‘Tablet-in-syringe’: A novel dosing device for dysphagic patients containing fast disintegrating tablets fabricated using semi-solid extrusion 3D printing

With the ability to fabricate personalized dosage forms and considerably shorter manufacturing time, semisolid extrusion (SSE) 3D printing has rapidly grown in popularity in recent years as a novel, versatile manufacturing method that powers a wide range of applications in the pharmaceutical field. In this work, the feasibility of using SSE 3D printing to fabricate fast-disintegrating tablets (FDTs) that are pre-filled in dosing syringes was evaluated. The novel design approach, ‘tablet-in-syringe’, was aimed to ease the oral drug administration and improve the dosing accuracy for dysphagic patients. The effect of varying polymer (hydroxypropyl methylcellulose E15) concentrations and printing parameters (e.g., extrusion rate) on dimensional accuracy, physicochemical properties, disintegration time, and content uniformity of 3D-printed FDTs was studied. An overall comparison of results demonstrated that the best FDT formulation among those developed was with a polymer:drug ratio (w/w) of 1:30, printed at extrusion rate of 3.5 μL/s. The diameter of printed filaments of this formulation was observed to be similar to the nozzle diameter (22G), proving that good printing accuracy was achieved. This FDTs also had the fastest disintegration time (0.81 ± 0.14 min) and a drug (phenytoin sodium, as the model drug) content uniformity that met pharmacopeial specifications. Although the flow characteristics of the dissolved formulation still need improvement, our findings suggested that the novel ‘tablet-in-syringe’ could potentially be considered as a promising fast-disintegrating drug delivery system that can be personalized and manufactured at—or close to—the point of care for dysphagic patients using SSE

Characterization of hydrophilic polymers as a syringe extrusion 3D printing material for orodispersible film

The application of hydrophilic polymers in designing and three-dimensional (3D) printing of pharmaceutical products in various dosage forms has recently been paid much attention. Use of hydrophilic polymers and syringe extrusion 3D printing technology in the fabrication of orodispersible films (ODFs) might hold great potential in rapid drug delivery, personalized medicine, and manufacturing time savings. In this study, the feasibility of 3D-printed ODFs fabrication through a syringe extrusion 3D printing technique and using five different hydrophilic polymers (e.g., hydroxypropyl methylcellulose E15, hydroxypropyl methylcellulose E50, high methoxyl pectin, sodium carboxymethylcellulose, and hydroxyethylcellulose) as film-forming polymers and printing materials has been investigated. Rheology properties and printability of printing gels and physicochemical and mechanical properties of 3D-printed ODFs were evaluated. Amongst the investigated hydrophilic polymers, sodium carboxymethylcellulose at a concentration of 5% w/v (SCMC-5) showed promising results with a good printing resolution and accurate dimensions of the 3D-printed ODFs. In addition, SCMC-5 3D-printed ODFs exhibited the fastest disintegration time within 3 s due to high wettability, roughness and porosity on the surface. However, the results of the mechanical properties study showed that SCMC-5 3D printed ODFs were rigid and brittle, thus requiring special packaging to prevent them from any damage before practical use

Characterization of Hydrophilic Polymers as a Syringe Extrusion 3D Printing Material for Orodispersible Film

The application of hydrophilic polymers in designing and three-dimensional (3D) printing of pharmaceutical products in various dosage forms has recently been paid much attention. Use of hydrophilic polymers and syringe extrusion 3D printing technology in the fabrication of orodispersible films (ODFs) might hold great potential in rapid drug delivery, personalized medicine, and manufacturing time savings. In this study, the feasibility of 3D-printed ODFs fabrication through a syringe extrusion 3D printing technique and using five different hydrophilic polymers (e.g., hydroxypropyl methylcellulose E15, hydroxypropyl methylcellulose E50, high methoxyl pectin, sodium carboxymethylcellulose, and hydroxyethylcellulose) as film-forming polymers and printing materials has been investigated. Rheology properties and printability of printing gels and physicochemical and mechanical properties of 3D-printed ODFs were evaluated. Amongst the investigated hydrophilic polymers, sodium carboxymethylcellulose at a concentration of 5% w/v (SCMC-5) showed promising results with a good printing resolution and accurate dimensions of the 3D-printed ODFs. In addition, SCMC-5 3D-printed ODFs exhibited the fastest disintegration time within 3 s due to high wettability, roughness and porosity on the surface. However, the results of the mechanical properties study showed that SCMC-5 3D printed ODFs were rigid and brittle, thus requiring special packaging to prevent them from any damage before practical use

Formulation and Characterization of Nicotine Microemulsion-Loaded Fast-Dissolving Films for Smoking Cessation

The present study aimed to develop a nicotine microemulsion (NCT-ME) and incorporate it into a fast-dissolving film. The NCT-ME was prepared by mixing the specified proportions of nicotine (NCT), surfactant, co-solvent, and water. The NCT-ME was measured by its average droplet size, size distribution, zeta potential, and morphology. NCT-ME fast-dissolving films were prepared by the solvent casting technique. The films were characterized by morphology, weight, thickness, disintegration time, and mechanical strength properties and the determined NCT loading efficiency and in vitro drug release. The results showed that almost all NCT-MEs presented droplet sizes of less than 100 nm with a spherical form, narrow size distribution, and zeta potentials of −10.6 to −73.7 mV. There was no difference in weight and thickness between all NCT-ME films, but significant changes in the disintegration times were noticed in NCT40-Smix[PEG-40H(2:1)]10 film. The mechanical properties of films varied with changes in type of surfactant. About 80% of the drug release was observed to be between 3 and 30 min. The drug release kinetics were fitted with the Higuchi matrix model. The NCT40-Smix[P-80(1:1)]10 film showed the highest dissolution rate. It was concluded that the developed ME-loaded fast-dissolving film can increase drug release to a greater extent than the films without ME

Fabrication of Hydroxypropyl Methylcellulose Orodispersible Film Loaded Mirtazapine Using a Syringe Extrusion 3D Printer

Depression is a mental illness causing a continuous negative feeling and loss of interest and affects physical and mental health. Mirtazapine (MTZ) is an effective medicine for treating depression, but patients lack compliance. However, transforming a pharmaceutical dosage form to an orodispersible film (ODF) could resolve this issue. This study aims to fabricate ODF-loading mirtazapine, using a syringe extrusion 3D printer, and compare its properties with the solvent-casting method. The ODFs were prepared by dissolving the mirtazapine in a hydroxypropyl methylcellulose E15 solution, and then fabricated by a 3D printer or casting. The 3D printing was accurate and precise in fabricating the ODFs. The SEM micrographs showed that the mirtazapine-printed ODF (3D-MTZ) was porous, with crystals of mirtazapine on the film’s surface. The 3D-MTZ exhibited better mechanical properties than the mirtazapine-casted ODF (C-MTZ), due to the 3D-printing process. The disintegration time of the 3D-MTZ in a simulated salivary fluid, pH 6.8 at 37 °C, was 24.38 s, which is faster than the C-MTZ (46.75 s). The in vitro dissolution study, in 0.1 N HCl at 37 °C, found the 3D-MTZ quickly released the drug by more than 80% in 5 min. This study manifested that 3D-printing technology can potentially be applied for the fabrication of ODF-containing mirtazapine

Hydroxypropyl Methylcellulose E15: A Hydrophilic Polymer for Fabrication of Orodispersible Film Using Syringe Extrusion 3D Printer

Extrusion-based 3D printing technology is a relatively new technique that has a potential for fabricating pharmaceutical products in various dosage forms. It offers many advantages over conventional manufacturing methods, including more accurate drug dosing, which is especially important for the drugs that require exact tailoring (e.g., narrow therapeutic index drugs). In this work, we have successfully fabricated phenytoin-loaded orodispersible films (ODFs) through a syringe extrusion 3D printing technique. Two different grades of hydroxypropyl methylcellulose (HPMC E5 and HPMC E15) were used as the film-forming polymers, and glycerin and propylene glycol were used as plasticizers. The 3D-printed ODFs were physicochemically characterized and evaluated for their mechanical properties and in vitro disintegration time. Then, the optimum printed ODFs showing good mechanical properties and the fastest disintegration time were selected to evaluate their drug content and dissolution profiles. The results showed that phenytoin-loaded E15 ODFs demonstrated superior properties when compared to E5 films. It demonstrated a fast disintegration time in less than 5 s and rapidly dissolved and reached up to 80% of drug release within 10 min. In addition, it also exhibited drug content uniformity within United States Pharmacopeia (USP) acceptable range and exhibited good mechanical properties and flexibility with low puncture strength, low Young’s modulus and high elongation, which allows ease of handling and application. Furthermore, the HPMC E15 printing dispersions with suitable concentrations at 10% w/v exhibited a non-Newtonian (shear-thinning) pseudoplastic behavior along with good extrudability characteristics through the extrusion nozzle. Thus, HPMC E15 can be applied as a 3D printing polymer for a syringe extrusion 3D printer

Fabrication of Hydroxypropyl Methylcellulose Orodispersible Film Loaded Mirtazapine Using a Syringe Extrusion 3D Printer

Depression is a mental illness causing a continuous negative feeling and loss of interest and affects physical and mental health. Mirtazapine (MTZ) is an effective medicine for treating depression, but patients lack compliance. However, transforming a pharmaceutical dosage form to an orodispersible film (ODF) could resolve this issue. This study aims to fabricate ODF-loading mirtazapine, using a syringe extrusion 3D printer, and compare its properties with the solvent-casting method. The ODFs were prepared by dissolving the mirtazapine in a hydroxypropyl methylcellulose E15 solution, and then fabricated by a 3D printer or casting. The 3D printing was accurate and precise in fabricating the ODFs. The SEM micrographs showed that the mirtazapine-printed ODF (3D-MTZ) was porous, with crystals of mirtazapine on the film’s surface. The 3D-MTZ exhibited better mechanical properties than the mirtazapine-casted ODF (C-MTZ), due to the 3D-printing process. The disintegration time of the 3D-MTZ in a simulated salivary fluid, pH 6.8 at 37 °C, was 24.38 s, which is faster than the C-MTZ (46.75 s). The in vitro dissolution study, in 0.1 N HCl at 37 °C, found the 3D-MTZ quickly released the drug by more than 80% in 5 min. This study manifested that 3D-printing technology can potentially be applied for the fabrication of ODF-containing mirtazapine

Preparation and Evaluation of Metronidazole-Loaded Pectin Films for Potentially Targeting a Microbial Infection Associated with Periodontal Disease

The objective of this study was to develop the metronidazole loaded high and low methoxyl pectin films (HM-G-MZ and LM-G-MZ) for the treatment of periodontal disease. The films were prepared by pectin 3% w/v, glycerin 40% w/v, and metronidazole 5% w/v. The developed films were characterized by scanning electron microscope and evaluated for thickness, weight variation, and elasticity. The developed films showing optimal mechanical properties were selected to evaluate radial swelling properties, in vitro release of metronidazole and the antimicrobial activity against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans by the disc diffusion method. The results demonstrated that LM-MZ and HM-G-MZ films were colorless and yellowish color, respectively, with the film thickness around 0.36–0.38 mm. Furthermore, both films exhibited good elasticity with low puncture strength (1.63 ± 0.37 and 0.84 ± 0.03 N/mm2, respectively) and also showed slight increase in radial swelling, so that they could be easily inserted and fitted into the periodontal pocket during a clinical use. However, HM-G-MZ showed a decrease in radial swelling after 1 h due to the film erosion. The in vitro release study of LM-G-MZ showed a burst release that was initially followed by a slow release rate profile, capable to maintain the therapeutic level in periodontal pocket for seven days, whereas HM-G-MZ showed an immediate release profile. The cumulative percentage of metronidazole release from HM-G-MZ was less than LM-G-MZ during the first 5 min as metronidazole was in a crystalline form inside HM-G-MZ film. For antimicrobial activity test, both films showed the inhibitory effect against P. gingivalis and A. actinomycetemcomitans, and there was no difference in the inhibition zone between LM-G-MZ and HM-G-MZ. The present study showed, for the first time, that low methoxyl pectin film containing glycerin and metronidazole could be potentially considered as a promising clinical tool for the drug delivery via intra-periodontal pocket to target an oral disease that is associated with polymicrobial infection

Low cytotoxicity, antibacterial property, and curcumin delivery performance of toughness-enhanced electrospun composite membranes based on poly(lactic acid) and MAX phase (Ti3AlC2)

MXenes, synthesized from their precursor MAX phases, have been extensively researched as additives to enhance the drug delivery performance of polymer matrices, whereas there is a limited number of previous reports on the use of MAX phases themselves for such applications. The use of MAX phases can exclude the complicated synthesis procedure and lessen resultant production and environmental costs required to convert MAX phases to MXenes. Herein, electrospun membranes of poly(lactic acid) (PLA) and a MAX phase (Ti3AlC2) have been fabricated for curcumin delivery. The composite membrane exhibits significantly higher toughness (8.82 MJ m-3) than the plasticized PLA membrane (0.63 MJ m-3) with low cytotoxicity, supporting proliferation of mouse fibroblast L929 cells. The curcumin-loaded composite membrane exhibits high water vapor transmission (~7350 g m-2 day-1), porosity (~85 %), water wettability, and antibacterial properties against E. coli and S. aureus. Seven-day curcumin release is enhanced from 45 % (PLA) to 67 % (composite) due to curcumin diffusion from the polymer fibers and MAX phase surface that contributes to overall increased curcumin adsorption and release sites. This work demonstrates the potential of the MAX phase to enhance both properties and curcumin delivery, promising for other eco-friendly systems for sustainable drug delivery applications