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Objective: Develop a child-friendly Fixed Dose Combination (FDC) water-dispersible tablet for Tuberculosis (TB) treatment, with 50, 150 and 75 mg of isoniazid (INH), pyrazinamide (PZA) and rifampicin (RFP) respectively. This new formulation must contain the lowest possible number of excipients, all accepted for pediatrics, and fulfill all the pharmacopoeia requirements for this type of tablet (friability, disintegration time, fineness of dispersion and content uniformity).Significance: TB is an infectious disease which caused the death of 233,000 children in 2017. At present there is no adequate market dosage form available for children. There is, however, one in a prequalification phase by the World Health Organization but its composition contains some excipients which may not be suitable for pediatrics.Therefore, this new formulation would cover this therapeutic gap.Methods: A factorial design, based on 3 quantitative factors (compression force and concentration of AcDiSol® and Explosol®) at three levels each, was performed to elucidate their influence over disintegration time and friability. In addition, the influence of the press speed on disintegration time, friability, tensile strength, fineness of dispersion and content uniformity over the target tablet was tested. A stability test was done following ICH guideline for accelerated conditions.Results: A water-dispersible tablet was developed according to international recommendations in terms of excipients for pediatrics and meeting Ph. Eur. requirements.In addition, its production has been optimized to be elaborated at maximum eccentric press speed but maintaining quality requirements.Conclusion: A high-quality child-friendly FDC water-dispersible tablet was developed improving the treatment of TB in pediatric.

The search for an ideal bone tissue replacement has led to the development of new composite materials designed to simulate the complex inorganic/organic structure of bone. The present work is focused on the development of mineralized calcium alginate hydrogels by the addition of marine derived calcium carbonate biomineral particles. Following a novel approach, we were able to obtain calcium carbonate particles of high purity and complex micro and nanostructure dependent on the source material. Three different types of alginates were selected to develop inorganic/organic scaffolds in order to correlate alginate composition with scaffold properties and cell behavior. The incorporation of calcium carbonates into alginate networks was able to promote extracellular matrix mineralization and osteoblastic differentiation of mesenchymal stem cells when added at 7 mg/ml. We demonstrated that the selection of the alginate type and calcium carbonate origin is crucial to obtain adequate systems for bone tissue engineering as they modulate the mechanical properties and cell differentiation.

An ultra high performance liquid chromatography method was developed and validated for the quantitation of triamcinolone acetonide in an injectable ophthalmic hydrogel to determine the contribution of analytical method error in the content uniformity measurement. During the development phase, the design of experiments/design space strategy was used. For this, the free R-program was used as a commercial software alternative, a fast efficient tool for data analysis. The process capability index was used to find the permitted level of variation for each factor and to define the design space. All these aspects were analyzed and discussed under different experimental conditions by the Monte Carlo simulation method. Second, a pre-study validation procedure was performed in accordance with the International Conference on Harmonization guidelines. The validated method was applied for the determination of uniformity of dosage units and the reasons for variability (inhomogeneity and the analytical method error) were analyzed based on the overall uncertainty.