Amino acids as stabilizers for spray-dried simvastatin powder for inhalation

Lu, Wangding; Rades, Thomas; Chan, Hak‐Kim; Yang, Mingshi

doi:10.1016/j.ijpharm.2019.118724

Cited by 41 publications

(14 citation statements)

References 49 publications

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“…The same behavior using different preparation pathways could be seen for indomethacin with the amino acid co-former histidine, which became co-amorphous upon spray drying [105,106] but not upon ball milling [29,41,54,103]. Interestingly, the exact opposite could be shown for the drug simvastatin and the amino acid co-former tryptophan, which became co-amorphous after ball milling [29,41,54] but not after spray drying [111]. Indomethacin became co-amorphous with the amino acid co-former lysine upon spray drying [105][106][107] and not after LAG, which resulted in the formation of the crystalline salt [108].…”

Section: Preparation Methods Of Camsmentioning

confidence: 66%

“…Table 2 gives an overview of different outcomes reported depending on the used preparation method or using different preparative parameters, e.g., milling time, within the same preparation method for the top five drugs. [111] in 26.1% of the CAMS prepared by the thermodynamic pathway and 20.4% were obtained by solvent removal, which is a method commonly used to obtain (co-)crystals but also exploited for the formulation of CAMS [92]. Other preparation methods include for example inkjet-printing (thermodynamic pathway) [93], hot melt extrusion (mainly thermodynamic pathway) [94][95][96], in situ co-amorphization [97][98][99][100], co-precipitation (thermodynamic pathway) [101], and co-grinding (kinetic pathway; defined as manually grinded) [102], of which some are difficult to assign to a certain pathway (thermodynamic or kinetic).…”

Section: Preparation Methods Of Camsmentioning

confidence: 99%

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Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies

Grohganz

Hempel

2021

Pharmaceutics

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Co-amorphous drug delivery systems (CAMS) are characterized by the combination of two or more (initially crystalline) low molecular weight components that form a homogeneous single-phase amorphous system. Over the past decades, CAMS have been widely investigated as a promising approach to address the challenge of low water solubility of many active pharmaceutical ingredients. Most of the studies on CAMS were performed on a case-by-case basis, and only a few systematic studies are available. A quantitative analysis of the literature on CAMS under certain aspects highlights not only which aspects have been of great interest, but also which future developments are necessary to expand this research field. This review provides a comprehensive updated overview on the current published work on CAMS using a quantitative approach, focusing on three critical quality attributes of CAMS, i.e., co-formability, physical stability, and dissolution performance. Specifically, co-formability, molar ratio of drug and co-former, preparation methods, physical stability, and in vitro and in vivo performance were covered. For each aspect, a quantitative assessment on the current status was performed, allowing both recent advances and remaining research gaps to be identified. Furthermore, novel research aspects such as the design of ternary CAMS are discussed.

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Section: Preparation Methods Of Camsmentioning

confidence: 66%

Section: Preparation Methods Of Camsmentioning

confidence: 99%

Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies

Grohganz

Hempel

2021

Pharmaceutics

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“…However, the use of alternative amino acids to achieve improved aerosolization is limited. The other amino acids that have been trialed as an aerosolization enhancer include methionine, phenylalanine, asparagine, tryptophan, arginine, histidine, threonine, glycine, and lysine [19][20][21][22][23][24]. Amino acid-based co-amorphous systems have recently been introduced as a potential strategy to improve the stability of amorphous material [25,26].…”

Section: Introductionmentioning

confidence: 99%

“…Spray-dried particles prepared from different solvent systems or feed concentrations are known to show varying aerodynamic behavior, hence, it would only be speculative to assume that the observed aerosolization improvement in these co-amorphous spray-dried particles is due to co-amorphization with amino acid [27][28][29]. Similarly, inhalable simvastatin-lysine and simvastatin-tryptophan co-amorphous spray-dried particles have also been reported; however, the aerosolization of formulation containing only simvastatin has not been discussed for comparison [21].…”

Section: Introductionmentioning

confidence: 99%

Co-Amorphization of Kanamycin with Amino Acids Improves Aerosolization

et al. 2020

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Different formulation techniques have been investigated to prepare highly aerosolizable dry powders to deliver a high dose of antibiotics to the lung for treating local infections. In this study, we investigated the influence of the co-amorphization of a model drug, kanamycin, with selected amino acids (valine, methionine, phenylalanine, and tryptophan) by co-spray drying on its aerosolization. The co-amorphicity was confirmed by thermal technique. The physical stability was monitored using low-frequency Raman spectroscopy coupled with principal component analysis. Except for the kanamycin-valine formulation, all the formulations offered improved fine particle fraction (FPF) with the highest FPF of 84% achieved for the kanamycin-methionine formulation. All the co-amorphous formulations were physically stable for 28 days at low relative humidity (25 °C/<15% RH) and exhibited stable aerosolization. At higher RH (53%), even though methionine transformed into its crystalline counterpart, the kanamycin-methionine formulation offered the best aerosolization stability without any decrease in FPF. While further studies are warranted to reveal the underlying mechanism, this study reports that the co-amorphization of kanamycin with amino acids, especially with methionine, has the potential to be developed as a high dose kanamycin dry powder formulation.

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“…Researchers are exploring different techniques to stabilize CAL, among them, microencapsulation, which is an alternative method used to protect bioactive compounds from oxidization and volatilization, thus increasing their shelf lives and allowing controlled release can be used 4,6–9 . Spray drying is performed at these low temperatures since CAL's boiling point (~248°C) is higher than this 10–12 . Spray‐drying mainly involves the emulsification by homogenization, followed by atomization of the emulsions.…”

Section: Introductionmentioning

confidence: 99%

Optimization of cinnamaldehyde microcapsule wall materials by experimental and quantitative methods

Zhou

et al. 2020

J of Applied Polymer Sci

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Microencapsulation is a widely‐investigated technique used for the unstable material preservation since the wall materials prevent the core materials from loss and deterioration. To improve the stability of cinnamaldehyde (CAL), different microcapsule wall systems are fabricated by spray‐drying, and then characterized by experimental methods to determine the most suitable wall materials. Surface morphology, encapsulation efficiency, effective loading capacity, as well as moisture absorption property are evaluated, and the results suggest that a three‐matrix system of methyl cellulose (MC)/sodium alginate (SA)/MC or MC/carboxymethyl chitosan (CMC)/SA wall formulation is more suitable for CAL microencapsulation. Moreover, a novel quantitative method is also proposed to verify the most stable wall material microencapsulation. The quantitative results show that the highest activation energy (53.00 ± 2.24 kJ/mol) is observed for the MC/CMC/SA‐encapsulated CAL microcapsule. Taken together, the results suggest that MC/CMC/SA wall formulation shows excellent barrier properties and is superior to other wall materials in preventing microencapsulated CAL deterioration. This study will be efficient in designing an ideal capsule for CAL microencapsulation.

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Amino acids as stabilizers for spray-dried simvastatin powder for inhalation

Cited by 41 publications

References 49 publications

Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies

Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies

Co-Amorphization of Kanamycin with Amino Acids Improves Aerosolization

Optimization of cinnamaldehyde microcapsule wall materials by experimental and quantitative methods

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