Correlation between drug dissolution and resistance to water-induced phase separation in solid dispersion formulations revealed by solid-state NMR spectroscopy

Publication date: Available online 25 January 2020Source: International Journal of PharmaceuticsAuthor(s): Hitomi Okada, Keisuke Ueda, Yuki Yasuda, Kenjirou Higashi, Motoki Inoue, Masataka Ito, Shuji Noguchi, Kohsaku Kawakami, Kunikazu MoribeAbstractWe aimed to elucidate the dissolution mechanism of solid dispersions (SDs) according to the carrier polymers used. Nifedipine (NIF) and polymers dissolved simultaneously from NIF/Eudragit® S (EUD-S), NIF/Eudragit® L (EUD-L), and NIF/hypromellose (HPMC)/EUD-S spray-dried samples (SPDs). In contrast, NIF dissolved separately from polymers from NIF/HPMC and NIF/HPMC/EUD-L SPDs due to the formation of an amorphous NIF-rich interface. Solid-state NMR spectroscopy indicated that NIF-EUD interactions were stronger than NIF-HPMC interactions. NIF/HPMC SPD exhibited weak interactions; thus, it failed to inhibit phase separation during the dissolution process and control NIF dissolution. The hygroscopicity of SPDs was higher with HPMC mixing and increased substitution ratio of methacrylic acid in EUD. Moreover, solid-state NMR spectroscopy revealed that the NIF-EUD interactions were hindered to a large extent by the absorbed water. During the dissolution process of NIF/HPMC/EUD-L SPD, the introduction of water to the NIF-EUD-L interaction site could induce the phase separation and poor controllability of NIF dissolution. Water-induced phase separation should be considered based on molecular-level characterization to obtain SDs with enhanc...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research