AAPS PharmSciTech最新文献

This work provides details of development of paclitaxel injection concentrate for nanodispersion (PICN) which includes excipient screening, optimization process, and stability studies of the PICN formulation. A systematic evaluation of various fatty acids, sterol analogues, polymers, and solvents led to the selection of a synergistic excipient system for PICN consisting of sodium cholesterol sulphate, caprylic acid and povidone K12 dissolved in polyethylene glycol 400 and ethanol. PICN reliably forms nanodispersion with particle sizes in the 50–150 nm range upon reconstitution in 5% dextrose solution (D5W). Transmission electron microscopy of nanodispersion demonstrated that the nanoparticles are amorphous and non-crystalline which was confirmed by differential scanning calorimetry and X-ray diffraction studies showing a complete loss of paclitaxel crystallinity. Small angle X-ray scattering data showed that the nanoparticles exist in sponge-like coacervate phase. Reconstitution studies in D5W infusion bag, mimicking injection time and shaking speed of the diluent bag, showed minimal impact on particle size of the nanodispersion. The in-vitro release profile was consistent from the range of particle sizes produced. Stability data of PICN under ICH conditions confirmed assay values of 97–101% with low total impurities (< 0.65%) over 24 months. The stability of the reconstituted nanodispersion did not show any change in physicochemical quality attributes over 24 h. These results not only validate our hypothesis of paclitaxel self-assembly driven in the presence of selected lipid and polymers reported in previous paper but also demonstrates that a convenient, scalable and stable protein-free alternative to existing paclitaxel formulations is offered for clinical use.

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This study reports the development of azithromycin-loaded polymeric films (AZF) composed of gellan gum (GG) and hyaluronic acid (HA) for localized periodontal drug delivery. A 3² full factorial design was employed to optimize formulation variables and assess critical attributes influencing film performance. The films exhibited uniform thickness (0.13–0.16 mm), high folding endurance (> 300 folds), and a physiologically compatible surface pH (6.8–7.0). Increasing HA content significantly enhanced swelling and drug release, with all formulations having achieved high drug-loading efficiencies (92-100%). In vitro drug release studies revealed a biphasic release profile, an initial burst for rapid antimicrobial action followed by sustained release over 72 hours. Kinetics modeling using the Peppas–Sahlin equation indicated contributions from both Fickian diffusion and polymer relaxation. AFM, SEM and XTM confirmed the films’ porous, uniform microstructure supporting sustained release behavior. AZF exhibited significantly superior antibacterial efficacy against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, compared to standard azithromycin and metronidazole discs. The localized, sustained drug delivery effectively overcomes limitations of systemic antibiotic therapy, including poor site retention and the need for systemic exposure. These findings support the potential of GG–HA films as biodegradable, patient-compliant platforms for targeted periodontal drug delivery, offering improved therapeutic outcomes and addressing biological barriers to effective treatment.

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Nanostructured lipid carriers (NLCs) have attracted considerable interest as drug delivery systems capable of enhancing the solubility and oral bioavailability of poorly water-soluble drugs. In our previous work, cannabidiol (CBD)-loaded NLCs prepared by hot homogenization demonstrated improved dissolution and oral bioavailability. In the present study, hot-melt extrusion (HME) was investigated as a rapid and easily scalable alternative method for the preparation of CBD NLCs. Additionally, spray drying was used to convert the prepared CBD NLCs into a solid dosage form. CBD NLCs were prepared using HME at different screw speeds (100, 200, and 300 rpm), followed by probe sonication, and characterized for particle size, entrapment efficiency (EE), and drug release. Spray drying was performed with different carriers (D-lactose, Kollidon® VA 64, maltodextrin 12, and Soluplus®) to evaluate their compatibility and performance. The results showed that the screw speed has an impact on the properties of the NLCs, while probe sonication further reduced particle size, resulting in enhanced entrapment efficiency, and drug release of all formulations. Although NLC produced at a screw speed of 300 rpm was the most stable in both 4 °C and 25 °C. Among the carriers tested for spray drying, maltodextrin achieved nearly complete CBD release, while Soluplus® led to increased particle size and reduced release. Overall, HME combined with probe sonication proved to be a robust approach for the preparation of CBD NLCs, which were successfully converted into solid powder formulations by spray drying, offering a promising strategy for scalable production of CBD NLCs.

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Berberine, an isoquinoline alkaloid, is a compound of interest due to its structural diversity and wide range of biological activities; however, its pharmacological effects are significantly limited by poor intestinal absorption. In this study, a novel formulation approach was employed to improve the bioavailability of berberine by formulating lipid-polymer hybrid nanoparticles (BER-LPHN) using a modified nanoprecipitation method. The formulation was optimized using a 3² full factorial design, incorporating Phospholipon 90 H as the lipid and Gantrez as the hydrophilic polymer. The optimized BER-LPHN exhibited a nanosize of 250–350 nm and a zeta potential of -25.00 ± 2.2 mV, with notably high drug loading (~ 87%). TEM analysis revealed the spherical morphology of the BER-LPHN, with the lipid coat surrounding the polymeric matrix, which facilitated controlled drug release from the polymeric core in vitro, resulting in an 18-fold increase in the oral bioavailability of berberine. In-vivo studies using fluorescently labeled nanoparticles demonstrated a significant concentration of BER-LPHN near the villi boundary and significant uptake by Peyer’s patches. Confocal microscopy further confirmed the lymphatic uptake of BER-LPHN through M cells of Peyer’s patches, suggesting that the formulated nanoparticles have the potential to enhance berberine's bioavailability by boosting permeability in the intestine via lymph transport.

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Objective

To develop and optimize a baicalin-loaded soluplus-based hydrogel patch for enhanced wound healing applications.

Methods

Baicalin-loaded hydrogel patches were formulated using freeze–thaw method and optimized through 3 × 2 factorial design with varying concentrations of PVA (1.0–2.0 g) and Soluplus (0.33–0.66 g). The patches were characterized for physicochemical properties, ex vivo permeation, stability, skin irritation potential, and wound healing efficacy in rat models.

Results

Solubility studies revealed poor aqueous solubility of baicalin (0.052 mg/ml) while FTIR confirmed drug-excipient compatibility. The optimized formulation BF6 (PVA 2.0 g, Soluplus 0.495 g) demonstrated superior folding endurance (378 ± 16.52), drug content (90.23 ± 1.32%), and swelling index (168.42 ± 5.93%). Ex vivo permeation studies showed enhanced baicalin delivery (93.24 ± 3.94% at 12 h) with a flux of 5.73 ± 0.28 mg/cm²/h. Accelerated stability studies confirmed minimal degradation (2.86% drug content reduction) after 3 months. The formulation exhibited zero Draize score in skin irritation tests and significantly accelerated wound healing (92.13 ± 4.82% contraction by day 9) compared to standard treatment (83.45 ± 4.65%) and control (68.27 ± 4.23%).

Conclusion

The optimized baicalin-loaded soluplus-based hydrogel patch offers a promising approach for chronic wound management with enhanced healing rates, excellent stability, and safety profile. This first-in-class baicalin-Soluplus combination addresses the challenges of baicalin's poor solubility through systematic factorial optimization. while providing controlled drug delivery and optimal wound microenvironment, presenting significant potential for clinical translation in advanced wound care therapy. Future mechanistic studies are warranted to elucidate molecular healing pathways.

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Pregnant women must take medications to treat or prevent specific health conditions that arise during the gestational period. Glibenclamide (GBC), metformin (MET), or insulin (INS) can be prescribed to treat gestational diabetes; Folic acid (FA) is also prescribed during pregnancy to prevent newborn malformations. GBC and FA have low solubility and, therefore, low bioavailability. Amino acids (AA) have been previously proven to be efficient co-formers in binary systems, enhancing drug solubility in water. In this study, highly soluble pharmaceutical ternary formulations of GBC were prepared with FA and the amino acid arginine (ARG). Although ARG has been previously reported as a co-former in GBC binary co-amorphous formulations, it has not been studied in molar ratios higher than 1:2. The results show that ARG may play a role as a co-former and wettability agent depending on its concentration. Ball milling was chosen to prepare the amorphous systems, testing different molar ratios (GBC:ARG: FA at 1:1:0.4, 1:2:0.4, and 1:10:0.4). The presence of glass transition, broad FT-IR bands, and the absence of X-ray diffraction peaks confirmed amorphization of GBC in the milled samples. Solubility results show that ARG may act as a wettability agent when present in the ratio GBC:ARG:FA 1:10:0.4, since even in the physical mixture, an enhancement of GBC solubility of 897-fold was achieved, and as a co-former since the amorphous GBC-ARG-FA formulation showed an increment of 1287-fold. The enhanced solubility of GBC in these ternary systems makes them potential formulations for simultaneously addressing health conditions through combination therapy with FA.

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Long-term controlled release in drug-loaded injectable hydrogels is challenging in the injection-based treatments of ocular diseases. Herein, injectable hyaluronic acid (HA)-based hydrogels were synthesized in situ via Schiff base reaction between amino-functionalized hyaluronic acid (NHA) and three aldehyde-functionalized β-cyclodextrin (β-CD) derivatives: aldehyde β-cyclodextrin (ACD), aldehyde linear poly-β-cyclodextrin (ALCD), and aldehyde branched poly-β-cyclodextrin (ABCD). The composition, structure, and properties of the prepared hydrogels were analyzed using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and dynamic rheometry. The hydrogels exhibited a pore size range of 50–250 μm, a swelling degree of 27.1–45.0%, and a gelation time of 60–300 s, demonstrating suitable microstructural and rheological properties for clinical applications. By leveraging the dual functionality of the aldehyde β-CD derivatives as both crosslinking agents and drug carriers (Voriconazole (VCZ) was as a model drug), the hydrogels achieved long-term controlled release (> 60 days) with quasi-zero-order kinetics in the later stage, alongside excellent cellular compatibility, particularly for NHA/ACD (R² = 0.99701) and NHA/ABCD (R² = 0.98931). This study presents the first comparative analysis of the effects of structurally distinct aldehyde β-CD/poly-β-CD derivatives on hydrogel properties. The findings provide novel insights into the structural design of aldehyde-functionalized β-CD derivatives for the development of long-term controlled release injectable hydrogels in about 30–60 days as well as tuned. Simultaneously, the corresponding in vivo animal safety and efficacy experiments could further validate the practical application potential of this gel platform in the future work. Conclusively, the injectable HA-based hydrogels have potential as promising candidates for treating chronic ocular pathologies requiring long-term therapy.

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The work at hand follows the pragmatic design and development of a tripartite controlled release tablet, motivated by the ongoing opioid epidemic and poor adherence to adjunct gastroprotective agents (GPAs) in chronic NSAID users. Taking heed of critical process parameters (CPPs) and critical material attributes (CMAs), a formulation capable of meeting the pre-defined Quality Target Product Profiles (QTPPs) and critical quality attributes (CQAs) was achieved. Delivering 50% of the Paracetamol (PAR) dose within the first 30 min, from an Immediate Release (IR) layer of 250 mg (PAR) for an early onset of analgesia; 100 mg of Diclofenac Sodium (DS) and 250 mg of PAR from the cup, formulated for a delayed and retarded release, and lastly 20 mg Esomeprazole Magnesium Trihydrate (ESM) from a press coated core pill, the latter often prescribed separately. The release mechanism of PAR and DS from the cup after the 2-h mark distinctly followed the Hixson-Crowell model where the geometrical characteristic of the cup was maintained with surface erosion. SEM analysis results prior to and during dissolution confirmed bulk and surface erosion release mechanisms. The obtained ex vivo analysis results showed retarded permeation rates of the tableted APIs compared to the APIs in their pure state.

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Allergic skin disease conditions represent a significant global health challenge, with conventional therapies frequently associated with local dermal irritation and systemic adverse effects. Nanotechnology-enabled transdermal drug delivery platforms present innovative approaches for the targeted and efficient administration of natural drugs. This paper presents an overview of the application of nanocarriers, including polymeric nanoparticles, lipid-based nanocarriers, and inorganic nanostructures, for managing allergic skin diseases by enhancing the solubility of natural drugs, improving transdermal permeation, and facilitating site-specific targeting. The synergistic integration of microneedle arrays and hydrogel matrices for sustained release and precise delivery is also analyzed. Furthermore, the potential of stimuli-responsive smart delivery systems to modulate the lesion microenvironment is explored. In future advancements, integrating artificial intelligence into the rational design of nanocarriers, developing 3D skin organoid models, and establishing dynamic efficacy assessment systems can expedite the clinical translation of novel nanomedicines. This approach offers a robust theoretical foundation and technical support for personalized therapy in allergic skin disease conditions.

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Pressurized metered dose inhalers (pMDIs) are among the most commonly prescribed inhalation devices; yet their performance often remains suboptimal. Although the inefficiencies of these inhalers have been recognized for a long time, the absence of a comprehensive numerical model that spans the entire process—from propellant injection to aerosol plume formation—has hindered efforts to identify the underlying causes of these issues. This study presents a novel multiphase framework based on the volume of fluid (VOF) approach, which captures key internal flow phenomena in pMDIs, including cavitation, flash boiling, and atomization. The model was validated using plume visualization data obtained via high-speed imaging, complemented by high-resolution X-ray imaging from prior in vitro studies. The proposed numerical framework demonstrates predictive capability by reproducing key plume characteristics in close agreement with multiple independent experimental datasets. It yields a mass median diameter of approximately 2.7 μm, which closely aligns with the experimental value of 3 μm. Additionally, the model captures the dynamics of the spray, predicting an initial velocity of around 110 m/s and a cone angle of approximately 21°. These predictions are in excellent agreement with the high-speed imaging data obtained in this study. By moving beyond one-size-fits-all approaches, this platform enables the optimization and adaptation of inhaler configurations based on formulation-specific performance criteria, offering a promising tool to support the development of pMDIs tailored to a broad range of therapeutic applications.

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