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

Abstract

Poly(N-vinyl pyrrolidone) (PVP), poly(2-methyl-2-oxazoline) (PMOZ), poly(2-ethyl-2-oxazoline) (PEOZ), poly(2-n-propyl-2-oxazoline) (PnPOZ), and poly(2-isopropyl-2-oxazoline) (PiPOZ) were used to prepare solid dispersions with ibuprofen (IB), a model poorly-water soluble drug. Dispersions, prepared by solvent evaporation, were investigated using powder X-ray diffractometry, differential scanning calorimetry, and FTIR spectroscopy; hydrogen bonds formed between IB and all polymers in solid dispersions. PMOZ, the most hydrophilic polymer, showed the poorest ability to reduce or inhibit the crystallinity of IB. In contrast, the more hydrophobic polymers PVP, PEOZ, PnPOZ, and PiPOZ provided greater but similar abilities to reduce IB crystallinity, despite the differing polymer hydrophobicity and that PiPOZ is semi-crystalline. These results indicate that crystallinity disruption is predominantly due to hydrogen bonding between the drug molecules and the polymer. However, carrier properties affected drug dissolution, where PnPOZ exhibited lower critical solution temperature that inhibited the release of IB, whereas drug release from other systems was consistent with the degree of ibuprofen crystallinity within the dispersions.

Molecular structure of ketoprofen-polyvinylpyrrolidone solid dispersions prepared by different amorphization methods

“…11 In studies on ASDs containing either nifedipine or ibuprofen, better thermal stability was observed when API-polymer interactions included greater degrees of hydrogen bonding. 24,59 For the ASD binaries in this study, hydrogen bonding is expected between KTP carboxyl and PVP carbonyl groups (Fig. 1), based on past work.…”

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

“…Surprisingly, the introduction of MTZ in the star PVP matrix causes a considerable red shift of the band (shift to lower wavenumbers from 1661 cm −1 for neat star PVP to 1651 cm −1 for 30:70 w / w mixtures) due to the formation of hydrogen bonding (HB) between the hydroxyl group of MTZ and the carbonyl group of PVP ( Figure 3 c). It is worth noting that HB interactions are typically detected between APIs and polymers in BMs, as reported extensively, for example, between ibuprofen and PVP [ 67 , 68 ], indomethacin and PVP [ 69 ], esomeprazole and hydroxypropyl methylcellulose (HPMC) [ 70 ], flurbiprofen and poly(ethylene oxide) [ 71 ], and nifedipine and Eudragit ® [ 72 ], indicating that this is a key mechanism in the successful formation of amorphous or semi-crystalline solid dispersions [ 73 ]. It can also be mentioned that similar spectral effects related to the influence of PVP on API behavior were detected for MTZ- star PVP BMs in the recrystallized samples ( Figure S9c ).…”

The future of poly(2-oxazoline)s

“…[99] Furthermore, poly(2oxazoline)s have been demonstrated for the formation of amorphous solid dispersions of various drugs, thereby enhancing the solubilization of poorly water-soluble drugs by suppression of drug crystallization. [100][101][102] Covalent drug-conjugation to polymers through cleavable linkers is a popular strategy for drug delivery as it enables stimuli-controlled or slow release of the active drug, while the polymerdrug conjugate usually is inactive. [103] This concept has been used by Serina Therapeutics for the development of injectable slow release formulations of rotigotine based on a rotigotine-PEtOx conjugate that revealed stable blood plasma concentration of the drug in humans upon once a week subcutaneous injection.…”