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Cannabidiol and hydroxypropyl-β-cyclodextrin inhalable powder : a breakthrough in spray drying technology
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Ao longo dos anos, a investigação sobre a administração pulmonar de fármacos avançou significativamente. Foram desenvolvidas estratégias inovadoras para enfrentar os desafios inerentes a esta via de administração, com o objetivo de aumentar a fração respirável de fármaco, normalizar os atributos dos produtos inaláveis e obter consistência na administração da dose.
Recentemente, surgiram diversos dispositivos para administração pulmonar, com destaque para os inaladores de pó seco devido à sua elevada estabilidade, ausência de contaminantes do ar e uso simplificado, ativado pela inspiração do utilizador.
A relação desta tecnologia com as abordagens terapêuticas que utilizam o canabidiol (CBD) revela uma via promissora para o tratamento de um vasto espetro de doenças localizadas e sistémicas. Embora as indicações terapêuticas definitivas para o CBD ainda não tenham sido definidas, um grande número de evidências sugere a sua eficácia em múltiplas vias fisiológicas, comprovando o seu potencial para diversas aplicações terapêuticas.
Neste estudo, foram desenvolvidos pós para inalação com CBD utilizando a tecnologia de spray drying. Os promotores de solubilidade, nomeadamente a hidroxipropil-β-ciclodextrina e o etanol, foram integrados nas formulações por forma a aumentar a quantidade de CBD nos pós atomizados.
As partículas atomizadas foram submetidas a uma série de análises. As imagens SEM revelaram formas colapsadas em todas as formulações, com um número e profundidade consistentes de depressões. A análise do tamanho das partículas demonstrou baixa polidispersibilidade (aproximadamente 3,3) e tamanhos dentro do intervalo adequado para a deposição pulmonar profunda, variando de 2,01 a 2,14 μm.
A concentração mais elevada de CBD (9,5 mg/g) foi observada no pó de HP-β-CD/CBD com 20% de conteúdo sólido. De facto, um teor de sólidos mais elevado nas soluções de alimentação está correlacionado com uma maior quantidade de CBD no pó resultante. Em oposição, o etanol provou estar associado a uma concentração reduzida de CBD nos pós produzidos, apresentando um impacto negativo na formulação.
Em suma, os pós para inalação produzidos induziram elevadas frações de partículas finas (> 56,98%), provavelmente atribuíveis à sua superfície colapsada. Além disso, a tecnologia de secagem por aspersão facilitou a modulação precisa da morfologia dos pós de CBD sem comprometer a sua estabilidade.
Over the years, our understanding and investigation into pulmonary drug delivery have advanced significantly. Innovative strategies have been developed to address inherent challenges associated with this delivery route, aiming to enhance drug respirable fraction, standardizing the attributes of inhalable products and achieve consistency in dose delivery. Recently, various devices for lung administration have emerged, showcasing significant promise. Notably, the dry powder inhaler stands out as the most promising option, primarily due to its considerable advantages, including high formulation stability, absence of air contaminants, and simplified usage procedure, as being triggered by the user's inspiration. Relating this technology to therapeutic approaches employing cannabidiol (CBD) reveals a promising avenue for treating a wide spectrum of both localized and systemic diseases. While definitive therapeutic indications for CBD are yet to be precisely defined, a wealth of evidence suggests its efficacy in multiple physiological pathways, underscoring its potential for diverse therapeutic applications. In this study, cannabidiol-engineered inhalation powders were developed using spray drying technology. Solubility enhancers, namely HP-β-CD and ethanol were integrated in the formulations to address higher CBD quantity in atomized powders. Atomized particles were submitted to a range of analysis. SEM images revealed deflated shapes in all formulations, with a consistent number and depth of dimples. Particle size analysis demonstrated low polydispersity (approximately 3.3) and sizes within the suitable range for deep lung deposition, ranging from 2.01 to 2.14 μm. The highest concentration of CBD (9.5 mg/g) was observed in HP-β-CD/CBD powder with 20% solid content. Indeed, higher solid content in the feeding solutions correlated with a greater quantity of CBD in the resulting powder. Conversely, ethanol linked to a reduced concentration of CBD in the powders, displaying a detrimental impact on the formulation. Overall, the engineered inhalation powders induced high fine particle fractions (> 56.98%), likely attributable to their deflated surface. Moreover, spray drying technology facilitated precise modulation of the morphology of CBD powders without compromising formulation stability.
Over the years, our understanding and investigation into pulmonary drug delivery have advanced significantly. Innovative strategies have been developed to address inherent challenges associated with this delivery route, aiming to enhance drug respirable fraction, standardizing the attributes of inhalable products and achieve consistency in dose delivery. Recently, various devices for lung administration have emerged, showcasing significant promise. Notably, the dry powder inhaler stands out as the most promising option, primarily due to its considerable advantages, including high formulation stability, absence of air contaminants, and simplified usage procedure, as being triggered by the user's inspiration. Relating this technology to therapeutic approaches employing cannabidiol (CBD) reveals a promising avenue for treating a wide spectrum of both localized and systemic diseases. While definitive therapeutic indications for CBD are yet to be precisely defined, a wealth of evidence suggests its efficacy in multiple physiological pathways, underscoring its potential for diverse therapeutic applications. In this study, cannabidiol-engineered inhalation powders were developed using spray drying technology. Solubility enhancers, namely HP-β-CD and ethanol were integrated in the formulations to address higher CBD quantity in atomized powders. Atomized particles were submitted to a range of analysis. SEM images revealed deflated shapes in all formulations, with a consistent number and depth of dimples. Particle size analysis demonstrated low polydispersity (approximately 3.3) and sizes within the suitable range for deep lung deposition, ranging from 2.01 to 2.14 μm. The highest concentration of CBD (9.5 mg/g) was observed in HP-β-CD/CBD powder with 20% solid content. Indeed, higher solid content in the feeding solutions correlated with a greater quantity of CBD in the resulting powder. Conversely, ethanol linked to a reduced concentration of CBD in the powders, displaying a detrimental impact on the formulation. Overall, the engineered inhalation powders induced high fine particle fractions (> 56.98%), likely attributable to their deflated surface. Moreover, spray drying technology facilitated precise modulation of the morphology of CBD powders without compromising formulation stability.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Cannabidiol Spray drying Inhalation Dry powder inhaler Hydroxypropyl-betacyclodextrin Mestrado Integrado - 2023