A majority of therapeutics are not available as suitable dosage forms for administration to pediatric patients. The first part of this review provides an overview of clinical and technological challenges and opportunities in the development of child-friendly dosage forms such as taste masking, tablet size, flexibility of dose administration, excipient safety and acceptability. In this context, developmental pharmacology, rapid onset of action in pediatric emergency situations, regulatory and socioeconomic aspects are also reviewed and illustrated with clinical case studies. The second part of this work discusses the example of Orally Dispersible Tablets (ODTs) as a child-friendly drug delivery strategy. Inorganic particulate drug carriers can thereby be used as multifunctional excipients offering a potential solution to address unique medical needs in infants and children while maintaining a favorable excipient safety and acceptability profile in these vulnerable patient populations.

Ayahuasca, a traditional psychoactive Amazonian brew, usually contains N,N-dimethyltryptamine (DMT) and β-carboline (harmine, harmaline, tetrahydroharmine) monoamine oxidase inhibitors. However, the pharmacological interactions between these compounds remain incompletely understood. In this study, we developed an ayahuasca-inspired formulation containing DMT and harmine, aiming to systematically evaluate their pharmacokinetic and pharmacodynamic drug-drug interactions (DDI) across a range of dosage levels. We hypothesized that escalating harmine doses would enhance DMT bioavailability, increase its plasma half-life, and reduce the variability in DMT plasma concentrations between individuals. Additionally, we expected that harmine would attenuate the plasma levels of the main DMT metabolite, indole-3-acetic acid (3-IAA), while increasing levels of the secondary metabolite DMT-N-oxide (DMT-NO). This single-blind, randomized, two-arm, factorial, dose-finding study included 16 healthy participants (9 males, 7 females), each receiving six dose combinations (0-120 mg DMT, 0-180 mg harmine) administered via a microcarrier-based transmucosal delivery system. We then evaluated the pharmacokinetics of DMT and harmine and their main metabolites, subjective effects, autonomic responses, and the safety profile of the combined preparation. All DMT-harmine combinations reliably induced dose-dependent subjective effects lasting 4-5 h, with peak DMT and harmine levels (C_max) reaching 33 ng/mL and 49 ng/mL, respectively. T_max, the time to maximum concentrations, increased with dose escalation for both compounds. The interactions between DMT and harmine were not unidirectional, i.e., harmine reduced the metabolism of DMT, while DMT altered harmine pharmacokinetics. Our novel formulation demonstrated a favorable safety profile, supporting its potential for further testing in patients with various affective disorders.

More challenging active pharmaceutical ingredients are entering the market, spurring the introduction of novel drug delivery strategies that necessitate a paradigm shift from exhausted excipients to materials with combined actions and multiple functionalities. In this study, an inorganic calcium phosphate microparticle with a hollow internal structure is introduced as a biocompatible and multifunctional microcapsule: the template inverted particle (TIP). A robust process is presented to create a unique particle geometry, which is characterized by a particle size of 20 µm and a hollow cavity enclosed by a specially engineered porous shell. This study focuses on the characterization of TIP as an excipient for the design of solid dosage forms. The cavities in the particle centers serve as an encapsulation space, resulting in boosted water uptake capacity of 5.3 cm³ g⁻¹. Benefiting from the material's high wettability and water uptake rates, TIP tablets immediately disperse in the oral cavity. Mechanistic studies reveal a viscoelastic behavior of empty TIP microcapsules in accordance with the Kelvin–Voigt model of a parallel spring‐dashpot configuration. The unique particle geometry is maintained during compaction thanks to its exceptional structural integrity. This study demonstrates how multifunctional TIP microcapsules can be applied as a pharmaceutical drug delivery device.

Background: Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization. Methods: This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes. Results: N,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2–3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation’s suitability for clinical applications. Conclusions: This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders. Clinical trial registration number: Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335

Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient‐friendly orodispersible tablet formulation designed for pediatric use (CHILD‐IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD‐IVITAB, 16 healthy adults were enrolled in a phase I, single‐center, open‐label, randomized, 2‐period, crossover, single‐dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD‐IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD‐IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD‐IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for C_max, AUC _0‐∞, and AUC_0‐last, which were 1.52 [90% CI: 1.13‐2.04], 1.27 [0.99‐1.62], and 1.29 [1.00‐1.66], respectively. Maximum drug concentrations occurred earlier with the CHILD‐IVITAB formulation, with a median T_max at 3.0 h [range 2.0‐4.0 h] versus 4.0 h [range 2.0‐5.0 h] with STROMECTOL (P = .004). With CHILD‐IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD‐IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient‐friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg.

Inorganic hydroxyapatite microcapsules are innovative drug delivery devices tailored for oral drug delivery. They were designed as novel excipients, the so-called template inverted particles (TIP), to assist in preparing the orally disintegrating tablets. This study characterized the drug loading capacity using 11 clinically relevant drugs covering all BCS classes, focusing on midazolam HCl, ivermectin, ibuprofen, and metronidazole benzoate. An exceptionally high drug loading capacity of 45 % (v/v) was observed for all studied drugs. Compaction of loaded TIP resulted in mechanically stable tablets with tensile strengths of up to 6 MPa and disintegrating in a few seconds upon contact with water. Accelerated dissolution of encapsulated drugs is explained by the microcapsules' high specific surface area and the inhibited crystallization due to spacial constraints for some tested drugs. Efficient drug loading into TIP's internal hollow cavity structure is facilitated by a self-loading mechanism, eliminating the need for complex, drug-specific loading strategies. A mathematical model is presented to describe the self-loading mechanism of TIP, which is responsible for exclusive drug deposition within the cavity of the particles. We demonstrate that TIP, being a versatile and cost-effective platform technology, has the potential to facilitate the formulation development process of patient-friendly medicines.