title: Selective imaging of active pharmaceutical ingredients in powdered blends with common excipients utilizing two-photon excited ultraviolet-fluorescence and ultraviolet-second order nonlinear optical imaging of chiral crystals.
abstract: Second order nonlinear optical imaging of chiral crystals (SONICC) and two-photon excited fluorescence measurements [both autofluorescence and two-photon excited UV-fluorescence (TPE-UVF)] were assessed for the selective detection of APIs relative to common pharmaceutical excipients. Active pharmaceutical ingredients (APIs) compose only a small percentage of most tabulated formulations, yet the API distribution within the tablet can affect drug release and tablet stability. Complementary measurements using either UV-SONICC (266 nm detection) or TPE-UVF were shown to generate signals >50-fold more intense for a model API (griseofulvin) than those produced by common pharmaceutical excipients. The combined product of the measurements produced signals >10(4)-fold greater than the excipients studied. UV-SONICC or TPE-UVF produced greater selectivity than analogous measurements with visible-light detection, attributed to the presence of aromatic moieties within the API exhibiting strong one and two photon absorption at ~266 nm. Complementary SONICC and fluorescence measurements allowed for the sensitive detection of the three-dimensional distribution of tadalafil within a Cialis tablet to a depth of >140 μm.
authors: Department of Chemistry, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.
authors: S J
authors: SJ
authors: Toth
authors: J T
authors: JT
authors: Madden
authors: L S
authors: LS
authors: Taylor
authors: P
authors: P
authors: Marsac
authors: G J
authors: GJ
authors: Simpson
mesh_terms: D002243:Carbolines / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D006118:Griseofulvin / Q000737:chemistry; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D055620:Optical Phenomena; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders; D013237:Stereoisomerism; D013607:Tablets; D000068581:Tadalafil; D014466:Ultraviolet Rays
chemical_list: D002243:Carbolines; D005079:Excipients; D004364:Pharmaceutical Preparations; D011208:Powders; D013607:Tablets; D006118:Griseofulvin; D000068581:Tadalafil