Considerations for the selection of co-formers in the preparation of co-amorphous formulations

Yarlagadda, Dani Lakshman; Anand, Vullendula Sai Krishna; Nair, Athira R; Sree, K. Sowjanya; Dengale, Swapnil J.; Bhat, Krishnamurthy

doi:10.1016/j.ijpharm.2021.120649

Cited by 43 publications

(13 citation statements)

References 134 publications

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“…Concomitantly, other unit operations, such as tableting, have also proved to be effective in the preparation of amorphous materials [ 19 , 20 ]. To date, a notable endeavor has been put into the development of CAMs, namely on the selection of the co-formers [ 13 , 21 , 22 , 23 ], the adequate drug: co-former molar ratio [ 24 ] and CAM preparation methods [ 11 , 25 , 26 ]. However, the formulation of CAMs in oral solid dosage forms (e.g., tablets) has been barely described [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends

et al. 2022

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The work evaluates the stability of amorphous and co-amorphous olanzapine (OLZ) in tablets manufactured by direct compression. The flowability and the compressibility of amorphous and co-amorphous OLZ with saccharin (SAC) and the properties of the tablets obtained were measured and compared to those of tablets made with crystalline OLZ. The flowability of the amorphous and mostly of the co-amorphous OLZ powders decreased in comparison with the crystalline OLZ due to the higher cohesiveness of the former materials. The stability of the amorphous and co-amorphous OLZ prior to and after tableting was monitored by XRPD, FTIR, and NIR spectroscopies. Tablets presented long-lasting amorphous OLZ with enhanced water solubility, but the release rate of the drug decreased in comparison with tablets containing crystalline OLZ. In physical mixtures made of crystalline OLZ and SAC, an extent of amorphization of approximately 20% was accomplished through the application of compaction pressures and dwell times of 155 MPa and 5 min, respectively. The work highlighted the stability of amorphous and co-amorphous OLZ during tableting and the positive effect of compaction pressure on the formation of co-amorphous OLZ, providing an expedited amorphization technique, given that the process development-associated hurdles were overcome.

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Section: Introductionmentioning

confidence: 99%

Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends

et al. 2022

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“…Approaches include the prediction of the miscibility of two compounds involving (a) Hansen Solubility parameters [ 18 ], (b) Flory–Huggins parameter [ 12 ], (c) co-former selection based on physicochemical properties of the co-former like glass transition temperature, melting point and molecular flexibility [ 18 ], or (d) certain other molecular descriptors [ 19 , 20 ]. More details and a good overview of the existing literature on the rational selection of co-formers can be found in the recent review by Yarlagadda et al [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Data-Driven Prediction of the Formation of Co-Amorphous Systems

Fink

Brunsteiner²,

Mitsche

et al. 2023

Pharmaceutics

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Co-amorphous systems (COAMS) have raised increasing interest in the pharmaceutical industry, since they combine the increased solubility and/or faster dissolution of amorphous forms with the stability of crystalline forms. However, the choice of the co-former is critical for the formation of a COAMS. While some models exist to predict the potential formation of COAMS, they often focus on a limited group of compounds. Here, four classes of combinations of an active pharmaceutical ingredient (API) with (1) another API, (2) an amino acid, (3) an organic acid, or (4) another substance were considered. A model using gradient boosting methods was developed to predict the successful formation of COAMS for all four classes. The model was tested on data not seen during training and predicted 15 out of 19 examples correctly. In addition, the model was used to screen for new COAMS in binary systems of two APIs for inhalation therapy, as diseases such as tuberculosis, asthma, and COPD usually require complex multidrug-therapy. Three of these new API-API combinations were selected for experimental testing and co-processed via milling. The experiments confirmed the predictions of the model in all three cases. This data-driven model will facilitate and expedite the screening phase for new binary COAMS.

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“…Co-amorphous systems are a new class of homogeneous amorphous solid phases, which are different from traditional amorphous solid dispersions. Low-molecular-weight components are employed to replace the traditional polymers to stabilize the amorphous state of drugs . The co-amorphous drug systems may achieve superior druggability due to their improved solubility, physicochemical stability, and drug loading capability over amorphous drugs alone. , Excipients and drugs are used as co-amorphous co-formers, forming two types of co-amorphous systems, that is, drug-excipient and drug–drug co-amorphous systems.…”

Section: Introductionmentioning

confidence: 99%

Co-amorphous Systems of Sinomenine with Platensimycin or Sulfasalazine: Physical Stability and Excipient-Adjusted Release Behavior

Chen

Zhang

et al. 2022

Mol. Pharmaceutics

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There is strong interest to develop affordable treatments for the infection-associated rheumatoid arthritis (RA). Here, we present a drug−drug co-amorphous strategy against RA and the associated bacterial infection by the preparation and characterization of two co-amorphous systems of sinomenine (SIN) with platensimycin (PTM) or sulfasalazine (SULF), two potent antibiotics. Both of them were comprehensively characterized using powder Xray diffraction, temperature-modulated differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The co-amorphous forms of SIN-PTM and SIN-SULF exhibited high T g s at 139.10 ± 1.0 and 153.3 ± 0.2 °C, respectively. After 6 months of accelerated tests and 1 month of drug-excipient compatibility experiments, two coamorphous systems displayed satisfactory physical stability. The formation of salt and strong intermolecular interactions between SIN and PTM or SULF, as well as the decreased molecular mobility in co-amorphous systems, may be the intrinsic mechanisms underlying the excellent physical stability of both co-amorphous systems. In dissolution tests, two co-amorphous systems displayed distinct reduced SINaccumulative releases (below 20% after 6 h of release experiments), which may lead to its poor therapeutic effect. Hence, we demonstrated a controlled release strategy for SIN by the addition of a small percentage of polymers and a small-molecule surfactant to these two co-amorphous samples as convenient drug excipients, which may also be used to improve the unsatisfactory dissolution behaviors of the previously reported SIN co-amorphous systems. Several hydrogen bonding interactions between SIN and PTM or SULF could be identified in NMR experiments in DMSO-d 6 , which may be underlying reasons of decreased dissolution behaviors of both co-amorphous forms. These drug−drug co-amorphous systems could be a potential strategy for the treatment of infectionassociated RA.

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Considerations for the selection of co-formers in the preparation of co-amorphous formulations

Cited by 43 publications

References 134 publications

Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends

Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends

Data-Driven Prediction of the Formation of Co-Amorphous Systems

Co-amorphous Systems of Sinomenine with Platensimycin or Sulfasalazine: Physical Stability and Excipient-Adjusted Release Behavior

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