title: Determination of content uniformity and distribution characteristics of an investigational drug in its tablets dosage form and granule by ICP-AES.
abstract: An investigational drug (A) in its calcium salt form has been developed as the tablet dosage form. Monitoring drug distribution and uniformity in granules and tablets during early stage formulation/process development is critical for drug product quality control and process robustness. In this report, an efficient and reliable analytical method for monitoring drug compound A uniformity and distribution has been developed by analyzing calcium, the counter ion of the drug substance, by Inductively Coupled Plasma Atomic Emission Spectrometer (ICP-AES). In this method, calcium in compound A granule and tablet samples was digested with 1 M hydrochloric acid by heating at 90 degrees C for 2 h. The resulting suspension was centrifuged, and the supernatant was directly aspirated into an ICP-AES. This method has been validated to demonstrate satisfactory precision, accuracy, specificity and sensitivity. Finally, this method has been used to analyze sieve fraction granules and tablets of drug compound A. The data generated were highly comparable to those by validated HPLC methods (UV method can not be applicable due to significant bias). In comparison with HPLC methods, this method demonstrates a significantly improved efficiency with very short analysis time (1 min per sample), and can be used as an excellent alternative for UV and HPLC methods to support formulation screening.
authors.affiliation: Pharmaceutical Research & Development, Merck Research Laboratories, WP44K, West Point, PA 19486, USA. lei_wang@merck.com
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Michelle
authors.initials: M
authors.lastname: Marley
authors.forename: Hossain
authors.initials: H
authors.lastname: Jahansouz
authors.forename: Carl
authors.initials: C
authors.lastname: Bahnck
mesh_terms: D015507:Drugs, Investigational / Q000032:analysis / Q000592:standards*; D013054:Spectrophotometry, Atomic / Q000379:methods* / Q000592:standards; D013607:Tablets / Q000032:analysis / Q000592:standards*
chemical_list: D015507:Drugs, Investigational; D013607:Tablets