Search Results (77)

The development of age-appropriate pediatric dosage forms remains an important challenge, particularly for acid-labile drugs requiring gastro-resistant protection. Pantoprazole, a proton pump inhibitor, must be protected from gastric acid until intestinal absorption; however, conventional enteric-coated tablets may be difficult to use in younger children, while manipulation of dosage forms or mixing with food can compromise dose accuracy and drug release performance. Multiparticulate systems, such as minitablets, pellets, or granules, offer flexible dosing but may still require a suitable vehicle to improve acceptability, handling, and ease of swallowing. In this study, enteric-coated pantoprazole minitablets were developed and evaluated after dispersion in selected hydrogel vehicles intended to serve as standardized alternatives to food-based carriers. Hydrogels based on hypromellose (HPMC), carbomer (CAR), and sodium alginate (SA) were characterized in terms of pH, rheological properties, firmness, acid penetration, and their effect on pantoprazole release. Dissolution performance was assessed using both conventional pharmacopoeial testing and dynamic non-pharmacopoeial conditions. Low-concentration gels prepared from high-viscosity HPMC grades showed the most favorable performance, combining suitable spoonable consistency with limited impact on drug release. Among them, 5% HPMC 65SH4000 was particularly promising, as it did not markedly delay pantoprazole release in either pharmacopoeial or dynamic dissolution testing. CAR gels provided advantageous rheological properties, including high viscosity at rest and shear-thinning behavior, and allowed efficient pantoprazole release after transition to buffer conditions; however, their interaction with enteric-coated minitablets should be further optimized with respect to gel amount, concentration, and neutralization strategy. SA gel showed strong structural persistence and delayed release under pharmacopoeial conditions, although this effect was less pronounced in the dynamic model. Overall, the findings indicate that appropriately selected hydrogels may improve the practical use of pediatric multiparticulate formulations, but their composition, pH, rheology, and interaction with enteric coatings must be carefully evaluated. Full article

Cellulose ether, like hypromellose (HM), is an extremely versatile material that is widely used in pharmaceutical products as film coatings. To modify the surface properties of HM films, additives are routinely included during the film formulation process, which are typically hydrophobic lubricants or hydrophilic plasticizers. Plasticizers increase the flexibility and reduce the brittleness of the film. The first goal of this study is to demonstrate that plasticization of HM films by low-molecular-weight (400 g∙mol⁻¹) polyethylene glycol (PEG) allows tuning adhesion and friction properties of HM films, both at nano- and macroscales. Surface morphology, surface energy, nano/macro adhesion, and nano/macro friction coefficient were studied by atomic force microscopy (AFM) in adhesion or friction modes at the nanoscale, wettability, and probe-tack adhesion, as well as pin-on-disk friction experiments at the macroscale. The results show that the addition of PEG decreases the Young’s modulus and the Tg of HM-plasticized films while increasing their strain at break and surface energy. The macroadhesion force increases from 9 to 90 mN by the addition of 40% w/w of PEG, whereas the macrofriction coefficient is reduced by 50%. The hypothesis of insertion of plasticizer molecules in HM chains’ nano-domains is evidenced and explains these results. The second goal of this study is to investigate nanoscale versus macroscale correlation of adhesion and friction properties and the role of adhesion in friction experiments. The results show, first, that the evolution of the adhesion energy at the macroscale as a function of adhesion energy at the nanoscale is linear. On the contrary, a high friction coefficient at the nanoscale corresponds to a low friction coefficient at the macroscale and vice versa, showing a first linear decrease for PEG contents ranging from 0 to 30% (w/w) and the second linear decrease, less pronounced, is observed for PEG contents ranging from 30 to 40% (w/w). The hypothesis of a difference in contact pressure applied on the probe at both scales, as well as HM-PEG surface phase separation at a high PEG content (>30% w/w), is proposed to explain this difference. The variations in friction coefficients are linear according to the PEG plasticizer content and suggest its lubricant role in HM-Plasticized films. Finally, the interplay between adhesion and friction, in friction experiments, is evidenced and appears dominant at the nanoscale. Full article

Poly(3-hydroxybutyrate) (P3HB) was used to produce biocompatible composites with hypromellose as an additive. The study aimed to assess their biological and mechanical properties, as well as specific thermal parameters and phase content. Differential scanning calorimetry was applied to analyze the phase transitions of both biocomposites and the polymer matrix. Furthermore, the thermal parameters—encompassing both non-equilibrium and equilibrium states—of the biocomposites and unfilled P3HB were evaluated according to their thermal history. Using equilibrium parameters such as the heat of fusion for fully crystalline materials and the heat capacity change at the glass transition for fully amorphous composites, we estimated the degrees of crystallinity as well as the mobile and rigid amorphous fractions. Adding hypromellose to the P3HB matrix reduced crystallinity compared to the unfilled material. At the same time, an increase in the amorphous phase was observed. It was also discovered that the rigid amorphous fraction exists solely in biocomposites containing 2% by mass of filler. Thermogravimetric analysis showed that the thermal stability of all biocomposites surpasses that of unfilled P3HB. Adding an extra 1% filler by mass raises the degradation temperature by about 37 °C compared to unfilled P3HB. The immunosafety of the tested biocomposites, with very low or no endotoxin contamination, was confirmed in accordance with Food and Drug Administration and European Medicines Agency guidelines. The study clearly demonstrates the influence of the filler in the P3HB matrix on various structural, thermal, mechanical, and biological properties of the prepared biocomposites. Full article

Background: Three-dimensional (3D) printing has been established in pharmaceutical sciences for preparing customized dosage forms with intricate release profiles. However, realizing this potential requires complex design strategies and the careful use of various excipients. This study was designed to evaluate the utility of hypromellose acetate succinate (HPMC-AS) as a singular release-modifying excipient for manufacturing oral solid dosage forms via fused deposition modeling (FDM) 3D printing. Methods: The scope of work encompassed comprehensive material characterization, formulation and production of drug-loaded filaments using hot-melt extrusion (HME), subsequent FDM 3D printing of tablet geometries, and in vitro dissolution studies using mebeverine hydrochloride (MebH) as the model drug. Results: Initial HME processing indicated that the HPMC-AS-based filaments were brittle, presenting technical challenges for direct 3D printing. This issue was successfully overcome by incorporating an additional preheating stage into the FDM printing process, which enabled production of the tablets. Dissolution analysis demonstrated that the 3D-printed mebeverine hydrochloride tablets exhibited delayed and sustained-release characteristics. Conclusions: These results confirm the viability of HPMC-AS as a standalone functional excipient in FDM 3D printing to produce tailored, complex drug delivery systems. Full article

Background/Objectives: This study aims to investigate the underexplored impact of capsule type on the performances of capsule-based dry powder inhalers (cDPIs). It compares specific properties of hard gelatin-based capsules (Hard Gelatin Capsules (HGC), HGC including polyethylene glycol (HGC + PEG)) and hypromellose-based capsules, (Zephyr^® Vcaps^® (VC), Zephyr^® Vcaps^® Plus (VCP) and Vcaps^® Plus Zephyr Inhance™ (VCP-I)) with aerosolization performances of model carrier-based formulation, providing insights into their impact on pulmonary drug delivery efficacy. Methods: Aerosolization properties of a model phenytoin/lactose blend formulation filled in the different capsules was evaluated using a Next Generation Impactor (NGI) with RS01 device. Capsule shell characteristics were evaluated in terms of water activity, static charges, and inner surface aspect and roughness. Results: Hypromellose-based capsules, especially VC and VCP-I, exhibited significantly higher drug delivery performances compared to gelatin-based capsules. In particular, VCP-I demonstrated good results with excellent batch-to-batch reproducibility and 51% of the nominal dose available for lung absorption. Although capsule inner surface showed clear differences between both polymer families, no clear correlation could be found between cDPI performances and capsule roughness and density of charge. All capsules presented good mechanical properties in the conditions of the tests. Conclusions: Capsule type exerts a significant impact on cDPI performances. These findings highlight the importance of capsule selection as a critical material attribute in the design and optimization of inhalation products. Full article

Background/Objectives: This study investigated how selected functionality-related characteristics (FRCs) of hypromellose (HPMC)—namely viscosity, hydroxypropoxy substitution, particle size, and the ratio of water-soluble (FlowLac^® 100) to water-insoluble (Avicel^® PH-102) fillers— affect the release of carvedilol from matrix tablets. Methods: Using a Central Composite Design (CCD) Design of Experiments (DoE), mixtures of HPMC QbD samples were prepared to achieve target HPMC FRC levels. Within the CCD, levels of FlowLac^® 100 and Avicel^® PH-102 were also varied. The mean and standard deviation of carvedilol release at each analyzed time point of the release profile were used as target variables for individual multiple linear regression (MLR) models. Results: Lactose, the water-soluble filler, significantly accelerated carvedilol release, whereas the water-insoluble MCC slowed and stabilized release by improving gel integrity. Among the HPMC FRCs, particle size had the strongest influence during the early release phase, while HPMC viscosity and hydroxypropoxy substitution degree became more important in later phases. Analysis of the results using optimized multiple linear regression (MLR) models revealed key interaction effects, particularly between HPMC viscosity and lactose content, and between viscosity and particle size, demonstrating their combined role in modulating release kinetics. Conclusions: These findings provide valuable insight into how controlling HPMC’s FRCs and filler composition can reduce interbatch variability in drug release and support the rational design of robust controlled release formulations. Full article

Background/Objectives: Fungal colonization and biofilm formation on intrauterine device (IUD) strings are known to contribute to recurrent infections and decreased contraceptive efficacy. This study aims to develop a novel approach to prevent Candida reservoir and biofilm formation on IUD strings, thereby lowering the risk of IUD-associated vulvovaginal candidiasis (VVC). Methods: Cervicovaginal samples were collected from human cervix using a sterile cytobrush, avoiding microbial contamination. Cytological examination using the Papanicolaou method was performed to detect the presence of Candida. The antifungal effect of the essential oils (EOs) was determined by broth dilution and disk diffusion methods. Antifungal and biofilm inhibitory effects of Thymus zygis (Tz) EO-coated IUD strings were determined by agar diffusion and crystal violet binding assays, while fungal growth on the coated strings was assessed using Scanning Electron Microscopy (SEM) and Energy-Dispersive X-ray (EDX) analysis. Results: Tz EO exhibited significantly lower minimum inhibitory concentration (MIC ≤ 0.06 µL/mL) and minimum fungicidal concentration (MFC = 0.24 µL/mL) values compared to Melaleuca alternifolia (Ma) EO (MIC > 0.24 µL/mL, MFC = 1.95 µL/mL), along with larger zones of inhibition (ZOI) against both Candida albicans (110.0 ± 6.0 mm vs. 91.3 ± 7.0 mm) and Candida glabrata (84.0 ± 13.1 mm vs. 50.0 ± 9.2 mm), indicating a stronger antifungal potential. On IUD strings coated with 4% (40 μL/g) Tz EO in hypromellose ointment, the biofilm formation of both C. albicans and C. glabrata strains was inhibited by 58.9% and 66.7%, respectively, as confirmed by SEM and EDX. Conclusions: Tz EO-coated IUD strings effectively inhibit Candida growth, suggesting a promising natural strategy to reduce recurrent IUD-associated fungal infections. However, before these results can be translated to clinical practice, additional research is needed. Future investigations may encompass an extended number of Candida isolates, stability and release studies of the EO in relation to the formulation, toxicity to vaginal mucosa, epithelial cells and sperm motility, and the effect on vaginal microbiotia. Full article

Objectives: This study evaluated the comfort of using silicone tubes installed in the oral cavity as a reservoir for a hydrogel that allows for a slow delivery of the active substance acting locally or systemically. Methods: Perforated silicone tubes 8 cm long with two internal diameters were used: T1 (1.5 mm) and T2 (2.4 mm). The reservoirs were filled with hydrogel placebo formulations: carbomer 1.5% (C), hydroxyethylcellulose 4% (HEC), or hydroxypropylmethylcellulose (hypromellose) 3% (HPMC). Physical parameters of the gel were determined with a viscometer and a texture analyzer. During 4 h of application, the volunteers reported sensory perceptions, and the rate of gel erosion was evaluated. The results were correlated with the viscosity, rheology, and dissolution rate of the gels measured in vitro. Results: Volunteers reported only mild discomfort wearing the device, preferring smaller-sized tubes. The tubes were easy to apply and generally comfortable, with no reports of significant discomfort. Despite similar viscosity and rheology, the polymer type had a significant impact on erosion rate, both in vitro and in vivo. After 4 h of application in vivo, more than 90% of the carbomer gel remained in the tube, while in the case of less cohesive HPMC or HEC gels, this was about 50%. A statistically significant correlation was observed between the in vitro and in vivo mean erosion percentages for the HEC and HPMC gels. Conclusions: This study supports the use of silicone tubes as effective reservoir devices for prolonging the residence time of drug formulations in the oral cavity. 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

Hydroxypropyl methylcellulose (Hypromellose, HPMC) is a well-known excipient used in the pharmaceutical and nutraceutical fields due to its versatile physicochemical properties. HPMC (derived from cellulose and obtained through etherification) varies in polymerization degree and viscosity, factors that both influence its functional applications. Usually, an increased polymerization degree implies a higher viscosity, depending also on the amount of polymer used. Hypromellose plays a crucial role in solid dosage forms, serving as a binder in the case of controlled-release tablets, a film-forming agent in the case of orodispersible films and mucoadhesive films, and a release modifier due to its presence in different polymerization degrees in the case of extended or modified release tablets. However, its compatibility with other excipients and the active ingredient must be carefully evaluated to prevent formulation challenges via several analytical methods such as differential scanned calorimetry (DSC), Fourier Transformed Infrared spectroscopy (FT-IR), X-Ray Particle Diffraction (XRPD), and Scanning Electron Microscopy (SEM). This review explores the physicochemical characteristics, and diverse applications of HPMC, emphasizing its significance in modern drug delivery systems. Full article

Objectives: This study aimed to develop and evaluate nanostructured lipid carriers (NLCs) loaded with meloxicam (Melox) and a therapeutic antibacterial and anti-inflammatory liquid lipid, clove oil (CO) for periodontitis treatment, a complex inflammatory condition necessitating advanced drug delivery systems. The NLC–Melox formulation was integrated into three hydrogels, hypromellose (HPMC), zinc hyaluronate (ZnHA), and sodium hyaluronate (NaHA), to conduct a comparative analysis focusing on enhanced localized drug delivery, improved mucoadhesion, prolonged retention, and significant therapeutic outcomes. Methods: NLC–Melox was prepared by homogenization and characterized by dynamic light scattering (DLS). Subsequently, NLC–Melox-loaded gels were subjected to transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Raman spectroscopy, and rheological analysis. In vitro drug release, anti-inflammatory activity (BSA denaturation assay), and antibacterial efficacy (MIC, MBC) were investigated to assess therapeutic potential. Results: DLS revealed a particle size of 183 nm with a polydispersity index of 0.26, indicating homogeneity. TEM confirmed consistent morphology and uniform nanoparticle distribution. DSC and XRD demonstrated the amorphous nature of Melox, enhancing solubility and stability. Spectroscopy confirmed no chemical interactions between components. Rheological studies identified ZnHA as the most mucoadhesive and structurally stable gel. In vitro release studies showed sustained drug release over 24 h. Melox and CO-loaded formulations demonstrated significant anti-inflammatory activity and notable antibacterial efficacy due to the antibacterial oil. Conclusions: The study highlighted the potential of NLC-based mucoadhesive hydrogels as an effective strategy for periodontitis treatment. The formulation offered improved drug solubility, therapeutic efficacy, mucoadhesivity, and prolonged delivery, making it a promising candidate for localized therapy. Full article

The incorporation of essential oils into the oil phase of oil-in-water microemulsions is an emerging strategy for the development of stable water-based topical formulations. The introduction of a suitable polymer to formulate film-forming microemulsions may improve topical administration; however, the effect of formulation variables on film quality attributes has not been studied. In this study, thermodynamically stable microemulsion concentrates consisting of surfactant (Kolliphor^® RH40), alone or in combination with cosurfactant Transcutol^® at surfactant-to-cosurfactant mass ratio 7:3, cosolvent (propylene glycol), and synthetic oils (medium-chain triglycerides or isopropyl myristate) with tea tree, cinnamon, or thyme essential oil were formulated and diluted with hypromellose solution in a water/isopropanol mixture (1:1 w/w) to produce film-forming microemulsions. The type and concentration of synthetic and essential oils and cosurfactant influenced the dynamics of structural transformations upon dilution as well as the rheological behavior, viscosity, and pH of film-forming microemulsions. Films obtained by casting film-forming microemulsions were opalescent, smooth, flexible, and swellable in artificial sweat and water. The weight and yield of films increase with the synthetic oils present and without cosurfactant added. Optimizing the ratio of essential oil/synthetic oil, the type of synthetic oil, and the inclusion/exclusion of cosurfactant allows for achieving the targeted film attributes for cosmetic and pharmaceutical applications, including wound treatment. Full article

Hydrogel delivery systems are popular dosage forms that have a number of advantages, such as ease of use, painlessness, increased efficiency due to prolongation of rheological, swelling and sorption characteristics, regulation of drug release, and stimulus sensitivity. Particular interest is shown in hydrogels of cellulose ether derivatives due to the possibility of obtaining their modified forms to vary the solubility, the degree of prolonged action, and the release of the active substance, as well as their widespread availability, affordability, and the possibility of sourcing raw materials from different sources. Hydroxypropyl methylcellulose (HPMC, “hypromellose”) is one of the most popular cellulose ethers in the production of medicines as a filler, coating and carrier. Research on hydrogel carriers based on polymer complexes and modified forms of HPMC using acrylic, citric, and lactic acids, PVP, chitosan, Na-CMC, and gelatin is of particular interest, as they provide the necessary rheological and swelling characteristics. There is growing interest in medical transdermal hydrogels, films, capsules, membranes, nanocrystals, and nanofibers based on HPMC with the incorporation of biologically active substances (BASs), especially those of plant origin, as antibacterial, wound-healing, antimicrobial, mucoadhesive, anti-inflammatory, and antioxidant agents. The aim of this article is to review modern research and achievements in the field of hydrogel systems based on cellulose ethers, particularly HPMC, analyzing their properties, methods of production, and prospects for application in medicine and pharmacy. Full article

Background: Methotrexate (MTX), a folic acid antagonist used in chemotherapy, faces limitations due to cancer cell resistance, high toxicity, and low bioavailability. Objective: This study developed nanoparticles (NPs) of chitosan (QS) and hydroxypropylmethylcellulose phthalate (HPMCP) to encapsulate MTX for potential effect investigation on glioblastoma cell targeting and P-gp efflux inhibition. Method: NPs were produced by the polyelectrolyte complexation method and were characterized by DLS, PDI, DSC, FTIR, PXRD, MEV, drug release profile, and an in vitro mucoadhesion test. Cell viability, flow cytometry, and LSCM using U251MG (glioblastoma) and CCD 1059Sk (fibroblasts) cells were used to evaluate glioblastoma and the P-gp efflux effect. Results: NPPM29 (QS3:1) showed 91.72% encapsulation efficiency, a mean diameter of 452.6 nm, and a zeta potential of +22.5 mV. DSC, FTIR, and PXRD confirmed the QS-HPMCP supramolecular interaction. Liquid falling mucoadhesion tests demonstrated strong retention of NPPM29 (84%) compared to free MTX (10.5%). In vitro release studies indicated controlled drug release at pH 7.4. Cytotoxicity assays in U251MG revealed enhanced efficacy of NPPM29 (IC₅₀ = 68.79 µg/mL) compared to free MTX (IC₅₀ = 80.54 µg/mL), with minimal impact on fibroblasts, confirming tumor specificity. Flow cytometry and LSCM confirmed improved cellular internalization and P-gp inhibition. Conclusions: These findings highlight the potential of MTX-QS-HPMCP-NPs for glioblastoma therapy. Full article

Multi-drug delivery systems have gained increasing interest from the pharmaceutical industry. Alongside this is the interest in amorphous solid dispersions as an approach to achieve effective oral delivery of compounds with solubility-limited bioavailability. Despite this, there is limited information regarding predicting the behavior of two or more drugs (in amorphous forms) in a polymeric carrier and whether molecular interactions between the compounds, between each compound, and if the polymer have any effect on the physical properties of the system. This work studies the interaction between model drug combinations (two of ibuprofen, malonic acid, flurbiprofen, or naproxen) dispersed in a polymeric matrix of hypromellose acetate succinate (HPMCAS) using a solvent evaporation technique. Hildebrand and Hansen calculations were used to predict the miscibility of compounds as long as the difference in their solubility parameter values was not greater than 7 MPa^1/2. It was observed that the selected APIs (malonic acid, ibuprofen, naproxen, and flurbiprofen) were miscible within the formed polymeric matrix. Adding the API caused depression in the Tg of the polymer to certain concentrations (17%, 23%, 13%) for polymeric matrices loaded with malonic acid, ibuprofen, and naproxen, respectively. Above this, large crystals started to form, and phase separation was seen. Adding two APIs to the same matrix resulted in reducing the saturation concentration of one of the APIs. A trend was observed and linked to Hildebrand and Hansen solubility parameters (HSP). Full article