Vapor-Phase-Mediated Encapsulation of Guest Drug Molecules in the Hexagonal Columnar Form Structure of Polyethylene Glycol/γ-Cyclodextrin-Polypseudorotaxane

Abstract

The drug/(PEG/γ-CD-PPRX) complex is a unique multicomponent supramolecular structure where the drug molecules are incorporated in the intermolecular spaces of the polypseudorotaxane (PPRX) prepared from polyethylene glycol (PEG) and γ-cyclodextrin (γ-CD). Herein, we report a sealed-heating preparation method to obtain an unanticipated polymorphic form of the drug/(PEG/γ-CD-PPRX) complex, which is the hexagonal-columnar (HC) form. The encapsulation efficiency of the six guest drugs was evaluated. The crystalline structural changes and the guest encapsulation monitored by powder X-ray diffraction revealed that a low sealed-heating temperature with a small amount of water was the optimal preparation condition for obtaining the HC form complex. The solution-state 1H nuclear magnetic resonance measurement demonstrated that stoichiometric complexation was dependent on the cross-sectional area of the guest drug molecule. However, stoichiometric complexation could not be achieved with all guest drugs, and the encapsulation efficiency was found to be governed by the guest drug properties, such as vapor pressure and molecular size. The findings of this study would contribute to understanding the complexation behavior of guest molecules in multicomponent supramolecular complexes and offer new insights into the fabrication of novel ordered supramolecular structures.

Controlled Sublimation Rate of Guest Drug from Polymorphic Forms of a Cyclodextrin-Based Polypseudorotaxane Complex and Its Correlation with Molecular Dynamics as Probed by Solid-State NMR

“…The PEG/γ-CD-PPRX and the three polymorphic forms of the SA/(PEG/γ-CD-PPRX) complex were prepared according to our previous report . The HC form of PEG/γ-CD-PPRX was used as the starting material, and its particle size was controlled at less than 150 μm.…”

“…SA is typically used in topical formulations to treat chronic skin diseases for its keratolytic, anti-inflammatory, and bacteriostatic properties. , A recent study by Murthy and co-workers demonstrated that SA suffers significant weight loss at skin temperature (32 °C) by sublimation due to its high vapor pressure from its crystalline state as well as topical formulations . The physical stability issues related to the high vapor pressure of APIs have been addressed by cocrystal/salt formation or complexation with CDs. − Herein, we investigated the sublimation suppression of SA from the three polymorphic forms of the SA/(PEG/γ-CD-PPRX) complex, which were prepared by the previously reported sealed-heating technique. , The sublimation rate of SA was determined by thermogravimetry under isothermal conditions. The molecular dynamics of the complexes were evaluated by variable temperature 13 C cross-polarization (CP), 13 C pulse saturation transfer (PST) with magic-angle spinning (MAS)-based solid-state NMR techniques, 1 H MAS, and 13 C spin–lattice relaxation time ( T 1 ) measurement using 13 C isotopically labeled SA.…”

“…Over the past two decades, CD-based polypseudorotaxanes (CD-PPRX) have garnered considerable interest as a drug delivery system for their versatility in delivering low- to high-molecular-weight compounds such as APIs, proteins, and nucleic acids. − The supramolecular structure of CD-PPRX consists of parallelly arranged stacked columns of CD-polymer inclusion complexes with intermolecular spaces between the columns . The intermolecular spaces of a CD inclusion complex structure can be accessed by guest compounds such as APIs, metal ions, or surfactants. ,− Previously, we have established that APIs can be incorporated in the intermolecular spaces of CD-PPRX prepared from γ-CD or α-CD and poly­(ethylene glycol) (PEG) by specific sealed-heating techniques to form a drug/(PEG/γ-CD-PPRX) complex. ,, Such complexes have shown promising results in improving the dissolution and stability of the encapsulated drugs. , Recently, we reported that the drug/(PEG/γ-CD-PPRX) complexes can exist in different crystalline polymorphic forms, which are tetragonal columnar (TC), monoclinic columnar (MC), and hexagonal columnar (HC) form . Toropainen et al described that the dissolution profile of budesonide from the TC and HC form structure of budesonide/γ-CD inclusion complexes was dependent on the host crystal structure .…”