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

Xiaoning Shan,Adrian C Williams,Maryam A Moghul,Vitaliy V Khutoryanskiy

doi:10.3390/pharmaceutics13050659

Xiaoning Shan, Adrian C Williams + Show 2 more

Open Access

https://doi.org/10.3390/pharmaceutics13050659

Copy DOI

Journal: Pharmaceutics	Publication Date: May 4, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: University of Reading

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.

Highlights

HinrichsWhilst oral delivery remains the most common route for drug administration, most new active pharmaceutical ingredients are poorly water soluble and not well-absorbed after oral administration
To evaluate the effects of different polymers on the crystallinity of IB, solid dispersions were prepared by solvent evaporation and were characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (PXRD), and Fourier Transform Infrared (FTIR), with DSC used to calculate the crystallinity of IB in the dispersions
Physical characterization of the dispersions showed that the polymers were able to disrupt the ibuprofen crystallinity, forming apparently amorphous dispersion at 1:1 mole ratios, and that hydrogen bonding was the prime mechanism for the interaction; the interactions between PMOZ and ibuprofen were more complex and hydrogen bonding was less

Summary

Introduction

HinrichsWhilst oral delivery remains the most common route for drug administration, most new active pharmaceutical ingredients are poorly water soluble and not well-absorbed after oral administration. Solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solid state, is an established platform technology to enhance the dissolution rate and improve the apparent solubility of a drug and, increase the bioavailability of a range of poorly water soluble drugs [1,2,3]. 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.

Methods

Results

Conclusion