Impact of grinding balls on the size reduction of Aprepitant in wet ball milling procedure.

One of the widely used approaches for improving the dissolution of poorly water-soluble drugs is particle size reduction. Ball milling is a mechanical, top-down technique used to reduce particle size. The effect of ball number, ball size, and milling speed on the properties of milled Aprepitant is evaluated. A full factorial design was employed to investigate the influence of affecting factors on particle size reduction. The initial suspension was made by suspending the drug in distilled water using excipients followed by milling in a planetary ball mill. Ball size, ball number, and milling speed modulated particle size distribution of Aprepitant. Increasing the number of balls from minimum to maximum for each ball size led to approximately a 28% reduction in mean particle size, a 37% decrease in D90%, and a 25% decrease in the ratio of volume mean particle diameter to numeric mean particle diameter. On average, using 10 mm balls instead of 30 mm balls reduced mean particle size by 1.689 µm. As a result, ball size, ball number, and milling speed are three effective factors in the process of ball milling. By increasing the ball number and decreasing the ball size, efficient micronization of drug particles takes place and the particle size is more uniform.

Physical and mechanical properties of ocular thin films: a systematic review and meta-analysis.

The ocular thin film presents a potential solution for addressing challenges to ocular drug delivery. In this review, we summarise the findings of a comprehensive review analysing 336 formulations from 68 studies. We investigated the physical and mechanical properties of ocular thin films, categorised into natural polymer-based, synthetic polymer-based, and combined polymer films. The results showed that the type of polymers used impacted mucoadhesion force, moisture absorption:moisture loss ratio, pH, swelling index, and elongation percentage. Significant relationships were found between these properties within each subgroup. The results also highlighted the influence of plasticisers on elongation percentage, mucoadhesion force, swelling index, and moisture absorption:moisture loss ratio. These findings have implications for designing and optimising ocular drug formulations and selecting appropriate plasticisers to achieve formulations with the desired properties.

Niosome as a promising tool for increasing the effectiveness of anti-inflammatory compounds.

Niosomes are drug delivery systems with widespread applications in pharmaceutical research and the cosmetic industry. Niosomes are vesicles of one or more bilayers made of non-ionic surfactants, cholesterol, and charge inducers. Because of their bilayer characteristics, similar to liposomes, niosomes can be loaded with lipophilic and hydrophilic cargos. Therefore, they are more stable and cheaper in preparation than liposomes. They can be classified into four categories according to their sizes and structures, namely small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs,), multilamellar vesicles (MLVs), and multivesicular vesicles (MVVs). There are many methods for niosome preparation, such as thin-film hydration, solvent injection, and heating method. The current study focuses on the preparation methods and pharmacological effects of niosomes loaded with natural and chemical anti-inflammatory compounds in kinds of literature during the past decade. We found that most research was carried out to load anti-inflammatory agents like non-steroidal anti-inflammatory drugs (NSAIDs) into niosome vesicles. The studies revealed that niosomes could improve anti-inflammatory agents' physicochemical properties, including solubility, cellular uptake, stability, encapsulation, drug release and liberation, efficiency, and oral bioavailability or topical absorption. See also the graphical abstract(Fig. 1).

Challenges and opportunities of medicines for treating tendon inflammation and fibrosis: A comprehensive and mechanistic review.

BACKGROUND: Tendinopathy refers to conditions characterized by collagen degeneration within tendon tissue, accompanied by the proliferation of capillaries and arteries, resulting in reduced mechanical function, pain, and swelling. While inflammation in tendinopathy can play a role in preventing infection, uncontrolled inflammation can hinder tissue regeneration and lead to fibrosis and impaired movement. OBJECTIVES: The inability to regulate inflammation poses a significant limitation in tendinopathy treatment. Therefore, an ideal treatment strategy should involve modulation of the inflammatory process while promoting tissue regeneration. METHODS: The current review article was prepared by searching PubMed, Scopus, Web of Science, and Google Scholar databases. Several treatment approaches based on biomaterials have been developed. RESULTS: This review examines various treatment methods utilizing small molecules, biological compounds, herbal medicine-inspired approaches, immunotherapy, gene therapy, cell-based therapy, tissue engineering, nanotechnology, and phototherapy. CONCLUSION: These treatments work through mechanisms of action involving signaling pathways such as transforming growth factor-beta (TGF-ß), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), all of which contribute to the repair of injured tendons.

Formulation and optimization of a single-layer coat for targeting budesonide pellets to the descending Colon.

The current budesonide formulations are inadequate for addressing left-sided colitis, and patients might hesitate to use an enema for a prolonged time. This study focuses on developing a single-layer coating for budesonide pellets targeting the descending colon. Pellets containing budesonide (1.5%w/w), PVP K30 (5%w/w), lactose monohydrate (25%w/w) and Avicel pH 102 (68.5%w/w) were prepared using extrusion spheronization technique. Coating formulations were designed using response surface methodology with pH and time-dependent Eudragits. Dissolution tests were conducted at different pH levels (1.2, 6.5, 6.8, and 7.2). Optimal coating formulation, considering coating level and the Eudragit (S + L) ratio to the total coating weight, was determined. Budesonide pellets were coated with the optimized composition and subjected to continuous dissolution testing simulating the gastrointestinal tract. The coating, with 48% S, 12% L, and 40% RS at a 10% coating level, demonstrated superior budesonide delivery to the descending colon. Coated pellets had a spherical shape with a uniform 30 µm thickness coating, exhibiting pH and time-dependent release. Notably, zero-order release kinetics was observed for the last 9 h in colonic conditions. The study suggests that an optimized single-layer coating, incorporating pH and time-dependent polymers, holds promise for consistently delivering budesonide to the descending colon.

Development of a PVA/PCL/CS-Based Nanofibrous Membrane for Guided Tissue Regeneration and Controlled Delivery of Doxycycline Hydrochloride in Management of Periodontitis: In Vivo Evaluation in Rats.

Antibiotic administration is an adjacent therapy to guided tissue regeneration (GTR) in the management of periodontitis. This is due to the major role of pathogen biofilm in aggravating periodontal defects. This study aimed to fabricate a GTR membrane for sustained delivery of doxycycline hydrochloride (DOX) while having a space-maintaining function. The membranes were prepared using a polymeric blend of polycaprolactone/polyvinyl alcohol/chitosan by the electrospinning technique. The obtained membranes were characterized in terms of physicochemical and biological properties. Nanofibers showed a mean diameter in the submicron range of < 450 nm while having uniform randomly aligned morphology. The obtained membranes showed high strength and flexibility. A prolonged in vitro release profile during 68 h was observed for manufactured formulations. The prepared membranes showed a cell viability of > 70% at different DOX concentrations. The formulations possessed antimicrobial efficacy against common pathogens responsible for periodontitis. In vivo evaluation also showed prolonged release of DOX for 14 days. The histopathological evaluation confirmed the biocompatibility of the GTR membrane. In conclusion, the developed nanofibrous DOX-loaded GTR membranes may have beneficial characteristics in favour of both sustained antibiotic delivery and periodontal regeneration by space-maintaining function without causing any irritation and tissue damage.

Development of Sustained Release Formulations Based on Lipid-Liquid Crystal to Control the Release of Deoxycholate: In Vitro and In Vivo Assessment.

Subcutaneous injections of phosphatidylcholine (PC), sodium deoxycholate (NADC), and a mixture of them were found to be an effective option for treating cellulite. However, it is noteworthy that the injection of NADC may result in inflammation as well as necrosis in the injection area. The preparation of a sustained release formulation based on lipid-liquid crystal that controls the release of NADC could be a potential solution to address the issue of inflammation and necrosis at the site of injection. To present a practical and validated approach for accurately determining the concentration of NADC in LLC formulations, spectrofluorimetry was used based on the International Council for Harmonization (ICH) Q2 guidelines. Based on the validation results, the fluorometric technique has been confirmed as a reliable, efficient, and economical analytical method for quantifying NADC concentrations. The method demonstrated favorable attributes of linearity, precision, and accuracy, with an r2 value of 0.999. Furthermore, it exhibited excellent interday and intraday repeatability, with RSD values below 4%. The recovery percentages ranged from 97 to 100%, indicating the method's ability to accurately measure NADC concentrations. The subcutaneous injection of the LLC-NADC demonstrated a reduction in inflammation and tissue necrosis in skin tissue, along with an increase in fat lysis within 30 days, when compared to the administration of only NADC solution. Moreover, the histopathological assessment confirmed that the use of the LLC formulation did not result in any detrimental side effects for kidney or heart tissue.

Nanohybrid Based on (Mn, Zn) Ferrite Nanoparticles Functionalized With Chitosan and Sodium Alginate for Loading of Curcumin Against Human Breast Cancer Cells.

This study reports on the synthesis of Mn1 - xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn0.8Zn0.2Fe2O4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.

Micro- and nanoformulations of antibiotics against Brucella.

Brucellosis, a zoonotic intracellular bacterial infection primarily transmitted through the consumption of unpasteurized milk from infected animals, remains a challenging condition to clinically control. This is mainly because of the limited effectiveness of conventional antibiotics in targeting intracellular Brucella. Micro- and nanoformulations of antibiotics, whether used as a mono- or combination therapy, have the potential to reduce the antibiotic doses required and treatment duration. Extensive research has been conducted on various organic, semiorganic, and inorganic nanomaterials with different morphologies, such as nanoparticles (NPs), nanotubes, nanowires, and nanobelts. Metal/metal oxide, lipidic, polymeric, and carbonic NPs have been widely explored to overcome the limitations of traditional formulations. In this review, we discuss the advances and challenges of these novel formulations based on recent investigations.

Current Advances in Nanotechnology-Mediated Delivery of Herbal and Plant-Derived Medicines.

Phytomedicine has been used by humans since ancient times to treat a variety of diseases. However, herbal medicines face significant challenges, including poor water and lipid solubility and instability, which lead to low bioavailability and insufficient therapeutic efficacy. Recently, it has been shown that nanotechnology-based drug delivery systems are appropriate to overcome the above-mentioned limitations. The present review study first discusses herbal medicines and the challenges involved in the formulation of these drugs. The different types of nano-based drug delivery systems used in herbal delivery and their potential to improve therapeutic efficacy are summarized, and common techniques for preparing nanocarriers used in herbal drug delivery are also discussed. Finally, a list of nanophyto medicines that have entered clinical trials since 2010, as well as those that the FDA has approved, is presented.

Hyaluronic Acid-Coated Chitosan/Gelatin Nanoparticles as a New Strategy for Topical Delivery of Metformin in Melanoma.

Metformin is a multipotential compound for treating diabetes II and controlling hormonal acne and skin cancer. This study was designed to enhance metformin skin penetration in melanoma using nanoparticles containing biocompatible polymers. Formulations with various concentrations of chitosan, hyaluronic acid, and sodium tripolyphosphate were fabricated using an ionic gelation technique tailored by the Box-Behnken design. The optimal formulation was selected based on the smallest particle size and the highest entrapment efficiency (EE%) and used in ex vivo skin penetration study. In vitro antiproliferation activity and apoptotic effects of formulations were evaluated using MTT and flow cytometric assays, respectively. The optimized formulation had an average size, zeta potential, EE%, and polydispersity index of 329 ± 6.30 nm, 21.94 ± 0.05 mV, 64.71 ± 6.12%, and 0.272 ± 0.010, respectively. The release profile of the optimized formulation displayed a biphasic trend, characterized by an early burst release, continued by a slow and sustained release compared to free metformin. The ex vivo skin absorption exhibited 1142.5 ± 156.3 µg/cm2 of metformin deposited in the skin layers for the optimized formulation compared to 603.2 ± 93.1 µg/cm2 for the free metformin. Differential scanning calorimetry confirmed the deformation of the drug from the crystal structure to an amorphous state. The attenuated total reflection Fourier transform infrared results approved no chemical interaction between the drug and other ingredients of the formulations. According to the MTT assay, metformin in nanoformulation exhibited a higher cytotoxic effect against melanoma cancer cells than free metformin (IC50: 3.94 ± 0.57 mM vs. 7.63 ± 0.26 mM, respectively, P < 0.001). The results proved that the optimized formulation of metformin could efficiently decrease cell proliferation by promoting apoptosis, thus providing a promising strategy for melanoma therapy.

Carrier-Free Inhalable Dry Microparticles of Celecoxib: Use of the Electrospraying Technique.

Upregulation of cyclooxygenase (COX-2) plays an important role in lung cancer pathogenesis. Celecoxib (CLX), a selective COX-2 inhibitor, may have beneficial effects in COVID-19-induced inflammatory storms. The current study aimed to develop carrier-free inhalable CLX microparticles by electrospraying as a dry powder formulation for inhalation (DPI). CLX microparticles were prepared through an electrospraying method using a suitable solvent mixture at two different drug concentrations. The obtained powders were characterized in terms of their morphology, solid state, dissolution behavior, and aerosolization performance. Electrosprayed particles obtained from the ethanol-acetone solvent mixture with a drug concentration of 3 % w/v exhibited the best in vitro aerosolization properties. The value of the fine particle fraction obtained for the engineered drug particles was 12-fold higher than that of the untreated CLX. When the concentration of CLX was increased, a remarkable reduction in FPF was obtained. The smallest median mass aerodynamic diameter was obtained from the electrosprayed CLX at a 3% concentration (2.82 µm) compared to 5% (3.25 µm) and untreated CLX (4.18 µm). DSC and FTIR experiments showed no change in drug crystallinity or structure of the prepared powders during the electrospraying process. The findings of this study suggest that electrospraying has potential applications in the preparation of DPI formulations.

Inhalation phage therapy as a new approach to preventing secondary bacterial pneumonia in patients with moderate to severe COVID-19: A double-blind clinical trial study.

Inhalation phage therapy is proposed as a replacement approach for antibiotics in the treatment of pulmonary bacterial infections. This study investigates phage therapy on bacterial pneumonia in patients with moderate to severe COVID-19 via the inhalation route. In this double-blind clinical trial, 60 patients with positive COVID-19 hospitalized in three central Mazandaran hospitals were chosen and randomly divided into two intervention and control groups. Standard country protocol drugs plus 10 mL of phage suspension every 12 h with a mesh nebulizer was prescribed for 7 days in the intervention group. The two groups were compared in terms of O2Sat, survival rate, severe secondary pulmonary bacterial infection and duration of hospitalization. Comparing the results between the intervention and control group, in terms of the trend of O2Sat change, negative sputum culture, no fever, no dyspnea, duration of hospitalization, duration of intubation and under ventilation, showed that the difference between these two groups was statistically different (P value < 0.05). In conclusion, inhalation phage therapy may have a potential effect on secondary infection and in the outcome of COVID-19 patients. However, more clinical trials with control confounding factors are needed to further support this concept.

The effect of anionic Eudragit polymers on drug supersaturation and in vitro permeation improvement.

OBJECTIVES: In the present study, Cinnarizine was selected as a weakly basic drug with poor aqueous solubility to investigate the supersaturation maintaining the ability of different types of anionic Eudragit polymers (Eudragits L100-55, L100 and S100). Furthermore, the interplay between polymer-mediated supersaturation maintenance and in vitro permeation enhancement was studied. METHODS: The effect of Eudragit polymers on the pH-induced supersaturation of Cinnarizine was examined under different pHs (6.4, 6.8, and 7.8). Moreover, the effect of Eudragit polymers on the permeation of Cinnarizine through the Caco-2 membrane was investigated. RESULTS: The aggregate size of Eudragit polymers in solution was determined and it was found that the size of polymer aggregate was bigger when lower pH or more hydrophobic polymer was used, which corresponded strongly with improved drug supersaturation. Based on the findings, hydrophobic Cinnarizine-polymer interactions seemed to be essential in determining the impact of Eudragit polymers on maintaining the Cinnarizine supersaturation. The permeation study demonstrated that the rate of drug permeation through the Caco-2 membrane increased in the presence of Eudragit polymers, but their effect on maintaining supersaturation was more significant than their effect on the drug permeation rate. Moreover, the highest level of Cinnarizine supersaturation observed in a non-permeation condition did not correlate with the optimal absorption in a permeation condition. CONCLUSION: This study revealed that the integration of permeation and supersaturation assays is needed to reliably predict the impact of supersaturation maintenance by polymers on the absorption of poorly soluble drugs.

Comparison of 5-ASA layered or matrix pellets coated with a combination of ethylcellulose and eudragits L and s in the treatment of ulcerative colitis in rats.

The aim of this study was to evaluate and optimize the combination of time and pH-dependent polymers as a single coating for the design of the colon-specific drug delivery system of 5-aminosalicylic acid (5-ASA) pellets. 5-ASA matrix pellets with a 70% drug load were prepared by the extrusion-spheronization method. The optimal coating formula which included Eudragit S (ES) + Eudragit L (EL) + Ethylcellulose (EC) was predicted for the targeted drug delivery to the colonic area by a 32 factorial design. The ratio of ES:EL:EC and coating level were considered as independent variables while the responses were the release of less than 10% of the drug within 2 h (Y1), the release of 60-70% within 10 h at pH 6.8 (Y2) and lag time of less than 1 h at pH 7.2 (Y3). Also, 5-ASA layered pellets were prepared by the powder layering of 5-ASA on nonpareils (0.4-0.6 mm) in a fluidized bed coater and then coated with the same optimum coating composition. The coated 5-ASA layered or matrix pellets were tested in a rat model of ulcerative colitis (UC) and compared with the commercial form of 5-ASA pellets (Pentasa®). The ratio of ES:EL:EC of 33:52:15 w/w at a coating level of 7% was discovered as the optimum coating for the delivery of 5-ASA matrix pellets to the colon. The coated 5-ASA pellets were spherical with uniform coating as shown by SEM and met all of our release criteria as predicted. In-vivo studies demonstrated that the optimum 5-ASA layered or matrix pellets had superior anti-inflammatory activities than Pentasa® in terms of colitis activity index (CAI), colon damage score (CDS), colon/body weight ratio and colon's tissue enzymes of glutathione (GSH) and malondialdehyde (MDA). The optimum coating formulation showed a high potential for colonic delivery of 5-ASA layered or matrix pellets and triggered drug release based on pH and time.

Injectable In-Situ Forming Depot Based on PLGA and PLGA-PEG-PLGA for Sustained-Release of Risperidone: In Vitro Evaluation and Pharmacokinetics in Rabbits.

In the current research, novel drug delivery systems based on in situ forming gel (ISFG) (PLGA-PEG-PLGA) and in situ forming implant (ISFI) (PLGA) were developed for one-month risperidone delivery. In vitro release evaluation, pharmacokinetics, and histopathology studies of ISFI, ISFG, and Risperdal CONSTA® were compared in rabbits. Formulation containing 50% (w/w %) of PLGA-PEG-PLGA triblock revealed sustained release for about one month. Scanning electron microscopy (SEM) showed a porous structure for ISFI, while a structure with fewer pores was observed in the triblock. Cell viability in ISFG formulation in the first days was more than ISFI due to the gradual release of NMP to the release medium. Pharmacokinetic data displayed that optimal PLGA-PEG-PLGA creates a consistent serum level in vitro and in vivo through 30 days, and histopathology results revealed nearly slight to moderate pathological signs in the rabbit's organs. The shelf life of the accelerated stability test didn't affect the results of the release rate test and demonstrated stability in 24 months. This research confirms the better potential of the ISFG system compared with ISFI and Risperdal CONSTA®, which would increase patients' compliance and avoid problems of further oral therapy.

A Review of the Benefits 3D Printing Brings to Patients with Neurological Diseases.

This interdisciplinary review focuses on how flexible three-dimensional printing (3DP) technology can aid patients with neurological diseases. It covers a wide variety of current and possible applications ranging from neurosurgery to customizable polypill along with a brief description of the various 3DP techniques. The article goes into detail about how 3DP technology can aid delicate neurosurgical planning and its consequent outcome for patients. It also covers areas such as how the 3DP model can be utilized in patient counseling along with designing specific implants involved in cranioplasty and customization of a specialized instrument such as 3DP optogenetic probes. Furthermore, the review includes how a 3DP nasal cast can contribute to the development of nose-to-brain drug delivery along with looking into how bioprinting could be used for regenerating nerves and how 3D-printed drugs could offer practical benefits to patients suffering from neurological diseases via polypill.

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances.

In vitro dissolution and permeability testing aid the simulation of the in vivo behavior of inhalation drug products. Although the regulatory bodies have specific guidelines for the dissolution of orally administered dosage forms (e.g., tablets and capsules), this is not the case for orally inhaled formulations, as there is no commonly accepted test for assessing their dissolution pattern. Up until a few years ago, there was no consensus that assessing the dissolution of orally inhaled drugs is a key factor in the assessment of orally inhaled products. With the advancement of research in the field of dissolution methods for orally inhaled products and a focus on systemic delivery of new, poorly water-soluble drugs at higher therapeutic doses, an evaluation of dissolution kinetics is proving crucial. Dissolution and permeability testing can determine the differences between the developed formulations and the innovator's formulations and serve as a useful tool in correlating in vitro and in vivo studies. The current review highlights recent advances in the dissolution and permeability testing of inhalation products and their limitations, including recent cell-based technology. Although a few new dissolution and permeability testing methods have been established that have varying degrees of complexity, none have emerged as the standard method of choice. The review discusses the challenges of establishing methods that can closely simulate the in vivo absorption of drugs. It provides practical insights into method development for various dissolution testing scenarios and challenges with dose collection and particle deposition from inhalation devices for dissolution tests. Furthermore, dissolution kinetic models and statistical tests to compare the dissolution profiles of test and reference products are discussed.

Chitosan-sialic acid nanoparticles of selenium: Statistical optimization of production, characterization, and assessment of cytotoxic effects against two human glioblastoma cell lines.

According to the favorable antitumor properties of selenium, this study aimed to design a novel form of selenium nanoparticles (Se NPs) functionalized with chitosan (Cs) and sialic acid to assess their antitumor effects on the human glioblastoma cell lines (T98 and A172). Se NPs were synthesized in the presence of chitosan and ascorbic acid (Vc) and the synthesis conditions were optimized using response surface methodology. Se NPs@Cs were obtained with a monoclinic structure with an average diameter of 23 nm under the optimum conditions (reaction time = 30 min, chitosan concentration = 1 % w/v, Vc/Se molar ratio = 5). To modify Se NP@Cs for glioblastoma treatment, sialic acid was used to cover the surface of the NPs. Sialic acid was successfully attached to the surface of Se NPs@Cs, and Se NPs@Cs-sialic acid were formed in the size range of 15-28 nm. Se NPs@Cs-sialic acid were stable for approximately 60 days at 4 ℃. The as-synthesized NPs exerted inhibitory effects on T98 greater than 3 T3 > A172 cells in a dose- and time-dependent manner. Additionally, sialic acid ameliorated the blood biocompatibility of Se NPs@Cs. Taken together, sialic acid improved both the stability and biological activity of Se NPs@Cs.

Effect of pH, Ionic Strength and Agitation Rate on Dissolution Behaviour of 3D-Printed Tablets, Tablets Prepared from Ground Hot-Melt Extruded Filaments and Physical Mixtures.

With the current focus on 3D-printing technologies, it is essential to understand the processes involved in such printing methods and approaches to minimize the variability in dissolution behaviour to achieve better quality control outcomes. For this purpose, two formulations of theophylline tablets were prepared using hydroxypropyl cellulose (HPC) and ethyl cellulose (EC). Among the two types of tablets, three different methods (physical mixture (PM), hot-melt extrusion (HME) and 3D-printing fused deposition modelling (FDM)) were applied and their dissolution behaviours were studied under various conditions using a biodissolution tester. This was carried out at pH values of 1.2, 2.2, 5.8, 6.8, 7.2 and 7.5, mimicking the medium in the gastrointestinal tract. Dissolution tests under two dipping rates (10 dpm and 20 dpm) and two ionic strengths (0.2 M and 0.4 M) were conducted to mimic fed and fasting conditions. The dissolution efficiency (DE%), release rate, similarity factor (f2) and difference factor (f1) were calculated. When comparing the DE%, the formulation containing EC showed less sensitivity to changes in the dipping rate and ionic strength compared to the HPC formulation. As for the manufacturing method, 3D-printing FDM could improve the robustness of the dissolution behaviour of both formulations to dipping rate changes. However, for ionic strength changes, the effect of the manufacturing method was dependent on the formulation composition. For example, the 3D-printed tablets of the HPC formulation were more sensitive to changes in ionic strength compared to the EC-containing formulation. The release mechanism also changed after the thermal process, where n values in the Korsmeyer-Peppas model were much higher in the printing and HME methods compared to the PM. Based on the formulation composition, the 3D-printing method could be a good candidate method for tablets with a robust dissolution behaviour in the GI tract. Compared to HPC polymers, using hydrophobic EC polymers in printable formulations can result in a more robust dissolution behaviour in fed and fasting states.