Predicting the Water Sorption in ASDs

Abstract

Water decreases the stability of amorphous solid dispersions (ASDs) and water sorption is, therefore, unwanted during ASD storage. This work suggests a methodology to predict the water-sorption isotherms and the water-sorption kinetics in amorphous pharmaceutical formulations like ASDs. We verified the validity of the proposed methodology by measuring and predicting the water-sorption curves in ASD films of polyvinylpyrrolidone-based polymers and of indomethacin. This way, the extent and the rate of water sorption in ASDs were predicted for drug loads of 0.2 and 0.5 as well as in the humidity range from 0 to 0.9 RH at 25 °C. The water-sorption isotherms and the water-sorption kinetics in the ASDs were predicted only based on the water-sorption isotherms and water-sorption kinetics in the neat polymer on the one hand and in the neat active pharmaceutical ingredient (API) on the other hand. The accurate prediction of water-sorption isotherms was ensured by combining the Perturbed-Chain Statistical Association Theory (PC-SAFT) with the Non-Equilibrium Thermodynamics of Glassy Polymers (NET-GP) approach. Water-sorption kinetics were predicted using Maxwell–Stefan diffusion coefficients of water in the ASDs.

Water Sorption in Rubbery and Glassy Polymers, Nifedipine, and Their ASDs

“…To determine the inter-diffusion coefficient of water in an ASD Đ Hd 2 O,ASD , the diffusion coefficient of water in an API Đ Hd 2 O,API and the one of water in the polymer Đ Hd 2 O,polymer were used according to eq 23. 14 w w…”

“…This leads to the following expression for water sorption in an ASD (eq ). normald m normalH 2 normalO normalL normald t = prefix− A · ρ ASD · Đ normalH 2 normalO , ASD · 1 italicRT · true( ∂ μ normalH 2 normalO normalL ∂ z true) T The rate of water sorption normald m normalH 2 normalO normalL normald t , where t is the time and m H 2 O L is the mass of water in ASD, can be calculated from the ASD surface area A , the density of the wet ASD ρ ASD , the gas constant R , the temperature T , and the spatial gradient of the chemical potential of water ∂ μ normalH 2 normalO normalL ∂ z in the wet ASD at constant temperature. The latter is the driving force for diffusion.…”

“…The intra-diffusion coefficient of the Free-Volume Theory D 12 FV can be related and compared with the inter-diffusion of Maxwell–Stefan diffusion coefficient Đ 12 using the conversion in eq Đ 12 = D 12 FV · ( 1 − w 1 ) To determine the inter-diffusion coefficient of water in an ASD Đ H 2 O,ASD , the diffusion coefficient of water in an API Đ H 2 O,API and the one of water in the polymer Đ H 2 O,polymer were used according to eq Đ normalH 2 normalO , ASD = true( w 0 , API Đ normalH 2 normalO , API + w 0 , polymer Đ normalH 2 normalO , polymer true) − 1 …”

“…This leads to the following expression for water sorption in an ASD (eq ). The rate of water sorption , where t is the time and m H 2 O L is the mass of water in ASD, can be calculated from the ASD surface area A , the density of the wet ASD ρ ASD , the gas constant R , the temperature T , and the spatial gradient of the chemical potential of water in the wet ASD at constant temperature. The latter is the driving force for diffusion.…”

“…The Non-Equilibrium Thermodynamics of Glassy Polymers (NET-GP) approach was combined with equilibrium models, like PC-SAFT, Sanchez–Lacombe, or Perturbed Hard Sphere Chain model . Borrmann et al , showed that the water sorption in poly­(vinylpyrrolidone) (PVP), in poly­(vinylpyrrolidone-co-vinyl acetate) (PVPVA), and in ASDs consisting of PVP and indomethacin and of PVPVA and indomethacin could be predicted over the full RH range of interest using PC-SAFT in combination with NET-GP for the glassy region.…”