Moisture Sorption by Polymeric Excipients Commonly Used in Amorphous Solid Dispersions and its Effect on Glass...

Moisture sorption by polymeric carriers used for the development of amorphous solid dispersions (ASDs) plays a critical role in the physical stability of dispersed drugs since moisture may decrease glass transition temperature (T_g) and thereby increase molecular mobility of drugs leading to their crystallization. To assist the selection of appropriate polymers for ASDs, we conducted moisture sorption by five types of cellulosic polymers, namely, hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), hydroxypropyl methyl cellulose acetate succinate (HPMCAS), hydroxypropyl methyl cellulose phthalate (HPMCP), and ethyl cellulose (EC), as functions of relative humidity (10 to 90% RH) and temperature (25 and 40 °C). The moisture sorption was in the order of HPC>HPMC>HPMCP>HPMCAS>EC, and there was no significant effect of the molecular weights of polymers on moisture uptake. There was also less moisture sorption at 40 °C than that at 25 °C. Glass transition temperatures (T_g) of the polymers decreased with the increase in moisture content. However, the plasticizing effect by moisture on HPC could not be determined fully since, despite being amorphous, there were very little baseline shifts in DSC scans. There was also very shallow baseline shift for HPMC at >1% moisture content. In contrast, T_g of HPMCAS and HPMCP decreased in general agreement with the Gordon-Taylor/Kelley-Bueche equation, and EC was semicrystalline having both T_g and melting endotherm, with only minor effect of moisture on T_g. The results of the present investigation would lead to a systematic selection of polymeric carriers for ASDs.