Preparation and Evaluation of Co-amorphous Formulations of Telmisartan—Amino Acids as a Potential Method for Solubility and Dissolution Enhancement

Khanfar, Mai; Al-Remawi, Mayyas; Al-Akayleh, Faisal; Hmouze, Suha

doi:10.1208/s12249-021-01952-9

Cited by 18 publications

(15 citation statements)

References 48 publications

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“…Amino acids, as low molecular weight, and generally recognized as safe (GRAS) compounds, are of particular interest in this respect [ 22 , 23 ]. Amino acids contain α-carboxylate and α-amino groups, allowing them to interact as hydrogen acceptors or donors and form molecular interactions with some active pharmaceutical ingredient (API) [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity

Garbiec

Rosiak

Tykarska

et al. 2023

IJMS

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The objective of this study was to obtain co-amorphous systems of poorly soluble sinapic acid using amino acids as co-formers. In order to assess the probability of the interaction of amino acids, namely, arginine, histidine, lysine, tryptophan, and proline, selected as co-formers in the amorphization of sinapic acid, in silico studies were carried out. Sinapic acid systems with amino acids in a molar ratio of 1:1 and 1:2 were obtained using ball milling, solvent evaporation, and freeze drying techniques. X-ray powder diffraction results confirmed the loss of crystallinity of sinapic acid and lysine, regardless of the amorphization technique used, while remaining co-formers produced mixed results. Fourier-transform infrared spectroscopy analyses revealed that the co-amorphous sinapic acid systems were stabilized through the creation of intermolecular interactions, particularly hydrogen bonds, and the potential formation of salt. Lysine was selected as the most appropriate co-former to obtain co-amorphous systems of sinapic acid, which inhibited the recrystallization of sinapic acid for a period of six weeks in 30 °C and 50 °C. Obtained co-amorphous systems demonstrated an enhancement in dissolution rate over pure sinapic acid. A solubility study revealed a 12.9-fold improvement in sinapic acid solubility after introducing it into the co-amorphous systems. Moreover, a 2.2-fold and 1.3-fold improvement in antioxidant activity of sinapic acid was observed with respect to the ability to neutralize the 2,2-diphenyl-1-picrylhydrazyl radical and to reduce copper ions, respectively.

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Section: Introductionmentioning

confidence: 99%

Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity

Garbiec

Rosiak

Tykarska

et al. 2023

IJMS

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“…Co-amorphous systems (CAMs), i.e., dispersions at the molecular level of drugs in low molecular weight compounds, have gained special interest [ 17 , 18 , 19 , 20 , 21 ] by enhancing the stability of the amorphous systems produced while increasing the solubility of the drugs [ 20 , 22 ]. The combination of drugs with a second substance (either a pharmaceutically accepted excipient or a second drug providing a sensible therapeutic combination [ 17 , 23 , 24 , 25 ]) enables the stabilization of the amorphous system, due to the establishment of intermolecular bonds between the two entities, often with a higher glass transition temperature (T g ) than the pure amorphous drug(s) or the physical mixture of the individual components [ 23 , 26 ]. Additionally, ternary systems have also been recently considered to ameliorate the stability of CAMs by dramatically increasing T g [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Amorphous and Co-Amorphous Olanzapine Stability in Formulations Intended for Wet Granulation and Pelletization

Costa

Daniels

Fernandes

et al. 2022

IJMS

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The preparation of amorphous and co-amorphous systems (CAMs) effectively addresses the solubility and bioavailability issues of poorly water-soluble chemical entities. However, stress conditions imposed during common pharmaceutical processing (e.g., tableting) may cause the recrystallization of the systems, warranting close stability monitoring throughout production. This work aimed at assessing the water and heat stability of amorphous olanzapine (OLZ) and OLZ-CAMs when subject to wet granulation and pelletization. Starting materials and products were characterized using calorimetry, diffractometry and spectroscopy, and their performance behavior was evaluated by dissolution testing. The results indicated that amorphous OLZ was reconverted back to a crystalline state after exposure to water and heat; conversely, OLZ-CAMs stabilized with saccharin (SAC), a sulfonic acid, did not show any significant loss of the amorphous content, confirming the higher stability of OLZ in the CAM. Besides resistance under the processing conditions of the dosage forms considered, OLZ-CAMs presented a higher solubility and dissolution rate than the respective crystalline counterpart. Furthermore, in situ co-amorphization of OLZ and SAC during granule production with high fractions of water unveils the possibility of reducing production steps and associated costs.

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“…Depending on the co-former used, COAMS can be divided into several classes: (a) amino acid based COAMS, (b) drug based COAMS, (c) organic acid based COAMS, and (d) other COAMS [ 11 ]. Experimental methods to obtain COAMS include co-melting or melt quenching [ 12 ], solvent evaporation [ 13 ], spray-drying [ 14 ] or freeze-drying [ 15 ], and milling [ 16 ].…”

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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Preparation and Evaluation of Co-amorphous Formulations of Telmisartan—Amino Acids as a Potential Method for Solubility and Dissolution Enhancement

Cited by 18 publications

References 48 publications

Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity

Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity

Amorphous and Co-Amorphous Olanzapine Stability in Formulations Intended for Wet Granulation and Pelletization

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

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