Novel Polyvinylpyrrolidones To Improve Delivery of Poorly Water-Soluble Drugs: From Design to Synthesis and Evaluation

Abstract

Polyvinylpyrrolidone is widely used in tablet formulations with the linear form acting as a wetting agent and disintegrant, whereas the cross-linked form is a superdisintegrant. We have previously reported that simply mixing the commercial cross-linked polymer with ibuprofen disrupted drug crystallinity with consequent improvements in drug dissolution behavior. In this study, we have designed and synthesized novel cross-linking agents containing a range of oligoether moieties that have then been polymerized with vinylpyrrolidone to generate a suite of novel excipients with enhanced hydrogen-bonding capabilities. The polymers have a porous surface and swell in the most common solvents and in water, properties that suggest their value as disintegrants. The polymers were evaluated in simple physical mixtures with ibuprofen as a model poorly water-soluble drug. The results show that the novel PVPs induce the drug to become "X-ray amorphous", which increased dissolution to a greater extent than that seen with commercial cross-linked PVP. The polymers stabilize the amorphous drug with no evidence for recrystallization seen after 20 weeks of storage.

Mutual Effects of Hydrogen Bonding and Polymer Hydrophobicity on Ibuprofen Crystal Inhibition in Solid Dispersions with Poly(N-vinyl pyrrolidone) and Poly(2-oxazolines)

“…Briefly, absorption bands between 3100–2800 cm −1 are attributed to C−H stretching modes, with peak intensities gradually reducing as the drug quantity falls in the solid dispersions ( Figure S2 ). Two medium intensity features, appearing at 2725 cm −1 and 2633 cm −1 in the spectrum of IB, can be assigned to the stretching vibration of the cyclic dimerized hydroxyl groups, which is subjected to intermolecular hydrogen bonding [ 19 , 36 ] ( Figure S1 ). However, these bands are lost in the spectra of amorphous solid dispersions, indicating that the drug dimeric structure is lost as a result of interaction with the polymers.…”

“…Common interactions between drugs and polymers include ionic, hydrophobic, dipole–dipole, Van der Waals, and hydrogen bonding [ 16 , 17 , 18 ]. Hydrogen bonding is typically detected between drugs and polymers in solid dispersions, as reported extensively, for example, between IB and PVP [ 19 , 20 ], esomeprazole and hydroxypropyl methylcellulose (HPMC) [ 21 ], flurbiprofen and poly(ethylene oxide) [ 22 ], and for nifedipine and Eudragit ® [ 23 ], indicating that this is a key mechanism in the successful formation of amorphous or semi-crystalline solid dispersions. In contrast, there are relatively few studies exploring the effects of carrier hydrophobicity on crystallization inhibition [ 16 , 24 , 25 ].…”

Polymer structure and property effects on solid dispersions with haloperidol: Poly(N-vinyl pyrrolidone) and poly(2-oxazolines) studies

“…Solid dispersions are defined as physical mixtures of poorly-soluble drugs with some hydrophilic materials (Vasconcelos et al, 2016) and include eutectic systems, solid solutions (which themselves can be continuous or discontinuous depending on component miscibility) and systems where a drug can be in an amorphous or partially crystalline state in an amorphous or crystalline carrier. Several classes of hydrophilic polymers have been exploited to prepare amorphous solid dispersions, including poly(N-vinyl pyrrolidone) (Knopp et al, 2016;Li and Buckton, 2015;Niemczyk et al, 2012), cellulose ethers (Chavan et al, 2019), polyethylene oxide (Abu-Diak et al, 2012;Ozeki et al, 1997) and poloxamers (Ali et al, 2010). In some studies, the reduction of drug crystallinity in solid dispersions with various polymers has been explored and related to the chemical structure and properties of water-soluble polymers.…”

“…In some studies, the reduction of drug crystallinity in solid dispersions with various polymers has been explored and related to the chemical structure and properties of water-soluble polymers. For example, in a series of studies of solid dispersions prepared from ibuprofen and PVP, it was demonstrated that reduced drug crystallinity was due to hydrogen bond formation between drug molecules and the polymer (Niemczyk et al, 2012;Rawlinson et al, 2007;Williams et al, 2005). However, systematic studies into the effects of polymer structures on their ability to reduce drug crystallinity are currently lacking because there are limited opportunities to vary polymer structures in a controlled manner; most studies use commercially available polymers.…”

Influence of mechanochemical technology on anthelmintic efficacy of the supramolecular complex of fenbendazole with polyvinylpyrrolidone

“…The reason for this is the increase of the plasticity of PVP that facilitates the mixing of the components on the molecular level. So, Niemczyk et al [38] showed that the new forms of PVP converted the drug-ibuprofen to be “X-ray amorphous” that expands dissolution a lot. IR-spectroscopy was not informative in our study because of the overlapping spectra of fenbendazole substance and SMCF.…”