Solid-state NMR (SSNMR) (1)H T1 and T1ρ relaxation times were used to evaluate the miscibility of amorphous solid dispersions of nifedipine (NIF) and polyvinylpyrrolidone (PVP) prepared by three different methods: melt quenching in the typical lab setting, spray drying and melt quenching in the NMR rotor while spinning. Of the five compositions prepared by melt quenching in the lab setting, the 95:5 and 90:10 NIF:PVP (w:w) amorphous solid dispersions were not miscible while 75:25, 60:40, and 50:50 NIF:PVP dispersions were miscible by the (1)H T1ρ measurements. The domain size of the miscible systems was estimated to be less than 4.5 nm. Amorphous solid dispersions with composition of 90:10 NIF:PVP prepared by spray drying and melt quenching in the NMR rotor showed miscibility by (1)H T1ρ values. Variable-temperature SSNMR (1)H T1ρ relaxation measurements revealed a change in relaxation time at approximately 20 °C below Tg, suggesting increased molecular mobility above that temperature.

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The purpose of this study is to determine whether sodium alginate solutions' rheological parameters are meaningful relative to sodium alginate's use in the formulation of calcium alginate gels. Calcium alginate gels were prepared from six different grades of sodium alginate (FMC Biopolymer), one of which was available in ten batches. Cylindrical gel samples were prepared from each of the gels and subjected to compression to fracture on an Instron Universal Testing Machine, equipped with a 1-kN load cell, at a cross-head speed of 120 mm/min. Among the grades with similar % G, (grades 1, 3, and 4), there is a significant correlation between deformation work (L(E)) and apparent viscosity (η(app)). However, the results for the partial correlation analysis for all six grades of sodium alginate show that L(E) is significantly correlated with % G, but not with the rheological properties of the sodium alginate solutions. Studies of the ten batches of one grade of sodium alginate show that η(app) of their solutions did not correlate with L(E) while tan δ was significantly, but minimally, correlated to L(E). These results suggest that other factors--polydispersity and the randomness of guluronic acid sequencing--are likely to influence the mechanical properties of the resultant gels. In summary, the rheological properties of solutions for different grades of sodium alginate are not indicative of the resultant gel properties. Inter-batch differences in the rheological behavior for one specific grade of sodium alginate were insufficient to predict the corresponding calcium alginate gel's mechanical properties.

Abstract. Polymeric excipients are often the least well-characterized components of pharmaceutical formulations. The aim of this study was to facilitate the QbD approach to pharmaceutical manufacturing by evaluating the inter-grade and inter-batch variability of pharmaceutical-grade polymeric excipients. Sodium alginate, a widely used polymeric excipient, was selected for evaluation using appropriate rheological methods and test conditions. The materials used were six different grades of sodium alginate and an additional ten batches of one of the grades. To compare the six grades, steady shear measurements were conducted on solutions at 1%, 2%, and 3% w/w, consistent with their use as thickening agents. Small-amplitude oscillation (SAO) measurements were conducted on sodium alginate solutions at higher concentrations (4-12% w/w) corresponding to their use in controlled-release matrices. In order to compare the ten batches of one grade, steady shear and SAO measurements were performed on their solutions at 2% w/w and 8% w/w, respectively. Results show that the potential interchangeability of these different grades used as thickening agents could be established by comparing the apparent viscosities of their solutions as a function of both alginate concentration and shear conditions. For sodium alginate used in controlled-release formulations, both steady shear behavior of solutions at low concentrations and viscoelastic properties at higher concentrations should be considered. Furthermore, among batches of the same grade, significant differences in rheological properties were observed, especially at higher solution concentrations. In conclusion, inter-grade and inter-batch variability of sodium alginate can be determined using steady shear and small-amplitude oscillation methods.

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