Near infrared spectroscopy to monitor drug release in-situ during dissolution tests.
Dissolution tests can be used to demonstrate suitable in vivo drug release through in vivo/in vitro correlations. This work explores the possibility of using near infrared spectroscopy (NIRS) to monitor in-situ dissolution tests. It aims at expanding surrogate methods in quality control of drug products. Laboratory designed tablets of an immediate-release formulation containing folic acid and four excipients were used as case study. The dissolution tests were performed on a 1L vessel filled with 500ml of Milli-Q water with a rotating paddle apparatus (apparatus 2, Ph. Eur.) at 50rpm and 37±0.5°C. Near infrared (NIR) spectra were acquired in-situ with a transflectance probe connected to a Fourier-transform near infrared spectrometer. NIR spectra were regressed against folic acid concentration by partial least squares (PLS) regression. Folic acid concentrations during dissolution tests were obtained by periodically sampling the dissolution vessel and resourcing to an UV method. The proposed real-time NIR method was tested on a validation run yielding a root mean squared error of 0.25μgml-1(0.16μgml-1for the calibration runs) and a R2of 0.93 (0.95 for the calibration runs). The results suggest that NIRS is a suitable analytical technique for monitoring in-situ dissolution tests.
LAQV/REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Mafalda Cruz
MC
Sarraguça
LAQV/REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Rita
R
Matias
LAQV/REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Raquel
R
Figueiredo
Centro de Ciências Sociais, Saúde e Tecnologia (CCSST), Universidade Federal do Maranhão (UFMA), CP: 65.900-410, Imperatriz, MA, Brazil.
Paulo Roberto S
PR
Ribeiro
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Ana Teixeira
AT
Martins
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: jlopes@ff.ulisboa.pt.
João Almeida
JA
Lopes
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry; D016018:Least-Squares Analysis; D011786:Quality Control; D012995:Solubility; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013607:Tablets
D005079:Excipients; D013607:Tablets; D005492:Folic Acid
Dissolution tests; Folic acid; In-situ measurements; near infrared spectroscopy