New insight into transdermal drug delivery with supersaturated formulation based on co-amorphous system

Hirakawa, Yuya; Ueda, Hiroshi; Miyano, Tetsuya; Kamiya, Noriho; Goto, Masahiro

doi:10.1016/j.ijpharm.2019.118582

Cited by 30 publications

(19 citation statements)

References 46 publications

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“…Apart from the above-mentioned co-former classes, other types of small molecules have been applied in the preparation of CAMS, for example urea [41,44,45] and nicotinamide [41,43,[45][46][47][48][49]. These CAMS contribute 17.5% of the total.…”

Section: Classes Of Investigated Camsmentioning

confidence: 99%

“…It is worth noting that the molar ratio optimization methods mentioned above mainly focus on achieving highest physical stability. It remains unclear how the optimal molar ratio can affect the third CQA, dissolution performance, compared to non-optimal molar ratios, as this was only (partly) investigated in three studies [44,83,86]. Thus, investigations of the effect of the optimal molar ratio on the dissolution performance of CAMS needs further investigation.…”

Section: Detection Of the Glass Transition Temperatures (T G )mentioning

confidence: 99%

“…Especially, as mentioned before, permeability studies are of interest for CAMS containing a drug from BCS Class IV. However, in the above-mentioned studies, molar ratio optimization only was performed in two studies [44,85].…”

Section: In Vitro and In Vivo Performance 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: Classes Of Investigated Camsmentioning

confidence: 99%

Section: Detection Of the Glass Transition Temperatures (T G )mentioning

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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“…However, several researchers have recently focused on the design of co-amorphous systems which can be administered by other routes, such as the transdermal route, the parenteral route, and the inhalation route, instead of the oral route ( Table 4 ). The applicability of co-amorphous systems in the transdermal delivery was investigated by generating a supersaturated co-amorphous formulation comprising atenolol and urea as the model drug with a low permeability and the co-former, respectively [ 52 ]. This supersaturated formulation maintained its inhibition effect of recrystallization for about two months and could largely enhance the in vitro skin permeation of the drug, even compared to the permeability predicted from the degree of supersaturation.…”

Section: Emerging Pharmaceutical Techniques For Amorphization Of Poorly Water-soluble Drugsmentioning

confidence: 99%

Recent Technologies for Amorphization of Poorly Water-Soluble Drugs

Kim

Tin

et al. 2021

Pharmaceutics

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Amorphization technology has been the subject of continuous attention in the pharmaceutical industry, as a means to enhance the solubility of poorly water-soluble drugs. Being in a high energy state, amorphous formulations generally display significantly increased apparent solubility as compared to their crystalline counterparts, which may allow them to generate a supersaturated state in the gastrointestinal tract and in turn, improve the bioavailability. Conventionally, hydrophilic polymers have been used as carriers, in which the amorphous drugs were dispersed and stabilized to form polymeric amorphous solid dispersions. However, the technique had its limitations, some of which include the need for a large number of carriers, the tendency to recrystallize during storage, and the possibility of thermal decomposition of the drug during preparation. Therefore, emerging amorphization technologies have focused on the investigation of novel amorphous-stabilizing carriers and preparation methods that can improve the drug loading and the degree of amorphization. This review highlights the recent pharmaceutical approaches utilizing drug amorphization, such as co-amorphous systems, mesoporous particle-based techniques, and in situ amorphization. Recent updates on these technologies in the last five years are discussed with a focus on their characteristics and commercial potential.

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“…However, the concept of amorphous drug dispersion can be applied to other routes of drug delivery apart from oral, like in transdermal drug delivery. The idea of combining amorphous drugs and transdermal delivery has been experimented by some researchers for better drug permeation and controlling the drug release [ 15 ]. Loading of amorphous drugs into a transdermal system acts on the principle of supersaturation.…”

Section: Introductionmentioning

confidence: 99%

Amorphization of Drugs for Transdermal Delivery-a Recent Update

et al. 2022

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Amorphous solid dispersion is a popular formulation approach for orally administered poorly water-soluble drugs, especially for BCS class II. But oral delivery could not be an automatic choice for some drugs with high first-pass metabolism susceptibility. In such cases, transdermal delivery is considered an alternative if the drug is potent and the dose is less than 10 mg. Amorphization of drugs causes supersaturation and enhances the thermodynamic activity of the drugs. Hence, drug transport through the skin could be improved. The stabilization of amorphous system is a persistent challenge that restricts its application. A polymeric system, where amorphous drug is dispersed in a polymeric carrier, helps its stability. However, high excipient load often becomes problematic for the polymeric amorphous system. Coamorphous formulation is another approach, where one drug is mixed with another drug or low molecular weight compound, which stabilizes each other, restricts crystallization, and maintains a single-phase homogenous amorphous system. Prevention of recrystallization along with enhanced skin permeation has been observed by the transdermal coamorphous system. But scalable manufacturing methods, extensive stability study and in-depth in vivo evaluation are lacking. This review has critically studied the mechanistic aspects of amorphization and transdermal permeation by analyzing recent researches in this field to propose a future direction.

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New insight into transdermal drug delivery with supersaturated formulation based on co-amorphous system

Cited by 30 publications

References 46 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

Recent Technologies for Amorphization of Poorly Water-Soluble Drugs

Amorphization of Drugs for Transdermal Delivery-a Recent Update

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