Signature of interfacial water structure at the air–drug–polymer aqueous interface studied by sum frequency generation vibrational spectroscopy

Abstract

The selection of polymers suitable for the formulation of supersaturating drug-delivery systems is imperative to improve the solubility, thermodynamic stability, precipitation inhibition ability, and bioavailability of drugs in vivo. However, a detailed molecular-level understanding of finding the right drug–polymer combination in the aqueous medium is still ambiguous and often selected based on the trial procedure. Here, we have employed sum frequency generation vibrational spectroscopy (SFG-VS) to probe the impact of drug–polymer interactions on the interfacial water structure at the model biorelevant medium (BM) interface to extract better insights into the molecular system. We investigated two different polymers, Eudragit EPO (E-EPO) and polyvinylpyrrolidone K30 (P-K30), resulting in a considerable difference in the supersaturation limits of the atorvastatin calcium (ATC), the model drug molecule in the BM solution. The solubility study suggests an ∼42 times enhancement in the solubility of ATC drug with the presence of E-EPO polymer and merely an ∼2.6 times enhancement for polymer P-K30. Interestingly, SFG spectroscopic studies showed that E-EPO supports a substantial orientational ordering of the interfacial water molecules with the signature of strongly hydrogen (H)-bonded water molecules. An opposite trend is witnessed for the P-K30 polymer with less preferential ordering and weakly H-bonded water molecules at the air–BM interface. The microscopic insights from the SFG spectroscopy, in correlation with the observations on drug solubility, present a new potential approach for probing drug–polymer interactions. The implementation of SFG vibrational spectroscopy can be beneficial in selecting suitable polymers to adopt better strategies for bioavailability enhancement in drug formulation development.