Experimental and theoretical study of polymorphic and solvate ampicillin forms

In literature, many active pharmaceutical ingredients (APIs) are known to crystallize in different crystalline packings (polymorphs) or with solvent molecules as an integral part of their structures (pseudopolymorphs). In a pharmaceutical dosage form, the active ingredient solid-state phase identity or conversion could dramatically alter the final pharmaceutical properties. In particular, the solid state administrated drug can influence important properties like bioavailability. In this study four α-aminobenzylpenicillin [1-3] forms were crystallized [4,5] and the molecular vibrations of the various ampicillin forms were investigated by ATR/FT-IR [2,3], micro-Raman and SERS (surface enhanced Raman spectroscopy) [4] spectroscopies (firstly reported). The HSRM (hot stage Raman microscopy) was also able to follow the transition from the trihydrate ampicillin to the amorphous monohydrate. DSC, TGA, XRPD data were also afforded [1,4,5]. For the first time, the Raman spectra of the four ampicillin forms are reported. Finally, for assisting experimental assignment bands quantum mechanical calculations were also performed and the density functional theory (DFT) predictions were used [6,7]. References: [1] E. Shefter et al., J. Pharm. Sci. 62/5 (1973) 791. [2] M. N. J. James et al. Nature 220 (1968), 168. [3] E. Ivashkiv, In: Analytical Profiles of Drug Substances, vol. 2., (1973) Academic Press, New York, K. Florey, (Ed.). [4] K. W. B. Austin et al., Nature 208 (1965) 999. [5] Parker et al., 1976, USP 3933796. [6] A. D. Becke, J. Chem. Phys. 98 (1993) 5648–5652. [7] W. T. Yang, R. G. Parr, Phys. Rev. B 37 (1988) 785–789.