For pharmaceutical applications, cellulose derivatives are promising raw materials for coatings or films obtained from aqueous systems. A case study is presented on hydrophilic biopolymer for the preparation of oral controlled drug delivery systems. Additives such as plasticizers, surfactants, lipids, colorants or other film-forming polymers are frequently incorporated into biopolymer matrices to produce high quality drug protective films. The matrix used is Hydroxypropyl methylcellulose (HPMC) .
The aim of this work is to formulate HPMC films by introducing additives, to explore their surface properties and to investigate the adhesive and frictional properties at nanoscopic scale. Our expertise  in contact mode Atomic Force Microscopy (AFM) allows us to quantify the behavior at nano scale. The influence of additives on HPMC structuration and morphology, permeation, hydrophilic/hydrophobic character as well as surface adhesion and friction are evaluated. The results clearly underline the strong dependence of film properties on additive nature, concentration or water sensitivity and the interplay with additive-biopolymer matrix compatibility.
Stearic acid additive has a strong influence on HPMC surface properties and morphology. The surface structure of HPMC films shows the presence of granular nano-domains, which disappear with fatty acid content. A sharp variation of nano-adhesion and nano-friction forces is observed with addition of fatty acid. The results show that the addition of only 1% (w/w HPMC) of stearic acid induces a strong decrease (25%) of the surface free energy. The hydrophobic character becomes predominant and the non-dispersive component to the surface energy tends towards zero. Tapping mode topographic images show that the surface mean roughness of the formulated films decreases with the introduction of stearic acid. These results suggest that stearic acid molecules can migrate at the film surface. As a consequence the torsional forces measured on the basis of AFM nano-friction experiments decrease. Nano adhesion results confirm this tendency and suggest the presence of a weak boundary layer at the film surface, the formation of which is driven by a phase separation process.
PEG additives induce an increase of the surface hydrophilicity and affect HPMC morphology by insertion mechanisms . Swelling of HPMC clusters is observed as PEG content increases. PEG additives also induce an increase of the surface free energy. At the nano scale, the increase of PEG content causes an increase of friction and adhesion forces. Good correlation is obtained at macro scale. Experimental results underline the major role of capillary forces at the nano scale and evidence that PEG behaves as a lubricant at macro scale.
The present study underlines the strong dependence of surface film properties on additive concentration and/or water sensitivity. Formulation appears then as an original and simple way to tune surface morphology and surface properties of bio-based polymer films. Finally the present study also shows that AFM is a powerful tool for studying surface adhesion and sliding properties of cellulose based formulated films for pharmaceutical applications such as coatings and films.
 M. Brogly, A. Fahs, S. Bistac, ARPN Journal of Engineering and Applied Sciences, 11, 7188- 7192 (2016).
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