Abstract:Cyclodextrin (CD) complexes are frequently used for enhancing the solubility or absorption of poorly water-soluble drugs. On the contrary, little is known about their complex formation with water-soluble drugs. Here, we have studied the interaction between 2-hydroxypropyl β-CD (HPβCD) and three water-soluble drugs, namely naloxone (NX), oxycodone (OC), and tramadol (TR), by isothermal titration calorimetry (ITC) combined with molecular modeling in view of the potential impact on drug release. The results showe… Show more
“…The addition of KLEPTOSE ® HPB might interact with polysorbates to prevent their degradation. KLEPTOSE ® HPB may also dissolve insoluble degradants of polysorbates due to its ability to form complexation with hydrophobic molecules [ 35 ], and hence suppress particle formation. Therefore, the combination of KLEPTOSE ® HPB and polysorbate was able to enhance the protein formulation.…”
Monoclonal antibodies require careful formulation due to their inherent stability limitations. Polysorbates are commonly used to stabilize mAbs, but they are prone to degradation, which results in unwanted impurities. KLEPTOSE® HPβCD (hydroxypropyl beta-cyclodextrin) has functioned as a stable stabilizer for protein formulations in our previous research. The current study investigates the collaborative impact of combining polysorbates and HPβCD as excipients in protein formulations. The introduction of HPβCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein–protein interactions by HPβCD. In bevacizumab formulations, the subvisible particle counts per 0.4 mL of samples in commercial formulations vs. formulations containing both HPβCD and polysorbates subjected to distinct stressors were as follows: agitation, 87,308 particles vs. 15,350 particles; light, 25,492 particles vs. 6765 particles; and heat, 1775 particles vs. 460 particles. Isothermal titration calorimetry (ITC) measurement indicated a weak interaction between PS 80 and HPβCD, with a KD value of 74.7 ± 7.5 µM and binding sites of 5 × 10–3. Surface tension measurements illustrated that HPβCD enhanced the surface activity of polysorbates. The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry.
“…The addition of KLEPTOSE ® HPB might interact with polysorbates to prevent their degradation. KLEPTOSE ® HPB may also dissolve insoluble degradants of polysorbates due to its ability to form complexation with hydrophobic molecules [ 35 ], and hence suppress particle formation. Therefore, the combination of KLEPTOSE ® HPB and polysorbate was able to enhance the protein formulation.…”
Monoclonal antibodies require careful formulation due to their inherent stability limitations. Polysorbates are commonly used to stabilize mAbs, but they are prone to degradation, which results in unwanted impurities. KLEPTOSE® HPβCD (hydroxypropyl beta-cyclodextrin) has functioned as a stable stabilizer for protein formulations in our previous research. The current study investigates the collaborative impact of combining polysorbates and HPβCD as excipients in protein formulations. The introduction of HPβCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein–protein interactions by HPβCD. In bevacizumab formulations, the subvisible particle counts per 0.4 mL of samples in commercial formulations vs. formulations containing both HPβCD and polysorbates subjected to distinct stressors were as follows: agitation, 87,308 particles vs. 15,350 particles; light, 25,492 particles vs. 6765 particles; and heat, 1775 particles vs. 460 particles. Isothermal titration calorimetry (ITC) measurement indicated a weak interaction between PS 80 and HPβCD, with a KD value of 74.7 ± 7.5 µM and binding sites of 5 × 10–3. Surface tension measurements illustrated that HPβCD enhanced the surface activity of polysorbates. The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry.
“…31 Nevertheless, the binding interactions of CD, even with water-soluble molecules, are spontaneous and favored. 32,33 Arg and Hist are both hydrophilic amino acids containing hydrophobic parts. Hist is more hydrophilic than Arg, but Arg is more flexible than Hist.…”
Section: Ph Measurements and Structural Visualization Of Complexesmentioning
confidence: 99%
“…So, no special preparation techniques are needed because the solubility of Arg and His does not affect the spontaneous complex formation with CD. 33 However, the encapsulation of the hydrophobic part of the amino acid is an entropy-driven process as it requires desolvation while releasing water molecules from the CD cavity. 36,37 The coprecipitation technique initially deals with the hydration of the amino acid and the CD molecules.…”
Section: Ph Measurements and Structural Visualization Of Complexesmentioning
The inclusion complexes of α-, β-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin with two amino acid stereoisomers (L-, D-arginine and L-, D-histidine) were studied by using differential scanning calorimetry, thermogravimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy methods. The solid inclusion compounds were prepared in a 1:1 molar ratio of the host and guest using the co-precipitation method. The pH measurements and structural visualization of complexes were carried out. The obtained results proved the formation of the complexes and revealed that the size and the symmetry of the cyclodextrin (CD) and also the structure and flexibility of the amino acid molecule had a significant influence on the complexation interaction. The correlation of the experimental data shows that βCD has a preference to form more stable complexes with levogir isomers of amino acid than αCD and 2-hydroxypropyl-α-cyclodextrin. The complexation of the amino acids isomers was accomplished by partial inclusion of the guest molecule in the CD cavity, and it was observed that CDs could better discriminate between histidine isomers than between arginine isomers.
“…HPβCD ( Fig. 1 (b)), on the other hand, is a hydrophilic derivative of cyclodextrin characterized by its hydroxyalkyl substituents, which impart water solubility and facilitate interactions with hydrophobic guest molecules [ 33 ]. Fig.…”
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