Co-amorphous solid dispersion systems of lacidipine-spironolactone with improved dissolution rate and enhanced physical stability

Wang, Zhaomeng; Sun, Mengchi; Liu, Tian; Gao, Zisen; Ye, Qing; Tan, Xiao; Hou, Yanxian; Sun, Jin; Wang, Dun; Zhang, He

doi:10.1016/j.ajps.2018.11.001

Cited by 33 publications

(11 citation statements)

References 27 publications

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“…Enhancing the solubility/dissolution of these drugs has become a vital issue for pharmaceutical enterprises to develop effective medicines with suitable dosage forms for patients [ 3 ]. Amorphization by disordering crystal lattice is a well-known approach to overcome the solubility/dissolution defects of poorly soluble drugs [ 4 , 5 , 6 ]. However, the application of amorphous systems is severely limited due to the inherent thermodynamic instability and devitrification risk during processing, storage, and dissolution [ 7 , 8 , 9 ], resulting in the loss of amorphous advantages.…”

Section: Introductionmentioning

confidence: 99%

Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Han

et al. 2021

Pharmaceutics

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Different from previously reported co-amorphous systems, a co-amorphous curcumin-magnolol (CUR-MAG CM) system, as compared with its crystalline counterparts, exhibited decreased dissolution due to its aggregation during dissolution. The main purpose of the present study is to deaggregate CUR-MAG CM to optimize drug dissolution and explore the deaggregation mechanism involved. Herein, a small amount of polymer (HPMC, HPC, and PVP K30) was co-formulated at 5% (w/w) with CUR-MAG CM as ternary co-amorphous systems. The polymer addition changed the surface properties of CUR-MAG CM including improved water wettability enhanced surface free energy, and hence exerted a deaggregating effect. As a result, the ternary co-amorphous systems showed faster and higher dissolution as compared with crystalline CUR/MAG and CUR-MAG CM. In addition, the nucleation and crystal growth of dissolved CUR and MAG molecules were significantly inhibited by the added polymer, maintaining a supersaturated concentration for a long time. Furthermore, polymer addition increased the Tg of CUR-MAG CM, potentially involving molecular interactions and inhibiting molecular mobility, resulting in enhanced physical stability under 25 °C/60% RH and 40 °C/75% RH conditions. Therefore, this study provides a promising strategy to optimize the dissolution and physical stability of co-amorphous systems by deaggregation and crystallization inhibition via adding small amounts of polymers.

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Section: Introductionmentioning

confidence: 99%

Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Han

et al. 2021

Pharmaceutics

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“…An example of a drug-drug combination is the spray drying of colistin with azithromycin to treat infections caused by multi-drug resistant bacteria [ 130 ]. A study conducted by Wang et al, showed an enhanced solubility profile between two APIs with low aqueous solubility: lacidipine and spironolactone [ 131 ]. Many other drug-excipient combinations are listed in Table 7 , by which commonly used coformers in CASDs for pulmonary drug delivery include mannitol, sugars and amino acids, such as leucine [ 132 , 133 ].…”

Section: The Design Of Carrier Free Formulations Using Coamorphous Solid Dispersions (Cacds)mentioning

confidence: 99%

Pulmonary Drug Delivery of Antimicrobials and Anticancer Drugs Using Solid Dispersions

et al. 2021

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It is well established that currently available inhaled drug formulations are associated with extremely low lung deposition. Currently available technologies alleviate this low deposition problem via mixing the drug with inert larger particles, such as lactose monohydrate. Those inert particles are retained in the inhalation device or impacted in the throat and swallowed, allowing the smaller drug particles to continue their journey towards the lungs. While this seems like a practical approach, in some formulations, the ratio between the carrier to drug particles can be as much as 30 to 1. This limitation becomes more critical when treating lung conditions that inherently require large doses of the drug, such as antibiotics and antivirals that treat lung infections and anticancer drugs. The focus of this review article is to review the recent advancements in carrier free technologies that are based on coamorphous solid dispersions and cocrystals that can improve flow properties, and help with delivering larger doses of the drug to the lungs.

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“…In the past decade, coamorphous systems prepared by solvent volatilization, spray drying, and liquid-assisted grinding, have been developed as potential drug delivery systems. For example, Wang et al 14 prepared coamorphous lacidipine-spironolactone by a solvent evaporation method, which showed a good therapeutic effect when the molar ratio was 1:6. Ojarinta et al 15 prepared coamorphous ibuprofen-arginine and coamorphous indomethacin-arginine by spray drying with water as the solvent.…”

Section: Introductionmentioning

confidence: 99%

Exploring the Formation Mechanism of Coamorphous Andrographolide-Oxymatrine Based on Molecular Dynamics and Spectroscopy

Fang

Huang

et al. 2022

Journal of Pharmaceutical Sciences

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Co-amorphous solid dispersion systems of lacidipine-spironolactone with improved dissolution rate and enhanced physical stability

Cited by 33 publications

References 27 publications

Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Pulmonary Drug Delivery of Antimicrobials and Anticancer Drugs Using Solid Dispersions

Exploring the Formation Mechanism of Coamorphous Andrographolide-Oxymatrine Based on Molecular Dynamics and Spectroscopy

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