The relevance of co-amorphous formulations to develop supersaturated dosage forms: In-vitro, and ex-vivo investigation of Ritonavir-Lopinavir co-amorphous materials

Anand, Vullendula Sai Krishna; Sakhare, Sujata D.; Navyasree, K. S.; Nair, Athira R; Varma, K. Raghava; Gourishetti, Karthik; Dengale, Swapnil J.

doi:10.1016/j.ejps.2018.07.046

Cited by 31 publications

(8 citation statements)

References 45 publications

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“…An ex vivo study concluded on the flux of the CAMS ritonavir-lopinavir (molar ratio 2:1) using rats. A 10-fold increase in the flux of ritonavir and a 3-fold increase for lopinavir was found for the CAMS formulation compared to the pure crystalline drugs [136].…”

Section: In Vitro and In Vivo Performance Of Camsmentioning

confidence: 89%

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: In Vitro and In Vivo Performance Of Camsmentioning

confidence: 89%

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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“…The quench cooling method is also commonly employed to prepare coamorphous binary systems by melting the mixture containing API and coformer and then quickly cooling the molten liquid using liquid nitrogen or an ice–water bath. , Generally, a rapid cooling rate is needed to inhibit the crystallization and promote the formation of a disordered molecular arrangement from molten components. Melt quenching is usually applicable for thermostable components with melting but no degradation.…”

Section: Preparation Methods Of Cocrystals and Coamorphous Systemsmentioning

confidence: 99%

Insights into Cocrystallization and Coamorphization Engineering Techniques in the Delivery of Traditional Chinese Medicine: Formation Mechanism, Solid-State Characterization, and Improved Pharmaceutical Properties

Song

Han

et al. 2022

Crystal Growth & Design

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Many active ingredients from traditional Chinese medicine (TCM) exhibit poor pharmaceutical properties (e.g., low aqueous solubility, slow dissolution, low bioavailability, poor stability, and high hygroscopicity, etc.), which are closely associated with various formulation performance issues. Cocrystals or coamorphous systems, incorporating drug and guest molecules into a homogeneous single crystalline or amorphous phase, have been shown to offer potential advantages in enhancing pharmaceutical properties of TCM. This review outlines the definition, classification, preparation methods, characterization techniques, and pharmaceutical properties (such as solubility, dissolution, stability, mechanical properties, permeability, and in vivo performance) of cocrystals and coamorphous systems. More insights into the formation mechanisms of cocrystals and coamorphous systems, the identification of single-phase homogeneous coamorphous systems, and the characterization of their intermolecular interactions between components are covered. Latest research studies on the delivery of TCM via cocrystallization and coamorphization technologies are also summarized. The mechanisms of enhancement in druggability-related properties through cocrystals and coamorphous systems are further discussed. In particular, several common kinetic solubility behaviors of cocrystal and coamorphous systems, including "spring and parachute" and "spring and hover" models, are deeply understood, which will contribute to the maintenance of high supersaturation and in vivo bioavailability.

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“…Acetonitrile (ACN):water (60:40; adjusted to pH 2.5 with orthophosphoric acid) was the mobile phase. The flow rate was 1.4 mL/ min, and 236 nm was the maximum wavelength (λ max) [21].…”

Section: Solubility Studiesmentioning

confidence: 99%

“…At regular intervals, 5 mL of the sample(s) was collected and immediately replaced with the fresh dissolution media. The collected samples were stored for further analysis [21].…”

Section: Dissolution Studiesmentioning

confidence: 99%

“…To mimic the biological conditions, intestinal tissue was used in a separate study. Since SDs prepared by HME recorded the maximum solubility and dissolution rate, an in vitro diffusion and ex vivo permeation study were performed [21]. Table III shows the in vitro diffusion and ex vivo permeation study results of plain GLB and the prepared SDs.…”

Section: In Vitro Diffusion and Ex Vivo Intestinal Permeation Studiesmentioning

confidence: 99%

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Drug-Carrier Miscibility in Solid Dispersions of Glibenclamide and a Novel Approach to Enhance Its Solubility Using an Effervescent Agent

et al. 2022

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The present research aims to investigate the miscibility, physical stability, solubility, and dissolution rate of a poorly water-soluble glibenclamide (GLB) in solid dispersions (SDs) with hydrophilic carriers like PEG-1500 and PEG-50 hydrogenated palm glycerides (Acconon). Mathematical theories such as Hansen solubility parameters, Flory Huggins theory, Gibbs free energy, and the in silico molecular dynamics simulation study approaches were used to predict the drug-carrier miscibility. To increase the solubility further, the effervescence technique was introduced to the conventional solid dispersions to prepare effervescent solid dispersions (ESD). Solid dispersions (SDs) were prepared by microwave, solvent evaporation, lyophilization, and hot melt extrusion (HME) techniques and tested for different characterization parameters. The theoretical and in silico parameters suggested that GLB would show good miscibility with the selected carriers under certain conditions. Intermolecular hydrogen bonding between the drug and carrier(s) was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Solid-state characterizations like powder X-ray diffraction, differential scanning calorimetry, and microscopy confirm the amorphous nature of SDs. The addition of the effervescent agent improved the amorphous nature, due to which the solubility and drug release rate was increased. In vitro and ex vivo intestinal absorption studies showed improved flux and permeability than the pure drug, suggesting an enhanced drug delivery. The GLB solubility, dissolution, and stability were greatly enhanced by the SD and ESD technology. Graphical Abstract

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The relevance of co-amorphous formulations to develop supersaturated dosage forms: In-vitro, and ex-vivo investigation of Ritonavir-Lopinavir co-amorphous materials

Cited by 31 publications

References 45 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

Insights into Cocrystallization and Coamorphization Engineering Techniques in the Delivery of Traditional Chinese Medicine: Formation Mechanism, Solid-State Characterization, and Improved Pharmaceutical Properties

Drug-Carrier Miscibility in Solid Dispersions of Glibenclamide and a Novel Approach to Enhance Its Solubility Using an Effervescent Agent

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