Preservation of the adsorption-relevant surface state is important for surface characterization of dehydration-sensitive pharmaceutical hydrates because hydration and surface structure may change during sample preparation and measurement. Humidity-controlled inverse gas chromatography (IGC) can prevent bulk hydrate-to-anhydrate transformation during specific surface area measurement; however, preservation of the bulk crystalline phase does not necessarily ensure preservation of the adsorption-relevant surface state. In this study, humidity-controlled IGC was investigated for characterizing the probe-accessible surface area of three pharmaceutical hydrate systems: sodium saccharin dihydrate, L-cysteine hydrochloride monohydrate, and citric acid monohydrate. Hydration behavior was characterized by dynamic vapor sorption, IGC measurements were performed under controlled relative humidity using n-nonane as an adsorption probe, and BET analysis was used to estimate the probe-accessible surface area. Measurements of the certified reference material BCR-170 supported the approach. Under humidity conditions selected based on DVS measurements, adsorption isotherms suitable for BET analysis were obtained for all three hydrate systems, and no detectable morphological changes were observed during the IGC measurement timescale. Importantly, the probe-accessible surface area depended on sample history and elapsed time even under humidity conditions selected to minimize dehydration. In L-cysteine hydrochloride monohydrate, the surface area decreased from 0.43 to 0.30 m2 g⁻1 after 1 day using the same packed column, accompanied by a substantial decrease in pressure drop. These findings indicate that maintaining the hydration environment does not necessarily ensure a time-invariant adsorption-relevant surface state. Humidity-controlled IGC provides an approach for characterizing the surface behavior of dehydration-sensitive pharmaceutical hydrates while minimizing dehydration-related perturbation during measurement.
Understanding the material deformation behavior in tablet dies is crucial for pharmaceutical development, as it directly influences manufacturability and final tablet properties. Heckel analysis provides a theoretical framework for assessing material deformation during compaction, but its direct correlation with real-world tableting behavior remains an area of interest. This study introduces a framework for characterizing the deformation mechanisms of pharmaceutical powders. It addresses limitations in conventional methods that rely solely on yield pressure (Py) and strain rate sensitivity (SRS), which fail to fully differentiate elastic and plastic deformation. The heuristic framework for comparative deformation mapping enables differentiation of excipients across the brittle-plastic-elastic space using two parameters from a compaction simulator: Py (from Heckel analysis) and pressure drop (ΔP, from an in-die stress relaxation test). ΔP is treated as a descriptor of time-dependent (viscoplastic and viscoelastic) deformation rather than as a direct measure of elasticity, and its use as an empirical surrogate for elastic character was benchmarked against independent force–displacement elastic energy. Applied to ten common pharmaceutical excipients, the framework differentiated materials that Py and SRS alone did not resolve (SRS was determined for the four reference materials). Across the ten materials, ΔP tracked elastic energy mainly between excipient classes, whereas within the six lactose grades the relationship was reversed, indicating that ΔP differences within a class reflect time-dependent deformation. The framework is therefore proposed as a comparative, material-sparing screening tool for early-stage excipient selection, not as a predictor of tableting performance or scale-up behavior.
Amorphous nanosuspensions can generate supersaturated drug concentrations far above crystalline solubility, but their performance depends on stabilizing both the metastable amorphous phase and the high interfacial energy of nanosized particles against recrystallization and Ostwald ripening. ATZ was selected as a model weakly basic drug because its poor dissolution and rapid desupersaturation at intestinal pH provide a rational formulation space for probing the biopharmaceutical relevance of amorphous nanosuspensions. The present study addressed these limitations through the development of ATZ amorphous nanosuspension using acid–base neutralization method. Polymer-surfactant screening was performed through desupersaturation assay and drug-rich droplet size analysis which identified HPMCAS-MG and Soluplus as optimal precipitation inhibitors. Box-Behnken design optimization yielded nanosuspension with a mean particle size of 146.7 ± 5.56 nm and polydispersity index of 0.261 ± 0.05, and a zeta potential of − 4.54 ± 0.78 mV. Solid-state and spectroscopic analyses confirmed successful amorphization of ATZ and the presence of hydrogen-bonding and hydrophobic interactions in ATZ-ANS. Further, non-sink in vitro dissolution testing revealed that ATZ-ANS effectively sustained supersaturation with limited precipitation. The formulation retained its nanoscale characteristics and did not show evidence of recrystallization during six months of accelerated stability testing at 40 °C/75
Mucopenetrating systems are drug delivery platforms designed to overcome the intestinal mucus barrier, facilitating access to epithelium and enhancing the bioavailability of lipophilic compounds. Copaiba oil (CO) is a compound displaying broad therapeutic potential but low aqueous solubility, which limits its bioavailability. This study aimed to assess how two CO-loaded delivery systems, an emulsion (EM) and a self-emulsifying system (SE), interact with the intestinal mucus layer and how effectively they permeate it. Thus, interactions with mucin and porcine intestinal mucosa were evaluated via oscillatory rheometry, by determining rheological synergism, and the in vitro and ex vivo mucoadhesion assays. The retention of the emulsion systems on the intestinal mucosa was also assessed, along with mucopermeation, using Transwell inserts coated with porcine intestinal mucus and mucin solution. Rheological analysis demonstrated a significant interaction between SE and mucin, evidenced by positive rheological synergism, whereas EM showed limited interaction. In mucoadhesion studies, EM behavior was primarily associated with its higher consistency, while SE exhibited more specific interactions with mucin. Ex vivo retention studies demonstrated greater retention of EM on the intestinal mucosa. In contrast, SE showed superior permeation through the mucus layer in mucopermeation assays, a behavior attributed to the presence of PEG 400. Overall, SE exhibited a more favorable balance between mucoadhesion and mucus penetration than EM. The SE demonstrated enhanced mucopermeation while maintaining adequate interaction with intestinal mucus, suggesting its potential as a promising oral delivery platform for improving the intestinal transport and bioavailability of copaiba oil.
