Investigation of Drug–Polymer Miscibility, Molecular Interaction, and Their Effects on the Physical Stabilities and Dissolution Behaviors of Norfloxacin Amorphous Solid Dispersions

Abstract

This study investigated the drug–polymer miscibility, intermolecular interaction, physical stability, and dissolution performance of amorphous solid dispersions (ASDs) of norfloxacin (NFX) with polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and hydroxypropyl methylcellulose phthalate (HPMCP). The NFX–polymer miscibility was evaluated based on the Hansen solubility parameter and Flory–Huggins interaction parameter. The results are in broad agreement with an order of NFX–HPMCP > NFX–HPMC > NFX–PVP. The NFX–polymer molecular interaction in the solution state was determined by nuclear magnetic resonance (NMR) spectroscopic studies. The strength of interaction was rank ordered as HPMC > HPMCP > PVP, which was different from the solid state. Powder X-ray diffraction (PXRD) detected the stability of ASDs, and the result indicates that the high drug–polymer miscibility and strong interactions could translate to high resistance to drug crystallization. Dissolution studies of ASDs were carried out across the gastrointestinal pH range. Interestingly, there was no significant dissolution enhancement, and a polymer-dependent drug release profile was observed. On the basis of the drug–polymer miscibility and hydrophilicity of polymers, a nonclassical drug release mechanism was revealed. Furthermore, it has been speculated that the effectiveness of a polymer in maintaining supersaturation of drug in solution can be more dependent on the specific drug–polymer interaction mode than on the strength.

Influence of Adsorption State and Molecular Interaction on Physical Stability of Confined Amorphous Vortioxetine

“…This indicated that the interactions between VXT molecules within MCM channels could be stronger than those in SBA channels, leading to aggregated adsorption of VXT in MCM channels. It has been reported that the intermolecular interactions of API can influence the physical stability of amorphous drugs. − The stronger interactions between VXT molecules adsorbed in MCM channels could facilitate the nucleation of VXT crystals.…”

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

“…Therefore, from the thermodynamic perspective, polymers that offer high drug–polymer solubility are favored as carrier candidates for generating stable ASDs. Some findings suggested that a strong drug–polymer interaction could lead to a reduction in the Gibbs free energy and enthalpy of mixing, which increased the drug–polymer miscibility/solubility [ 27 ]. Such intermolecular interaction was also reported to be a critical attribute to the increase of configurational entropy of API molecules, which promoted the thermodynamic stability of ASDs by connecting the drug and the polymer as a single entity [ 28 ].…”

Ambipolar organic phototransistors with bulk heterojunction films of p-type and n-type indacenodithienothiophene-containing conjugated polymers

“…[1][2][3][4][5][6][7] To date, OFETs with conjugated polymers have been attempted for various applications such as photodetectors, [8][9][10][11] tactile sensors, [12][13][14] biosensors, [15][16][17] memory devices, [18][19][20] etc. In particular, keen attention has been paid to the photodetector applications of OFETs, leading to organic phototransistors (OPTRs), as most conjugated polymers with monomeric units of short conjugation lengths exhibit strong optical absorptions in the ultraviolet [21][22][23][24][25][26] and visible light ranges. [27][28][29][30][31] Interestingly, most of these polymers are composed of sulfur-containing monomeric units.…”