The Impact of Various Poly(vinylpyrrolidone) Polymers on the Crystallization Process of Metronidazole

Abstract

In this paper, we propose one-step synthetic strategies for obtaining well-defined linear and star-shaped polyvinylpyrrolidone (linPVP and starPVP). The produced macromolecules and a commercial PVP K30 with linear topology were investigated as potential matrices for suppressing metronidazole (MTZ) crystallization. Interestingly, during the formation of binary mixtures (BMs) containing different polymers and MTZ, we found that linear PVPs exhibit maximum miscibility with the drug at a 50:50 weight ratio (w/w), while the star-shaped polymer mixes with MTZ even at a 30:70 w/w. To explain these observations, comprehensive studies of MTZ-PVP formulations with various contents of both components were performed using Fourier-transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The obtained results clearly showed that the polymer’s topology plays a significant role in the type of interactions occurring between the matrix and MTZ. Additionally, we established that for MTZ-PVP 50:50 and 75:25 w/w BMs, linear polymers have the most substantial impact on inhibiting the crystallization of API. The star-shaped macromolecule turned out to be the least effective in stabilizing amorphous MTZ at these polymer concentrations. Nevertheless, long-term structural investigations of the MTZ-starPVP 30:70 w/w system (which is not achievable for linear PVPs) demonstrated its complete amorphousness for over one month.

The Influence of PVP Polymer Topology on the Liquid Crystalline Order of Itraconazole in Binary Systems

“…The created binary mixtures consisted of ITZ (known for its liquid crystalline character) and three different polymeric materials: ( i ) commercial PVP K30 ( M n = 40,500, Đ = 2.05), ( ii ) self-synthesized linear PVP, lin PVP ( M n = 37,600, Đ = 1.22), and ( iii ) self-synthesized three-armed star-shaped PVP, star PVP ( M n = 38,700, Đ = 1.48). 56 While preparing ASDs, we noticed an extremely intriguing relationship. Both linear polymeric matrices (PVP K30, lin PVP) are mixed with ITZ in a polymer amount of up to 5 wt %, whereas star PVP exhibits a significantly better capability for homogeneous mixing with the API (even up to 15 wt %).…”

“…Therefore, a highly interesting scientific issue would be to investigate how these innovative self-synthesized materials will affect the properties of a completely different API, namely, ITZ, classified as a liquid crystal, and thereby exhibiting interesting molecular ordering that further influences its solubility. The detailed synthesis procedures, 1 H and 13 C NMR spectra confirming the structures of the obtained polymers, and SEC traces allowing the determination of the macrostructural parameters ( M n , Đ ) can be found in our previous publication . However, as a reminder, all key information regarding the synthesis of well-defined PVPs with various topologies is also provided in the Supporting Information, SI of this work (see Figures S1–S7 and the description).…”

“…So far, we have used these PVPs only once to study their influence on the physical stability of amorphous metronidazole and the rate of its recrystallization from ASDs. 56 Therefore, a highly interesting scientific issue would be to investigate how these innovative self-synthesized materials will affect the properties of a completely different API, namely, ITZ, classified as a liquid crystal, and thereby exhibiting interesting molecular ordering that further influences its solubility. The detailed synthesis procedures, 1 H and 13 C NMR spectra confirming the structures of the obtained polymers, and SEC traces allowing the determination of the macrostructural parameters (M n , Đ) can be found in our previous publication.…”

“…The detailed synthesis procedures, 1 H and 13 C NMR spectra confirming the structures of the obtained polymers, and SEC traces allowing the determination of the macrostructural parameters (M n , Đ) can be found in our previous publication. 56 However, as a reminder, all key information regarding the synthesis of well-defined PVPs with various topologies is also provided in the Supporting Information, SI of this work (see Figures S1−S7 and the description).…”

“…Moreover, the chain-end functionalization of polymers synthesized via RAFT allows for further modifications of the macromolecules as needed (for example, through copolymerization), contrary to the commercially available PVP (see Figure ). So far, we have used these PVPs only once to study their influence on the physical stability of amorphous metronidazole and the rate of its recrystallization from ASDs . Therefore, a highly interesting scientific issue would be to investigate how these innovative self-synthesized materials will affect the properties of a completely different API, namely, ITZ, classified as a liquid crystal, and thereby exhibiting interesting molecular ordering that further influences its solubility.…”