Current Issue : October-December Volume : 2025 Issue Number : 4 Articles : 5 Articles
Background/Objectives: Lipid-based formulations (LBFs) are enabling formulations for poorly water-soluble, mostly lipophilic drugs. In LBFs, the drug is pre-dissolved in the formulation which can consist of lipids, surfactants, and/or cosolvents. In cases where the administration of high amounts of a drug is required, exceeding the drug solubility in the lipidic vehicle at the administration temperature, supersaturated LBFs are an option. The standard method described in the literature for inducing supersaturation in LBFs is to dissolve the drug substance in the lipidic vehicle at an elevated temperature, e.g., at 60 ◦C, and then subsequently let the formulation cool to ambient temperature before administration (heat-based approach). In this work, an alternative approach to induce supersaturation in LBFs was investigated in order to evaluate if higher drug loads, i.e., the concentration of drug dissolved in the vehicle, could be reached compared to the loading obtainable via heating. Methods: A volatile solvent that is miscible with the lipid matrix and in which the compound has a high solubility is added to the lipid matrix, after which the solvent is evaporated. Both approaches were compared in this work investigating two different LBFs loaded with the BCS-class II drugs celecoxib and fenofibrate. Results: When inducing supersaturation by heat, drug loads of 238% for celecoxib and 278% for fenofibrate could be achieved relative to the solubility at ambient temperature. Using the solvent-based approach, drug loads of up to 475% for celecoxib and 557% for fenofibrate could be prepared in the LBFs using dichloromethane (DCM) as the volatile solvent. However, those highly supersaturated preparations showed suboptimal physical stability and quickly led to precipitation when the LBFs were stored at ambient temperature. In addition, selected formulations were analyzed with GC-headspace to determine the residual DCM after solvent evaporation using a vacuum evaporator. This analysis revealed that the DCM content exceeded regulatory requirements, with up to 21,883 ppm DCM in the formulations. Conclusions: Overall, the relatively high residual DCM concentration and the suboptimal physical stability do not make the approach easily usable for generating supersaturated lipid-based formulations....
The development of robust and scalable tablet manufacturing methods remains a key objective in pharmaceutical technology, especially when dealing with active pharmaceutical ingredients (APIs) and excipients that exhibit suboptimal processing properties. This study evaluated two alternative manufacturing strategies for tablets containing sodium naproxen (20%, API), dolomite (65%, sustainable mineral filler), cellulose (7%), polyvinylpyrrolidone (5%, binder), and magnesium stearate (3%, lubricant). The direct compression method used a vibrating ball mill (SPEX SamplePrep 8000M), while the indirect method employed wet granulation using a pan granulator at different inclination angles. Physical properties of raw materials and granules were assessed, and final tablets were evaluated for mass, thickness, mechanical resistance, abrasiveness, and API content uniformity. Direct compression using vibratory mixing for 5–10 min (DT2, DT3) resulted in average tablet masses close to the target (0.260 g) and improved reproducibility compared to a reference V-type blender. Wet granulation produced tablets with the lowest abrasiveness (<1.0%) and minimal variability in dimensions and API content. The best uniformity (SD < 0.5%) was observed in batch IT2. Overall, vibratory mixing proved capable of achieving tablet quality comparable to that of wet granulation, while requiring fewer processing steps. This highlights its potential as an efficient and scalable alternative in solid dosage manufacturing....
Background/Objectives: Microneedles represent an innovative transdermal drug delivery approach, especially for protein antigens. This study aimed to develop a dual-functional, dissolvable microneedle system loaded with β-glucan and fucoidan in a hyaluronic acid matrix to achieve transdermal immunomodulation and reactive oxygen species (ROS) regulation, exploring its potential in inflammatory disease management and antigen delivery. Methods: The microneedles were fabricated using a two-step casting method. Their morphology, mechanical strength, and dissolution kinetics were characterized. In vitro experiments evaluated the ROS-modulating effects on human dermal fibroblasts, while in vivo studies on C57 mice investigated immune activation and lymph node accumulation of ovalbumin antigen. Results: The microneedles exhibited a mechanical strength exceeding 7.45 N/needle and dissolved within 50 s. β-glucan transiently reduced ROS levels at 6 h followed by a rebound, whereas fucoidan sustained ROS suppression after 12 h. In mice, β-glucan-loaded microneedles triggered local immune activation, and fucoidan-incorporated microneedles enhanced ovalbumin accumulation in lymph nodes by 2.1-fold compared to controls. Conclusions: Integrating β-glucan’s immunostimulatory and fucoidan’s ROS-scavenging/lymphatic-targeting properties within a single microneedle platform offers a promising multifunctional strategy for treating inflammatory diseases and delivering protein antigens....
Background/Objectives: The work presented herein focused on the development and characterization of a transdermal caffeine platform fabricated from ultrathin micro- and submicron fibers produced via electrospinning. Methods: The formulations incorporated caffeine encapsulated in a polyethylene oxide (PEO) matrix, combined with various permeation enhancers. A backing layer made of annealed electrospun polycaprolactone (PCL) facilitated the lamination of the two layers to form the final multilayer patch. Comprehensive characterization was conducted, utilizing scanning electron microscopy (SEM) to assess the fiber morphology, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) for chemical detection and to assess the stability of the caffeine, and differential scanning calorimetry (DSC) along with wide-angle X-ray scattering (WAXS) to analyze the physical state of the caffeine within the fibers of the active layer. Additionally, Franz cell permeation studies were performed using both synthetic membranes (Strat-M) and ex vivo human stratum corneum (SC) to evaluate and model the permeation kinetics. Results: These experiments demonstrated the significant role of enhancers in modulating the caffeine permeation rates provided by the patch, achieving permeation rates of up to 0.73 mg/cm2 within 24 h. Conclusions: This work highlights the potential of using electro-hydrodynamic processing technology to develop innovative transdermal delivery systems for drugs, offering a promising strategy for enhancing efficacy and innovative therapeutic direct plasma administration....
Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, temperature control, and integration into continuous manufacturing. This study investigates vertical HME as an innovative approach in order to optimize drug polymer interactions and generate stable amorphous dispersions with controlled release behavior. Methods: Extrusion trials were conducted using a vertical hot-melt extruder developed by Rondol Industrie (Nancy, France). Acetylsalicylic acid (ASA) supplied by Seqens (Écully, France) was used as a model API and processed with Soluplus® and Kollidon® 12 PF (BASF, Ludwigshafen, Germany). Various process parameters (temperature, screw speed, screw profile) were explored. The extrudates were characterized by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to evaluate crystallinity and microstructure. In vitro dissolution tests were performed under sink conditions using USP Apparatus II to assess drug release profiles. Results: Vertical HME enabled the formation of homogeneous amorphous solid dispersions. PXRD confirmed the absence of residual crystallinity, and SAXS revealed nanostructural changes in the polymer matrix influenced by drug loading and thermal input. In vitro dissolution demonstrated enhanced drug release rates compared to crystalline ASA, with good reproducibility. Conclusions: Vertical HME provides a compact, cleanable, and modular platform that supports the development of stable amorphous dispersions with controlled release. It represents a robust and versatile solution for pharmaceutical innovation, with strong potential for cost-efficient continuous manufacturing and industrial-scale adoption....
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