Percorrer por autor "Chiarentin, Lucas"
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- Particle size by design : standardizing measurements for complex topical drug product assessmentPublication . Chiarentin, Lucas; Moura, Vera; Major, Fabio; Catita, José; Miranda, Margarida; Vitorino, CarlaThe physicochemical and biopharmaceutical properties of drug substances and dosage forms can be significantly influenced by particle size. However, the diversity of equivalent particle diameters generated by different methods poses a fundamental challenge in particle size analysis. This study aimed to develop an Analytical Quality by Design (AQbD) approach to accurately assess the particle size of a complex formulation – clobetasol propionate (CP) 0.5 mg/g cream – through automated microscopy (AM) and laser light diffraction (LD). Additionally, Raman spectroscopy was utilized to determine the chemical composition of the formulation particles. In the AQbD approach, prior knowledge was considered for the construction of the Ishikawa diagram and estimate failure mode and effects analysis (FMEA). The methods were developed following the ICH Q8-Q10, and ICH Q14 guidelines, and validated according to ICH Q2, ISO 13320:2020, and EP2.9.31./USP<429>. Results indicate that a trade-off between the techniques must be established for a particle size by design: while LD offers higher throughput and more precise values at the expense of peak resolution and broadening, AM has higher variability but more reliable information in terms of size and shape analysis. The validated methods successfully demonstrated the implementation of an AQbD method in the definition of particle size methods.
- Rheology of complex topical formulations : an analytical quality by design approach to method optimization and validationPublication . Chiarentin, Lucas; Cardoso, Catarina; Miranda, Margarida; Vitorina, CarlaAnalytical method validation ensures that a method provides trustworthy information about a particular sample when applied in accordance with the predefined protocol. According to regulatory standards, the rheological characteristics of topically applied semisolid formulations are one of the key elements involved in microstructure equivalence documentation. Therefore, for generic drug product manufacturers, it is a dire need to take a step forward in rheology method development and validation procedures. This paper aims to apply Analytical Quality by Design (AQbD) principles towards the development and validation of rheology methods for topical creams, as complex semisolid formulations. Risk assessment was carried out through an Ishikawa diagram and an estimate failure mode, effects, and criticality analysis (FMECA). Sample application, peltier temperature control, and sample rest time were identified as critical method variables (CMVs), and a 23 full factorial design was applied to understand their impact on rotational, creep recovery and, oscillatory measurements. The development of the method was carried out as per the ICH Q8-Q10, and Q14 guidelines and validated according to ICH Q2 (R2) guideline. The method demonstrated adequate precision (RSD < 15%), as well as selectivity. AQbD provided a comprehensive framework for developing a reliable and effective rheology method for this type of formulation.