Pharmaceutics

Background/Objectives: Avocado (Persea americana Mill.) seed is an agro-industrial by-product with significant pharmacological potential. This study aimed to conduct a preformulation assessment of aqueous seed extracts from Criollo (M1) and Hass (M2) cultivars. Methods: The extracts were characterized for total phenolic content (TPC) and ABTS^•+ scavenging capacity, and their compatibility with pharmaceutical excipients was evaluated in binary mixtures by Fourier transform infrared (FTIR) spectroscopy with Pearson correlation and hierarchical cluster analysis (HCA), differential scanning calorimetry (DSC), and isothermal stress testing (50 °C, 15 days) with HPLC quantification of epicatechin (IST-HPLC). Results: M2 showed significantly higher TPC (192.80 ± 4.90 µg GAE/mg) than M1 (27.08 ± 0.51 µg GAE/mg; p < 0.0001). ABTS^•+ inhibition was 59.92 ± 1.76% for M1 (0.05 mg/mL) and 50.79 ± 1.19% for M2 (0.01 mg/mL). The DSC transition enthalpies of both extracts did not differ significantly (p = 0.1271). Maltodextrin and gum arabic were compatible with both extracts, suggesting that they could serve as common excipients for both cultivars, whereas the chemical stability of five M2 mixtures could not be determined by IST-HPLC. Sodium carboxymethylcellulose (CMC) was incompatible with M1, as shown by a 29.44 percentage-point decrease in epicatechin recovery (p < 0.0001), separate HCA clustering (Euclidean distance > 0.009), and the lowest FTIR spectral correlation (r = 0.990). Conclusions: These findings provide a scientific basis for the rational development of solid dosage forms from avocado seed extracts.

Background/Objectives: Direct intratumoral injection of doxorubicin (DOX) can increase local drug exposure, but rapid escape from the tumor limits retention and contributes to systemic toxicity. This study developed a thermoreversible chitosan/β-glycerophosphate (CS/β-GP) hydrogel designed to form an in situ depot and prolong local DOX delivery. Methods: A three-factor Box–Behnken design was used to optimize CS, β-GP, and DOX concentrations against gelation temperature, gelation time, viscosity, and 7-day cumulative release. The optimized formulation was characterized by rheology, injectability, degradation, swelling, porosity, and 4T1 cytotoxicity. Intratumoral retention, plasma and organ biodistribution, antitumor efficacy, body-weight changes, and cardiac toxicity were then evaluated in 4T1 tumor-bearing BALB/c mice. Results: The optimized hydrogel contained 1.684% w/v CS, 6.601% w/v β-GP, and 0.200% w/v DOX, gelled at 36.3 ± 0.55 °C within 1.65 ± 0.28 min, and released 84.66 ± 8.38% of DOX over 7 days. DOX-loaded hydrogel preserved concentration-dependent cytotoxicity. During in vivo studies, hydrogel delivery lowered the observed plasma DOX peak by approximately 55% and retained measurable intratumoral DOX for 168 h, whereas free DOX solution was no longer detectable. Tumor growth suppression was sustained, with tumor volumes of 205.62 ± 36.85 versus 701.69 ± 69.35 mm³ for free DOX solution on day 24. Repeated hydrogel treatment also markedly attenuated cardiac troponin-I (cTnI) and creatine kinase-MB (CK-MB) elevations relative to free DOX solution. Conclusions: Thermoreversible CS/β-GP delivery reshaped DOX exposure from a rapidly dispersing intratumoral dose into a sustained local depot, improving tumor control while reducing the early plasma peak and attenuating cardiac-injury biomarker elevations.

Background/Objectives: The aim of this study was to design a nanosuspension (NS) of tegoprazan (TPZ), a novel potassium-competitive acid blocker (P-CAB), to overcome its low aqueous solubility and improve oral absorption. Methods: TPZ NSs were prepared using a lab-scale bead-milling technique. Subsequently, their physicochemical properties, in vitro dissolution profiles, storage stability, and in vivo pharmacokinetic profiles were evaluated. Results: Among various screened stabilizers, polyvinyl alcohol was selected as the suspending agent due to its favorable physicochemical stability. The optimized NS exhibited a mean particle size of approximately 270 nm and a zeta potential of −12.1 mV, preserving the crystalline state of TPZ. In vitro dissolution studies revealed that the NS and its freeze-dried form (NS-FD) markedly enhanced drug dissolution across all tested dissolution media (pH 1.2, 4.0, 6.8, and distilled water) compared to the raw drug material. Furthermore, the NS formulations remained physically and chemically stable for up to 12 weeks under long-term and accelerated storage conditions (25 °C/60% relative humidity (RH) and 40 °C/75% RH). In vivo pharmacokinetic studies in male Sprague–Dawley rats revealed that the oral TPZ NS resulted in approximately a 2.1-fold increase in systemic exposure compared to the raw material and microsuspension. Conclusions: These findings suggest that TPZ NS is a promising strategy to enhance the oral absorption of P-CAB, using a simple, organic-solvent-free fabrication process.