Identification of contaminants on lactose using Ultrasound Acoustic-AFM. Impact on the interactions drug-carrier
Cedric Thomas1, N. Pocholle1, E. Bourillot1, A. Kervinio², L. Kerriou², V. Gamerre², C. Andrès1, E. Lesniewska1
1ICB UMR CNRS 6303, Univ. Bourgogne Franche-Comté, Dijon, France
2Armor Pharma, Armor Proteines SAS, Saint Brice-en-Cogles, France
The quality of pharmaceutical products are the top concerns of regulators. Recently, US regulators have banned imports from more than 40 laboratories. Regulatory agencies have strengthened their position on preventing drug adulteration in both active pharmaceutical ingredients (API) and excipients by enacting new regulations. Identification of entities and contaminants inside and on surface of excipients used in the pharmaceutical industry with non-destructive techniques is a challenging procedure. We propose to couple ultrasound acoustic investigation with atomic force microscopy for tomographic reconstruction. The acoustic microscopy technique (1-20 MHz) operates in the attenuated total reflectance (ATR) configuration and is sensitive to the local density variation. A home-built platform was used to detect the variation of density properties of material in the bulk at specified depth of investigation by varying the ultrasound acoustic. The present study focused on different lactose of pharmaceutical grade. Thus, this new analytical approach yielded data of potential value for comparative examinations and possibly for legal purposes. The combination of ultrasound atomic force microscopy (UA-AFM), microwave microscopy (SMM) is probably the only non-destructive approach capable of acquiring both depth investigation, density and chemical information of pharmaceutical sample at the nanometer scale without specific labelling. That is a major technological break-through. After the characterisation of contaminants, it is important to understand the impact of their presence on the interactions drug-carrier. Force spectroscopy based on atomic force microscopy provides an appropriate response on the impact of contaminants on the interactions between drug and excipients.