Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz

AbstractEfavirenz (EFZ) is one of the most used drugs in the treatment of AIDS and is the first antiretroviral choice. However, since it has low solubility, it does not exhibit suitable bioavailability, which interferes with its therapeutic action and is classified as a class II drug according Biopharmaceutical Classification System (low solubility and high permeability). Among several drug delivery systems, the multicomponent systems with cyclodextrins and hydrophilic polymers are a promising alternative for increasing the aqueous solubility of the drug. The present study aimed to develop and characterize in a ternary system of EFZ, MβCD and PVP K30. The results showed that the solid ternary system provided a large increase in the dissolution rate which was greater than 80% and was characterized by DSC, TG, XRD, FT-IR and SEM. The use of the ternary system (EFZ, MβCD and PVP K30 1%) proved to be a viable, effective and safe delivery of the drug. The addition of the hydrophilic polymer appeared to be suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and with low concentration of CDs (cyclodextrins)

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications

Desenvolvimento farmacotécnico industrial da forma farmacêutica comprimido associação em dose fixa para tratamento da AIDS

O presente trabalho apresenta o desenvolvimento tecnológico de um novo produto comprimido contendo a associação em dose fixa dos antirretrovirais zidovudina (AZT, 300 mg), lamivudina (3TC, 150 mg) e efavirenz (EFV, 300 mg), de primeira escolha no tratamento antirretroviral. O produto visa agregar novas vantagens à terapia atual, devido ao menor número de comprimidos e redução dos custos produtivos, ao modificar a posologia do EFV e ao associar este ao produto combinado contendo AZT e 3TC. Foi realizado estudo de compatibilidade fárma-fármaco, tendo por finalidade compreender as possíveis interações no estado sólido entre os insumos farmacêuticos ativos (IFA); avaliando a possibilidade de se processá-los em um único produto, sem mecanismos de segregação dos pós. O estudo possibilitou observar que a associação destes não apresenta impedimentos físicos, desde que estes não sejam fundidos durante o processo. Observou-se também uma influência positiva no incremento do percentual dissolvido do EFV [devido a sua baixa solubilidade aquosa (± 9 μg/mL)], quando associado aos outros dois IFA. O desenvolvimento tecnológico do comprimido apresentou três principais entraves tecnológicos solucionados, dentre estes a dissolução do EFV, a compatibilidade da formulação e a obtenção de um comprimido com dimensões adequadas, devido ao grande aporte de fármaco. Foi realizado estudo de compatibilidade fármacos-excipiente, selecionando assim, os melhores excipientes para a formulação. O comprimido foi obtido com peso de 900 mg, sendo 750 mg de IFA e 150 mg de excipientes (celulose microcristalina, croscarmelose sódica, polivinilpirrolinona, estearato de magnésio, dióxido de silício coloidal e lauril sulfato de sódio). Todos os IFA apresentaram características inadequadas de fluxo, evidenciando a necessidade de um processo produtivo de compressão por granulação via úmida para a sua produção. Por meio do teste de dissolução desenvolvido e validado obteve-se, em 30 minutos, os valores médios de 91,5% para o 3TC, 95,0% para o AZT e 90,2% para o EFV. As condições estabelecidas para o teste de dissolução foram aparato pá com rotação a 100 rpm e 1000 mL do meio de lauril sulfato de sódio a 1% (pH 6,8) a 37°C ± 0,5°C. O doseamento do comprimido foi realizado por método analítico desenvolvido e validado utilizando coluna cromatográfica C18, fase móvel gradiente de acetonitrila e água purificada, λ 248 nm e tempo de corrida de 14 minutos. Concluí-se que a abordagem integrada da tecnologia farmacêutica proporcinou a obtenção de um novo produto farmacêutico dentro das exigências regulatórias e requisitos técnicos selecionado

Ferramentas analíticas aplicadas à caracterização de complexos de inclusão fármaco-ciclodextrina

As ciclodextrinas (CDs) têm sido bastante utilizadas no desenvolvimento de produtos farmacêuticos, particularmente devido às suas propriedades complexantes, a qual promove incremento na solubilidade de fármacos poucos solúveis. O ambiente lipofílico da cavidade interna das CDs propicia condições favoráveis para a formação de complexos de inclusão (CI) com compostos hidrófobos. Variações nas propriedades físico-químicas das moléculas hóspedes podem ser identificadas através de metodologias analíticas, que permitem detectar a formação dos complexos. O objetivo deste trabalho foi discutir os principais métodos utilizados na caracterização de CI com base numa revisão da literatura. Entre as diversas técnicas para caracterizar CI com CDs, nos estados líquido e sólido, tem-se a espectroscopia de absorção visível e ultravioleta, técnica de fluorescência, espectroscopia de Ressonância Magnética Nuclear, cromatografia líquida de alta eficiência, cristalográficas de Raio-X, estudos térmicos, espectroscopia de infravermelho com transformada de Fourier, microscopia eletrônica de varredura, espectroscopia de Raman, calorimetria de titulação isotérmica, ensaios de dissolução, dentre outros. Palavras-chave: espectroscopia, complexo de inclusão, ciclodextrinas, métodos analíticos ABSTRACT Cyclodextrins (CDs) are widely used in pharmaceutical product development, on account of their complex-forming properties, mainly to increase the solubility of poorly soluble molecules. The lipophilic environment in the cavity of CDs provides favorable conditions for the formation of inclusion complexes (ICs) with hydrophobic compounds. Variations in the physicochemical properties of the guest molecules are identified by analytical methods that allow the formation of the complexes to be detected. This article is a discussion of the main methods used in the characterization of ICs, based on a review of the literature. There are many techniques available to characterize the CD-containing ICs, in the liquid and solid states, such as visible and ultraviolet absorption, fluorescence and nuclear magnetic resonance spectroscopy, high performance liquid chromatography, X-ray crystallography, thermal analysis, Fourier-transform infrared spectroscopy, scanning electron microscopy, Raman spectroscopy, isothermal titration calorimetry and dissolution tests. Keywords: spectroscopy, inclusion complex, cyclodextrins, analytical method