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Research Project
Applied Molecular Biosciences Unit
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Publications
Overcoming challenges in pediatric formulation with a patient-centric design approach: a proof-of-concept study on the design of an oral solution of a bitter drug
Publication . Ogbonna, John Dike N.; Cunha, Edite; Attama, Anthony A.; Ofokansi, Kenneth C.; Ferreira, Helena; Pinto, Susana; Gomes, Joana; Marx, Ítala; Peres, António M.; Lobo, José Manuel Sousa; Almeida, Isabel F.
Designing oral formulations for children is very challenging, especially considering their
peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues
of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric
solution of a model bitter drug (ranitidine) following a patient centric design process which
includes the definition of a target product profile (TPP). To conclude on the matching of the developed
solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored
at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a
syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation
relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine
and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness
in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C.
However, differences were noted between the stability protocols (unopened recipient and in‐use
stability) showing the contribution of the simulation of use to the formation of degradation products.
Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation
and a photo degradation stability assessment. The developed pediatric solution matched the
TPP in all dimensions, namely composition suitable for children, preparation and handling adapted
to hospital pharmaceutical compounding and adequate stability and quality. According to the results,
in‐use stability protocols should be preferred in the stability evaluation of pediatric formulations.
Mediterranean woody agroecosystems in a warming and drier climate: the importance of knowledge-based management
Publication . Pinheiro, Carla; David, Teresa S.; Baptista, Paula; Guerra-Guimarães, Leonor
The Mediterranean region is often described as a climate change hotspot. Not surprisingly, climate change impact
on Medieterranean Agroecosystems sustainability, biodiversity, and productivity has been receiving a lot of
interest from the research community. It is reported that the frequency, intensity and duration of droughts, as
well as hotter droughts, are interfering with ecosystems’ structure, composition, and functions. To minimize
some of the risks of the ongoing climate change, and maintain the economic viability of the agroecosystems,
management strategies and practices need to be changed/adapted at the local and regional levels. This is of
fundamental importance for the design of future human societies and their relationships with other species.
Characterization of Liquid Dosage Forms of Atenolol and Enalapril Maleate for Oral and Enteral Feeding Administration
Publication . Mota, Sandra; Torres, Ana; Quintas, Clara; Peres, António M.; Ferreiro, Nuno Manuel; Cruz, Rebeca; Ferreira, Helena; Almeida, Isabel F.; Casal, Susana
The limited availability of pharmaceutical formulations tailored for cardiovascular diseases in both pediatric and geriatric populations generates the need for compounded dosage forms to guarantee precise dosing and medication adherence. This study aimed to analyze the physicochemical properties and stability of formulations of atenolol and enalapril maleate prepared with a proprietary oral vehicle, SuspendIt®. To this end, palatability, injectability, pH, rheological behavior, and physical, microbiological, and chemical stability over a 180-day storage period at 25 ◦C and 5 ◦C were evaluated. Injectability tests confirmed the suitable use of both formulations for administration through enteral feeding tubes. By using a potentiometric electronic tongue, it was confirmed that the SuspendIt® vehicle effectively served as a bitter-blocking strategy for atenolol and enalapril maleate. Adequate stability throughout the storage period was confirmed in terms of the mechanical properties, pH, and effectiveness of the preservative system. The atenolol concentration remained above 90% of the initial amount, while the concentration of enalapril maleate decreased to 88% after 90 days of storage at 25 ◦C. In summary, the atenolol formulation maintained suitable chemical, physical, and microbiological stability after 180 days at both storage temperatures, while the enalapril maleate formulation remained stable up to 60 days at 25 ◦C and for 180 days at 5 ◦C.
In vitro interactions between the ectomycorrhizal Pisolithus tinctorius and the saprotroph Hypholoma fasciculare fungi: morphological aspects and volatile production
Publication . Baptista, Paula; Pinho, P. Guedes de; Moreira, Nathalie; Malheiro, Ricardo; Reis, Francisca; Padrão, Jorge; Tavares, Rui Manuel; Lino-Neto, Teresa
Ectomycorrhizal fungi are crucial for forests sustainability. For Castanea sativa, ectomycorrhizal fungus
Pisolithus tinctorius is an important mutualist partner. Saprotrophic fungi Hypholoma fasciculare,
although used for biocontrol of Armillaria root disease, it negatively affected the interaction between the
P. tinctorius and plant host roots, by compromise the formation of P. tinctorius-C. sativa mycorrhizae. In
this work, fungal morphology during inhibition of H. fasciculare against P. tinctorius was elucidated. P.
tinctorius growth was strongly affected by H. fasciculare, which was significantly reduced after six days
of co-culture and become even more significant through time. During this period, P. tinctorius developed
vesicles and calcium oxalate crystals, which were described as mechanisms to stress adaption by fungi.
H. fasciculare produced different volatile organic compounds in co-cultures over time and differ between
single or in dual-species. H. fasciculare highly produced sesquiterpenes (namely, α-muurolene) and
nitrogen-containing compounds, which are recognised as having antimicrobial activity.
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Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
6817 - DCRRNI ID
Funding Award Number
UIDB/04378/2020