Search Results (52)

Three-dimensional (3D) printing has emerged as a versatile platform in pharmaceutical sciences, enabling fabrication of personalized dosage forms with controlled drug release and tailored properties using printable hydrogel bioinks. This study aimed to develop mucoadhesive hydrogel buccal films for cannabinoid delivery using extrusion-based 3D bioprinting. The films incorporated cannabidiol (CBD) and tetrahydrocannabinol (THC) as cyclodextrin inclusion complexes with HPMC or Carbopol as mucoadhesive hydrogel-forming polymers, while terpenes were evaluated as permeation enhancers. Terpenes including 1,8-cineole, d-limonene, α-pinene, and L-menthol were investigated individually and in combinations to assess their ability to enhance buccal cannabinoid permeation. Hydrogel bioinks were prepared and characterized for viscosity, pH, and drug content prior to printing under optimized conditions. The printed films were evaluated for mechanical properties, swelling behaviour, mucoadhesion, in vitro drug release, and ex vivo buccal mucosal penetration. Ex vivo penetration studies demonstrated that combinations of natural terpenes significantly improved CBD penetration compared with individual terpenes and the synthetic enhancer Azone. HPMC-based hydrogel films exhibited superior mechanical strength, cohesive gel matrices, and sustained non-Fickian cannabinoid release, while enhancing transmucosal penetration compared with unformulated drugs. Carbopol-based films showed higher mucoadhesion but weaker mechanical properties and faster erosion-driven release. These findings demonstrate the potential of 3D-printed mucoadhesive hydrogel films as gel-based systems for transmucosal cannabinoid delivery. Full article

Children are often underserved by adult-oriented oral medicines, leading to off-label use and dosage-form manipulation that may compromise dosing accuracy. This review summarises recent advances in paediatric orodispersible tablets (ODTs), focusing on manufacturing technologies, superdisintegrants, taste masking, and in vitro disintegration testing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance and a protocol registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (registration number INPLASY2025110022), we searched PubMed, EMBASE, MEDLINE, Scopus, and Google Scholar for experimental studies on paediatric-relevant ODT formulation and evaluation. Two reviewers screened studies and extracted data on manufacturing methods, excipients, disintegration/dissolution testing, and key outcomes. Risk of bias was assessed using a six-domain framework. Overall, 65 studies met the inclusion criteria for this review. Direct compression was the dominant method, with freeze-drying, sublimation, spray-drying, nanoparticle-in-tablet systems, and semi-solid extrusion/3D printing also reported. Crospovidone, croscarmellose sodium, and sodium starch glycolate were the most common superdisintegrants, while natural and co-processed disintegrants showed promise as cost-effective alternatives. Disintegration was usually assessed using pharmacopoeial methods, with some modified set-ups to better simulate oral conditions. Paediatric ODT development is advancing rapidly. Broader translation requires harmonised disintegration testing, age-stratified acceptability reporting, and GMP-ready workflows, alongside benchmarking of superdisintegrants and attention to dose flexibility, packaging, and affordability. Full article

Additive manufacturing can be regarded as a game-changing approach for paediatric drug development, as children have special drug-related requirements which are rarely met by conventional technologies. Traditional dosage forms have considerable drawbacks, among them dose, excipient safety, and taste issues, which can be resolved by using three-dimensional (3D) printing. Ease of swallowing and an appealing design are among the improvements brought forth by 3D printing techniques. Techniques that have been thoroughly researched in the paediatric field include hot-melt extrusion (HME) coupled with fused deposition modelling (FDM), direct powder extrusion (DPE) and semisolid extrusion (SSE) 3D printing. Selective Laser Sintering (SLS) 3D bioprinting and binder-jet (BJ) 3D printing are other less known but highly useful techniques. A number of studies focus on significant subjects for the paediatric medicine domain, such as the acceptability of the produced formulations, the size of tablets, the design, the concealment of bitter API flavour, and the stability of the dosage forms. The 3D-printed oral formulations are varied: conventional-sized tablets, miniaturised tablets, chewable tablets, and orodispersible films or tablets. Most of the drugs used in the presented studies are essential medicines for children, for which commercial products with flexible doses and age-appropriate characteristics are often lacking. The practical implications of currently published studies and future directions for paediatric pharmaceutical 3D printing are described. Although there is a substantial amount of technical and in vitro data as well as paediatric engagement work on this subject, its translation into clinical practice is still limited. The clinical efficacy of 3D-printed dosage forms has to be further researched, since only a few studies have targeted this aspect. Full article

Background/Objectives: Semi-solid extrusion (SSE) three-dimensional (3D) printing offers a versatile approach for fabricating personalized oral dosage forms. This study aimed to develop and optimize losartan potassium tablets produced via SSE 3D printing, focusing on the effects of polymer composition, tablet geometry, drug loading, and superdisintegrant concentration on printability and performance characteristics. Methods: Formulations containing hydroxypropyl methylcellulose (HPMC) 4500 at various concentrations were evaluated for suitability in an ethanol–water (9:1 v/v) solvent system. The optimized formulation (5% w/w HPMC 4500) was used to print tablets with varying shapes, drug loadings (5–15% w/w; approximately 50–150 mg losartan potassium per tablet), and croscarmellose sodium concentrations (0–3% w/w). Printed tablets were characterized for dimensional accuracy, mass uniformity, disintegration time, and drug release behavior. Drug release kinetics were modeled to elucidate the release mechanism. Results: All SSE-printed tablets exhibited excellent dimensional precision (SD < 0.8 mm) and mass uniformity (SD < 0.12 g). Increasing drug loading enhanced the initial release rate, reaching up to 63% in 45 min for 15% loading. The addition of 1% croscarmellose sodium reduced disintegration time to approximately 25 min. Drug release profiles were best described by the Korsmeyer–Peppas model (R² > 0.96), indicating diffusion-controlled release. Conclusions: SSE 3D printing demonstrated robustness and flexibility in producing losartan potassium tablets with consistent quality, tunable release properties, and strong potential for personalized pharmaceutical manufacturing. Full article

Background/Objectives: Hospital compounding is essential for the delivery of patient-tailored therapies—particularly for pediatric and oncology patients and other groups requiring precise dosing. Its role is expected to grow as, for instance, the UK MHRA’s new Guidance on Decentralised Manufacturing promotes alternative manufacturing pathways that integrate hospital preparation units. However, drug substances that remain stable in commercial oral formulations may undergo rapid degradation under alternative conditions (e.g., aqueous suspension, light exposure, or in the presence of specific excipients). Despite these risks, formulation strategies in hospital compounding often rely on empirical practices and lack structured guidance regarding stability, impurity control, and reproducibility. Methods: This study proposes a risk-based scientific framework for formulation design, integrating degradation profiling with predictive toxicology. Potential degradation pathways (hydrolytic, oxidative, and photolytic) are systematically identified through forced-degradation studies combined with ab initio modeling. These risks are translated into formulation strategies using a structured decision tree encompassing solvent selection, pH adjustment, excipient compatibility, and packaging considerations, even in the absence of a pharmacopeial monograph. The toxicological relevance of degradation products is evaluated using in silico approaches aligned with ICH M7 guidelines, thereby defining critical quality attributes (cQAs) and critical process parameters (CPPs). Results: The applicability of the framework is demonstrated through hospital compounding case studies, with further extension toward advanced applications such as semi-solid extrusion (SSE) 3D printing. Conclusions: By integrating mechanistic understanding of drug degradation into formulation planning, the proposed framework enhances the safety, reproducibility, and quality of compounded preparations. This approach reinforces Good Preparation Practices (GPPs) and is consistent with international quality-by-design (QbD) principles in the context of personalized medicine. Full article

Vervain (Verbena officinalis L., Verbenaceae family) is a perennial plant which grows widely in Europe. It is rich in iridoids, phenolic acids, phenylpropanoid glycosides, flavonoids and terpenoids. Verbena has traditionally been used in folk medicine to calm the nervous system, but there is a lack of scientific data about it. The aim of this study was to explore and characterise the chemical profile and neurotropic effects of V. officinalis dry extracts and their amino acid-based preparations. We determined a total of eight main phenolic compounds and 17 amino acids in the V. officinalis dry extracts. To evaluate the neurotropic effects of the verbena extracts, the following behavioural pharmacology tests were used: Open Field Test, Elevated Plus Maze, Black-and-White Box Test and Tail Suspension Test. The dry aqueous–ethanolic extract (extractant 70% ethanol) demonstrated strong anxiolytic and antidepressant effects, while its dry modified extracts with valine and arginine consistently exhibited pronounced sedative activity across all studies. For example, the Tail Suspension Test demonstrated that the total immobility time in animals receiving the dry aqueous–ethanolic extract was the lowest, being 1.22-fold (p < 0.05) lower than in control animals and 2.25-fold (p < 0.05) lower than in the animals treated with the reference drug preparation (“Sedaphyton”). A novel aqueous-based gel formulation feasible for semi-solid extrusion (SSE) 3D printing was designed. This printing gel enables the fabrication of new oral dosage forms for V. officinalis dry extracts. The effects of pharmaceutical preparations on the human central nervous system require clinical studies. Full article

Background: Automated semi-solid extrusion (SSE) material deposition is a promising new technology for preparing personalized medicines for different patient groups and veterinary applications. The technology enables the preparation of custom-made oral elastic gel tablets of active pharmaceutical ingredient (API) by using a semi-solid polymeric printing ink. Methods: An automated SSE material deposition method was used for generating chewable gel tablets loaded with propranolol hydrochloride (-HCl) at three different API content levels (3.0 mg, 4.0 mg, 5.0 mg). The physical appearance, surface morphology, dimensions, mass and mass variation, process-derived solid-state changes, mechanical properties, and in-vitro drug release of the gel tablets were studied. Results: The inclusion of API (1% w/w) in the semi-solid CuraBlend^TM printing mixture decreased viscosity and increased fluidity, thus promoting the spreading of the mixture on the printed (material deposition) bed and the printing performance of the gel tablets. The printed gel tablets were elastic, soft, jelly-like, chewable preparations. The mechanical properties of the gel tablets were dependent on the printing ink composition (i.e., with or without propranolol HCl). The maximum load for the final deformation of the CuraBlend™-API (3.0 mg) gel tablets was very uniform, ranging from 73 N to 80 N. The in-vitro dissolution test showed that more than 85% of the drug load was released within 15–20 min, thus verifying the immediate-release behavior of these drug preparations. Conclusions: Automated SSE material deposition as a modified 3D printing method is a feasible technology for preparing customized oral chewable gel tablets of propranolol HCl. Full article

Background/Objectives. Flavonoids are a vast class of phenolic substances. To date, approximately 6000 plant-origin flavonoids have been discovered, with many of them being used in drug therapy. Therapeutic flavonoids are commonly formulated to conventional “one-size-fits-all” dosage forms, such as conventional tablets or hard capsules. However, the current trends in pharmacy and medicine are centred on personalised drug therapy and drug delivery systems (DDSs). Therefore, 3D printing is an interesting technique for designing and preparing novel personalised pharmaceuticals for flavonoids. The aim of the present study was to develop aqueous polyethylene oxide (PEO) gel inks loaded with rutin for semisolid extrusion (SSE) 3D printing. Methods. Rutin (a model substance for therapeutic flavonoids), Tween 80, PEO (MW approx. 900,000), ethanol, and purified water were used in PEO gels at different proportions. The viscosity and homogeneity of the gels were determined. The rutin–PEO gels were printed with a bench-top Hyrel 3D printer into lattices and discs, and their weight and effective surface area were investigated. Results. The key SSE 3D-printing process parameters were established and verified. The results showed the compatibility of rutin as a model flavonoid and PEO as a carrier polymer. The rutin content (%) and content uniformity of the 3D-printed preparations were assayed by UV spectrophotometry and high-performance liquid chromatography (HPLC). Conclusions. The most feasible aqueous PEO gel ink formulation for SSE 3D printing contained rutin 100 mg/mL and Tween 80 50 mg/mL in a 12% aqueous PEO gel. The 3D-printed dosage forms are intended for the oral administration of flavonoids. Full article

Background: Pharmaceutical compounding remains a predominantly manual process with limited innovation, particularly in non-sterile applications. This study explores the implementation of an automated compounding platform based on 3D printing to enhance precision, efficiency, and adaptability in pediatric corticosteroid formulations. Methods: Personalized hydrocortisone dosage forms were prepared in a hospital pharmacy setting using a proprietary excipient base and standardized procedures, including automated dosing and syringe heating when required. Three dosage forms—3.2 mg gel tablets, 2.8 mg water-free troches, and 1.2 mg orodispersible films (ODFs)—were selected to demonstrate the platform’s versatility and to address pediatric needs for varying strengths and dosage types. All products were prepared using a reproducible semi-solid extrusion (SSE)-based workflow with the consistent API-excipient blending and automated deposition. Results: Analytical testing confirmed that all formulations met pharmacopeial criteria for mass and content uniformity. The ODF and troche forms achieved rapid drug release, exceeding 75% within 5 min, while the gel tablet showed a slower release profile, reaching 86% by 60 min. Additionally, in-process homogeneity testing across syringe printing cycles confirmed the consistent API distribution. Conclusions: The results support the feasibility of integrating automated compounding technologies into pharmacy workflows. Such systems can improve accuracy, minimize variability, and streamline the production of customized pediatric medications, particularly for drugs with poor palatability or narrow therapeutic windows. Overall, this study highlights the potential of automation to modernize non-sterile compounding, and to better support individualized therapy. Full article

Background/Objectives: Effective drug delivery systems require precise formulation and understanding of excipient impact on active pharmaceutical ingredient (API) stability and efficacy, as uncontrolled interactions can compromise outcomes. This study developed and validated a semi-solid extrusion (SSE) 3D printing method for polyvinyl alcohol (PVA)-based hydrogel disks with metronidazole (MET). These disks served as a standardized platform to assess excipient influence on MET’s antimicrobial activity, focusing on plasticizers (polyethylene glycol 400, glycerol, propylene glycol, and diethylene glycol monoethyl ether)—excipients that modify hydrogel properties for their application in printing dressing matrices—with the platform’s capabilities demonstrated using in vitro antimicrobial susceptibility testing against Bacteroides fragilis. Methods: Hydrogel inks based on PVA with added plasticizers and MET were prepared. These inks were used to 3D-print standardized disks. The MET content in the disks was precisely determined. The antimicrobial activity of all formulation variants was evaluated using the disk diffusion method against B. fragilis. Results: The incorporated plasticizers did not negatively affect the antimicrobial efficacy of MET against B. fragilis. All printed hydrogel matrices exhibited clear antimicrobial activity. The 3D-printed disks showed high repeatability and precision regarding MET content. Conclusions: SSE 3D printing is viable for manufacturing precise, reproducible MET-loaded PVA hydrogel disks. It provides a standardized platform to evaluate diverse excipient impacts, like plasticizers, on API antimicrobial performance. The tested plasticizers were compatible with MET. This platform aids rational formulation design and screening for optimal excipients in designed formulations and for various pharmaceutical applications. Full article

Gels are semi-solid colloidal systems characterized by three-dimensional networks capable of retaining up to 99% of liquid while exhibiting both solid-like and liquid-like properties. A novel biphasic system, the bigel, consists of hydrogel and oleogel, enabling the encapsulation of hydrophilic and lipophilic compounds. Their structure and functionality are influenced by the distribution of gel phases (e.g., oleogel-in-hydrogel or hydrogel-in-oleogel). This study aims to review current trends in polysaccharide-based bigels derived from seeds, vegetable oils and waxes, highlighting their biocompatibility, sustainability and potential food applications. A bibliometric analysis of 157 documents using VOSviewer identified four key thematic clusters: structured materials, delivery systems, pharmaceutical applications, and physicochemical characterization. Principal component analysis revealed strong correlations between terms, while also highlighting emerging areas such as 3D printing. This analysis demonstrated that seed-derived polysaccharides, including chia seed mucilage and guar gum, improve bigel structure and rheological properties, offering sustainable plant-based alternatives. Additionally, innovations such as extrusion-based 3D printing, functional food design, controlled drug release, bioactive compound delivery, and fat replacement are helping to support the further development of these systems. Finally, bibliometric tools remain instrumental in identifying research gaps and guiding future directions in this field. Full article

Background/Objectives: Pediatric drug administration is hindered by difficulties in swallowing conventional medications and the unpalatable taste of many drugs. Among diseases highlighting the need for improved pediatric delivery, tuberculosis (TB) stands out. One form of the disease is latent TB infection (LTBI), which is concerning in children. Effective LTBI treatment is crucial for prevention, with isoniazid (INH) widely used for its proven efficacy and safety. This study aims to develop innovative 3D-printed chewable gels containing INH for LTBI treatment. Methods: The gels were formulated using gelatin and carrageenan gum, sugar-free sweeteners, and flavoring. Two batches were prepared, and using 3D printing (3DP) with a semi-solid extrusion (SSE) module, chewable gels were produced. Rheological properties were measured to assess the feasibility of 3DP-SSE, evaluating the structural integrity and adequate fluidity of the formulation. The 3D-printed chewable gels were evaluated by visual, mass, and dimensional characteristics. In addition, the water activity, texture profile, INH and degradation product content, in vitro release, and taste-masking were investigated. Results: The optimized formulation maintained suitable rheological properties for 3DP-SSE, demonstrating consistent weight, dimensions, and stability after the process. The texture achieved a balance between printing parameters and shape maintenance, and the INH presented an immediate-release profile (>85% within 30 min). The chewable gels showed an improvement in palatability compared to conventional INH tablets. Conclusions: This innovative approach offers a promising solution for pediatric LTBI treatment, as it improves efficacy, medication acceptability, and on-demand access. Full article

Background/Objectives: Semi-solid extrusion (SSE) 3D printing is an innovative method utilized for preparation of various drug dosage forms, allowing for individualization by means of incorporation of one or multiple drugs in adjustable doses. SSE provides repeatable results and can be conveniently utilized in small batch production. This study aimed to develop a chewable formulation for pediatric patients which could be easily printed using SSE. Methods: Pectin and gelatin were utilized as gel-forming agents, polyvinylpyrrolidone as a thickener, glycerol as a plasticizer, citric acid as a pH modifier, and potassium sorbate as a conserving agent. Obtained tablets were evaluated for mass and content homogeneity and their mechanical properties compared to the long-time market standard for gummies. Results: Gummy formulation with texture properties comparable to the selected standard and mass homogeneity were prepared. The linear correlation between the model size and ondansetron content was proven. Conclusions: SSE 3D printing thus presents a suitable method of gummy formulation production with possible adjustment of dose by defining the object size. Full article

This study investigates the phytochemical profile, antioxidant and anti-inflammatory properties, and 3D-printing application of Origanum vulgare L. ssp. hirtum extract. The extract revealed a diverse range of phenolic compounds, with rosmarinic acid as the predominant compound (47.76%). The extract showed moderate to high lipoxygenase inhibition (IC₅₀ = 32.0 µg/mL), suggesting its potential as an anti-inflammatory agent. It also exhibited strong antioxidant activity, with hydrogen peroxide scavenging (SC₅₀ = 99.2 µg/mL) and hydroxyl radical scavenging (IC₅₀ = 64.12 µg/mL) capabilities. In cellular studies, high concentrations (50 µg/mL and 100 µg/mL) significantly decreased intracellular ROS production in Caco-2 cells (reductions exceeding 53% and 64%, respectively). Moreover, the extract suppressed NO production in LPS-stimulated J774A.1 macrophages in a concentration-dependent manner. The study also explores the incorporation of the extract into 3D-printed gummies. The gels exhibited a shear-thinning behavior, which was essential for successful extrusion-based 3D printing. The incorporation of Origanum extract significantly influenced the mechanical strength and compaction properties of the 3D-printed gummies before breaking (1.6-fold increase) allowing for a better mouth feeling. PXRD and FTIR analyses confirmed the amorphous nature of the 3D-printed gummies and the interaction between active ingredients and excipients utilized for printing. These findings demonstrated the potential for semisolid extrusion 3D printing at room temperature to transform a culinary herb (Origanum vulgare spp. hirtum) into a healthcare product with antioxidant and anti-inflammatory properties. Full article

Over the past years, numerous novel dosage forms, including gels, have been investigated for paediatric treatment due to the need to provide flexible dose adjustment possibilities, as well as a patient-friendly approach to drug delivery. Simultaneously, 3D printing technology is continuously advancing and gaining interest as a tool for personalised formulation development. Multiple additive manufacturing methods, including the semi-solid extrusion, especially used in gel printing, provide flexibility regarding the dose of active ingredients and the adjustment of the design of soft dosage forms. 3D printing techniques can be considered as a possible answer to the demand for medicines tailored to small patients’ needs. This review intends to present an overview of the current possibilities, comparing gel-like and non-gel-formulated dosage forms and crucial aspects of developing those cutting-edge dosage forms by 3D printing. This paper discusses soft formulations such as chewing gums, which still require extensive evaluation, and explores the question of the three-dimensional printing process. Furthermore, it highlights soft dosage forms, such as gel-based gummies and hydrogels, for which 3D fabrication has been intensively studied in previous years. However, the research still needs to advance. Full article