The present study aimed to develop and evaluate a novel self-microemulsifying mouth dissolving film (SMMDF) of felodipine (FDP) to enhance its physicochemical properties and oral bioavailability. FDP, a poorly water-soluble BCS class II drug, exhibits low and variable bioavailability due to limited dissolution and extensive presystemic metabolism. The solubility of FDP was systematically determined in various lipid excipients, followed by screening of surfactants and co-surfactants for their self-emulsification efficiency. Based on these findings, liquid self-microemulsifying drug delivery system (SMEDDS) was developed and characterized for key physicochemical parameters. The optimized SMEDDS was subsequently incorporated into mouth-dissolving film via the solvent casting technique. Eleven batches of films were formulated employing central composite design. SMMDF was optimized considering critical quality attributes, including disintegration time, folding endurance, and percentage drug release. The liquid SMEDDS formulation was composed of Capryol 90, Kolliphor RH-40, and Transcutol P. The prepared SMMDF of FDP exhibited excellent physicochemical characteristics, with folding endurance exceeding 200 and rapid disintegration within 3 min. Solid-state characterization studies (DSC, XRD, and SEM) confirmed the amorphous dispersion of FDP within the polymeric matrix. In vitro dissolution release profiles proved significantly superior drug release from SMMDF compared to FDP suspension. In vivo studies revealed statistically significant improvement in pharmacokinetic parameters (p < 0.05) confirming enhanced systemic exposure from SMMDF. The enhanced performance is attributed to improved solubilization, nanosized dispersion, and increased dissolution of FDP from SMEDDS-based film system. Overall, the developed SMMDF represents a promising and patient-friendly approach for improving oral bioavailability of poorly water-soluble drugs.
Amphiphilic hyaluronic acid conjugates form micellar nanostructures with critical micelle concentration (CMC) values that vary widely across studies due to differences in analytical methodology and experimental conditions. In particular, probe-based fluorescence approaches may influence micelle stability, thereby complicating direct comparison of published data. In this work, we investigated the self-assembly of oleate-modified hyaluronic acid (HA-C18:1) micelles using spectrofluorimetry (CMC = 0.071 +/- 0.005 mg/mL), pendant drop surface tension (CMC = 0.140 +/- 0.012 mg/mL), dynamic light scattering, and isothermal titration calorimetry (ITC; CMC = 0.025 +/- 0.007 mg/mL). ITC provided a probe-independent thermodynamic assessment, revealing the lowest, most consistent CMC for primary micellization and highlighting method-dependent variability in conventional approaches. Encapsulation of hydrophobic guests-paclitaxel (PTX), carbobenzoxy-etoposide (ETP-Cbz), and oleic acid-stabilized iron oxide nanoparticles-stabilized the micelles and further reduced the apparent CMC. Notably, PTX-loaded micelles exhibited rod-like morphology and the lowest CMC (0.006 mg/mL), contrasting with spherical ETP-Cbz micelles (0.025 mg/mL), indicating guest-induced restructuring and enhanced stability. Overall, the results provide a comparative thermodynamic analysis of HA-based amphiphilic systems and highlight the influence of analytical methodology and guest molecules on micellar stability.
Near-wellbore formation damage in carbonate reservoirs is commonly characterized by the coexistence of complex organic and inorganic deposits, which severely deteriorate reservoir permeability and oil well productivity. Conventional acidizing schemes are largely based on experimental data obtained from pure mineral cores, which fail to realistically represent the compositional characteristics of in-situ plugging materials and their influence on acid-rock reaction behavior, thereby limiting their engineering applicability. To address this issue, the organic-inorganic composite composition of near-wellbore plugging materials was first systematically characterized, and artificially damaged cores that reflect the actual damage features were subsequently constructed. On this basis, a targeted hybrid acid system was developed. Core-flooding tests demonstrated that this system achieved a permeability ratio of 18 times (i.e., a 1700% increase), significantly outperforming conventional hydrochloric acid. Key reaction kinetics parameters obtained from static dissolution and rotating disk experiments were utilized to construct and calibrate a dual-scale model. Numerical simulations confirmed that the hybrid acid system generates smoother, more elongated wormholes at lower injection rates compared to the HCl system, explaining its superior deep-penetration capability. This study demonstrates that the hybrid acid system developed herein, benefiting from the synergistic complementarity between organic and inorganic acids, effectively targets the organic-inorganic composite plugging characteristics of ZH Well. The system simultaneously achieves efficient dissolution and enhanced deep penetration, thereby significantly improving stimulation performance in complex and severely damaged carbonate reservoirs.
