Characterisation of freeze dried amino acids and gelatin based rapidly Disintegrating tablets
Recent research has shown the feasibility of using individual or a combination of amino acids as a replacement component for sugars in RDT formulations. What has emerged from this work is the notion of an optimal concentration of amino acid, i.e. one that is sufficiently high to provide the desired mechanical strength but not too high to impact disintegration time. In this study, the degree of amino acid crystallinity in gelatin/amino acid based RDTs was investigated using terahertz pulsed spectroscopy. Three amino acids were investigated: alanine (89 g mol-1), serine (105 g mol-1), and proline (115 g mol-1). The three amino acids were studied by terahertz pulsed spectroscopy (in the frequency band 0.1 to 3 THz; 3 to 100 cm-1), both in the pure crystalline form (as received from the manufacturer) and in the form of a co-freeze-dried matrix with gelatin (in weight fractions of 10:90, 30:70, 50:50, 70:30). Each pure crystalline form of amino acid displayed one or two resonance peaks at characteristics wave numbers, which were in general agreement with the literature (with alanine at 75 cm-1 and 85 cm-1; proline at 48 cm-1 and 66 cm-1 and serine centred on 67 cm-1). Irrespective of the amino acid in question (viz. alanine, proline, or serine) all freeze-dried formulations containing 10% amino acid and 90% gelatin were found to have no crystallinity with respect to the amino acid component. On increasing the amino acid to 30%, only those formulations manufactured from serine showed evidence of crystallisation behaviour. Only on increasing the concentration of amino acid to 50% did the spectra of alanine display the distinct absorption bands of their crystalline reference counterparts. The degree of crystallinity in serine and alanine was estimated using calibration model built from partial least square regression (PLSR). The increased concentration of alanine to 50%w/w and 70% w/w in freeze dried gelatin matrix showed an estimated degree of crystallinity to be ~62% and ~72% (± 16%) respectively. Similarly the degree of crystallinity in 30%w/w and 50% w/w serine/gelatin freeze dried matrix were estimated to be ~55% and ~97% (± 10%) respectively. This work has shown a rank order of solubility within the freeze-dried gelatin matrix of proline > alanine > serine. Unsurprisingly, the same rank order exists for the aqueous solubility, with serine being the least soluble (~5 g ml-1) and proline being the most soluble (~162 g ml-1). The impact of hydrophobic interactions between the amino acid and gelatin are therefore less dominant in defining the crystallinity of the amino acid within the freeze-dried material.
- MPhil