Amiodarone chewable gels as a potential appproach for paediatric congenital cardiopathies treatment: Comparison between animal and vegetal gelling agents.

The difficulty in swallowing is a frequent problem when oral solid dosage forms (conventional tablets or capsules) are administered to paediatric population or patients with dysphagia. An interesting alternative to overcome these problems are non-conventional formulations like chewable gels, commonly known as 'gummies'. Therefore, this work addresses the design, development and characterization of gummies using gelatine and pectin, for the vehiculization of the antiarrhythmic amiodarone (AMIO). Applying a Design of Experiments (DoE) approach, four gelatine (GG1-GG4) and eight pectin formulations (PG1-PG8) were developed. Considering the obtained results for responses during DoE evaluation (i.e., volume, syneresis, hardness, and gumminess), GG3 and PG8 were selected for complete characterization. Water activity, pH, drug content, texture parameters (adhesiveness, springiness, cohesiveness, and fracturability), disintegration time, in vitro dissolution, and microbiological features were evaluated. The obtained results were within the expected values for this type of formulation. The dissolution profiles showed a 94 % - 99 % of the AMIO content released for GG3 and PG8, respectively, so they could be considered suitable as immediate release dosage forms. In conclusion, the chewable gels were successfully developed and characterised, suggesting a potential means to accomplish a final prototype for the improvement of congenital cardiopathies treatment.

Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient's Compliance.

The development of suitable dosage forms is essential for an effective pharmacological treatment in children. Orally disintegrating tablets (ODTs) are attractive dosage forms that avoid swallowing problems, ensure dosage accuracy and are easy to administer as they disintegrate in the oral cavity. This study aimed to develop ODTs containing losartan potassium (LP) for the treatment of arterial hypertension in children. The ODTs, produced by the cost-effective manufacturing process of direct compression, consisted of a mixture of diluent, superdisintegrant, glidant and lubricant. Five superdisintegrants (croscarmellose sodium, two grades of crospovidone, sodium starch glycolate and pregelatinized starch) were tested (at two concentrations), and combined with three diluents (mannitol, lactose and sorbitol). Thus, thirty formulations were evaluated based on disintegration time, hardness and friability. Two formulations, exhibiting the best results concerning disintegration time (< 30 s), hardness and friability (≤ 1.0%), were selected as the most promising ones for further evaluation. These ODTs presented favourable drug-excipient compatibility, tabletability and flow properties. The in vitro dissolution studies demonstrated 'very rapid' drug release. Preliminary stability studies highlighted the requirement of a protective packaging. All quality properties retained appropriate results after 12 months of storage in airtight containers. In conclusion, the ODTs were successfully developed and characterised, suggesting a potential means to accomplish a final prototype that enables an improvement in childhood arterial hypertension treatment.

Nanoparticle-based chewable gels of praziquantel.

Chewable gels present significant advantages over conventional dosage forms, despite their development is not comprehensively assessed. In this sense, six formulations, varying gelatine concentration, dose, and form of incorporation of praziquantel, were developed and characterized. The novelty of this approach focused not only on the development of the formulation itself but also on the incorporation of the drug in a nanoparticulated form. The obtained results for moisture content, water activity, pH, and drug content were within the expected values for this type of formulation. On the other hand, texture and disintegration parameters were influenced by the form of incorporation of praziquantel and the amount of gelatine added. Finally, in vitro dissolution of chewable gels showed significant differences with intermediate products, though the improved dissolution of the nanoparticulated drug was maintained. In conclusion, nanoparticulate drugs can be incorporated into these semisolid formulations and could be successfully applied to other low-aqueous solubility drugs.

Design and in vitro characterization of ivermectin nanocrystals liquid formulation based on a top-down approach.

The aim of this study was to develop ivermectin (IVM) nanosuspensions (NSs) to improve the dissolution rate of this poorly water-soluble drug. Different NSs combining different stabilizers, i.e. poloxamer 188 (P188), polysorbate 80 (T80), polyvinylpyrrolidone (PVP), and sodium lauryl sulfate (SLS), were prepared by high-pressure homogenization. The stabilizers were selected based on the saturation solubility and IVM stability within 72 h. The screening of formulations was performed by considering the drug content within the nanosize range. The best formulation (IVM:T80:PVP 1:0.5:0.5 wt%) was characterized in terms of the particle size distribution, morphology, crystallinity, drug content, and in vitro dissolution profile. This NS was also evaluated from a stability point of view, by conditioning samples at a constant temperature and relative humidity for six months. The fresh and conditioned best NSs Z-sizes were 174.6 and 215.7 nm, respectively; while both NSs showed low polydispersity indexes. The faster dissolution rate for the IVM NS was attributed to the presence of nanoparticles and changes to the crystal structure (i.e. amorphization) that further improved solubility. The best NS had a 4-fold faster initial dissolution rate than raw IVM, and is thus a promising formulation for the treatment of human and animal parasitic diseases.