Publicação
Evaluation of the parameters of a bead milling process to produce a non-aqueous nanosuspension
| Resumo: | The increasing number of poorly soluble drugs requires innovative formulation approaches to reach high drug bioavailability. Nanosuspensions have many advantages, including improved solubility and bioavailability of drugs. Bead milling process is a method frequently used to produce nanosuspensions due to the simple use and wide application, independently of drug properties. Wet bead milling in aqueous medium has been extensively studied, although, bead milling process in lipophilic medium is not so common and requires further research to assess the impact on release profiles and simplification of the formulation process. This work aimed to produce nanoparticles in lipophilic medium using bead milling process, to identify the relevant parameters and understand how they influence the final nanosuspension. Medium-chain triglycerides (Miglyol® 812) were used as milling medium and diclofenac sodium as a hydrophilic drug model. In each experiment the amount of API, milling medium, beads and surfactant were varied, as well as the type of surfactant, type of API and the stirring speed. The final nanosuspensions were characterized by photon correlation spectroscopy and optical microscopy. Non-aqueous nanosuspensions of diclofenac sodium were successfully prepared during a 6-hour process. The mean particle size of the obtained nanoparticles ranged from 326.63 to 836.50 nm. The results of this research work indicate that the use of distinct drugs influences the final nanosuspension properties. The type and amount of surfactant seem not to influence particle size reduction when considered alone, although, they have played a major role in avoiding particle agglomeration. In the studied range, the API amount did not directly influence particle size reduction. However, the decrease in surfactant/drug ratio appears to increase both particle size and agglomeration of particles. Increasing speed and beads amount usually favours particle size reduction, although, an excess of energy input may also favour the development of agglomerates. Milling time is a very important factor, which decreases MPS and particle size distribution. It is crucial to evaluate all parameters together and not individually to optimise the process and obtain the best results. |
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| Autores principais: | Ribeiro, Carolina Janardo |
| Assunto: | Non-aqueous nanosuspension Bead milling Medium-chain triglycerides Diclofenac sodium Mestrado Integrado - 2017 |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | The increasing number of poorly soluble drugs requires innovative formulation approaches to reach high drug bioavailability. Nanosuspensions have many advantages, including improved solubility and bioavailability of drugs. Bead milling process is a method frequently used to produce nanosuspensions due to the simple use and wide application, independently of drug properties. Wet bead milling in aqueous medium has been extensively studied, although, bead milling process in lipophilic medium is not so common and requires further research to assess the impact on release profiles and simplification of the formulation process. This work aimed to produce nanoparticles in lipophilic medium using bead milling process, to identify the relevant parameters and understand how they influence the final nanosuspension. Medium-chain triglycerides (Miglyol® 812) were used as milling medium and diclofenac sodium as a hydrophilic drug model. In each experiment the amount of API, milling medium, beads and surfactant were varied, as well as the type of surfactant, type of API and the stirring speed. The final nanosuspensions were characterized by photon correlation spectroscopy and optical microscopy. Non-aqueous nanosuspensions of diclofenac sodium were successfully prepared during a 6-hour process. The mean particle size of the obtained nanoparticles ranged from 326.63 to 836.50 nm. The results of this research work indicate that the use of distinct drugs influences the final nanosuspension properties. The type and amount of surfactant seem not to influence particle size reduction when considered alone, although, they have played a major role in avoiding particle agglomeration. In the studied range, the API amount did not directly influence particle size reduction. However, the decrease in surfactant/drug ratio appears to increase both particle size and agglomeration of particles. Increasing speed and beads amount usually favours particle size reduction, although, an excess of energy input may also favour the development of agglomerates. Milling time is a very important factor, which decreases MPS and particle size distribution. It is crucial to evaluate all parameters together and not individually to optimise the process and obtain the best results. |
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