Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism, hemangiomas, etc. Commercial liquid formulations are available in Europe and the US, but they have disadvantages, such as limited stability, bitter taste, and the need for multiple daily doses due to the drug’s short half-life. Considering these limitations, controlled-release solid formulations, such as microparticles, may offer a better solution for pediatric administration. The main objective of this study was to formulate an encapsulation system for propranolol hydrochloride, based on sodium alginate and other polysaccharide polymers, to control and prolong its release. Microparticles were prepared using the ionotropic gelation method, which involves instilling a polymer solution into a solution of gelling ions via the extrusion technique. Physicochemical characterization was conducted by assessing the entrapment efficiency, drug loading, swelling index, microparticle size, rheological properties, and surface tension. In order to improve the characteristics of the tested microparticles, selected formulations were coated with chitosan. Further experimental work included differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis, and SEM imaging. This in vitro release study showed that chitosan-coated microparticles demonstrate favorable properties, suggesting a novel approach to formulating pediatric dosage forms, although further optimization is necessary.

Dissolvable microarray patches (MAP) represent a promising drug delivery platform; however, the absence of standardised protocols for their preclinical evaluation poses a significant barrier to regulatory approval and clinical translation. Physiologically Based Pharmacokinetic (PBPK) modelling is a powerful tool for predicting drug kinetics following MAP application, addressing key challenges associated with in vitro and in vivo studies such as experimental variability, complex study design, and data extrapolating across different populations. However, adapting PBPK models for dissolvable MAP is inherently complex due to the interplay between microneedle geometry, drug release kinetics, and skin physiology. In this study, an existing dermal PBPK model in MoBi ^® was optimised for dissolvable MAP by incorporating microneedle geometry and in vitro release profiles of MAP formulations containing the antihistamines loratadine (LOR) and chlorpheniramine maleate (CPM), as well as the antifungal drug itraconazole (ITZ). Model refinement involved systematically optimising input parameters related to skin thickness and drug-skin diffusion, partitioning and binding, to enhance predictive accuracy. Validation was performed using in vitro permeation testing with porcine skin for CPM and LOR MAP, alongside in vivo preclinical studies in pigs for ITZ MAP. The optimised model demonstrated robust predictive performance across the diverse drug molecules and experimental conditions investigated, highlighting its value as a powerful tool to accelerate preclinical MAP development. Graphical abstract

Drug-loaded dissolvable microarray patches (MAP) have gained significant attention due to their patient-friendly, economical, and environmentally beneficial attributes. Despite extensive research and advancements, only a limited number of MAP have progressed to clinical trials. While existing literature predominantly covers the initial stages of MAP development (e.g., manufacturing techniques, materials, design), there remains a notable gap in examining an experimental design during preclinical evaluation phase undertaken to inform progression to clinical studies. To address this gap, we present a comprehensive review of the experimental factors influencing MAP performance in preclinical research. Our in-depth analysis of the skin environment and its implications to in vitro MAP performance revealed that skin insertion methodology, media used for release and permeation testing, skin models for permeation studies, and skin metabolism are key factors that need to be considered. We critically assess current research trends and propose potential optimisations to enhance efficacy and biorelevance of in vitro methods for MAP. Additionally, we review factors influencing in vivo and in silico performance, underscoring the promising potential of in silico approaches. This article aims to provide insights that will facilitate the development and standardisation of reliable methodologies in preclinical studies of drug-loaded MAP, ultimately advancing their clinical translation.

Dissolvable microarray patches (MAP) represent a promising platform for the skin delivery of small-molecule drugs, yet preclinical evaluation of their safety and efficacy remains limited by the lack of relevant testing methods. This study addresses this gap by developing and applying cell-based assays to assess the local safety and antihistamine efficacy of chlorpheniramine maleate (CPM) and loratadine (LOR) delivered via MAP. Human keratinocytes (HaCaT) and dermal fibroblasts (HDF) were used to evaluate skin cytocompatibility, while human mast cells (HMC-1.2) were employed to assess modulation of histamine release. Both LOR and CPM demonstrated good cytocompatibility with predominant skin cell types across a broad concentration range. LOR, but not CPM or CPM MAP formulation, inhibited spontaneous histamine release from mast cells in a concentration-dependent manner, reinforcing its potential for the treatment of localised allergic reactions.This work proposes protocols for the in vitro safety and efficacy assessment of antihistamine drugs delivered via dissolvable MAP, highlighting key limitations related to the physiological relevance of in vitro and in vivo concentrations, drug solubility and formulation constraints, the choice of cell line to represent the target tissue, and the suitability of the selected assays for the intended readouts. Collectively, these findings provide valuable insights into the translational potential of such assays and underscore the promise of MAPs as a safe and effective delivery platform for antihistamines. The study offers both conceptual and methodological perspectives that can inform the future development of MAP-based delivery systems for antihistamines and other therapeutic agents.