A THz spectroscopy method for quantifying the degree of crystallinityin freeze-dried gelatin/amino acid mixtures: An application for the development of rapidly disintegrating tablets

Objective: In rapidly disintegrating tablets (RDTs) manufactured by freeze-drying processes, the % crystallinity of the freeze-dried matrix underpins the physical properties such as mechanical strength and dissolution profile. This study examines the feasibility of using terahertz pulsed spectroscopy (TPS) as an off-line tool (in the first instance) for assessing the degree of crystallinity in co-freeze dried aminoacid/gelatine mixtures. Materials and methods: Three amino acids (L-alanine, serine and proline) were studied by TPS (in the wave number range of 3-100 cm(-1)) both in the pure crystalline form and in the form of a co-freeze-driedmatrix with gelatin (in weight fractions of 10: 90, 30: 70, 50: 50, and 70: 30). Results: In co-freeze dried proline/gelatin matrix no crystallinity was observed using TPS, whereas similar to 62 +/- 1% (n = 3) and 72 +/- 0.5% (n = 3) crystallinity was observed in the co-freeze dried alanine/gelatinmatrix (50% w/w and 70% w/w, respectively). Similarly, similar to 41 +/- 0.5% (n = 3) and similar to 80 +/- 0.5% (n = 3) crystallinity was observed in the serine/gelatin matrix (30% w/w and 50% w/w respectively). Conclusion: The potential for using TPS as a quantitative in-line tool for determining the degree of crystallinity in a range of complex systems such as RDTs, conventional tablets, sprayed dried micro particles, is suggested from these results. (C) 2013 Elsevier B.V. All rights reserved.