Search Results (287)

Background: Although teriparatide is efficacious, its once-daily subcutaneous injections cause local adverse events, inconvenience, and higher cost, limiting long-term adherence. Therefore, this research aims to engineer a pH-responsive oral formulation of teriparatide for osteoporosis therapy. Methods: A layered silicate nanocomplex was obtained by spontaneous self-assembly of teriparatide (Teri) with 3-aminopropyl magnesium phyllosilicate (AC). The nanocomplex (AC-Teri) was then coated with a 1:1 blend of two polymethacrylic acid derivatives (Eudragit^® L100 and Eudragit^® S 100) to provide pH-triggered drug release along the gastrointestinal tract. Results: AC-Teri and the coated nanocomplex (EE/AC-Teri) displayed high encapsulation efficiency (>90%) with narrow size distributions. In a stepwise buffer transition system, EE/AC-Teri demonstrated pH-dependent release, with less than 25% drug liberated at pH 1.2, approximately 54% at pH 6.8, and 74% at pH 7.4 over 24 h. Particle size and ζ-potential of EE/AC-Teri shifted in parallel with dissolution of the outer polymer shell. EE/AC-Teri also protected the peptide against enzymatic degradation, preserving the secondary structure of encapsulated teriparatide in simulated intestinal fluids. Compared with free drug, EE/AC-Teri enhanced transcellular drug permeation 2.7-fold in Caco-2 cells. In dexamethasone-induced osteoporotic rats, oral EE/AC-Teri significantly stimulated bone formation while suppressing resorption; micro-CT and histology confirmed recovery of trabecular architecture. Conclusions: EE/AC-Teri represents a promising oral teriparatide formulation for the effective management of osteoporosis. Full article

Background/Objectives: Paediatric patients continue to lack access to age-appropriate oral medicines for their treatment and have to depend on the off-label use of medicines approved for adults, which compromises dosing accuracy and exposes children to unpleasant bitterness. Building on previous proof-of-concept work with flucloxacillin sodium, this study investigated the effects of fatty-acid chain length on the formation, stability, dissolution, and sensory acceptability of diclofenac sodium (DS)–Eudragit® EPO (EE)–fatty acid (FA) polyelectrolyte complexes (PECs). Four saturated fatty acids, lauric (C12), myristic (C14), palmitic (C16), and stearic acid (C18), were evaluated at stoichiometric equimolar DS:EE:FA ratio (1:1:1). Methods: PEC microparticles were prepared by solvent evaporation. A stability-indicating RP-HPLC assay was developed and validated according to ICH guidelines to quantify DS content. Drug content and stability were monitored over 3 months at ambient storage. In vitro dissolution was performed in pH 5.5 medium at 37 °C. Taste acceptability and willingness to take again was assessed with 25 healthy adult volunteers using 11-point scale. Results: All PECs retained >90% of expected drug content after 3 months. Compared with neat DS, PECs markedly suppressed early drug release (32–39% vs. 94% at 2 min) but achieved >87% cumulative drug release in 60 min. Sensory evaluation showed significant differences across samples (p < 0.001): neat DS was least acceptable (20.8% willing to take again), while DS-EE-PA was most acceptable (92%), followed by DS-EE-SA and DS-EE-MA. DS-EE-LA was least favoured among PECs. Conclusions: Fatty-acid chain length influenced PEC formation and taste acceptability, but not the PEC stability and drug dissolution profile. Palmitic acid (DS-EE-PA) offered the best overall profile and represents a promising candidate for further development of paediatric-appropriate diclofenac formulations. Full article

Epicatechin is a flavonoid of the catechin subclass, found in fruits and medicinal plants such as açaí and green tea, widely studied for its anti-inflammatory properties. However, flavonoids often present chemical instability, low aqueous solubility, and poor bioavailability, limiting their therapeutic potential. This study aimed to incorporate epicatechin into nanocapsules to improve its applicability and evaluate whether the formulation maintains its anti-inflammatory effects via modulation of the NLRP3 inflammasome. Nanocapsules containing 0.25 mg/mL of epicatechin (NC-ECs) were prepared with Eudragit L-100 using interfacial deposition of a preformed polymer. The formulations were characterized for particle size, polydispersity index, zeta potential, and pH, as well as thermal stability over 45 days. Encapsulation efficiency and drug content were determined by high-performance liquid chromatography (HPLC), and morphology analyzed by atomic force microscopy (AFM). Cytocompatibility was assessed in VERO cells, and anti-inflammatory activity was investigated in THP-1-derived macrophages stimulated with LPS + nigericin. The NC-ECs displayed suitable physicochemical properties, high encapsulation efficiency (96%), and full drug loading. The formulation also showed good cytocompatibility and preserved anti-inflammatory activity through NLRP3 inflammasome modulation at low concentrations. These findings indicate NC-ECs as a promising nanotechnological strategy for treating inflammatory diseases involving NLRP3, highlighting its potential contribution to nanomedicine. Full article

Goji berries (Lycium barbarum L.) are extremely rich in bioactive compounds, including phenolics, flavonoids, and vitamin C, which contribute to the strong antioxidant and immunomodulatory properties, positioning them as a promising candidate for nutraceutical applications. However, due to some limitations such as poor bioavailability and instability, encapsulation via spray drying with polymeric carriers provides a practical strategy to improve their stability, bioavailability, and applicability in the health sector. In this study, goji berry extract (GBE) was obtained via ultrasound-assisted extraction (UAE) and encapsulated using spray drying with four different polymers: alginate, pectin, Eudragit E100 and RS30D. GBE-loaded microparticles showed improved production yields (e.g., 40.3% for Alginate + GBE vs. 13.9% for Alginate alone) and varying particle sizes (1.9–4.4 µm). The antioxidant/antiradical activities were retained to different extents, depending on the carrier, with RS30D + GBE displaying the highest TPC (15.51 mg GAE (gallic acid equivalents)/g), FRAP (59.83 µmol FSE (ferrous sulphate equivalents)/g), and DPPH activities (3.50 mg TE (Trolox equivalents)/g). Biocompatibility was confirmed in HT29-MTX cell lines for all produced microparticles. These findings support the use of spray-dried polymeric carriers to enhance the functional performance and stability of goji berry bioactive compounds in future nutraceutical applications. Full article

Controlling Rhipicephalus microplus is currently one of the main challenges in livestock farming due to the significant economic losses it causes. Traditionally, managing this parasite has been based on the use of synthetic ixodicides, among which fipronil has proven to be highly effective. However, its low water solubility and the limitations of commercially available formulations can affect the bioavailability of this compound, favoring the emergence of resistance in tick populations. In this context, fipronil-loaded nanoparticles were developed using the Eudragit^® E PO polymer (NP_F) (Helm, Naucalpan, Mexico, Mexico), which were physicochemically characterized and evaluated against fipronil-susceptible R. microplus larvae. NP_F had an average size of 143.43 ± 1.88 nm, a polydispersity index (PDI) of 0.162 ± 0.01, a ζ (P ζ) of 21.16 ± 0.54, an encapsulation percentage (%E) of 7.36 ± 0.30, and an encapsulation efficiency percentage (%EE) of 66.28 ± 3.5%. Free fipronil showed an LC₅₀ of 0.582 µg/mL and an LC₉₀ of 2.503 µg/mL against R. microplus. The NP_F formulation showed an LC₅₀ of 0.427 µg/mL and an LC₉₀ of 2.092 µg/mL. These results suggest that incorporating fipronil into nanoparticles improves its ixodicide efficacy, positioning it as an innovative and promising alternative for the development of effective tick control formulations. Full article

Background/Objectives: Lipid-based formulations are widely used to enhance the oral bioavailability of poorly water-soluble drugs. However, for weakly basic drugs with higher solubility under acidic conditions, precipitation and recrystallisation after gastric emptying can compromise a formulation’s ability to maintain the drug in a solubilised, absorbable state. To address this, we evaluated an enteric coating strategy to preserve the biopharmaceutical performance of a silica-solidified lipid-based formulation. Methods and Results: The model weakly basic BCS Class IV drug, abiraterone acetate, was loaded into a lipid-based formulation and solidified using mesoporous silica nanoparticles. In an in vitro lipolysis model, introducing the formulation only after the onset of the intestinal phase led to lower precipitation and over 50% greater drug presence in the aqueous phase compared to a two-stage gastric–intestinal digestion. In an in vivo pharmacokinetic study in Sprague Dawley rats, the silica–lipid formulation (6 mg/kg), delivered in gelatine minicapsules enteric-coated with Eudragit L100-55, resulted in a 2.6-fold higher systemic exposure compared to the non-coated formulation (p < 0.0001). Conclusions: These findings support the use of enteric coating for lipid-based formulations and silica nanoparticles containing weakly basic drugs as a strategy to maintain formulation integrity until reaching the small intestine. Full article

Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, S_mix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM. Full article

Additive manufacturing using fused deposition modelling (FDM) is increasingly explored for personalised drug delivery, but the lack of suitable biodegradable and printable filaments limits its pharmaceutical application. In this study, we investigated the influence of formulation and structural design on the performance of polyvinyl alcohol (PVA)-based filaments doped with theophylline anhydrous for 3D printing. To address the intrinsic brittleness and poor printability of PVA, cassava pulp-derived fibres—a sustainable and underutilised agricultural by-product—were incorporated together with polyethylene glycol (PEG 400), Eudragit^® NE 30 D, and calcium stearate. The addition of fibres modified the mechanical properties of PVA filaments through hydrogen bonding, improving flexibility but increasing surface roughness. This drawback was mitigated by Eudragit^® NE 30 D, which enhanced surface smoothness and drug distribution uniformity. The optimised composite formulation (P₁₀F₅E₅T₅) was successfully extruded and used to fabricate 3D-printed constructs. Release studies demonstrated that drug release could be modulated by pore geometry and construct thickness: wider pores enabled rapid Fickian diffusion, while narrower pores and thicker constructs shifted release kinetics toward anomalous transport governed by polymer swelling. These findings demonstrate, for the first time, the potential of cassava fibre as a functional additive in pharmaceutical FDM and provide a rational formulation–structure–performance framework for developing sustainable, geometry-tuneable drug delivery systems. Full article

Objectives: Although 3D-printing has been identified as a promising technique for personalised medicine manufacturing, developing complex formulations that are suitable for the process can be challenging. This study evaluates the use of a mixture design for the targeted development of an optimised formulation designed for the 3D-printing of oral dosage forms containing the drug sertraline hydrochloride featuring immediate-release drug dissolution. Methods: The polymers Eudragit E PO, Kollidon 17 PF and hydroxypropyl cellulose were compared in simple screening experiments regarding their extrudability, printability and disintegration. A combination of Eudragit E PO and Kollidon 17 PF proved superior and therefore served as the basis for the mixture design. The resulting blends were processed via hot melt extrusion to produce filaments, which were then measured for bending stress using a 3-point-bending-test, and 3D-printed sample plates were used to determine the crystallinity index of sertraline hydrochloride using X-ray diffraction in a previously identified range with low interference from the other components. The formulation was optimised using statistically based models with the aim of minimising the bending stress to obtain flexible, process-robust filaments and simultaneously minimising the crystallinity index with the intention of improving the solubility of the drug by maximising its amorphous content. Results: The filaments made from the optimised formulation could be reliably printed, and the amorphous state of the active ingredient therein was confirmed. The oral dosage forms produced from these showed immediate release characteristics in an acidic medium. Conclusions: This study demonstrates the advantages of a mixture design for optimising complex formulations in a time- and resource-efficient way and could serve as a basis for other research groups to develop innovative, customisable drug delivery systems more effectively. Full article

Background: The encapsulation of hydrophilic drugs within microparticles has gained significant interest in drug delivery systems due to their potential to improve stability, bioavailability, and controlled release of therapeutic agents. Biotin, a water-soluble vitamin, presents challenges such as rapid degradation and limited membrane permeability, which constrain its therapeutic effectiveness. Objectives: This study aims to develop and characterize biotin-loaded microparticles formulated with alginate, Eudragit^® E100, and CaCl₂, and to evaluate their characterization and potential applications. Methods: The microparticles were produced using the external ionic gelation method, where alginate and CaCl₂ solutions were mixed under probe sonication. Eudragit^® E100 was added as a complexing agent. The optimized formulation was used to encapsulate biotin, and various experimental variables were screened to study their influence on the properties of the microparticles. Results: Biotin was encapsulated in alginate microparticles (size: 634 nm; polydispersity index: 0.26; zeta potential: −45 mV) with an encapsulation efficiency of 90.5%. In vitro release studies using vertical diffusion Franz cells demonstrated a controlled release profile following the Weibull kinetic model. Conclusions: Encapsulation techniques offer a promising approach to overcome the limitations of hydrophilic drug delivery. The biotin-loaded microparticles developed in this study have potential applications in both topical and oral formulations, providing controlled release and improved therapeutic efficacy, and illustrate the broader applicability of polymeric encapsulation systems for improving the delivery of labile, hydrophilic bioactives. Full article

Significant efforts have been dedicated to developing controlled-release systems for the effective management of colorectal cancer. In this study, a once-daily, delayed-release regorafenib (REG) tablet was fabricated using 3D printing technology for the treatment of colorectal cancer. For this, a hydrogel containing 80 mg of the drug in a matrix of hyaluronic acid, carboxymethyl cellulose, Pluronic F127, and glycerol was prepared to incorporate into the shell cavity of tablet via a pressure-assisted microsyringe (PAM). The shell was printed from an optimized ink formulation of Soluplus^®, Eudragit^® RS-100, corn starch 1500, propylene glycol 4000, and talc through melt extrusion-based 3D printing. In vitro release assays showed a drug release rate of 91.1% in the phosphate buffer medium at 8 h and only 8.5% in the acidic medium. Drug release kinetics followed a first-order model. The results showed smooth and uniform layers based on scanning electron microscopy (SEM) and drug stability at 135 °C upon TGA. FTIR analysis confirmed the absence of undesired covalent interactions between the materials. Weight variation and assay results complied with USP standards. Mechanical strength testing revealed a Young’s modulus of 5.18 MPa for the tablets. Overall, these findings demonstrate that 3D printing technology enables the precise fabrication of delayed-release REG tablets, offering controlled-release kinetics and accurate dosing tailored for patients in intensive care units. Full article

Ferulic acid (FA) is a bioactive compound known for its potent antioxidant and anti-inflammatory properties; however, its poor water solubility significantly limits its bioavailability and therapeutic potential. In this study, a solid dispersion of FA (FA-SD) was developed using Eudragit^® EPO via the solvent evaporation method, achieving a 24-fold increase in solubility (42.7 mg/mL) at a 1:3 drug-to-polymer ratio. Expandable gastroretentive films were subsequently formulated using starches from Hom-Nil rice, glutinous rice, and white rice, combined with chitosan as the primary film-forming agents, via the solvent casting technique. Hydroxypropyl methylcellulose (HPMC) K100 LV was incorporated as an adjuvant to achieve controlled release. At optimal concentrations (3% w/w starch, 2% w/w chitosan, and 2% w/w HPMC), the films exhibited favorable mechanical properties, swelling capacity, and unfolding behavior. Sustained release of FA over 8 h was achieved in formulations containing HPMC with either Hom-Nil or glutinous rice starch. Among the tested formulations (R6, G6, and H6), those incorporating Hom-Nil rice starch demonstrated the most significant antioxidant (10.38 ± 0.23 μg/mL) and anti-inflammatory (9.26 ± 0.14 μg/mL) effects in murine macrophage cell line (RAW 264.7), surpassing the activities of both free FA and FA-SD. These results highlight the potential of anthocyanin-rich pigmented rice starch-based expandable films as effective gastroretentive systems for enhanced FA delivery. Full article

Background: The limited aqueous solubility of BCS Class II drugs, exemplified by itraconazole (ITR), continues to hinder their bioavailability and therapeutic performance following oral administration. The present study investigated the development of amorphous solid dispersions (ASDs) of ITR via continuous manufacturing technologies, such as hot melt extrusion (HME) and spray drying (SD), to improve drug release. Methods: Polymer selection was guided by Hansen solubility parameter (HSP) analysis, film casting, and molecular modeling, leading to the identification of aminoalkyl methacrylate copolymer type A (Eudragit^® EPO), polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus^®), and hypromellose acetate succinate HG (AQOAT^® AS-HG) as suitable carriers. ASDs were prepared at drug-to-polymer ratios of 1:1, 1:2, and 2:1. Comprehensive characterization was performed using ATR-FTIR, NMR, DSC, PXRD, SEM, PLM, and contact angle analysis. Results: HME demonstrated higher process efficiency, solvent-free operation, and superior dissolution enhancement compared to SD. Optimized HME-based ASDs were formulated into tablets. The ITR–Eudragit^® EPO formulation achieved 95.88% drug release within 2 h (Weibull model, R² > 0.99), while Soluplus^® and AQOAT^® AS-HG systems achieved complete release, best described by the Peppas–Sahlin model. Molecular modeling confirmed favorable drug–polymer interactions, correlating with the formation of stable complex and enhanced release performance. Conclusions: HME-based continuous manufacturing provides a scalable and robust strategy for improving the oral delivery of poorly water-soluble drugs. Integrating predictive modeling with experimental screening enables the rational design of ASD formulations with optimized dissolution behavior, offering potential for improved therapeutic outcomes in BCS Class II drug delivery. Full article

Lipid nanoparticle (LNP)-based delivery systems are promising tools for advancing RNA-based therapies. However, there are underlying challenges for the oral delivery of LNPs. In this study, we optimized an LNP formulation, which we encapsulated in a pH-sensitive Eudragit^® S 100 (Eu) coating. LNPs were prepared using the DLin-MC3-DMA ionizable lipid, cholesterol, DMG-PEG, and DSPC at a molar ratio of 50:38.5:10:1.5. LNPs were coated with 1% Eu solution via nanoprecipitation using 0.25% acetic acid to get Eu-coated LNPs (Eu-LNPs). Particle characteristics of LNPs were determined by using dynamic light scattering (DLS). Ribogreen and agarose gel retardation assays were used to evaluate nucleic acid entrapment and stability. LNPs and Eu-LNPs were ~120 nm and 4.5 μm in size, respectively. Eu-LNPs decrease to an average size of ~191 ± 22.9 nm at a pH of 8. Phosphate buffer (PB)-treated and untreated Eu-LNPs and uncoated LNPs were transfected in HEK-293 cells. PB-treated Eu-LNPs showed significant transfection capability compared to their non-PB-treated counterparts. Eu-LNPs protected their nucleic acid payloads in the presence of a simulated gastric fluid (SGF) with pepsin and maintained transfection capacity following SGF or simulated intestinal fluid. Hence, Eu coating is a potentially promising approach for the oral administration of LNPs. Full article

Background/Objectives: The formulation of microspheres for lipophilic drugs using aqueous methods, such as spray drying, faces significant challenges. The main objective of this study was to evaluate the effect of the process parameters and polymer selection on the production of microspheres by spray drying for a lipophilic drug. Methods: Lipophilic drug-loaded microspheres were developed using various polymers via the aqueous spray drying method. The effects of the factors on the yield percentage and encapsulation efficiency were analyzed. Microspheres preparation included Agave inulin, guar gum, hydroxypropyl methylcellulose, and Eudragit^® S100. A 2³ factorial design was performed, and the parameters were optimized. Results: Inlet temperature, feed flow, and polymer percentage showed a significant effect (p < 0.05) on the yield percentage of guar gum microspheres and encapsulation efficiency of the inulin microspheres. Inulin and guar gum microspheres showed the best yield percentage (75.41%) and encapsulation efficiency (100%), respectively. In addition, guar gum microspheres had the best morphology, and hydroxypropyl methylcellulose microspheres were smaller and had an irregular surface. Eudragit did not maintain its delayed release property due to limitations of the aqueous method; inulin released the drug immediately, and guar gum and hydroxypropyl methylcellulose microspheres prolonged release only by a few additional hours. Conclusions: The experimental design showed that optimizing the parameters (inlet temperature, feed flow, and the type and percentage of polymer) can regulate the microsphere development process to obtain improved product yield and encapsulation efficiency results. Full article