The focus of the present work was to develop co-amorphous dispersion (CAD) formulations of tacrolimus (TAC) using sucrose acetate isobutyrate as a carrier, evaluate by in vitro and in vivo methods and compare its performance with hydroxypropyl methylcellulose (HPMC) based amorphous solid dispersion (ASD) formulation. CAD and ASD formulations were prepared by solvent evaporation method followed by characterization by Fourier transformed infrared spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), dissolution, stability, and pharmacokinetics. XRPD and DSC indicated amorphous phase transformation of the drug in the CAD and ASD formulations, and dissolved more than 85% of the drug in 90 min. No drug crystallization was observed in the thermogram and diffractogram of the formulations after storage at 25 °C/60% RH and 40 °C/75% RH. No significant change in the dissolution profile was observed after and before storage. SAIB-based CAD and HPMC-based ASD formulations were bioequivalent as they met 90% confidence of 90–11.1% for C_max and AUC. The CAD and ASD formulations exhibited C_max and AUC 1.7–1.8 and 1.5–1.8 folds of tablet formulations containing the drug’s crystalline phase. In conclusion, the stability, dissolution, and pharmacokinetic performance of SAIB-based CAD and HPMC-based ASD formulations were similar, and thus clinical performance would be similar.

The objectives of the present work were to simultaneously quantify digoxin (DGX) and its impurities by a common analytical method, compare dissolution data

Background: Digoxin (DGX) is a narrow therapeutic index (NTI) and Biopharmaceutics Classification System (BCS) class IV drug whose clinical performance can be influenced by physicochemical properties, formulation composition, manufacturing processes, and stability-related solid-state transformations. Objective: The objective of the paper was to understand the effect of process and formulation variables on digoxin formulations. Methods: This study reports the effect of particle size, lactose types (LA and LM), manufacturing methods, and granulating fluid (ethanol and water–ethanol) on the critical quality attributes of DGX tablets (XRPD, DT, assay, impurity, and dissolution). Accordingly, 10 formulations were prepared using a full factorial design and monitored for 30 days at 40 °C/75% RH. Results: Assay values of the formulations did not change significantly (p > 0.05) compared to initial values after storage. No impurities or new peaks were detected in the stability samples, indicating either no drug degradation or the degradation products were below the limit of detection of the method (31.5–44.6 ng/mL). The dissolution rate and extent of the formulations changed after exposure, indicating the effect of composition and process variables. In direct compression formulations, a decrease in dissolution rate, especially at 10 and 20 min, was higher than at 60 min, which may be related to an increase in hardness and DT values. However, a decrease in dissolution of 5.6–8.7% at 60 min was observed after storage from the initial values, which may be due to an increase in crystallinity. Conclusions: Particle size, manufacturing method, and granulating fluid significantly influenced the solid-state characteristics and dissolution performance of DGX tablets. Wet granulation promoted partial amorphization and improved initial dissolution but reduced stability due to recrystallization during storage. These findings highlight the importance of formulation and process selection in ensuring the quality and stability of NTI drug products.