Amorphous systems for delivery of nutraceuticals: challenges opportunities

Tomar, Devendrasingh; Singh, Pankaj Kumar; Hoque, Sajidul; Modani, Sheela; Sriram, Anitha; Kumar, Rahul; Madan, Jitender; Khatri, Dharmendra Kumar; Dua, Kamal

doi:10.1080/10408398.2020.1836607

Cited by 14 publications

(6 citation statements)

References 138 publications

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“…Compared to solvent evaporation, quench-cool and freeze-drying techniques have excellent scalability and e ciency. However, quench cooling cannot always be employed because the drug(s) may undergo higher temperature treatment, which increases the probability of drug degradation during processing [9,15,[25][26][27]. Here, the solvent-based technique was employed to synthesize CAMs of SUL and NARI in molar ratios of 1:1, 1:2, 1:3, and 2:1 because naringin is a heat-labile substance.…”

Section: Solid State Characterization Of Cammentioning

confidence: 99%

“…Poor solubility and poor permeability of BCS class II and class IV drugs could be enhanced by the amorphous solid dispersion (ASD) approach. The scale-up of ASD could be possible by using the hot melt extrusion (HME) and spray drying methods [9]. However, ASD has some limitations, such as low drug loading capacity, phase separation, poor miscibility of the drug with the polymer, lower glass transition temperature (Tg) during stability due to its hygroscopic nature of polymer, which may induce crystallization during processing, transport, utilization, and storage.…”

Section: Introductionmentioning

confidence: 99%

“…However, drug degradation can occur during manufacturing of CAM system by HME process due to the high-temperature melting required for CAM synthesis. On the other hand, CAMs prepared using the solvent evaporation method can be easily scaled up to a commercial level by spray drying and freeze-drying and can be more readily formulated into a solid dosage form, such as tablets and capsule [9,16].…”

Section: Introductionmentioning

confidence: 99%

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A study of monophasic supramolecular formulation of Sulpiride with P-glycoprotein efflux inhibitor to enhance solubility and intestinal permeability with molecular modeling insights

Pardhi¹,

Tomar²,

Khemchandani³

et al. 2023

Preprint

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The aim of the study was to design and develop a supramolecular formulation of sulpiride (SUL) to enhance its solubility, dissolution, and permeability. This was accomplished by co-amorphizing SUL with Naringin (NARI) to improve its physicochemical properties. In addition, NARI was incorporated as a co-former to enhance the drug's intestinal permeability by targeting P-glycoprotein (P-gp) inhibition. To confirm the intermolecular interaction and formation of the co-amorphous system, extensive characterization was performed. This included quantum mechanics-based molecular dynamics simulation studies investigating intermolecular interactions and phase transformation. The findings of the miscibility study, Radial Distribution Function (RDF) analysis, and quantitative simulations of hydrogen/π-π bond interactions helped in comprehending the co-amorphization aspects of SUL-NARI systems. Molecular docking studies were conducted to predict the in-silico biological activity. The solubility, dissolution, and ex-vivo permeability studies were performed to determine the extent of improvement in solubility, dissolution and flux, demonstrating 31.88-fold, 9.13-fold, and 1.91-fold increments, respectively. In conclusion, this study demonstrates the benefits of synthesizing a drug-nutraceutical supramolecular formulation to enhance the solubility and permeability of poorly soluble and permeable drug.

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Section: Solid State Characterization Of Cammentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A study of monophasic supramolecular formulation of Sulpiride with P-glycoprotein efflux inhibitor to enhance solubility and intestinal permeability with molecular modeling insights

Pardhi¹,

Tomar²,

Khemchandani³

et al. 2023

Preprint

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“…Amorphous active pharmaceutical ingredients (APIs) are among the top sought-out solutions for increasing the bioavailability of modern drugs [ 1 , 2 , 3 , 4 , 5 ]. The disordered state of amorphous/glassy materials significantly (often multifold) enhances the dissolution of the API in the bloodstream, being particularly beneficial in the case of drugs of low solubility [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Indomethacin: Effect of Diffusionless Crystal Growth on Thermal Stability during Long-Term Storage

et al. 2023

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Differential scanning calorimetry and Raman spectroscopy were used to study the nonisothermal and isothermal crystallization behavior of amorphous indomethacin powders (with particle sizes ranging from 50 to 1000 µm) and their dependence on long-term storage conditions, either 0–100 days stored freely at laboratory ambient temperatures and humidity or placed in a desiccator at 10 °C. Whereas the γ-form polymorph always dominated, the accelerated formation of the α-form was observed in situations of heightened mobility (higher temperature and heating rate), increased amounts of mechanically induced defects, and prolonged free-surface nucleation. A complex crystallization behavior with two separated crystal growth modes (originating from either the mechanical defects or the free surface) was identified both isothermally and nonisothermally. The diffusionless glass–crystal (GC) crystal growth was found to proceed during the long-term storage at 10 °C and zero humidity, at the rate of ~100 µm of the γ-form surface crystalline layer being formed in 100 days. Storage at the laboratory temperature (still below the glass transition temperature) and humidity led only to a negligible/nondetectable GC growth for the fine indomethacin powders (particle size below ~150 µm), indicating a marked suppression of GC growth by the high density of mechanical defects under these conditions. The freely stored bulk material with no mechanical damage and a smooth surface exhibited zero traces of GC growth (as confirmed by microscopy) after >150 days of storage. The accuracy of the kinetic predictions of the indomethacin crystallization behavior was rather poor due to the combined influences of the mechanical defects, competing nucleation, and crystal growth processes of the two polymorphic phases as well as the GC growth complex dependence on the storage conditions within the vicinity of the glass transition temperature. Performing paired isothermal and nonisothermal kinetic measurements is thus highly recommended in macroscopic crystallization studies of drugs with similarly complicated crystal growth behaviors.

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“…4 On the other hand, the amorphous forms are often less stable thermodynamically than crystalline forms, necessitating specialized strategies in drug formulations. [5][6][7][8] The molecular packing in crystals can be studied by means of X-ray crystallography [9][10][11] and NMR crystallography, [12][13][14] while molecular reorientation, and broadly molecular mobility, can be explored across different time scales by using several experimental (nuclear magnetic resonance, [15][16][17] dielectric spectroscopy 18 or neutron scattering [19][20][21][22][23][24] ) and calculation methods (first principles, MD). 19,[25][26][27][28][29] Molecular arrangement and intra-and intermolecular forces also influence the molecular mobility and reorientations of the molecular groups, 3,30,31 and it is a significant parameter because it is considered to be a crucial factor for reliably predicting the physical stability of pharmaceutical solids.…”

Section: Introductionmentioning

confidence: 99%

Experimental and theoretical insights into the structure and molecular dynamics of 2,3,3′,4′-tetramethoxy-trans-stilbene – a chemopreventive agent

Pajzderska

Wierzchowski

Łażewski

et al. 2023

Phys. Chem. Chem. Phys.

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Amorphous systems for delivery of nutraceuticals: challenges opportunities

Cited by 14 publications

References 138 publications

A study of monophasic supramolecular formulation of Sulpiride with P-glycoprotein efflux inhibitor to enhance solubility and intestinal permeability with molecular modeling insights

A study of monophasic supramolecular formulation of Sulpiride with P-glycoprotein efflux inhibitor to enhance solubility and intestinal permeability with molecular modeling insights

Indomethacin: Effect of Diffusionless Crystal Growth on Thermal Stability during Long-Term Storage

Experimental and theoretical insights into the structure and molecular dynamics of 2,3,3′,4′-tetramethoxy-trans-stilbene – a chemopreventive agent

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