphs. We focus our attention on mesoporous silicon, due to the ability of its surface to be easily modified, enabling it to be stabilised and functionalised for the loading of various drug compounds. The use of neutron and synchrotron X-ray to examine compounds and the mesoporous materials in which they are confined is also discussed, moving away from the conventional analysis methods.

Combining Surface Templating and Confinement for Controlling Pharmaceutical Crystallization

“…As noted previously, each polymorph has a characteristic free energy of formation (ΔG cryst ) and while a certain polymorph may be more stable in the bulk, metastable forms can have a lower ΔG cryst at r crit leading to stabilization of the metastable form under confinement [ 31 ]. Confinement within pores also limits the amount of space available for the growth of a drug crystal, leading to smaller crystals, which have a higher surface area-to-volume ratio and thus a faster dissolution rate [ 30 , 32 ]. Variations in the pore sizes can also lead to different crystal habits due to interactions with the solvent or availability of/access to certain crystal faces [ 30 , 32 , 97 , 98 ].…”

“…Additionally, while some reviews have presented the current state of studies relating to heterogeneous crystallization from surfaces [ 27 , 28 ] and crystallization within nanopores [ 29 , 30 , 31 ], this review focuses on studies using a combination of these methods to tailor the drug form. We first introduce polymorphism in Section 2 , then discuss heterogeneous crystallization and crystallization under confinement in Section 3 and Section 4 to provide a strong context for Section 5 , which reviews the state of the art on combined approaches to controlling crystallization.…”

Degrees of order: A comparison of nanocrystal and amorphous solids for poorly soluble drugs

“…These systems involve nanoscale pores that are large enough to load drug within them, but are too small to allow crystallization (including nanocrystallization). Mesoporous formulations are also expected to reach the market in the near future, and the systems are well reviewed elsewhere (Laitinen et al, 2012, Maleki et al, 2017, Bremmell and Prestidge, 2019, Jones and Bimbo, 2020.…”

Porous Silicon Preparation by Electrochemical Etching in Ionic Liquids

“…Besides dominating solar cells market [1][2][3][4] silicon and its porous form are widely used in various research fields such as optoelectronics, [5][6] biosensing [7][8][9] and biomedical applications. [10][11][12][13][14][15][16] The primary method of obtaining PSi is oxidative etching of a non-porous silicon precursor in hydrofluoric acid solutions. [17] In electrochemical version of silicon etching in fluoride solutions the process can be carried out both in potentiostatic and in galvanostatic mode; the latter option is often preferable because of easier control of the process.…”

“…Silicon-based materials, in particular porous silicon (PSi), are of high demand in the materials sciences. Besides dominating the solar cells market, − silicon and its porous form are widely used in various research fields such as optoelectronics, , biosensing, − and biomedical applications. − …”