Role of polymers in the physical and chemical stability of amorphous solid dispersion: A case study of carbamazepine

Incorporating the amorphous drug in polymeric components has been demonstrated as a feasible approach to enhance the bioavailability of poorly water-soluble drugs. The objective of this study was to investigate the role of polymers in the stability of amorphous solid dispersion (ASD) by evaluating the drug-polymer interaction, microenvironmental pH, and stability of ASD. Carbamazepine (CBZ), a Biopharmaceutics Classification System Class II compound, was utilized as a model drug. Polyvinylpyrrolidone (PVP), poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA), polyacrylic acid (PAA), and hydroxypropyl methylcellulose (HPMCAS) were selected as model polymers.

CBZ ASDs were characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, and dissolution studies. Molecular modeling was conducted to understand the strength of interaction between CBZ and each polymer. FTIR spectroscopy and molecular modeling results show that the interaction between CBZ and PAA is the strongest among all the ASDs, as PAA is an acidic polymer with the potential to form strong hydrogen bonding with CBZ. Besides, hydrophobic interaction is detected between CBZ and HPMCAS. CBZ-PAA and CBZ-HPMCAS ASDs reveal better physical stability than CBZ-PVP and CBZ-PVPVA ASDs under 40°C/75% RH for 8 weeks.

However, CBZ-PAA ASD shows chemical degradation after stability testing due to its acidic microenvironmental pH. This paper shows that strong intermolecular interactions between CBZ and polymers contribute to the physical stability of the ASDs. Additionally, acidic polymers yield an acidic microenvironment pH of the ASDs that causes chemical degradation during storage. Hence, a balance between the ability of a given polymer to promote physical stability and chemical stability may need to be considered.

Download the full article as a PDF here or read it here

Article information: Dongyue Yu, Jinghan Li, Hanxun Wang, Hao Pan, Ting Li, Tianshi Bu, Wei Zhou, Xiangrong Zhang, Role of polymers in the physical and chemical stability of amorphous solid dispersion: A case study of carbamazepine, European Journal of Pharmaceutical Sciences, 2021. https://doi.org/10.1016/j.ejps.2021.106086.