Search Results (20)

Background: Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy, and LY-11h is a novel acylhydrazide-based histone deacetylase inhibitor with promising therapeutic potential for AML. However, its poor aqueous solubility, limited intestinal dissolution, and narrow therapeutic window hinder oral formulation development and motivate the development of dosage forms with flexible dose-design capabilities. Herein, an integrated hot-melt extrusion (HME)–fused deposition modeling (FDM) strategy was developed to convert LY-11h into printable amorphous solid dispersion (ASD) dosage forms. Methods: HPMC-AS was used as a pH-responsive carrier to enhance intestinal release while restricting premature gastric release, and HPC-EF was incorporated to improve filament processability. Single-factor and DoE studies identified critical formulation and process variables and established formulation–process–property relationships, while machine learning further modeled nonlinear interactions and guided optimization. In-line near-infrared spectroscopy combined with polarized light microscopy enabled real-time monitoring of LY-11h amorphization and melt homogenization during HME. Results: ExtraTrees and Bagging models showed promising predictive performance for key filament properties, and PAT-stage validation confirmed strong agreement with experimental values. The 15 DoE-designed ASD filaments were successfully fabricated into FDM-printed tablets with reproducible geometry. Equilibrium-solubility and in vitro dissolution studies demonstrated enhanced intestinal-pH solubility and reproducible pH-responsive release. Conclusions: Collectively, these findings establish a technological proof of concept for the manufacture of LY-11h dosage forms with adjustable formulation and geometric attributes. Further in vivo pharmacokinetic studies are required to determine whether these manufacturing capabilities translate into predictable dose–exposure relationships and individualized dose control. Full article

Guanidinoacetic acid (GAA), an important feed additive, shows poor powder properties due to its morphological characteristics. In this study, GAA was employed as a model compound to investigate the regulatory effects of polymeric additives (hydroxypropyl methyl cellulose, hydroxypropyl cellulose, and polyacrylamide) on its crystal growth and powder properties through integrated experimental and molecular simulation approaches. In situ single-crystal growth experiments reveal that hydroxypropyl methyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) can selectively suppress the growth of the (11–1) crystal face while slightly promoting the growth of the (011) crystal face, thereby altering the relative growth rates and modifying the final crystal morphology. However, polyacrylamide (PAM) inhibits the growth of both the (11–1) and (011) crystal faces, resulting in negligible alteration of GAA crystal morphology. Growth kinetic analysis indicates that crystal growth is governed by a surface integration-controlled mechanism. Molecular dynamics simulations further demonstrate that the additive preferentially adsorbs onto specific crystal faces, reducing interfacial solute accumulation and inhibiting molecular diffusion. Collectively, these findings demonstrate that additives exert synergistic control over crystal morphology and particle size distribution through selective adsorption and modulation of interfacial mass transfer. This research provides mechanistic insights and theoretical guidance for the regulation of crystallization processes via additive intervention. Full article

Background: Individualized care in veterinary practice optimizes pharmaceutical dose regimens, facilitates disease prevention, and supports animal health by considering the animal’s individual profile. Three-dimensional (3D) printing is a suitable technology for manufacturing both tailored drugs and supplements with enhanced efficacy and reduced adverse reactions. Zinc is used to correct deficiencies, support growth, boost the immune system, and treat specific conditions like zinc-responsive dermatosis in dogs. The purpose of the study was to develop and analyze tailored zinc-loaded filaments for the design of custom-made 3D-printed shapes. Methods: Zinc oxide (ZnO) and artificial beef flavor were incorporated into hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC), respectively, to produce tailored 5% or 10% ZnO-containing filaments for 3D printing. The obtained filaments and 3D-printed forms were characterized using sieve analysis, moisture determination, melting point, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction analysis. Results: The characterization of two placebo and four custom-made 3D-printed ZnO supplements suggested that HPMC is a polymer with poor processability, whereas HPC is suitable for incorporating artificial beef flavor and ZnO. FTIR analysis indicated no interaction between the components. Conclusion: The HPC and 10% flavor mixture can be applied as a matrix for manufacturing 3D-printed forms with ZnO for individualized animal care. Full article

Objectives: Sen Ling Cao (SLC) is an excellent health food that has health-promoting functions, such as alleviating physical fatigue and boosting immune function. Currently, SLC is predominantly marketed and administered as an oral liquid, which suffers from the disadvantages of inconvenient transport and limited versatility. In this study, we investigated the preparation of direct compression (DC) tablets of SLC. Methods: Hydroxypropyl methylcellulose E3 (HPMC E3), polyvinylpyrrolidone K30 (PVP K30), hydroxypropyl cellulose EF (HPC EF), and maltodextrin (MD) were selected as modifying agents; and ammonium bicarbonate (NH₄HCO₃) and sodium bicarbonate (NaHCO₃) were employed as pore-forming agents. Co-spray drying was utilized to prepare 13 kinds of composite particles with different structures. Subsequently, their physical properties and compacting parameters were characterized comprehensively. Finally, the various composite particles were directly compacted into tablets to study the respective effects on the properties of DC tablets. Results: The results demonstrated that (i) the SLC composite particles have been successfully produced by co-spray drying, and processing involves physical changes; (ii) the tensile strength (TS) values of PCP-SLC-HPMC-NH₄HCO₃, PCP-SLC-PVP-NaHCO₃, PCP-SLC-HPC-NaHCO₃, and PCP-SLC-HPMC-NaHCO₃ were 9.8, 7.2, 8.3, and 7.7 times higher than that of SLC; (iii) all the modifiers studied could improve the DC properties of problematic SLC to some degree, and the combination of HPMC and NH₄HCO₃ showed to be the best to markedly improve both the compactibility and flowability of SLC. Conclusions: Overall, the design of porous composite particles, composite particles, and porous composite particles in this study successfully produced qualified tablets with high SLC loadings via DC. These findings are favorable for promoting the development and application of natural botanical tablets through DC. Full article

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

Three-dimensional printing is promising in the pharmaceutical industry for personalized medicine, on-demand production, tailored drug loading, etc. Pressure-assisted microsyringe (PAM) printing is popular due to its low cost, simple operation, and compatibility with heat-sensitive drugs but is limited by ink formulations lacking the essential characteristics, impacting their performance. This study evaluates inks based on sodium alginate (SA), hydroxypropyl cellulose (HPC H), and hydroxypropyl methylcellulose (HPMC K100 and K4) for PAM 3D printing by analyzing their rheology. The formulations included the model drug Fenofibrate, functional excipients (e.g., mannitol, polyethylene glycol, etc.), and water or water–ethanol mixtures. Pills and thin films as an oral dosage were printed using a 410 μm nozzle, a 10 mm/s speed, a 50% infill density, and a 60 kPa pressure. Among the various formulated inks, only the ink containing 0.8% SA achieved successful prints with the desired shape fidelity, linked to its rheological properties, which were assessed using flow, amplitude sweep, and thixotropy tests. This study concludes that (i) an ink’s rheological properties—viscosity, shear thinning, viscoelasticity, modulus, flow point, recovery, etc.—have to be considered to determine whether it will print well; (ii) printability is independent of the dosage form; and (iii) the optimal inks are viscoelastic solids with specific rheological traits. This research provides insights for developing polymer-based inks for effective PAM 3D printing in pharmaceuticals. Full article

Background/Objectives: Orally disintegrating film (ODF) is prepared using water-soluble polymers as film-forming agents. To improve mechanical and disintegration properties, some polymers need to be blended with others. This study aimed to investigate the utility of hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC) as blend film-forming components for ODFs. Methods: Placebo ODFs were prepared using polymer mixtures with blend ratios ranging from 20% to 80% HPC with HPMC. Mechanical properties, including tensile strength, elastic modulus, elongation at break, and folding endurance, as well as disintegration times, were evaluated. Additionally, blend films incorporating donepezil hydrochloride (DH) as a model active pharmaceutical ingredient (API) were prepared and assessed to determine their mechanical properties and disintegration behavior. Results: Blend films were successfully formed using HPMC/HPC solutions. The 40/60 and 20/80 HPMC/HPC blends exhibited the lowest mechanical strength and elongation, whereas blends containing more than 40% HPC demonstrated shorter disintegration times. Films with DH were successfully formed, though the addition of DH reduced tensile strength and elongation. The decline in mechanical properties was mitigated in HPMC/HPC blend films. Our results, including DSC and FTIR results, led us to conclude that the HPMC/HPC blend films were micro-immiscible, but they were macro-miscible when the amount of the minor component was sufficiently small. Conclusions: HPMC/HPC blends in appropriate ratios are effective as film-forming polymers for ODFs. The addition of DH impacts the mechanical properties, but the decline is less pronounced when using HPMC/HPC blends. Full article

The study focuses on the development of an in situ gelling dexamethasone (DEX) oromucosal formulation designed for the treatment of aphthous stomatitis. Three series of formulations were prepared; a first series containing DEX suspended, a second series containing DEX and, in addition, mint essential oil (EO), and a third series containing EO and DEX solubilized in propylene glycol (PG). In the composition, polymers in the role of mucoadhesive agent were interchanged (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methyl cellulose (MC), carboxymethyl cellulose (CMC), and sodium carboxymethyl cellulose (NaCMC). Specifically, DEX was incorporated at a concentration of 0.1% (w/w) in each formulation. The influence of mint EO and DEX solubilization on the physical properties (pH measurements, rheological analysis, swelling ability, and texture analysis) and in vitro drug release was studied. Key findings revealed that HPMC-based formulation containing mint EO and PG exhibited best swelling properties (700 ± 46% after 5 h), adequate adhesiveness and in vitro drug release (34.7 ± 5.9%). Furthermore, the irritation potential assessed via the hen’s egg test on the chorioallantoic membrane (HET-CAM) demonstrated low irritancy risk. Finally, Fourier-transform infrared spectroscopy (FT-IR) showed no incompatibility between DEX and excipients. Overall, the research highlights the potential of mucoadhesive systems in improving the therapeutic efficacy of oromucosal drug delivery for managing painful oral lesions. Full article

Loratadine (LOR) is a second-generation antihistamine that exhibits a low and variable oral bioavailability (10–40%) and delayed onset owing to poor solubility and an extensive first-pass effect. Therefore, in light of the clinical need, the main goal of the present study was to develop sublingual fast-dissolving thin films of LOR–citric acid co-amorphous systems (LOR-CAs) with the aim of eliciting a faster onset and improving the bioavailability. We formulated sublingual fast-dissolving thin films of LOR by a film-casting technique using hydrophilic polymers like hydroxypropyl methylcellulose (HPMC E15), polyvinyl pyrrolidone K30 (PVP K30), and hydroxypropyl cellulose EL (HPC-EF) and citric acid as a pH modulator, while glycerin served as a plasticizer. The sublingual fast-dissolving thin films were characterized by FTIR, SEM, DSC, and XRD and evaluated for in vitro dissolution and ex vivo mucoadhesion. The best formulation (F1) developed using HPMC E15 as a polymer, glycerin as a plasticizer, and citric acid as a pH modulator was found to be the optimized formulation as it was smooth, clear, flexible, and displayed good mucoadhesion (11.27 ± 0.418 gm/cm²) and uniform thickness (0.25 ± 0.02 mm). The formulation F1 was found to display a significantly shorter DT (30.30 ± 0.6 s) and rapid release of LOR (92.10 ± 2.3% in 60 min) compared to other formulations (ANOVA, p < 0.001). The results indicated that the prepared sublingual films are likely to elicit a faster therapeutic effect, avoid first-pass metabolism, and improve the bioavailability. Full article

Currently, there are several types of materials for the treatment of wounds, burns, and other topical injuries available on the market. The most used are gauzes and compresses due to their fluid absorption capacity; however, these materials adhere to the surface of the lesions, which can lead to further bleeding and tissue damage upon removal. In the present study, the development of a polymer-based gel that can be applied as a spray provides a new vision in injury protection, respecting the requirements of safety, ease, and quickness of both applicability and removal. The following polymeric sprays were developed to further obtain gels based on different polymers: hydroxypropyl cellulose (HPC), polyvinyl pyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) using polyethylene glycol (PEG) as a plasticizer. The developed sprays revealed suitable properties for use in topical injuries. A protective film was obtained when sprayed on a surface through a casting mechanism. The obtained films adhered to the surface of biological tissue (pig muscle), turning into a gel when the exudate was absorbed, and proved to be washable with saline solution and contribute to the clotting process. Moreover, biocompatibility results showed that all materials were biocompatible, as cell viability was over 90% for all the materials. Full article

Cobalamin (vitamin B₁₂), an essential vitamin with low oral bioavailability, plays a vital role in cellular functions. This research aimed to enhance the absorption of vitamin B₁₂ using sublingual mucoadhesive tablets by increasing the residence time of the drug at the administration site. This research involved the preparation of different 50 mg placebo formulas using different methods. Formulas with disintegration times less than one minute and appropriate physical characteristics were incorporated into 1 mg of cyanocobalamin (S1–S20) using the direct compression method. The tablets obtained were evaluated ex vivo for residence time, and only those remaining for >15 min were included. The final formulas (S5, S8, S11, and S20) were evaluated in several ways, including pre- and post-compression, drug content, mucoadhesive strength, dissolution, and Permeapad^® permeation test employed in the Franz diffusion cell. After conducting the evaluation, formula S11 (Eudragit L100-55) emerged as the most favorable formulation. It exhibited a mucoadhesive residence time of 118.2 ± 2.89 min, required a detachment force of 26 ± 1 g, maintained a drug content of 99.124 ± 0.001699%, and achieved a 76.85% drug release over 22 h, fitting well with the Peppas–Sahlin kinetic model (R²: 0.9949). This suggests that the drug release process encompasses the Fickian and non-Fickian kinetic mechanisms. Furthermore, Eudragit L100-55 demonstrated the highest permeability, boasting a flux value of 6.387 ± 1.860 µg/h/cm²; over 6 h. These findings indicate that including this polymer in the formulation leads to an improved residence time, which positively impacts bioavailability. Full article

Luteolin (LUT), a bioactive flavonoid, possesses various pharmacological properties, including antioxidant, antimicrobial, anti-allergic, cardio-protective, and anti-cancer activity. Among them, LUT’s administration for the treatment of periodontal disease is very promising. However, its low water solubility magnifies the challenge of formulating LUT into an effective dosage form. In this vein, the aim of the present study examines the preparation of amorphous solid dispersions (ASD) for the solubility improvement of LUT in saliva. At first, the physicochemical properties of the active pharmaceutical ingredient (API) were studied before the selection of the most suitable ASD matrix/carrier. For this reason, six commonly used polymeric ASD matrix/carriers (namely, povidone, PVP; copovidone, coPVP; hydroxypropyl cellulose, HPC-SL; hydroxypropyl methyl cellulose acetate succinate, HPMC-AS; Eudragit^® RS, Eud-RS; and Soluplus^®, SOL) were screened via the film casting method, as to whether they could suspend the drug’s recrystallization. The most promising matrix/carriers were then evaluated, based on their ability to inhibit LUT’s precipitation after its solubilization, via the solvent shift method. Based on both screening methods, it was determined that PVP was the most promising matrix/carrier for the preparation of LUT’s ASDs. Hence, in a further step, after the successful testing of components’ miscibility, LUT-PVP ASDs were prepared via the solvent evaporation method. These systems (examined via powder X-ray diffractometry, pXRD) showed full API amorphization immediately after preparation and excellent physical stability (since they were stable after 3 months of storage). The study of LUT-PVP ASD’s ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared) spectra demonstrated strong H-bonds between the molecules of the drug and the matrix/carrier, while molecular dynamics (MD) simulations were able to shed light on these drug–matrix/carrier interactions, at a molecular level. Finally, in vitro dissolution studies in simulated saliva proved that the prepared ASDs were able to significantly enhance LUT’s dissolution profile. Hence, according to findings of the present work, the preparation of LUT-ASDs utilizing PVP as the polymeric matrix/carrier is regarded as a highly promising technique for the improvement of API’s solubility in the oral cavity. Full article

The viscoelastic nature of polymeric formulations utilised in drug products imparts unique thermomechanical attributes during manufacturing and over the shelf life of the product. Nevertheless, it adds to the challenge of understanding the precise mechanistic behaviour of the product at the microscopic and macroscopic level during each step of the process. Current thermomechanical and rheological characterisation techniques are limited to assessing polymer performance to a single phase and are especially hindered when the polymers are undergoing thermomechanical transitions. Since pharmaceutical processing can occur at these transition conditions, this study successfully proposes a thermomechanical characterisation approach combining both mechanical and rheological data to construct a comprehensive profiling of polymeric materials spanning both glassy and rubbery phases. This approach has been used in this study to assess the mechanical and rheological behaviour of heterogenous polymer blends of hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) over a shearing rate range of 0.1–100 s⁻¹ and a temperature range of 30–200 °C. The results indicate that HPC and HPMC do not appear to interact when mixing and that their mixture exhibits the mechanistic properties of the two individual polymers in accordance with their ratio in the mixture. The ability to characterise the behaviour of the polymers and their mixtures before, throughout, and after the glassy to rubbery phase transition by application of the combined techniques provides a unique insight towards a quality-by-design approach to this and other polymer-based solid dosage forms, designed with the potential to accelerate their formulation process through obviating the need for multiple formulation trials. Full article

Cellulose ethers are naturally derived ingredients that are commonly used in personal care products as rheology modifiers, film formers, stabilizers, and sensorial agents. In this work, we investigated the physicochemical properties of various grades of hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), and sodium carboxymethylcellulose (CMC). In addition, we also studied the influence of hydrophobic modification on the structure of HEC by carrying out experiments with cetyl hydroxyethylcellulose (HMHEC). Rheological, friction coefficient, dynamic vapor sorption (DVS), surface tension analysis, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) data were generated for the cellulose ethers in order to obtain information about their viscosity, lubricity, moisture absorption, solubility in the bulk solution phase, physical properties, and thermal degradation profile, respectively. Full article

High-molecular-weight hypromellose (HPMC) and hydroxypropyl cellulose (HPC) are widely known, extended-release polymers. Conventional high-molecular-weight HPMCs are preferred in extended-release applications but not widely used in twin-screw melt granulation due to processability difficulties at low operating temperatures and potential drug degradation if high processing temperatures are used. Conversely, high-molecular-weight grade HPC (Klucel^®) can be used in melt granulation processes. The purpose of this study was to evaluate the processability and dissolution behavior of HPC GXF ((Klucel^® GXF) and a recently introduced type of hot-melt extrudable HPMC (Affinisol^®) in extended-release metformin hydrochloride formulations using twin-screw melt granulation. Powder blends were prepared with 75% w/w metformin HCl and 25% w/w polymeric binder. Blends were granulated at processing temperatures of 160, 140, 120 and 100 °C. HPMC HME 4M (Affinisol^® 4M) provided a fine powder, indicating minimum granulation at processing temperatures lower than 160 °C, and the tablets obtained with these granules capped during tableting. In contrast, acceptable tablets could be obtained with HPC GXF at all processing temperatures. Rheological studies including capillary rheometry to measure steady shear rate viscosity, and rotational rheometry to obtain time and temperature superposition data, showed that HPC GXF had a greater thermoplasticity than HPMC HME 4M, which made granulation possible with HPC GXF at low temperatures. Tablets compressed with granules obtained at 160 °C with both binders showed comparable dissolution profiles. High-molecular-weight HPC GXF provided a better processability at low temperatures and adequate tablet strength for the melt granulation of metformin HCl. Full article