Evaluation of the solid state form of tadalafil in sub-micron thin films using nanomechanical infrared spectroscopy.

Assessing physical stability of drugs is important both in the development as well as in the production phase in the pharmaceutical industry. We used nanomechanical infrared (NAM-IR) spectroscopy based on photothermal response of a nanomechanical resonator, to investigate the solid state forms of tadalafil (TAD), under various storage conditions in sub-micron thin films. The amorphous TAD was stable, when kept at normal storage conditions of 24 °C, 45% relative humidity (RH) and shielded from light, however, it crystallized after four days when it was at stress storage conditions (40 °C, 70% RH, and direct sunlight). Additionally, we found that the signals recorded with NAM-IR were comparable with the attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and that NAM-IR proved to be a suitable and time efficient method when evaluating TAD in sub 500 nm layers.

Thin Film Analysis by Nanomechanical Infrared Spectroscopy.

There is a fundamental need for techniques for thin film characterization. The current options for obtaining infrared (IR) spectra typically suffer from low signal-to-noise-ratios (SNRs) for sample thicknesses confined to a few nanometers. We present nanomechanical infrared spectroscopy (NAM-IR), which enables the measurement of a complete infrared fingerprint of a polyvinylpyrrolidone (PVP) layer as thin as 20 nm with an SNR of 307. Based on the characterization of the given NAM-IR setup, a minimum film thickness of only 160 pm of PVP can be analyzed with an SNR of 2. Compared to a conventional attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) system, NAM-IR yields an SNR that is 43 times larger for a 20 nm-thick PVP layer and requires only a fraction of the acquisition time. These results pave the way for NAM-IR as a highly sensitive, fast, and practical tool for IR analysis of polymer thin films.