Monitoring the weight and dimensional expansion of pyridostigmine bromide tablets under dynamic vapor sorption and impact of deliquescence on tablet strength and drug release

Abstract

Changes of weight and axial expansion of tablets of the deliquescent drug pyridostigmine bromide with Kollidon SR were followed with relative humidity (RH) using dynamic vapor sorption and displacement transducer. The effects of RH on placebo and drug containing (API) tablets prepared at low and high compression were related to tablet strength and molecular changes. Tablet weight and expansion increased with RH, especially above RH 40%. Tablet rigidity and strength decreased linearly with moisture for placebo tablets whereas for API tablets there was decrease up to 50% followed by large drop at 60%. Raman spectra of tablets did not show chemical interactions due to moisture, but decreased intensity of drug peak at 2370 cm−1 indicating solid state changes. Decrease of polymer peak intensities at 805 and 1740 cm−1 occurred only in API tablets implicating drug deliquescence in polymer moisture sorption. X-ray diffraction and thermal analysis of tablets indicated complete drug liquefaction after exposure at 60% RH, which impacted great loss of strength but did not affect the sustained release profile. In conclusion, monitoring of the physical properties of tablets during production of deliquescent drugs is necessary to avoid pitfalls during downstream processes such as coating, packaging and storage.