Enhancement of the Physical Stability of Amorphous Indomethacin by Mixing it with Octaacetylmaltose. Inter and Intra Molecular Studies

Kamińska, Ewa; Adrjanowicz, Karolina; Żakowiecki, Daniel; Milanowski, Bartłomiej; Tarnacka, Magdalena; Hawełek, ᴌ.; Dulski, Mateusz; Pilch, Jerzy; Smółka, Wojciech; Kaczmarczyk-Sedlak, Ilona; Kamiński, Kamil

doi:10.1007/s11095-014-1385-4

Cited by 15 publications

(29 citation statements)

References 92 publications

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“…Molecules of an excipient, which are able to specifically interact with the drug molecules, prevent the recrystallization process of the drug. 10 , 31 − 33 , 22 …”

Section: Introductionmentioning

confidence: 99%

“…Kaminska et al have shown that acMAL might be very effective in stabilizing the amorphous form of indomethacin (IMC). 22 The authors found that strong interactions between the IMC and acMAL by forming hydrogen bonds between molecules of both compounds led to the improvement in the physical stability of amorphous API even at temperatures higher than T g of the binary systems. The water solubility of amorphous IMC was also enhanced in solid dispersions with acMAL.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose

et al. 2020

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In this paper, we explore the strategy increasingly used to improve the bioavailability of poorly water-soluble crystalline drugs by formulating their amorphous solid dispersions. We focus on the potential application of a low molecular weight excipient octaacetyl-maltose (acMAL) to prepare physically stable amorphous solid dispersions with ibuprofen (IBU) aimed at enhancing water solubility of the drug compared to that of its crystalline counterpart. We thoroughly investigate global and local molecular dynamics, thermal properties, and physical stability of the IBU+acMAL binary systems by using broadband dielectric spectroscopy and differential scanning calorimetry as well as test their water solubility and dissolution rate. The obtained results are extensively discussed by analyzing several factors considered to affect the physical stability of amorphous systems, including those related to the global mobility, such as plasticization/antiplasticization effects, the activation energy, fragility parameter, and the number of dynamically correlated molecules as well as specific intermolecular interactions like hydrogen bonds, supporting the latter by density functional theory calculations. The observations made for the IBU+acMAL binary systems and drawn recommendations give a better insight into our understanding of molecular mechanisms governing the physical stability of amorphous solid dispersions.

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“…Molecules of an excipient, which are able to specifically interact with the drug molecules, prevent the recrystallization process of the drug. 10 , 31 − 33 , 22 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose

et al. 2020

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“…The δ values of IMC, Kollicoat IR, and HPMC were 24.8 MPa 1/2 (δ d = 22.2 MPa 1/2 , δ p = 6.0 MPa 1/2 , δ h = 9.4 MPa 1/2 ) [35], 32.5 MPa 1/2 [36], and 30.6 MPa 1/2 (δ d = 18.0 MPa 1/2 , δ p = 15.3 MPa 1/2 , δ h = 19.4 MPa 1/2 ) [37] based on Equations (6) and (7). Thus, the difference in solubility parameters between IMC and HPMC was calculated to be less than 7 MPa 1/2 based on Equations (6) and (7), indicating that IMC-MSNs@HPMC (F9) had the best solubility enhancement effect. As shown in Figure 5, the same result was obtained in Figure 6, where the solubility value of IMC-MSNs@HPMC (F9) was the largest.…”

Section: Permeability and Bioavailability Studiesmentioning

confidence: 99%

“…Indomethacin (IMC, Figure 1) is a non-steroidal anti-inflammatory drug used widely for relieving symptoms of fever, rheumatoid arthritis, cardiovascular and Alzheimer diseases, etc. [7]. However, the application of IMC was limited, because it belongs to BCS Class II drugs.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Solid Dispersion System Engineered from Mesoporous Silica and Polymers for the Poorly Water Soluble Drug Indomethacin: In Vitro and In Vivo

Xi¹,

Zhang²,

Fei³

et al. 2020

Pharmaceutics

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This work explored absorption efficacy via an in vivo imaging system and parallel artificial membrane penetration in indomethacin (IMC) solid dispersion (SD) systems. Two different polymer excipients-hydroxypropyl methylcellulose (HPMC) and Kollicoat IR as precipitation inhibitors (PIs)-combined with mesoporous silica nanoparticles (MSNs) as carriers were investigated. The IMC-SDs were prepared using the solvent evaporation method and characterized by solubility analysis, infrared (IR) spectroscopy, powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), and differential scanning calorimetry (DSC). It was confirmed that IMC successfully changed into an amorphous state after loading into the designed carriers. The in vitro release and stability experiments were conducted to examine the in vitro dissolution rates of IMC-SDs combined with HPMC and Kollicoat IR as PIs which both improved approximately three-fold to that of the pure drug. Finally, in vivo studies and in vitro parallel artificial membrane penetration (PAMPA) experiments ensured the greater ability of enhancing the dissolution rates of pure IMC in the gastrointestinal tract by oral delivery. In brief, this study highlights the prominent role of HPMC and Kollicoat IR as PIs in MSN SD systems in improving the bioavailability and gastrointestinal oral absorption efficiency of indomethacin.

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“…Low molecular weight co-formers such as amino acids and saccharides have shown to stabilise amorphous poorly soluble drugs by generation of co-amorphous systems [21,22]. Active ingredients are also used as low molecular weight co-formers with the advantage of the co-administration of therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Physico-chemical characterisation of three-component co-amorphous systems generated by a melt-quench method

D’Angelo

Edgar

Hurt

et al. 2018

J Therm Anal Calorim

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The purpose of this work was to evaluate the possibility of creating a ternary co-amorphous system and to determine how the properties of a co-amorphous material are altered by the addition of a selected third component. Piroxicam and indomethacin form a stable co-amorphous with the T g above room temperature. The third component added was selected based on tendency to crystallise (benzamide, caffeine) or form amorphous (acetaminophen, clotrimazole) on cooling. Generated co-amorphous systems were characterised with TGA, HSM, DSC, FTIR and XRD. Stable ternary co-amorphous systems were successfully generated, which were confirmed using XRD, DSC and FTIR analysis. In all cases, T g of the ternary system was lower than the T g of the binary system, although higher than that of the individual third component. Upon storage for 4 weeks, all created ternary systems showed significantly smaller variation in T g compared to the binary system. Stable three-component co-amorphous systems can be generated via melt-quench method using either a crystalline or an amorphous third component. Addition of third component can alter the T g of co-amorphous system and in all cases created more stable co-amorphous system upon storage. Physical parameters may not be sufficient in predicting the resulting T g ; therefore, knowledge of chemical interaction must be brought into equation as well.

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Enhancement of the Physical Stability of Amorphous Indomethacin by Mixing it with Octaacetylmaltose. Inter and Intra Molecular Studies

Cited by 15 publications

References 92 publications

Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose

Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose

Evaluation of the Solid Dispersion System Engineered from Mesoporous Silica and Polymers for the Poorly Water Soluble Drug Indomethacin: In Vitro and In Vivo

Physico-chemical characterisation of three-component co-amorphous systems generated by a melt-quench method

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