Customizable Three-Dimensional Printed Earring Tap for Treating Affections Caused by Aesthetic Perforations.

This work aimed to develop a three-dimensional (3D) wearable drug-loaded earring tap to treat affections caused by aesthetic perforations. The initial phase involved a combination of polymers to prepare filaments for fused deposition modeling (FDM) 3D printing using a centroid mixture design. Optimized filament compositions were used in the second phase to produce 3D printed earring taps containing the anti-inflammatory naringenin. Next, samples were assessed via physicochemical assays followed by in vitro skin permeation studies with porcine ear skin. Two filament compositions were selected for the study's second phase: one to accelerate drug release and another with slow drug dissolution. Both filaments demonstrated chemical compatibility and amorphous behavior. The use of the polymer blend to enhance printability has been confirmed by rheological analysis. The 3D devices facilitated naringenin skin penetration, improving drug recovery from the skin's most superficial layer (3D device A) or inner layers (3D device B). Furthermore, the devices significantly decreased transdermal drug delivery compared to the control containing the free drug. Thus, the resulting systems are promising for producing 3D printed earring taps with topical drug delivery and reinforcing the feasibility of patient-centered drug administration through wearable devices.

Medicated lacquer for application on adornments to treat affections in aesthetic perforations.

Aesthetic perforations are often associated with health issues, such as itching, inflammation, or microbial infection. Accordingly, this work proposed a lacquer to be applied on the adornment accessory forming a film from which a proper drug is released. For this, lacquers were formulated containing three different permeation enhancers (limonene - LIM, propylene glycol - PG, and oleic acid - AO) combined according to a mixture design with a model anti-inflammatory natural drug (naringenin) and a soluble film-former polymer (polyvinyl alcohol). Formulations were characterized by physicochemical tests and in vitro and in vivo skin permeation studies. The lacquers were stable and provided a vectorized drug release. LIM, combined with one of the other permeation enhancers, showed a synergic effect, enhancing topical skin penetration in vitro by 53% while preventing permeation to the receptor medium. The in vivo evaluation of lacquers in rodent models showed these systems could provide higher levels of drug retention in the ear (166.4 ± 14.9 µg per ear for F4 and 174.9 ± 29.3 µg per ear for F5) compared to the control (109.2 ± 16.3 µg) without allowing its permeation into the bloodstream, confirming the local drug delivery. Moreover, the anti-inflammatory activity was achieved in the animal model developed for lacquer application on the earring, obtaining inhibition of ear swelling up to 40.8% ± 2.3 compared to the untreated ear. Thus, such an innovative lacquer proved a promising vehicle for treating affections caused by adornments, enhancing skin permeation while avoiding a systemic effect.

Three-dimensional printed personalized drug devices with anatomical fit: a review.

OBJECTIVES: Three-dimensional printing (3DP) has opened the era of drug personalization, promising to revolutionize the pharmaceutical field with improvements in efficacy, safety and compliance of the treatments. As a result of these investigations, a vast therapeutic field has opened for 3DP-loaded drug devices with an anatomical fit. Along these lines, innovative dosage forms, unimaginable until recently, can be obtained. This review explores 3DP-engineered drug devices described in recent research articles, as well as in patented inventions, and even devices already produced by 3DP with drug-loading potential. KEY FINDINGS: 3D drug-loaded stents, implants and prostheses are reviewed, along with devices produced to fit hard-to-attach body parts such as nasal masks, vaginal rings or mouthguards. The most promising 3DP techniques for such devices and the complementary technologies surrounding these inventions are also discussed, particularly the scanners useful for mapping body parts. Health regulatory concerns regarding the new use of such technology are also analysed. SUMMARY: The scenario discussed in this review shows that for wearable 3DP drug devices to become a tangible reality to users, it will be necessary to overcome the existing regulatory barriers, create new interfaces with electronic systems and improve the mapping mechanisms of body surfaces.

Preformulation Studies to Guide the Production of Medicines by Fused Deposition Modeling 3D Printing.

Fused deposition modeling (FDM) 3D printing has demonstrated high potential for the production of personalized medicines. However, the heating at high temperatures inherent to this process causes unknown risks to the drug product's stability. The present study aimed to assess the use of a tailored preformulation protocol involving physicochemical assessments, including the rheological profiles of the samples, to guide the development of medicines by FDM 3D printing. For this, polymers commonly used in FDM printing, i.e., high impact polystyrene (HIPS), polylactic acid (PLA), and polyvinyl alcohol (PVA), and their common plasticizers (mineral oil, triethyl citrate, and glycerol, respectively) were evaluated using the thermolabile model drug isoniazid (INH). Samples were analyzed by chemical and physical assays. The results showed that although the drug could produce polymorphs under thermal processing, the polymeric matrix can be a protective element, and no polymorphic transformation was observed. However, incompatibilities between materials might impact their chemical, thermal, and rheological performances. In fact, ternary mixtures of INH, PLA, and TEC showed a major alteration in their viscoelastic behavior besides the chemical changes. On the other hand, the use of plasticizers for HIPS and PVA exhibited positive consequences in drug solubility and rheologic behavior, probably improving sample printability. Thus, the optimization of the FDM 3D printing based on preformulation studies can assist the choice of compatible components and seek suitable processing conditions to obtain pharmaceutical products.

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products.

Here, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability of the effervescent salts. Formulations showed vigorous and rapid effervescent disintegration (<3 min), adequate flow characteristics, and complete solubilization of paracetamol instantly after the effervescent reaction. Formulations containing PVPVA in the concentration range of 15-20% m/m were demonstrated to be sensitive to accelerated aging conditions, undergoing marked microstructural changes, since the capture of water led to the agglomeration and loss of their functional characteristics. HPMC matrices, in contrast, proved to be resistant to storage conditions in high relative humidity, showing superior performance to controls, including the commercial product. Moreover, the combined mixture design allowed us to identify significant interactions between the polymeric materials and the disintegrating agents, showing the formulation regions in which the responses are kept within the required levels. In conclusion, this study demonstrates that HME can bring important benefits to the elaboration of effervescent drug products, simplifying the production process and obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability.

Predictive models of FDM 3D printing using experimental design based on pharmaceutical requirements for tablet production.

The present study aimed to analyze how the printing process affects the final state of a printed pharmaceutical product and to establish prediction models for post-printing characteristics according to basic printing settings. To do this, a database was constructed through analysis of products elaborated with a distinct printing framework. The polymers acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), and high-impact polystyrene (HIPS) were tested in a statistically-based experiment to define the most critical printing factors for mass, mass variation, printing time, and porosity. Then, a predictive model equation was established and challenged to determine two different medical prescriptions. The factors of size scale, printlet format, and print temperature influenced printlet mass, while the printing time was impacted by size scale, printing speed, and layer height. Finally, increased printing speed leads to more porous printlets. The prescript-printed tablets showed average mass, mass variations, and porosity close to theoretical values for all filaments, which supports the adequacy of the optimized design of experiments for tablet production. Hence, printing settings can be preselected according to the desired product's characteristics, resulting in tablets produced with higher precision than usually achieved by compounding pharmacies.

Hydroxypropyl-ß-cyclodextrin-complexed naringenin by solvent change precipitation for improving anti-inflammatory effect in vivo.

The flavonoid naringenin (NAR) exhibits an outstanding anti-inflammatory potential; however, stability problems and reduced solubility hinder its commercial insertion. This work aimed to obtain solid-state hydroxypropyl-ß-cyclodextrin (CD) inclusion complexes with NAR using, for the first time, the solvent change precipitation method. For this, molecular modeling and physicochemical characterizations were conducted, followed by in vitro and in vivo assays. The complexation method showed thermal and spectroscopic evidence of NAR inclusion complexes formation, suggesting an improvement of its stability. Additionally, 30 min-dissolution efficiency of the complex was 57.2 %, whereas NAR, as supplied, showed only 14.3 %, a four-fold enhancement. In vitro and in vivo performance attested the potent anti-inflammatory and antinociceptive profile of NAR with significant suppression of TNF-α production. Moreover, NAR complexation with CD improved its therapeutic effect, which showed similar activity to that achieved with NAR as supplied but employing only 1/5 of its dose.

Preformulation studies of finasteride to design matrix systems for topical delivery.

A preformulation study with finasteride (FIN) was conducted to enable the development of a topical matrix system to treat androgenic alopecia. The compatibility of the drug with hidroxypropyl-ß-cyclodextrin (HPßCD) and the hydrophilic polymers Klucel EXF (KLU) and Soluplus (SOL) were evaluated according to a simplex centroid mixture design. An extensive analytical arsenal was used to encompass the stability of the drug in the different mixtures. The selected excipients showed to have intense thermal interaction with FIN, which was dependent on the composition of the sample, shifting FIN melting peak to reduced temperatures along with the decrease of its associated enthalpy. The mixture design allowed measuring the interactions between components, showing that KLU enhanced the ability of the drug to form inclusion complexes with HPßCD, while SOL exhibited the opposite effect. The stability of samples was preserved even after a thermal treatment used to simulate pharmaceutical processing. Indeed, no drug content decaying was observed, which corroborates the chemical stability of the systems as indicated by thermogravimetry, chromatographic, morphological and spectroscopic assays. The original crystalline phase of the drug (orthorhombic form I) did not change after the heating treatment of the samples, demonstrating its physical stability. Thus, these series of experiments may guide the development of delivery systems for topical use of FIN, showing which combinations and proportions of components can lead to better results in terms of stability and drug delivery.

Dissolution Enhancement in Cocoa Extract, Combining Hydrophilic Polymers through Hot-Melt Extrusion.

The aim of this study was to improve the physicochemical properties of cocoa extract (CE) using hot-melt extrusion (HME) for pharmaceutical proposes. A mixture design was applied using three distinct hydrophilic polymeric matrices (Soluplus, Plasdone S630, and Eudragit E). Systems obtained by HME were evaluated using morphologic, chromatographic, thermic, spectroscopic, and diffractometric assays. The flow, wettability, and dissolution rate of HME powders were also assessed. Both CE and its marker theobromine proved to be stable under heating according to thermal analysis and Arrhenius plot under isothermal conditions. Physicochemical analysis confirmed the stability of CE HME preparations and provided evidence of drug⁻polymer interactions. Improvements in the functional characteristics of CE were observed after the extrusion process, particularly in dissolution and flow properties. In addition, the use of a mixture design allowed the identification of synergic effects by excipient combination. The optimized combination of polymers obtained considering four different aspects showed that a mixture of the Soluplus, Plasdone S630, and Eudragit E in equal proportions produced the best results (flowability index 88%; contact angle 47°; dispersibility 7.5%; and dissolution efficiency 87%), therefore making the pharmaceutical use of CE more feasible.

Synthesis of fluorescent heterocycles via a Knoevenagel/[4 + 1]-cycloaddition cascade using acetyl cyanide.

A concise one-pot three-component reaction that affords fluorescent indolizines, benzo[d]pyrrolo[2,1-b]thiazoles, and pyrrolo[1,2-a]pyrazines is reported. The methodology involves the formation of a heterocyclic 1-aza-1,3-diene derived from a Knoevenagel condensation between an aldehyde and 2-methyl-ene-cyano aza-heterocycles, followed by [4 + 1] cycloaddition of acetyl cyanide behaving as a non-classical isocyanide replacement.

Simultaneous determination of benznidazole and itraconazole using spectrophotometry applied to the analysis of mixture: A tool for quality control in the development of formulations.

The aim of this work was the development of an analytical procedure using spectrophotometry for simultaneous determination of benznidazole (BNZ) and itraconazole (ITZ) in a medicine used for the treatment of Chagas disease. In order to achieve this goal, the analysis of mixtures was performed applying the Lambert-Beer law through the absorbances of BNZ and ITZ in the wavelengths 259 and 321 nm, respectively. Diverse tests were carried out for development and validation of the method, which proved to be selective, robust, linear, and precise. The lower limits of detection and quantification demonstrate its sensitivity to quantify small amounts of analytes, enabling its application for various analytical purposes, such as dissolution test and routine assays. In short, the quantification of BNZ and ITZ by analysis of mixtures had shown to be efficient and cost-effective alternative for determination of these drugs in a pharmaceutical dosage form.