Nanoconfinement Effects on the Glass Transition and Crystallization Behaviors of Nifedipine

Abstract

The impact of nanoconfinement on the crystallization and glass transition behaviors of nifedipine (NIF) has been investigated using differential scanning calorimetry. Nanoconfinement was provided by imbibing the NIF into a porous medium (controlled pore glass, CPG), and results were compared with the unconfined bulk material. Consistent with previous results from the literature, both glass transition temperature T g and melting temperature T m decrease with decreasing pore size. The melting temperature was found to decrease with the reciprocal of pore diameter and could be analyzed with the Gibbs–Thomson equation. In addition, for confinement sizes of 7.5 and 12 nm, it was found that no cold-crystallization occurs upon heating from the glassy state to above the expected melting transition. Finally, at intermediate confinements we find evidence of a possible new, confinement-induced polymorph of NIF.

Manipulating the physical states of confined ibuprofen in SBA-15 based drug delivery systems obtained by solid-state loading: Impact of the loading degree

“…[16][17][18][19] ). This amorphous layer was indeed observed for several systems like benzene 13 , water 19 , nifedipine 11 , acetaminophen 18 or ibuprofen 20 , to name a few.…”

“…The amorphous state can be stabilized when the pore diameter is small enough to inhibit the crystallization, i.e. the nucleation process being inhibited by spatial restriction [8][9][10][11] . The attempt to establish an empirical correlation between the diameter of the pores and the size of the molecule and its physical state or states under confinement can be found in the literature.…”

Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

“…Even though many studies have reported drug loading into various silica carriers under specific conditions [21,22,[26][27][28][29], the determination of the maximum drug loading amount into MPS is not clearly understood, particularly for the amorphous drugs categorized in class III, based on Taylor's classification, which has good glass formers that neither crystallize upon cooling nor reheating [15,29]. It is necessary to determine maximum drug loading experimentally to maximize its effect because drugs in MPS have shown incomplete release, although a supersaturated solution has been shown to be generated.…”

Encapsulation of drug into mesoporous silica by solvent evaporation: A comparative study of drug characterization in mesoporous silica with various molecular weights

“…In a previous study, it was reported that TV of NIF was observed even though the NIF was incorporated into controlled pore glasses (CPG) with a size of 7.5, which is similar to the size of the pores of MS, although the T g decrease. Furthermore, the T g of NIF was reduced by nanoconfinement due to an intrinsic size effect indicating that the mobility of NIF in MS was higher than amorphous NIF ( Cheng and McKenna, 2019 ). However, in this study, the T g of NIF was not observed after incorporating into MS, even in the weight ratio of 4:6.…”

“…Although NIF was categorized into class II base on Taylor's classification and the crystallization of NIF was not observed in MS. A previous study reported a crystallization of NIF within controlled pore glass at a size above 22.6nm, while no crystallization was detected at 7.5nm and 12 nm, which is similar to the pore size of MS. The nanoconfinement effect of MS inhibits the formation of the critical nucleus size and crystallization of NIF ( Ambrogi et al., 2007 ; Cheng and McKenna, 2019 ).…”