Artificial intelligence has revolutionized many sectors with unparalleled predictive capabilities supported by machine learning (ML). So far, this tool has not been able to provide the same level of development in pharmaceutical nanotechnology. This review discusses the current data science methodologies related to polymeric drug-loaded nanoparticle production from an innovative multidisciplinary perspective while considering the strictest data science practices. Several methodological and data interpretation flaws were identified by analyzing the few qualified ML studies. Most issues lie in following appropriate analysis steps, such as cross-validation, balancing data, or testing alternative models. Thus, better-planned studies following the recommended data science analysis steps along with adequate numbers of experiments would change the current landscape, allowing the exploration of the full potential of ML.

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.

Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient’s adherence to the treatment, this study prepares polymeric and lipidic nanoparticles (PNPs and NLCs) to co-entrap minoxidil and betamethasone and compares the follicular drug delivery provided by topical application of these nanoparticles. The prepared PNPs loaded 99.1 ± 13.0% minoxidil and 70.2 ± 12.8% betamethasone, while the NLCs entrapped 99.4 ± 0.1 minoxidil and 80.7 ± 0.1% betamethasone. PNPs and NLCs presented diameters in the same range, varying from 414 ± 10 nm to 567 ± 30 nm. The thermal analysis revealed that the production conditions favor the solubilization of the drugs in the nanoparticles, preserving their stability. In in vitro permeation studies with porcine skin, PNPs provided a 2.6-fold increase in minoxidil penetration into the follicular casts compared to the control and no remarkable difference in terms of betamethasone; in contrast, NLCs provided a significant (specifically, a tenfold) increase in minoxidil penetration into the hair follicles compared to the control, and they delivered higher concentrations of betamethasone in hair follicles than both PNPs and the control. Neither PNPs nor NLCs promoted transdermal permeation of the drugs to the receptor solution, which should favor a topical therapy. Furthermore, both nanoparticles targeted approximately 50% of minoxidil delivery to the follicular casts and NLCs targeted 74% of betamethasone delivery to the hair follicles. In conclusion, PNPs and NLCs are promising drug delivery systems for enhancing follicular targeting of drugs, but NLCs showed superior performance for lipophilic drugs.

Although the administration of drugs on the skin is a safe and noninvasive therapeutic alternative, producing formulations capable of disrupting the cutaneous barriers is still a challenge. In this scenario, extrusion-based techniques have emerged as disruptive technologies to ensure unique drug-excipient interactions that facilitate drug skin diffusion for systemic or local effect and even mean the key to obtain viable industrial products. This article presents a comprehensive overview of extrusion-based techniques in developing pharmaceutical dosage forms for topical or transdermal drug delivery. First, the theoretical basis of how extrusion-based techniques can optimize the permeation of drugs through the skin is examined. Then, the current state-of-the-art of drug products developed by extrusion-based techniques, specifically by hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing, are discussed and contrasted with the current pharmaceutical processes. A wide variety of pharmaceutical products can be obtained using HME and FDM 3D printing, including new dosage forms designed for a perfect anatomical fit. Despite the limitations of pharmaceutical products produced with HME and FDM 3D printing regarding thermal stability and available excipients, the advantages in industrial adaptability and improved bioavailability allied with patient-match devices certainly deserve full attention and investment.

Iontophoresis has been extensively studied for topical and transdermal drug delivery to stimulate the absorption of molecules that would hardly pass through the outermost layer of the skin passively. Recent research has focused on its combination with nanoparticle-based systems or microneedles to expand its therapeutic applications. This review explores the fundamental principles of iontophoresis, focusing on key factors influencing its drug transport mechanisms, and provides a discussion of the field's current state. A comprehensive analysis of articles published or available online in 2024 was conducted, categorizing studies by their application areas, drug delivery systems, iontophoretic conditions, and experimental limitations. The findings reveal a recent focus on wound healing and skin repair, and advancements in treating inflammation, pain, and skin cancer. Market translation requires standardized experimental protocols, particularly for iontophoretic parameters and preclinical models, along with the development of cost-effective commercial devices. Additionally, while advancements in cutaneous drug delivery have increasingly benefited from machine learning approaches, their application to iontophoresis remains underexplored. With the growing interest in associating iontophoresis with the Internet of Things, such an integration, if combined with AI tools, could offer promising opportunities for personalized, real-time treatments in modern dermatology, and therapeutic systems.

Background/Objectives: Chagas disease is a neglected tropical disease caused by infection with the parasite Trypanosoma cruzi. Benznidazole and nifurtimox are the only approved drugs for treating this condition, but their low aqueous solubility may lead to erratic bioavailability. This work aimed for the first time to formulate tablets of nifurtimox by hot melt extrusion coupled with 3D printing as a strategy to increase drug dissolution and the production of tablets with dosage on demand. Methods: Different pharmaceutical-grade polymers were evaluated through film casting, and those with promising nifurtimox amorphization capacity were further used to prepare filaments by hot melt extrusion. The printability of the obtained filaments was tested, and the polyvinyl alcohol filament was further used for printing tablets containing 120 and 60 mg of nifurtimox. Results: Three-dimensional tablets showed a remarkable improvement in the drug dissolution rate compared to commercial tablets and a dissolution efficiency 2.8 times higher. In vivo studies were carried out on Swiss mice. Parasitemia curves of nifurtimox printed tablets were significantly superior to the pure drug. Moreover, NFX 3D tablets provided a similar Trypanosoma cruzi reduction in plasmatic concentration to benznidazole, the gold-standard drug for acute-phase treatment of the Chagas disease. Conclusions: The findings of this work showed that hot melt extrusion coupled with 3D printing is a promising alternative for increasing nifurtimox biopharmaceutical properties and an attractive approach for personalized medicine.