The current study was to understand how process variables of high shear wet granulations affect physical properties of granules and tablets. The knowledge gained was intended to be used for Quality-by-Design based pro...The current study was to understand how process variables of high shear wet granulations affect physical properties of granules and tablets. The knowledge gained was intended to be used for Quality-by-Design based process design and optimization. The variables were selected based on the risk assessment as impeller speed, liquid addition rate, and wet massing time. Formulation compositions were kept constant to minimize their influence on granules properties. Multiple linear regression models were built providing understanding of the impact of each variable on granule hardness, Carr’s index, tablet tensile strength, surface mean diameter of granules, and compression behavior. The experimental results showed that the impact of impeller speed was more dominant compared to wet massing time and water addition rate. The results also revealed that quality of granules and tablets could be optimized by adjusting specific process variables(impeller speed 1193 rpm, water spray rate 3.7 ml/min, and wet massing time 2.84 min). Overall desirability was 0.84 suggesting that the response values were closer to the target one. The SEM image of granules showed that spherical and smooth granules produced at higher impeller speed, whereas rough and irregular shape granules at lower speed. Moreover, multivariate data analysis demonstrated that impeller speed and massing time had strong correlation with the granule and tablet properties. In overall, the combined experimental design and principal component analysis approach allowed to better understand the correlation between process variables and granules and tablet attributes.展开更多
Glyceryl monooleate(GMO)is a polar lipid that can exist in various liquid crystalline phases in the presence of different amounts of water.It is regarded as a permeation enhancer due to its amphiphilic property.Variou...Glyceryl monooleate(GMO)is a polar lipid that can exist in various liquid crystalline phases in the presence of different amounts of water.It is regarded as a permeation enhancer due to its amphiphilic property.Various phases of GMO/solvent system containing sodium fluorescein were prepared to compare permeability using confocal laser scanning microscopy(CLSM).GMO was melted in a vial in a water bath heated to 45℃.Propylene glycol and hexanediol were homogeneously dissolved in the melted GMO.Sodium fluorescein in aqueous solution was diluted to various ratios and thoroughly mixed by an ultrasonic homogenizer.Each GMO/Solvent system with fluorescein was applied onto the epidermal side of excised pig skin and incubated overnight.CLSM was performed to observe how the GMO/solvent system in its different phases affect skin permeability.Cubic and lamellar phase formulations enhanced the fluorescein permeation through the stratum corneum.A solution system had the weakest permeability compared to the other two phases.Due to the amphiphilic nature of GMO,cubic and lamellar phases might reduce the barrier function of stratum corneum which was observed by CLSM as fluorescein accumulated in the dermis.Based on the results,the glyceryl monooleate lyotropic mixtures could be applied to enhance skin permeation in various topical and transdermal formulations.展开更多
基金supported by the National Research Foun-dation of Korea(NRF)grant,funded by the Korean govern-ment(MSIT)(2015R1A1A1A05000942)the National Re-search Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(NRF-2018R1A5A2023127)
文摘The current study was to understand how process variables of high shear wet granulations affect physical properties of granules and tablets. The knowledge gained was intended to be used for Quality-by-Design based process design and optimization. The variables were selected based on the risk assessment as impeller speed, liquid addition rate, and wet massing time. Formulation compositions were kept constant to minimize their influence on granules properties. Multiple linear regression models were built providing understanding of the impact of each variable on granule hardness, Carr’s index, tablet tensile strength, surface mean diameter of granules, and compression behavior. The experimental results showed that the impact of impeller speed was more dominant compared to wet massing time and water addition rate. The results also revealed that quality of granules and tablets could be optimized by adjusting specific process variables(impeller speed 1193 rpm, water spray rate 3.7 ml/min, and wet massing time 2.84 min). Overall desirability was 0.84 suggesting that the response values were closer to the target one. The SEM image of granules showed that spherical and smooth granules produced at higher impeller speed, whereas rough and irregular shape granules at lower speed. Moreover, multivariate data analysis demonstrated that impeller speed and massing time had strong correlation with the granule and tablet properties. In overall, the combined experimental design and principal component analysis approach allowed to better understand the correlation between process variables and granules and tablet attributes.
基金This study was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Korean Ministry of Education,Science and Technology(2012002399)a grant of the Korean Healthcare Technology R&D Project,Ministry of Health and Welfare,Republic of Korea.(Grant No.:A103017).
文摘Glyceryl monooleate(GMO)is a polar lipid that can exist in various liquid crystalline phases in the presence of different amounts of water.It is regarded as a permeation enhancer due to its amphiphilic property.Various phases of GMO/solvent system containing sodium fluorescein were prepared to compare permeability using confocal laser scanning microscopy(CLSM).GMO was melted in a vial in a water bath heated to 45℃.Propylene glycol and hexanediol were homogeneously dissolved in the melted GMO.Sodium fluorescein in aqueous solution was diluted to various ratios and thoroughly mixed by an ultrasonic homogenizer.Each GMO/Solvent system with fluorescein was applied onto the epidermal side of excised pig skin and incubated overnight.CLSM was performed to observe how the GMO/solvent system in its different phases affect skin permeability.Cubic and lamellar phase formulations enhanced the fluorescein permeation through the stratum corneum.A solution system had the weakest permeability compared to the other two phases.Due to the amphiphilic nature of GMO,cubic and lamellar phases might reduce the barrier function of stratum corneum which was observed by CLSM as fluorescein accumulated in the dermis.Based on the results,the glyceryl monooleate lyotropic mixtures could be applied to enhance skin permeation in various topical and transdermal formulations.