Stability of indomethacin with relevance to the release from amorphous solid dispersions studied with ATR-FTIR spectroscopic imaging.
This work presents the use of attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and spectroscopic imaging to study the stability and dissolution behaviour of amorphous solid dispersions (ASDs). ASDs are employed to improve the bioavailability of drugs which are poorly soluble in aqueous solutions. Selecting the appropriate polymeric excipients for use in pharmaceutical tablets is crucial to control drug stability and subsequent release. In this study, indomethacin was used as a model poorly-aqueous soluble drug since the amorphous-form has improved dissolution properties over its crystalline forms. ASDs of indomethacin/polyethylene glycol (PEG) and indomethacin/hydroxypropyl methylcellulose (HPMC) in a 1:3 wt ratio were compared. Firstly, ATR-FTIR spectroscopy was employed to monitor the stability of indomethacin in the ASDs over 96 h. While the indomethacin/HPMC ASD showed the ability to maintain the amorphous indomethacin form for longer periods of time, ATR-FTIR spectra revealed that indomethacin in the drug/PEG ASD crystallised to the stable γ-form, via the α-form. Secondly, ATR-FTIR spectroscopic imaging was used to study the dissolution of ASD tablets in a phosphate buffer (pH 7.5). Crystallisation of amorphous indomethacin was characterised in the spectra collected during the dissolution of the indomethacin/PEG ASD which consequently hindered release into the surrounding solution. In contrast, release of amorphous indomethacin was more effective from HPMC.
Department of Chemical Engineering, Imperial College London, London SW7 2AZ, United Kingdom.
Andrew V
AV
Ewing
Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral, Merseyside CH46 1QW, United Kingdom.
Graham S
GS
Clarke
Department of Chemical Engineering, Imperial College London, London SW7 2AZ, United Kingdom. Electronic address: s.kazarian@imperial.ac.uk.
Sergei G
SG
Kazarian
D004355:Drug Stability; D065347:Hypromellose Derivatives / Q000737:chemistry*; D007213:Indomethacin / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D007213:Indomethacin
Amorphous; Chemical imaging; Dissolution; FT-IR spectroscopy; Hydroxypropyl methylcellulose (PubChem CID: 57503849); Indomethacin; Indomethacin (PubChem CID: 3715); Polyethylene glycol (PubChem CID: 174); Solid dispersion