Application of a handheld NIR spectrometer in prediction of drug content in inkjet printed orodispersible formulations containing prednisolone and levothyroxine

Abstract

Quality control tools to assess the quality of printable orodispersible formulations are yet to be defined. Four different orodispersible dosage forms containing two poorly soluble drugs, levothyroxine and prednisolone, were produced on two different edible substrates by piezoelectric inkjet printing. Square shaped units of 4cm² were printed in different resolutions to achieve an escalating drug dose by highly accurate and uniform displacement of droplets in picoliter range from the printhead onto the substrates. In addition, the stability of drug inks in a course of 24h as well as the mechanical properties and disintegration behavior of the printed units were examined. A compact handheld near-infrared (NIR) spectral device in the range of 1550-1950nm was used for quantitative estimation of the drug amount in printed formulations. The spectral data was treated with mean centering, Savitzky-Golay filtering and a third derivative approach. Principal component analysis (PCA) and orthogonal partial least squares (OPLS) regression were applied to build predictive models for quality control of the printed dosage forms. The accurate tuning of the dose in each formulation was confirmed by UV spectrophotometry for prednisolone (0.43-1.95mg with R²=0.999) and high performance liquid chromatography for levothyroxine (0.15-0.86mg with R²=0.997). It was verified that the models were capable of clustering and predicting the drug dose in the formulations with both Q² and R²Y values between 0.94-0.99.

Keywords: Dimethyl sulfoxide (PubChem CID: 24893977); Glycerol (PubChem CID: 753); Hydrochloric acid (PubChem CID: 313); Hydroxypropyl cellulose (PubChem CID: 123706); Hydroxypropyl methylcellulose (PubChem CID: 57503849); Levothyroxine sodium salt pentahydrate (PubChem CID: 24900041); Methanol (PubChem CID: 887); Multivariate analysis; NIR spectroscopy; Orodispersible formulations; Personalized medicine; Piezoelectric inkjet printing; Potassium dihydrogen phosphate (PubChem CID: 516951); Prednisolone (PubChem CID: 24898725); Propylene glycol (PubChem CID: 24901410); Quality control; Sodium hydroxide (PubChem CID: 14798).