title: 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.
abstract: 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 amino-acid/gelatine mixtures.
  
  
  METHODS
  Three amino acids (l-alanine, serine and proline) were studied by TPS (in the wave number range of 3-100cm(-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).
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Leicester School of Pharmacy, De Montfort University, Leicester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Darkwah
authors.forename: G
authors.initials: G
authors.lastname: Smith
authors.forename: I
authors.initials: I
authors.lastname: Ermolina
authors.forename: M
authors.initials: M
authors.lastname: Mueller-Holtz
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D005612:Freeze Drying; D005780:Gelatin / Q000737:chemistry; D012995:Solubility; D013057:Spectrum Analysis / Q000379:methods*; D013607:Tablets
chemical_list: D000596:Amino Acids; D013607:Tablets; D005780:Gelatin
keywords: Amino acid; Crystallinity; Gelatin; Partial least squares; Rapidly disintegrating tablets; Terahertz pulsed spectroscopy