The paediatric population has always suffered from a lack of medicines tailored to their needs, especially in terms of accurate dosage, stability and acceptability. Orodispersible dosage forms have gone through a resurrection as an alternative to liquid formulations or fractioned solid formulations, although they are still subject to several inconveniences, among which the unpleasant taste and the low oral bioavailability of the API are the most significant hurdles in the way of achieving an optimal drug product. Nanostructures can address these inconveniences through their size and variety, owing to the plethora of materials that can be used in their manufacturing. Through the formation and functionalisation of nanostructures, followed by their inclusion in orodispersible dosage forms, safe, stable and acceptable medicines intended for paediatric use can be developed.

Orodispersible tablets (ODTs) represent a growing category of dosage forms intended to increase the treatment acceptability for special groups of patients. ODTs are designed to rapidly disintegrate in the oral cavity and to be administered without water. In addition, ODTs are easy to manufacture using standard excipients and pharmaceutical equipment. This study adds to previously published research that developed an instrumental tool to predict oral disintegration and texture-related palatability of ODTs with different formulations. The current study aimed to challenge the predictive capacity of the models under variable process conditions. The studied process parameters with potential impact on the pharmaceutical properties, texture profiles, and palatability were the compression pressure, punch shape and diameter. Subsequently, for all the placebo and drug-loaded ODTs, the in vivo disintegration time and texture-related palatability were determined with healthy volunteers. Previously developed regression models were applied to predict the formulation's disintegration time and texture-related palatability characteristics of ODTs obtained under different experimental conditions. The influence of process variables on the predictive performance of the models was estimated by calculating the residuals as the difference between the predicted and observed values for the investigated response. Increasing the speed of the analyser`s probe from 0.01 mm/s to 0.02 mm/s led to an improved differentiation of the texture profiles. The in vivo disintegration time and texture-related palatability scores were only influenced by the mechanical resistance and the tablet shape. Lower score was observed for the larger diameter tablets (10 mm). Overall, the prediction of the disintegration time at 0.02 mm/s was more accurate, except for stronger tablets. The best prediction of texture-related palatability was achieved for the 10 mm tablets, tested at 0.01 mm/s speed. The same model achieved good predictions of the oral disintegration time for all API-loaded formulations, which confirmed the ability of the texture analysis to capture process-related variability. Drug loading decreased the predictive capacity of the texture-related palatability because of the taste effect.

In recent years, solid dosage forms have gained interest in pediatric therapy because they can provide valuable benefits in terms of dose accuracy and stability. Particularly for orodispersible films (ODFs), the literature evidences increased acceptability and dose flexibility. Among the various available technologies for obtaining ODFs, such as solvent casting, hot-melt extrusion, and ink printing technologies, the solvent-free preparation methods exhibit significant advantages. This study investigated Vacuum Compression Molding (VCM) as a solvent-free manufacturing method for the preparation of flexible-dose pediatric orodispersible films. The experimental approach focused on selecting the appropriate plasticizer and ratios of the active pharmaceutical ingredient, diclofenac sodium, followed by the study of their impacts on the mechanical properties, disintegration time, and drug release profile of the ODFs. Additional investigations were performed to obtain insights regarding the solid-state properties. The ODFs obtained by VCM displayed adequate quality in terms of their critical characteristics. Therefore, this proof-of-concept study shows how VCM could be utilized as a standalone method for the production of small-scale ODFs, enabling the customization of doses to meet the individual needs of pediatric patients.

Patient-friendly solid oral dosage forms remain a rather understudied part of pharmaceutical development, particularly in paediatric patients. Thus, patients and caregivers around the world must resort to traditional approaches, such as liquid dosage forms or division of solid dosage forms, which can lead to inaccurate dosing and drug inactivation. To avoid these issues, as well as the swallowing problems and choking risk of conventional solid oral dosage forms, there is a need for modern, safe and effective oral dosage forms. Orodispersible tablets enhance the ease of administration for patients with deglutition difficulties, but their use is typically confined to immediate-release delivery systems. In this study, we addressed these shortcomings by developing orodispersible tablets as delivery platform for oral administration of loratadine-loaded zein-based nanostructures to paediatric patients. First, the nanostructures were freeze-dried with mannitol and maltodextrin as cryoprotectants. The resulting powders were compressed as such or mixed with different ratios of co-processed excipients for orodispersible tablets, in order to understand their compression behaviour. To ensure dose uniformity and powder homogeneity, a near infrared spectroscopic method was developed for non-destructive assessment of the API content. With the aid of the co-processed excipients and supplementary lubrication to reduce the tablet ejection stress, tablets with adequate mechanical properties and a disintegration time within the required range of 180 s were obtained from the nanostructures lyophilised with mannitol. Through this methodology, we have transformed loratadine-based nanosystems into an innovative and patient-friendly oral delivery system that meets the specific quality requirements of orodispersible pharmaceutical forms.