Search Results (23)

Docetaxel (DTX)-loaded polymeric nanoparticles composed of Eudragit RL and RS 100 were developed by solvent evaporation using D-α-tocopheryl polyethene glycol 1000 succinate as an emulsifier and optimised by Central Composite Design. The effects of homogenisation and sonication times on entrapment efficiency (%EE) and drug release (%DR) were statistically analysed across nine batches. Particle size (PS) ranged from 302 ± 1.0 to 502 ± 2.0 nm, and zeta potential (ZP) from 25.8 ± 2.5 to 42.9 ± 1.7 mV. %EE and %DR (pH 1.2 for 2 h, then pH 7.4 for 22 h, 40 mL medium at 37 ± 0.5 °C) ranged from 69.32 ± 3.77 to 92.71 ± 0.16% and 19.24 ± 3.03 to 49.17 ± 1.98%, respectively. Optimised DTX nanoparticles (DNPs) showed EE of 78.18 ± 0.56%, DR of 46.21 ± 1.41% at 24 h, PS of 357.9 ± 2.4 nm, and ZP of 42.9 ± 3.7 mV. Scanning electron microscopy revealed ~300 nm cuboidal particles with smooth surfaces. X-Ray Diffraction and Differential Scanning Colorimetry confirmed reduced drug crystallinity in DNPs. In vitro haemolysis assays showed ~11.5-fold lower haemolytic potential (p < 0.0001) versus DTX, confirming improved safety. Fluorescence microscopy indicated enhanced cellular uptake of DNPs in MDA-MB-231 cells, while cytotoxicity assays of DNPs showed a lower IC₅₀ (39.52 µM) compared to DTX (60.81 µM), demonstrating superior anticancer efficacy. Overall, DNPs represent a promising oral chemotherapy platform for breast cancer management. Full article

Background/Objectives: Cutaneous melanoma is a potent neoplasm whose advancement is linked to catecholamine-induced angiogenesis through β-adrenergic receptors. Propranolol (PROP), a non-selective β-blocker, holds potential in oncology, but its systemic side effects restrict its viability. This study aims to nanoencapsulate PROP in Eudragit RL^®100 polymeric nanocapsules for topical melanoma treatment. Methods: Nanocapsules were created through interfacial deposition of preformed polymer and characterized in terms of particle size, zeta potential, pH, drug content, and encapsulation efficiency. In vitro evaluations include release profile, antioxidant activity, bioadhesiveness, hemolysis, cytotoxicity, and antitumor effect on melanoma cells. Additionally, migration assays were conducted. Results: The nanocapsules displayed an acidic pH, an average size of 151 nm, and a positive zeta potential. An encapsulation efficiency of 81% was achieved, even with the hydrochloride form of the drug. The release profile exhibited sustained release of PROP, showcasing enhanced antioxidant activity in the nanoencapsulated form. The formulations also exhibited significant bioadhesion with mucin and an in vitro hemolysis rate over 50%, attributed to the cationic polymer and surfactants present. Moreover, in the cell viability assays, the NC-PROP formulations significantly reduced melanoma cell viability. In the migration assay, both the nanocapsules with and without the drug significantly inhibited cell migration, supporting the potential therapeutic benefits of these formulations. Conclusions: The nanoencapsulation of PROP in Eudragit RL^®100 presents a viable strategy for topical treatment of cutaneous melanoma, enhancing release duration and reducing systemic effects. The assessments indicated distinct physical properties and substantial therapeutic potential. Full article

Background/objectives: The aim of the study was to create a nanofiber insert incorporating Timolol (TIM) and Dorzolamide (DOR), targeting the management of glaucoma. This condition encompasses a variety of chronic, advancing ocular disorders typically associated with elevated intraocular pressure (IOP). Methods: The insert was made of Eudragite RL100 (EUD) polymer, a biocompatible material with high bioavailability, using the electrospinning method. The inserts were studied for morphology, drug–polymer interaction, physicochemical properties, and in vitro drug-release study. The pharmacokinetic properties of fibers were examined alongside consideration for irritation using a rabbit model and cell compatibility. Results: The results of the in vitro drug-release test showed retention and controlled release of both DOR/TIM over 80 h. Morphological examination demonstrated uniform nanofibers with mean diameters < 465 nm. The cell compatibility test showed a high percentage of cell survival, and none of the formulations irritated the rabbit’s eye. The Area Under the Curve (AUC0-72) for DOR and TIM in EDT formulations was approximately 3216.63 ± 63.25 µg·h/mL and 2598.89 ± 46.65 µg·h/mL, respectively, with Mean Residence Times (MRTs) of approximately 21.6 ± 0.19 h and 16.29 ± 6.44 h. Conclusions: Based on the results, the dual drug-loaded nanofiber preservative-free system can potentially be a suitable alternative to eye drops and can be used to reduce fluctuation and dose frequency. Full article

This research evaluated two methods of arginine encapsulation, melt emulsification and nanoprecipitation, using a lipid matrix of carnauba wax and commercial polymers (Eudragit^®) as a protective material. The ratios of wax–arginine were 1:1, 2:1, 3:1, and 4:1, while those of Eudragit^® RS:RL were 30:70 and 40:60 in proportions of 1:0.5 and 1:1 Eudragit^®–arginine. The microcapsules were morphostructurally characterized by scanning electron microscopy, and a microelement analysis was performed via energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. Additionally, in vitro digestibility was used to determine the protection efficiency. Both encapsulated systems presented regular (crystals) and spherical (microcapsules) polyhedral morphologies. Qualitative nitrogen decreased significantly as the wax ratio increased in the wax–arginine formulations. The formulations with a 1:1 Eudragit:–arginine ratio (1000 mg arginine) produced a higher nitrogen content in the encapsulated systems than the formulations containing 500 mg of arginine. The 2:1 and 3:1 wax–arginine formulations had the lowest degradability after 5 h of rumen fluid exposure (40.7 and 21.26%, respectively) in comparison with 100% unencapsulated arginine. The 3:1 wax–arginine formulation is an efficient encapsulating system which protects against rumen degradation. The more intense absorption bands at 1738 cm⁻¹ and 1468 cm⁻¹ associated with the C=O and C-H groups in carnauba wax indicate that arginine was more protected than in the other systems. Full article

Polymers are the backbone of drug delivery. Electrospinning has greatly enriched the strategies that have been explored for developing novel drug delivery systems using polymers during the past two decades. In this study, four different kinds of polymers, i.e., the water-soluble polymer poly (vinyl alcohol) (PVA), the insoluble polymer poly(ε-caprolactone) (PCL), the insoluble polymer Eudragit RL100 (ERL100) and the pH-sensitive polymer Eudragit S100 (ES100) were successfully converted into types of tri-layer tri-polymer core–shell fibers through bi-fluid coaxial electrospinning. During the coaxial process, the model drug metronidazole (MTD) was loaded into the shell working fluid, which was an emulsion. The micro-formation mechanism of the tri-layer core–shell fibers from the coaxial emulsion electrospinning was proposed. Scanning electron microscope and transmission electron microscope evaluations verified the linear morphology of the resultant fibers and their obvious tri-layer multiple-chamber structures. X-ray diffraction and Fourier transform infrared spectroscopy measurements demonstrated that the drug MTD presented in the fibers in an amorphous state and was compatible with the three polymeric matrices. In vitro dissolution tests verified that the three kinds of polymer could act in a synergistic manner for a prolonged sustained-release profile of MTD in the gut. The drug controlled-release mechanisms were suggested in detail. The protocols reported here pioneer a new route for creating a tri-layer core–shell structure from both aqueous and organic solvents, and a new strategy for developing advanced drug delivery systems with sophisticated drug controlled-release profiles. Full article

Lipid and/or polymer-based drug conjugates can potentially minimize side effects by increasing drug accumulation at target sites and thus augment patient compliance. Formulation factors can present a potent influence on the characteristics of the obtained systems. The selection of an appropriate solvent with satisfactory rheological properties, miscibility, and biocompatibility is essential to optimize drug release. This work presents a computational study of the effect of the basic formulation factors on the characteristics of the obtained in situ-forming particulates (IFPs) encapsulating a model drug using a 2¹.3¹ full factorial experimental design. The emulsion method was employed for the preparation of lipid and/or polymer-based IFPs. The IFP release profiles and parameters were computed. Additionally, a desirability study was carried out to choose the optimum formulation for further morphological examination, rheological study, and PBPK physiological modeling. Results revealed that the type of particulate forming agent (lipid/polymer) and the incorporation of structure additives like Brij 52 and Eudragit RL can effectively augment the release profile as well as the burst of the drug. The optimized formulation exhibited a pseudoplastic rheological behavior and yielded uniformly spherical-shaped dense particulates with a PS of 573.92 ± 23.5 nm upon injection. Physiological modeling simulation revealed the pioneer pharmacokinetic properties of the optimized formulation compared to the observed data. These results assure the importance of controlling the formulation factors during drug development, the potentiality of the optimized IFPs for the intramuscular delivery of piroxicam, and the reliability of PBPK physiological modeling in predicting the biological performance of new formulations with effective cost management. Full article

Hot-melt extrusion is a well-established tool in the pharmaceutical industry, mostly implemented to increase the solubility of poorly soluble drugs. A less frequent application of this technique is to obtain formulations with extended release. This study investigated the influence of polymer choice, drug loading, milling and hydrodynamics on the release of a model drug, flurbiprofen, from sustained-release hot-melt extrudates with Eudragit polymers. The choice of polymer and degree of particle size reduction of the extrudate by milling were the two key influences on the release profile: the percentage release after 12 h varied from 6% (2 mm threads) to 84% (particle size <125 µm) for Eudragit RL extrudates vs. 4.5 to 62% for the corresponding Eudragit RS extrudates. By contrast, the release profile was largely independent of drug loading and robust to hydrodynamics in the dissolution vessel. Thus, hot-melt extrusion offers the ability to tailor the release of the API to the therapeutic indication through a combination of particle size and polymer choice while providing robustness over a wide range of hydrodynamic conditions. Full article

Clozapine (CZP) is the only effective drug in schizophrenia resistant to typical antipsychotics. However, existing dosage forms (oral or orodispersible tablets, suspensions or intramuscular injection) show challenging limitations. After oral administration, CZP has low bioavailability due to a large first-pass effect, while the i.m. route is often painful, with low patient compliance and requiring specialised personnel. Moreover, CZP has a very low aqueous solubility. This study proposes the intranasal route as an alternative route of administration for CZP, through its encapsulation in polymeric nanoparticles (NPs) based on Eudragit^® RS100 and RL100 copolymers. Slow-release polymeric NPs with dimensions around 400–500 nm were formulated to reside and release CZP in the nasal cavity, where it can be absorbed through the nasal mucosa and reach the systemic circulation. CZP-EUD-NPs showed a controlled release of CZP for up to 8 h. Furthermore, to reduce mucociliary clearance and increase the residence time of NPs in the nasal cavity to improve drug bioavailability, mucoadhesive NPs were formulated. This study shows that the NPs already exhibited strong electrostatic interactions with mucin at time zero due to the presence of the positive charge of the used copolymers. Furthermore, to improve the solubility, diffusion and adsorption of CZPs and the storage stability of the formulation, it was lyophilised using 5% (w/v) HP-β-CD as a cryoprotectant. It ensured the preservation of the NPs’ size, PDI and charge upon reconstitution. Moreover, physicochemical characterisation studies of solid-state NPs were performed. Finally, toxicity studies were performed in vitro on MDCKII cells and primary human olfactory mucosa cells and in vivo on the nasal mucosa of CD-1 mice. The latter showed non-toxicity of B-EUD-NPs and mild CZP-EUD-NP-induced tissue abnormalities. Full article

The local treatment of diseases by drug-eluting implants is a promising tool to enable successful therapy under potentially reduced systemic side effects. Especially, the highly flexible manufacturing technique of 3D printing provides the opportunity for the individualization of implant shapes adapted to the patient-specific anatomy. It can be assumed that variations in shape can strongly affect the released amounts of drug per time. This influence was investigated by performing drug release studies with model implants of different dimensions. For this purpose, bilayered model implants in a simplified geometrical shape in form of bilayered hollow cylinders were developed. The drug-loaded abluminal part consisted of a suitable polymer ratio of Eudragit^® RS and RL, while the drug-free luminal part composed of polylactic acid served as a diffusion barrier. Implants with different heights and wall thicknesses were produced using an optimized 3D printing process, and drug release was determined in vitro. The area-to-volume ratio was identified as an important parameter influencing the fractional drug release from the implants. Based on the obtained results drug release from 3D printed implants with individual shapes exemplarily adapted to the frontal neo-ostial anatomy of three different patients was predicted and also tested in an independent set of experiments. The similarity of predicted and tested release profiles indicates the predictability of drug release from individualized implants for this particular drug-eluting system and could possibly facilitate the estimation of the performance of customized implants independent of individual in vitro testing of each implant geometry. Full article

A micro-in-macro gastroretentive and gastrofloatable drug delivery system (MGDDS), loaded with the model-drug ciprofloxacin, was developed in this study to address the limitations commonly experienced in narrow-absorption window (NAW) drug delivery. The MGDDS, which consists of microparticles loaded in a gastrofloatable macroparticle (gastrosphere) was designed to modify the release of ciprofloxacin, allowing for an increased drug absorption via the gastrointestinal tract. The prepared inner microparticles (1–4 µm) were formed by crosslinking chitosan (CHT) and Eudragit^® RL 30D (EUD), with the outer gastrospheres prepared from alginate (ALG), pectin (PEC), poly(acrylic acid) (PAA) and poly(lactic-co-glycolic) acid (PLGA). An experimental design was utilized to optimize the prepared microparticles prior to Fourier Transition Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM) and in vitro drug release studies. Additionally, the in vivo analysis of the MGDDS, employing a Large White Pig model and molecular modeling of the ciprofloxacin-polymer interactions, were performed. The FTIR results determined that the crosslinking of the respective polymers in the microparticle and gastrosphere was achieved, with the SEM analysis detailing the size of the microparticles formed and the porous nature of the MGDDS, which is essential for drug release. The in vivo drug release analysis results further displayed a more controlled ciprofloxacin release profile over 24 h and a greater bioavailability for the MGDDS when compared to the marketed immediate-release ciprofloxacin product. Overall, the developed system successfully delivered ciprofloxacin in a control-release manner and enhanced its absorption, thereby displaying the potential of the system to be used in the delivery of other NAW drugs. Full article

Retentive drug delivery systems (DDSs) are intended for prolonged residence and release inside hollow muscular organs, to achieve either local or systemic therapeutic goals. Recently, formulations based on shape memory polymers (SMPs) have gained attention in view of their special ability to recover a shape with greater spatial encumbrance at the target organ (e.g., urinary bladder or stomach), triggered by contact with biological fluids at body temperature. In this work, poly(vinyl alcohol) (PVA), a pharmaceutical-grade SMP previously shown to be an interesting 4D printing candidate, was employed to fabricate expandable organ-retentive prototypes by hot melt extrusion. With the aim of improving the mechanical resistance of the expandable DDS and slowing down relevant drug release, the application of insoluble permeable coatings based on either Eudragit^® RS/RL or Eudragit^® NE was evaluated using simple I-shaped specimens. The impact of the composition and thickness of the coating on the shape memory, swelling, and release behavior as well as on the mechanical properties of these specimens was thoroughly investigated and the effectiveness of the proposed strategy was demonstrated by the results obtained. Full article

Fenofibrate (FE) has been shown to markedly reduce the progression of diabetic retinopathy and age-related macular degeneration in clinical trials and animal models. Owing to the limited aqueous solubility of FE, it may hamper ocular bioavailability and result in low efficiency to treat such diseases. To enhance the solubility of FE, water-soluble FE/cyclodextrin (CD) complex formation was determined by a phase-solubility technique. Randomly methylated-β-CD (RMβCD) exhibited the best solubility and the highest complexation efficiency (CE) for FE. Additionally, water-soluble polymers (i.e., hydroxypropyl methyl cellulose and polyvinyl alcohol [PVA]) enhanced the solubility of FE/RMβCD complexes. Solid- and solution-state characterizations were performed to elucidate and confirm the formation of inclusion FE/RMβCD complex. FE-loaded Eudragit^® nanoparticle (EuNP) dispersions and suspensions were developed. The physicochemical properties (i.e., pH, osmolality, viscosity, particle size, size distribution, and zeta potential) were within acceptable ranges. Moreover, in vitro mucoadhesion, in vitro release, and in vitro permeation studies revealed that the FE-loaded EuNP eye drop suspensions had excellent mucoadhesive properties and sustained FE release. The hemolytic activity, hen’s egg test on chorioallantoic membrane assay, and in vitro cytotoxicity test showed that the FE formulations had low hemolytic activity, were cytocompatible, and were moderately irritable to the eyes. In conclusion, PVA-stabilized FE/RMβCD-loaded EuNP eye drop suspensions were successfully developed, warranting further in vivo testing. Full article

Intranasal administration has assumed in the last years an increasing value as an alternative strategy for the systemic adsorption of drugs, as an alternative to oral and parenteral routes thanks to the high vascularized nasal mucosa. Nevertheless, different drug features may restrict its absorption through the nasal mucosa with an insufficient diffusion to the systemic circulation. Several technological strategies are under investigation to improve drug absorption during nasal formulation design and production. The use of bioadhesive polymers can be considered a valid approach to pursue the aforementioned goal. Based on this consideration, Eudragit^® Retard RS100 and RL100 resins were selected as positively charged copolymers to prepare polymeric NPs with potential mucoadhesive properties suitable for intranasal application. NPs were produced by the Quasi-emulsion Solvent Evaporation (QESD) method and loaded with diclofenac acid (DIC) or its epolamine salt (DIEP). Preliminary investigations were performed to obtain the optimized blank formulation and drugs loaded NPs evaluating different parameters that can affect particles size and polydispersity. The optimized formulations unloaded and loaded with DIC and DIEP were further evaluated for their thermotropic behavior by differential scanning calorimetry. Mucoadhesive evaluation was assessed by measuring variation in zeta potential and by turbidimetric assay after incubation of particles with mucin in simulated nasal fluid (SNF) at 37 °C at different time points (0, 1 and 24 h) compared to the pure suspensions. Stability of DIC and DIEP loaded NPs was also evaluated in SNF to predict potential aggregation phenomena after nasal administration. Finally, in vivo experiments showed absence of toxicity on the nasal mucosa of mice. Full article

Azithromycin (AZI) is one of the most commonly used macrolide antibiotics in children, but has the disadvantages of a heavy bitter taste and poor solubility. In order to solve these problems, hot-melt extrusion (HME) was used to prepare azithromycin amorphous solid dispersion. Preliminary selection of a polymer for HME was conducted by calculating Hansen solubility parameter to predict the miscibility of the drug and polymer. Eudragit^® RL PO was chosen as the polymer due to its combination of taste-masking effect and dissolution. Moreover, the solubility was improved with this polymer. Design of experiments (DoE) was used to optimize the formulation and process, with screw speed, extrusion temperature, and drug percentage as independent variables, and content, dissolution, and extrudates diameter as dependent variables. The optimal extrusion parameters were obtained as follows: temperature—150 °C; screw speed—75 rpm; and drug percentage—25%. Differential scanning calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies of the powdered solid dispersions showed that the crystalline AZI transformed into the amorphous form. Fourier transform infrared spectroscopy (FTIR) results indicated that the formation of a hydrogen bond between AZI and the polymer led to the stabilization of AZI in its amorphous form. In conclusion, this work illustrated the importance of HME for the preparation of amorphous solid dispersion of AZI, which can solve the problems of bitterness and low solubility. It is also of great significance for the development of compliant pediatric AZI preparation. Full article

Transdermal drug delivery is important to maintain plasma drug concentrations for therapeutic efficacy. The current study reports the design, formulation, and evaluation of tizanidine transdermal patches formulated using chitosan and thiolated chitosan, ethyl cellulose (EC), polyvinylpyrrolidone (PVP), and Eudragit RL100 in different ratios. The tizanidine patches were formulated using flaxseed oil and coriander oil in the concentrations of 1% v/w, 2% v/w, 3% v/w, 4% v/w, 5% v/w, and 10% v/w. The patches were subjected to characterization of physicochemical property (thickness, weight uniformity, drug content, efficiency, percentage moisture uptake/loss), in vitro drug release and drug permeation, skin irritation, in vivo application, pharmacokinetics analysis, and stability studies. The results indicate that the interaction of thiolated chitosan with the negative charges of the skin opens the tight junctions of the skin, whereas flaxseed and coriander oils change the conformational domain of the skin. The novelty of this study is in the use of flaxseed and coriander oils as skin permeation enhancers for the formulation of tizanidine transdermal patches. The formulations follow non-Fickian drug release kinetics. The FTZNE23, FTZNE36 and FTZNE54, with 5% v/w flaxseed oil loaded formulations, exhibited higher flux through rabbit skin compared with FTZNE30, FTZNE35, FTZNE42, and FTZNE47, formulations loaded with 10% v/w coriander oil. The study concludes that flaxseed oil is a better choice for formulating tizanidine patches, offering optimal plasma concentration and therapeutic efficacy, and recommends the use of flaxseed and coriander oil based patches as a novel transdermal delivery system for tizanidine and related classes of drugs. Full article