RESUMEN

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.

RESUMEN

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.

Asunto(s)

Solubilidad , Comprimidos , Gusto , Comprimidos/química , Humanos , Administración Oral , Análisis Multivariante , Masculino , Adulto , Femenino , Excipientes/química , Química Farmacéutica/métodos , Adulto Joven , Composición de Medicamentos/métodos

RESUMEN

In the past few decades, texture analysis (TA) has gained importance as a valuable method for the characterization of solid oral dosage forms. As a result, an increasing number of scientific publications describe the textural methods that evaluate the extremely diverse category of solid pharmaceutical products. Within the current work, the use of texture analysis in the characterization of solid oral dosage forms is summarised with a focus on the evaluation of intermediate and finished oral pharmaceutical products. Several texture methods are reviewed regarding the applications in mechanical characterization, and mucoadhesion testing, but also in estimating the disintegration time and in vivo specific features of oral dosage forms. As there are no pharmacopoeial standards for pharmaceutical products tested through texture analysis, and there are important differences between reported results due to different experimental conditions, the choice of testing protocol and parameters is challenging. Thereby, this work aims to guide the research scientists and quality assurance professionals involved in different stages of drug development into the selection of optimal texture methodologies depending on the product characteristics and quality control needs.

Asunto(s)

Administración Oral , Control de Calidad , Preparaciones Farmacéuticas , Formas de Dosificación

RESUMEN

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.