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

ObjectiveIn 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 amino-acid/gelatine mixtures.Materials and methodsThree 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-dried matrix with gelatin (in weight fractions of 10:90, 30:70, 50:50, and 70:30).ResultsIn co-freeze dried proline/gelatin matrix no crystallinity was observed using TPS, whereas ∼62 ± 1% (n = 3) and 72 ± 0.5% (n = 3) crystallinity was observed in the co-freeze dried alanine/gelatin matrix (50% w/w and 70% w/w, respectively). Similarly, ∼41 ± 0.5% (n = 3) and ∼80 ± 0.5% (n = 3) crystallinity was observed in the serine/gelatin matrix (30% w/w and 50% w/w respectively).ConclusionThe 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.

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