A novel gelatin composite film with melt extrusion for walnut oil packaging.

Gelatin have excellent film-forming and barrier properties, but its lack of biological activity limits its application in packaging. In this study, fish gelatin incorporated with apple polyphenol/cumin essential oil composite films were successfully prepared by melt extrusion. The cross-linking existed in gelatin and apple polyphenol improved the thermal stability and oxidation resistance of the film. The synergistic effect of apple polyphenols and cumin essential oil decreased the sensitivity of the film to water, especially the water solubility decreased from 41.60 % to 26.07 %. The plasticization of essential oil nearly doubled the elongation at break while maintaining the tensile strength of the film (11.45 MPa). Furthermore, the FG-CEO-AP film can inhibit peroxide value to extend the shelf life about 20 days in the walnut oil preservation. In summary, the apple polyphenol/cumin essential oil of FG film exhibits excellent comprehensive properties and high preparation efficiency for utilization as an active packaging material.

Biodegradable antimicrobial films prepared in a continuous way by melt extrusion using plant extracts as effective components.

Packaging plays an important role in delaying food spoilage. However, conventional packaging films do not have antimicrobial properties. Films with antimicrobial components are receiving growing research interest. However, many of the reported studies use conventional non-degradable polymers during film preparation, posing a significant threat to the environment and sustainable development. Furthermore, conventional inorganic antibacterial agents are commonly used during film preparation, posing a risk to food safety. In this study, antibacterial compounds were extracted from diverse plants, and then biodegradable antimicrobial films were prepared in a continuous way via the melt extrusion method. Especially, films prepared using Vernicia fordii and Phyllanthus urinaria extracts showed effective antibacterial activities against common foodborne pathogens. This study is the first to prepare antibacterial films in a continuous way using natural plant extracts as the effective components, and may shed new light on future research in preparing green antibacterial films via environment-friendly approaches.

Development of Mathematical Function Control-Based 3D Printed Tablets and Effect on Drug Release.

PURPOSE: The application of 3D printing technology in drug delivery is often limited by the challenges of achieving precise control over drug release profiles. The goal of this study was to apply surface equations to construct 3D printed tablet models, adjust the functional parameters to obtain multiple tablet models and to correlate the model parameters with the in vitro drug release behavior. METHODS: This study reports the development of 3D-printed tablets using surface geometries controlled by mathematical functions to modulate drug release. Utilizing fused deposition modeling (FDM) coupled with hot-melt extrusion (HME) technology, personalized drug delivery systems were produced using thermoplastic polymers. Different tablet shapes (T1-T5) were produced by varying the depth of the parabolic surface (b = 4, 2, 0, -2, -4 mm) to assess the impact of surface curvature on drug dissolution. RESULTS: The T5 formulation, with the greatest surface curvature, demonstrated the fastest drug release, achieving complete release within 4 h. In contrast, T1 and T2 tablets exhibited a slower release over approximately 6 h. The correlation between surface area and drug release rate was confirmed, supporting the predictions of the Noyes-Whitney equation. Differential Scanning Calorimetry (DSC) and Scanning Electron Microscope (SEM) analyses verified the uniform dispersion of acetaminophen and the consistency of the internal structures, respectively. CONCLUSIONS: The precise control of tablet surface geometry effectively tailored drug release profiles, enhancing patient compliance and treatment efficacy. This novel approach offers significant advancements in personalized medicine by providing a highly reproducible and adaptable platform for optimizing drug delivery.

Effect of Printing Parameters on the Surface Roughness of 3D-Printed Melt-Cast Explosive Substitutes Based on Melt Extrusion Technology.

In recent years, the application of 3D printing technology in the energetic materials field has proved its ability to innovate traditional charging methods and fabricate complex structures to improve combustion/detonation performance. The melt extrusion technology is the most promising way to fabricate complex structures and multiple components of melt-cast explosives. In this study, a paraffine-based composite was used to substitute melt-cast explosives, and a Design of Experiments approach based on central composite design was adopted to investigate the influence of layer thickness, percent infill, extrusion temperature, and printing velocity on the roughness of printed samples. The results showed that layer thickness and printing velocity could significantly influence the roughness of printed specimens, and no obvious voids or cracks inside the specimens can be detected in computed tomography. In addition, a composite-shaped grain was successfully fabricated via the EAM-D-1 printer, which proved the feasibility of 3D printing melt-cast explosives with complex structures. This work will greatly help to achieve 3D printing melt-cast explosives with complex structures and higher accuracy.

Investigating a novel therapeutic composition for dry eye syndrome management: In vitro and in vivo studies.

Dry eye syndrome (DES) presents a significant challenge in ophthalmic care, necessitating innovative approaches for effective management. This research article introduces a multifaceted strategy to address DES through the development of ocular inserts utilizing advanced technologies such as hot-melt extrusion (HME) and the CaliCut post-extrusion system. The formulation includes key ingredients targeting different layers of the tear film and associated inflammation, including hydroxypropyl cellulose (HPC), polyethylene glycol (PEG), castor oil, and dexamethasone. The study incorporates a Design of Experiments (DoE) approach, integrating HME and the precise stretching and cutting technique of CaliCut for manufacturing consistency and dimensional control of the inserts. The developed insert(s) have been systematically characterized for their physicochemical properties, release profile, and in vivo efficacy. In silico molecular docking studies have also been conducted to assess the binding affinities of formulation components with ocular mucin, elucidating their binding affinities. Preliminary results demonstrate promising potential for the developed insert in managing DES, offering preservative-free treatment, sustained drug delivery, and improved patient compliance. This study highlights the integration of advanced technologies and formulation strategies in ocular drug delivery for effective DES management.

Quality by Design (QbD) Approach to Develop Colon-Specific Ketoprofen Hot-Melt Extruded Pellets: Impact of Eudragit® S 100 Coating on the In Vitro Drug Release.

BACKGROUND: A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work. METHODS: The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit® S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box-Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit® S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon. RESULTS: Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit® S 100 coating, and 93.96% in extended release up to 24 h in the colonic region. CONCLUSIONS: Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen.

Advancements in Ocular Therapy: A Review of Emerging Drug Delivery Approaches and Pharmaceutical Technologies.

Eye disorders affect a substantial portion of the global population, yet the availability of efficacious ophthalmic drug products remains limited. This can be partly ascribed to a number of factors: (1) inadequate understanding of physiological barriers, treatment strategies, drug and polymer properties, and delivery systems; (2) challenges in effectively delivering drugs to the anterior and posterior segments of the eye due to anatomical and physiological constraints; and (3) manufacturing and regulatory hurdles in ocular drug product development. The present review discusses innovative ocular delivery and treatments, encompassing implants, liposomes, nanoparticles, nanomicelles, microparticles, iontophoresis, in situ gels, contact lenses, microneedles, hydrogels, bispecific antibodies, and gene delivery strategies. Furthermore, this review also introduces advanced manufacturing technologies such as 3D printing and hot-melt extrusion (HME), aimed at improving bioavailability, reducing therapeutic dosages and side effects, facilitating the design of personalized ophthalmic dosage forms, as well as enhancing patient compliance. This comprehensive review lastly offers insights into digital healthcare, market trends, and industry and regulatory perspectives pertaining to ocular product development.

Comparing Low-Dose Carvedilol Continuous Manufacturing by Solid and Liquid Feeding in Self-Emulsifying Delivery Systems via Hot Melt EXtrusion (SEDEX).

Background/Objectives: This study compared two pilot scale continuous manufacturing methods of solid self-emulsifying drug delivery systems (SEDDSs) via hot melt extrusion (HME). Methods: A model poorly water-soluble drug carvedilol in low dose (0.5-1.0% w/w) was processed in HME either in a conventional powder form or pre-dissolved in the liquid SEDDS. Results: HME yielded a processable final product with up to 20% w/w SEDDS. Addition of carvedilol powder resulted in a non-homogeneous drug distribution in the extrudates, whereas a homogeneous drug distribution was observed in pre-dissolved carvedilol. SEDDSs were shown to have a plasticizing effect, reducing the HME process torque up to 50%. Compatibility between excipients and carvedilol in the studied ratios after HME was confirmed via DSC and WAXS, demonstrating their amorphous form. Solid SEDDSs with Kollidon® VA64 self-emulsified in aqueous medium within 15 min with mean droplet sizes 150-200 nm and were independent of the medium temperature, whereas reconstitution of Soluplus® took over 60 min and mean droplet size increased 2-fold from 70 nm to 150 nm after temperature increased from 25 °C to 37 °C, indicating emulsion phase inversion at cloud point. Conclusions: In conclusion, using Kollidon® VA64 and pre-dissolved carvedilol in SEDDS has shown to yield a stabile HME process with a homogenous carvedilol content in the extrudate.

Assessing processability of milled HME extrudates: Consolidating the effect of extrusion temperature, drug loading, and particle size via Non-dimensional cohesion.

The downstream processability of Hot Melt Extrusion (HME) Amorphous Solid Dispersions (ASD), an underexplored topic of importance, was assessed through a multi-faceted particle engineering approach. Extrudates, comprised of griseofulvin (GF), a model poorly water-soluble drug, and hydroxypropyl cellulose (HPC), were prepared at four drug concentrations and three HME temperature profiles to yield cases with and without residual crystallinity and subsequently milled to five sieve cuts ranging from < 45 µm to 355 - 500 µm. Solid state characterization was performed with XRPD, FT-IR, and TGA. Particle scale properties of the milled extrudates were evaluated including particle size, density, surface energy, and morphologies imaged via SEM. It was observed that regardless of sieve cut size, drug concentration and HME conditions impacted the flowability trends, quantified via Flow Function Coefficient (FFC) and bulk density. As a novelty, the effects of various process parameters and drug loadings were consolidated into a dimensionless interparticle cohesion measure, granular Bond Number (Bog), to better correlate them with bulk powder properties. The significant contrast in particle morphologies, particle size, and densities among selected cases demonstrated that particle size alone should not be the sole consideration when correlating particle scale to bulk powder scale properties of milled extrudates. Instead, the HME temperature profile and ASD drug loading may be more suitable parameters affecting the bulk powder properties of the milled extrudates.

Advancements in Colon-Targeted Drug Delivery: A Comprehensive Review on Recent Techniques with Emphasis on Hot-Melt Extrusion and 3D Printing Technologies.

This review investigates the progression and effectiveness of colon-targeted drug delivery systems, offering a comprehensive understanding of the colon's anatomy and physiological environment. Recognizing the distinctive features of the colon is crucial for successfully formulating oral dosage forms that precisely target specific areas in the gastrointestinal tract (GIT) while minimizing side effects through mitigating off-target sites. This understanding forms the basis for designing effective targeted drug delivery systems. The article extensively examines diverse approaches to formulating drugs for colonic targeting, highlighting key polymers and excipients in their production. Special emphasis is given to innovative approaches such as hot-melt extrusion (HME) and three-dimensional printing (3D-P), renowned for their accuracy in drug release kinetics and intricate dosage form geometry. However, challenges arise regarding material standardization and the complex network of regulatory clearances required to confirm safety and effectiveness. The review provides insights into each application's advantages and potential challenges. Furthermore, it sheds light on the local diseases that necessitate colon targeting and the available marketed products, providing an overview of the current state of colon-targeted drug delivery systems. Additionally, the review emphasizes the importance of testing drugs in a controlled in vitro environment during the development phase. It also discusses the future directions for successful development in this field. By integrating knowledge across anatomy, formulation techniques, and assessment methodologies, this review is a valuable resource for researchers navigating the dynamic field of colonic drug delivery.

Exploring the preparation of griseofulvin CAMS with amino acids of different hydrophobicity as co-formers using a modified hot-melt extrusion process.

Co-amorphous systems (CAMS) of griseofulvin (GRI) with the amino acids (AA): L-lysine (LYS), L-valine (VAL) and L-methionine (MET) of increasing hydrophobicity were prepared using a solvent assisted hot-melt extrusion (HME). Co-formability was evaluated by thermodynamic miscibility prediction, thermal analysis (DSC), powder crystallography (pXRD) and vibrational spectroscopy (ATR-FTIR). Decomposition temperature range was defined by thermogravimetry (TGA) and DSC. Solubilities of crystalline and amorphous drug were determined by the UV-extinction method. The physical stability of GRI/AA CAMS was evaluated by accelerated tests and for ratios 1:1 and 1:2 was excellent. Non-sink dissolution tests of equimolar CAMS of the more hydrophobic MET and VAL revealed long lasting supersaturation, above the solubility of amorphous drug, whereas ratios 2:1 and 1:2 gave lower supersaturation due to partial recrystallization during dissolution, despite the good physical stability. CAMS of the hydrophilic LYS were physically stable but showed poor dissolution, possibly due to self-association of LYS in water. Addition of wetting agent in the dissolution medium improved dissolution without altering the profile. Since previous attempts to formulate GRI/AA CAMS with purely mechanical methods found only moderate success, the feed pretreatment HME method employed in this work makes an excellent alternative for drug/AA CAMS where mechanical or solvent evaporation methods fail.

Single-Step Extrusion Process for Formulation Development of Self-Emulsifying Granules for Oral Delivery of a BCS Class IV Drug.

This study aimed to develop and optimize formulations containinga BCS Class IV drug by improving its solubility and permeability. Herein development of self-emulsifying solid lipid matrices was investigated as carrier systems for a BCS Class IV model drug. Self-emulsifying drug delivery systems (SEDDS) have been extensively investigated for formulating drugs with poor water solubility. However, manufacturing SEDDS is challenging. These systems usually have low drug-loading capacities, and the incorporated drugs tend to recrystallize during storage, which severely impacts the storage stability in vitro and performance in vivo. Moreover, they require greater amounts (>80%) of lipid carriers, cosolvents, surfactants, and other excipients to keep them from recrystallizing. This in turn is again challenging for high-dose drugs as it affects the size of the final drug product (tablets and capsules). Also, the final liquid nature of the formulation affects the handling and processability of the formulation, which poses challenges during the manufacturing and packaging steps. In this work, we have studied the feasibility of a single-step extrusion process to formulate and optimize solid self-emulsifying granules with a relatively higher drug loading of Ritonavir (RTV), a BCS Class IV drug. Further, we have compared the performance of using these granules as the feedstock for direct powder extrusion-based 3D printing as opposed to the use of physical blends. The stability and solubility-permeability advantage of these granules was also evaluated where SEDDS showed about 27 and 20 fold increase in apparent solublity and permeability compared to bulk drug, respectively. Combining the capabilities of HME to form drug-loaded homogeneous granules as a continuous process along with application of direct printing extruiosn (DPE) 3D printing improves the drug delivery prospects for such candidates.

Development and in vitro Evaluation of Cannabidiol Mucoadhesive Buccal Film Formulations Using Hot-Melt Extrusion Technology.

Introduction: Cannabidiol (CBD) has sparked considerable interest because of its wide range of pharmacological uses and the fact that it does not induce psychoactive effects. CBD formulation development presents significant challenges due to its limited water solubility and susceptibility to first-pass metabolism, both of which restrict its overall bioavailability. The current research aimed to use hot-melt extrusion (HME) technology to develop mucoadhesive buccal films to improve CBD solubility and reduce first-pass metabolism. Methods: Five formulations containing 10% w/w CBD were extruded using a counter-rotating twin-screw extruder (Haake Minilab II, Thermo Fisher Scientific). Different characterization studies were conducted on the developed formulations. Results: Differential scanning calorimetry (DSC) revealed that the CBD endothermic peak disappeared in some of the developed films, indicating that CBD was converted from crystalline to amorphous form. A bio-adhesion study showed that the formulations containing Carbopol® (BF2, BF3, BF4, and BF5) had higher adhesiveness properties. In vitro release and solubility studies showed an increase in CBD release and water solubility in the developed formulations when compared to pure CBD. Stability studies revealed that CBD content and release in the lead formulation (BF2) was stable over 15 months. Conclusion: The current study demonstrates that HME was successfully used as an approach to develop CBD mucoadhesive buccal films and CBD solubility was enhanced.

Computational Support to Explore Ternary Solid Dispersions of Challenging Drugs Using Coformer and Hydroxypropyl Cellulose.

A majority of drugs marketed in amorphous formulations have a good glass-forming ability, while compounds less stable in the amorphous state still pose a formulation challenge. This work explores ternary solid dispersions of two model drugs with a polymer (i.e., hydroxypropyl cellulose) and a coformer as stabilizing excipients. The aim was to introduce a computational approach by preselecting additives using solubility parameter intervals (i.e., overlap range of solubility parameter, ORSP) followed by more advanced COSMO-RS theory modeling. Thus, a mapping of calculated mixing enthalpy and melting points is proposed for in silico evaluation prior to hot melt extrusion. Following experimental testing of process feasibility, the selected formulations were tested for their physical stability using conventional bulk analytics and by confocal laser scanning and atomic force microscopy imaging. In line with the in silico screening, dl-malic and l-tartaric acid (20%, w/w) in HPC formulations showed no signs of early drug crystallization after 3 months. However, l-tartaric acid formulations displayed few crystals on the surface, which was likely a humidity-induced surface phenomenon. Although more research is needed, the conclusion is that the proposed computational small-scale extrusion approach of ternary solid dispersion has great potential in the formulation development of challenging drugs.

Thermal and mechanical performance assessment of composite (CPCM) for energy storage.

Phase change materials (PCMs) face obstacles in being widely used due to issues with heat transfer and maintaining their shape. In this research, instead of using binders, the Hexadecane (H) is melted in such a way that the capillary forces of the molten wax allow it to be impregnated into the low-density polyethylene (P) molecules and bind it together as a composite. It was found that the hot melt extrusion (HME) combines the two materials at the micro-scale, forming a phase change composite (CPCM) with various geometries that possesses superior latent heat and shape stability during phase transition. The structure can incorporate a higher percentage of PCM (60 %) using this method, which also results in lower costs. According to the thermal analysis, (H60P40) provides great thermal stability and can store a lot of energy per unit of weight. It has a high capacity of storing latent heat at 129.56 J/g and can also prevent Hexadecane leakage. Based on the mechanical properties results, hexadecane acts like plasticizer thus the addition of PCM decreases Young's modulus, stress in break, and stress at yield. This trend is observed as the PCM content increases. The high values of elongation at break also indicates the strong plasticizing properties of PCM. Based on the obtained results, the CPCMs as a potential candidate for an application in buildings for thermal regulation, reducing energy consumption, and reducing indoor temperature swing.

Continuously producible aztreonam-loaded inhalable lipid nanoparticles for cystic fibrosis-associated Pseudomonas aeruginosa infections - Development and in-vitro characterization.

Cystic fibrosis (CF) is a genetic disorder affecting nearly 105,000 patients worldwide and is characterized by poor respiratory function due to accumulation of thick mucus in the lungs, which not just acts as a physical barrier, but also provides a breeding ground for bacterial infections. These infections can be controlled with the help of antibiotics which can be delivered directly into the lungs for amplifying the local anti-bacterial effect. More than 50 % of CF patients are associated with Pseudomonas aeruginosa infection in their lungs which requires antibiotics such as Aztreonam (AZT). In this study, we prepared inhalable AZT-loaded lipid nanoparticles using Hot-melt extrusion (HME) coupled with probe sonication to target Pseudomonas aeruginosa infection in the lungs. The optimized nanoparticles were tested for physicochemical properties, stability profile, in-vitro aerosolization, and antimicrobial activity against Pseudomonas aeruginosa. The optimized nanoparticles with a PEI concentration of 0.1 % demonstrated a uniform particle size of <50 nm, a spherical shape observed under a transmission electron microscope, and >70 % drug entrapment. Incorporating cationic polymer, PEI, resulted in sustained drug release from the lipid nanoparticles. The in-vitro aerosolization studies exhibited a mass median aerodynamic diameter (MMAD) of <4.3 µm, suggesting deposition of the nanoparticles in the respirable airway. The antimicrobial activity against Pseudomonas aeruginosa showed the minimum inhibitory concentration of the formulation is 2-fold lower than plain AZT. Stability profile showed the formulations are stable after exposure to accelerated conditions. In conclusion, hot-melt extrusion in combination with probe sonication can be used as a potential method for the continuous production of AZT-loaded lipid nanoparticles with enhanced anti-bacterial activity.

EVA implants for controlled drug delivery to the inner ear.

This study evaluated the potential of poly(ethylene vinyl acetate) (EVA) copolymers as matrix formers in miniaturised implants, allowing to achieve controlled drug delivery into the inner ear. Due to the blood-cochlea barrier, it is impossible to reliably deliver a drug to this tiny and highly sensitive organ in clinical practice. To overcome this bottleneck, different EVA implants were prepared by hot melt extrusion, altering the vinyl acetate content and implant diameter. Dexamethasone was incorporated as a drug with anti-inflammatory and anti-fibrotic activity. Its release was measured into artificial perilymph, and the systems were thoroughly characterised before and after exposure to the medium by optical and scanning electron microscopy, SEM-EDX analysis, DSC, X-ray powder diffraction, X-ray microtomography and texture analysis. Notably, the resulting drug release rates were much higher than from silicone-based implants of similar size. Furthermore, varying the vinyl acetate content allowed for adjusting the desired release patterns effectively: With decreasing vinyl acetate content, the crystallinity of the copolymer increased, and the release rate decreased. Interestingly, the drug was homogeneously distributed as tiny crystals throughout the polymeric matrices. Upon contact with aqueous fluids, water penetrates the implants and dissolves the drug, which subsequently diffuses out of the device. Importantly, no noteworthy system swelling or shrinking was observed for up to 10 months upon exposure to the release medium, irrespective of the EVA grade. Also, the mechanical properties of the implants can be expected to allow for administration into the inner ear of a patient, being neither too flexible nor too rigid.

An Additive Manufacturing MicroFactory: Overcoming Brittle Material Failure and Improving Product Performance through Tablet Micro-Structure Control for an Immediate Release Dose Form.

Additive manufacturing of pharmaceutical formulations offers advanced micro-structure control of oral solid dose (OSD) forms targeting not only customised dosing of an active pharmaceutical ingredient (API) but also custom-made drug release profiles. Traditionally, material extrusion 3D printing manufacturing was performed in a two-step manufacturing process via an intermediate feedstock filament. This process was often limited in the material space due to unsuitable (brittle) material properties, which required additional time to develop complex formulations to overcome. The objective of this study was to develop an additive manufacturing MicroFactory process to produce an immediate release (IR) OSD form containing 250 mg of mefenamic acid (MFA) with consistent drug release. In this study, we present a single-step additive manufacturing process employing a novel, filament-free melt extrusion 3D printer, the MicroFactory, to successfully print a previously 'non-printable' brittle Soluplus®-based formulation of MFA, resulting in targeted IR dissolution profiles. The physico-chemical properties of 3D printed MFA-Soluplus®-D-sorbitol formulation was characterised by thermal analysis, Fourier Transform Infrared spectroscopy (FTIR), and X-ray Diffraction Powder (XRPD) analysis, confirming the crystalline state of mefenamic acid as polymorphic form I. Oscillatory temperature and frequency rheology sweeps were related to the processability of the formulation in the MicroFactory. 3D printed, micro-structure controlled, OSDs showed good uniformity of mass and content and exhibited an IR profile with good consistency. Fitting a mathematical model to the dissolution data correlated rate parameters and release exponents with tablet porosity. This study illustrates how additive manufacturing via melt extrusion using this MicroFactory not only streamlines the manufacturing process (one-step vs. two-step) but also enables the processing of (brittle) pharmaceutical immediate-release polymers/polymer formulations, improving and facilitating targeted in vitro drug dissolution profiles.

Enhanced Minor Ginsenoside Contents of Nano-Sized Black Korean Ginseng through Hot Melt Extrusion.

Black ginseng (BG), a traditional medicinal herb produced through a nine-stage steaming and drying process, exhibits stronger pharmacological efficacy, including antioxidant, anti-inflammatory, and anti-cancer properties, when compared to white and red ginseng. The ginsenosides in BG are classified as major and minor types, with minor ginsenosides demonstrating superior pharmacological properties. However, their low concentrations limit their availability for research and clinical applications. In this study, hot melt extrusion (HME) was utilized as an additional processing technique to enhance the content of minor ginsenoside in BG, and the physicochemical properties of the formulation were analyzed. Ginsenoside content in BG and HME-treated BG (HME-BG) was analyzed using high-performance liquid chromatography (HPLC), while their physicochemical properties were evaluated through dynamic light scattering (DLS), electrophoretic light scattering (ELS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FT-IR). HME treatment resulted in a significant increase in minor ginsenosides Rg3 and compound K (CK) by 330% and 450%, respectively, while major ginsenosides Rg1 and Rb1 decreased or were not detected. Additionally, HME-BG demonstrated reduced particle size, improved PDI, and decreased crystallinity. HME treatment effectively converts major ginsenosides in BG into minor ginsenosides, enhancing its pharmacological efficacy and showing great potential for research and development applications.

Dosage by design - 3D printing individualized cabozantinib tablets with immediate release.

Production of patient-specific dosage forms is important to improve patient adherence and effectiveness while reducing the prevalence and severity of adverse effects. Due to its possibility of rapid prototyping 3D printing can be used to produce individual dosages while utilizing techniques such as hot melt extrusion to increase the bioavailability of poorly soluble drugs. In this work, Parteck MXP and Kollicoat IR were used as water-soluble polymer bases for formulation development for 3D printing of various dosages incorporating cabozantinib while enabling immediate release. The effect of tablet design and the excipients sorbitol, croscarmellose sodium, and sodium starch glycolate was investigated for this goal. A way to calculate the size of tablets for predetermined dosages is proposed to enable the printing of individual strengths from one formulation. Rheological data were collected to deepen the understanding of the role of melt viscosity in 3D printing and hot melt extrusion processes. The production of immediate-release cabozantinib tablets containing every therapeutically relevant dosage in a single unit produced by two-step 3D printing was realized.