Terahertz study on porosity and mass fraction of active pharmaceutical ingredient of pharmaceutical tablets.
In this study, terahertz time-domain spectroscopic (THz-TDS) technique has been used to ascertain the change in the optical properties, as a function of changing porosity and mass fraction of active pharmaceutical ingredient (API), of training sets of pharmaceutical tablets. Four training sets of pharmaceutical tablets were compressed with microcrystalline cellulose (MCC) excipient and indomethacin API by varying either the porosity, height, and API mass fraction or all three tablet parameters. It was observed, as far as we know, for the first time, that the THz time-domain and frequency-domain effective refractive index, as well as, the frequency-domain effective absorption coefficient both show linear correlations with the porosity and API mass fraction for training sets of real pharmaceutical tablets. We suggest that, the observed linear correlations can be useful in basic research and quality inspection of pharmaceutical tablets. Additionally, we propose a novel optical strain parameter, based on THz measurement, which yields information on the conventional strain parameter of a tablet as well as on the change of fill fraction of solid material during compression of porous pharmaceutical tablets. We suggest that the THz measurement and proposed method of data analysis, in addition to providing an efficient tool for basic research of porous media, can serve as one of the novel quality by design (QbD) implementation techniques to predict critical quality attributes (CQA) such as porosity, API mass fraction and strain of flat-faced pharmaceutical tablets before production.
Institute of Photonics, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland. Electronic address: prince.bawuah@uef.fi.
Prince
P
Bawuah
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom.
Nicholas
N
Tan
Institute of Photonics, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland.
Samuel Nana A
SN
Tweneboah
School of Pharmacy, Promis Centre, University of Eastern Finland, P.O. Box 1617, FI-70211 Kuopio, Finland.
Tuomas
T
Ervasti
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom.
J
J
Axel Zeitler
School of Pharmacy, Promis Centre, University of Eastern Finland, P.O. Box 1617, FI-70211 Kuopio, Finland.
Jarkko
J
Ketolainen
Institute of Photonics, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland.
Kai-Erik
KE
Peiponen
D002626:Chemistry, Pharmaceutical; D016062:Porosity; D013607:Tablets
D013607:Tablets
Active pharmaceutical ingredient; Effective absorption coefficient; Effective refractive index; Microcrystalline cellulose; Pharmaceutical tablet; Porosity; Strain; Terahertz