scholarly journals Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues

2020 ◽  
Vol 21 (16) ◽  
pp. 5741
Author(s):  
Verônica Muniz Couto ◽  
Laura de Oliveira-Nascimento ◽  
Luiz Fernando Cabeça ◽  
Danilo Costa Geraldes ◽  
Juliana Souza Ribeiro Costa ◽  
...  
Keyword(s):  
Titration Calorimetry ◽  
Phase Solubility ◽  
Cyclodextrin Complex ◽  
Scanning Calorimetry ◽  
High Association ◽  
Solubility Study ◽  
Freeze Dried ◽  
Phase Solubility Study ◽  
Charged Form

Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-β-CD), as shown by the phase solubility study. The resulting complex (HP-β-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and 1H-NMR. The freeze-dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2% mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug delivery.

scholarly journals Investigating the phase-solubility and compatibility study of anticancer drug complexed with β-cyclodextrin and HP–β-cyclodextrin

2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Preeti Dhurve ◽  
Atul Tripathi ◽  
Bina Gidwani ◽  
Amber Vyas
Keyword(s):  
Aqueous Solubility ◽  
Phase Solubility ◽  
Compatibility Study ◽  
Formulation Development ◽  
Scanning Calorimetry ◽  
Solubility Study ◽  
Kneading Method ◽  
Phase Solubility Study ◽  
Critical Problems ◽  
Ft Ir

Poor  aqueous  solubility  and  dissolution  rates  are  critical  problems  that  hinders  the  formulation, development  and  delivery  of  most  of  BCS  class  II  and  class  IV  drugs.  Gefitinib  is  a  cytotoxic chemotherapeutic  drug  used  in  treatment  of  cancer.    The  objective  of  the  present  study  was  to investigate  the  drug-cyclodextrin  compatibility  study  by  FTIR  and  DSC  study.  The  phase solubility  study  revealed  formation  of  1:1  stoichiometry  binary  inclusion  complex.  The  complex was  prepared  by  kneading  method.  FT-IR  spectra  provided  the  data  indicating  that  the  HP-β-CD was  more  effective  than  β-CD.  Differential  scanning  calorimetry  thermograms  indicated  stronger amorphization and entrapment of  gefitinib with HP-β-CD.

scholarly journals Preparation, Characterization, and Bioavailability of Host-Guest Inclusion Complex of Ginsenoside Re with Gamma-Cyclodextrin

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7227
Author(s):  
Hui Li ◽  
Guolei Zhang ◽  
Wei Wang ◽  
Changbao Chen ◽  
Lili Jiao ◽  
...  
Keyword(s):  
Inclusion Complex ◽  
Water Solubility ◽  
Area Under The Curve ◽  
Relative Bioavailability ◽  
Docking Studies ◽  
Solubility Parameters ◽  
Phase Solubility ◽  
Scanning Calorimetry ◽  
Ginsenoside Re

This work aimed at improving the water solubility of Ginsenoside (G)-Re by forming an inclusion complex. The solubility parameters of G-Re in alpha (α), beta (β), and gamma (γ) cyclodextrin (CD) were investigated. The phase solubility profiles were all classified as AL-type that indicated the 1:1 stoichiometric relationship with the stability constants Ks which were 22 M−1 (α-CD), 612 M−1 (β-CD), and 14,410 M−1 (γ-CD), respectively. Molecular docking studies confirmed the results of phase solubility with the binding energy of −4.7 (α-CD), −5.10 (β-CD), and −6.70 (γ-CD) kcal/mol, respectively. The inclusion complex (IC) of G-Re was prepared with γ-CD via the water-stirring method followed by freeze-drying. The successful preparation of IC was confirmed by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In-vivo absorption studies were carried out by LC-MS/MS. Dissolution rate of G-Re was increased 9.27 times after inclusion, and the peak blood concentration was 2.7-fold higher than that of pure G-Re powder. The relative bioavailability calculated from the ratio of Area under the curve AUC0–∞ of the inclusion to pure G-Re powder was 171%. This study offers the first report that describes G-Re’s inclusion into γ-CD, and explored the inclusion complex’s mechanism at the molecular level. The results indicated that the solubility could be significantly improved as well as the bioavailability, implying γ-CD was a very suitable inclusion host for complex preparation of G-Re.

scholarly journals Enhanced Solubility, Stability, and Herbicidal Activity of the Herbicide Diuron by Complex Formation with β-Cyclodextrin

Polymers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1396 ◽  
Author(s):  
Shuang Gao ◽  
Jing-Yu Jiang ◽  
Yan-Yan Liu ◽  
Ying Fu ◽  
Li-Xia Zhao ◽  
...  
Keyword(s):  
Inclusion Complex ◽  
1H Nmr ◽  
Water Solubility ◽  
Herbicidal Activity ◽  
Environmental Damage ◽  
Phase Solubility ◽  
Scanning Calorimetry ◽  
Enhanced Solubility ◽  
Phase Solubility Study ◽  
Herbicide Diuron

The herbicide diuron is hardly soluble in water and most organic solvents and is usually made into a wettable powder or mixed with soil when used, which causes environmental risk and a reduction in herbicidal efficacy. In this study, the physicochemical properties were changed by using β-cyclodextrin (β-CD) to encapsulate diuron to form an inclusion complex. Some key technologies, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and nuclear magnetic resonance (1H NMR), were used to characterize the inclusion complex. The stoichiometry of the inclusion complex was determined by recording the 1H NMR spectrum or by using a diagram of inclusion ratios. A phase solubility study proved that the formed inclusion complex exhibited higher water solubility. Thermogravimetric analysis (TGA) demonstrated that the formed inclusion complex exhibited better thermal stability. Biological activity studies indicated that the herbicidal activity, in terms of herbicide removal, of the formed inclusion complex was higher than that of the original diuron. In general, the formation of the inclusion complex could reduce the environmental damage caused by diuron and enhance its herbicidal activity, providing an environmentally friendly method for using diuron.

Development and Characterization of the Neuroregenerative Xanthohumol C/Hydroxypropyl-β-cyclodextrin Complex Suitable for Parenteral Administration

Planta Medica ◽  
2019 ◽  
Vol 85 (16) ◽  
pp. 1233-1241
Author(s):  
Michael Kirchinger ◽  
Lara Bieler ◽  
Julia Tevini ◽  
Michael Vogl ◽  
Elisabeth Haschke-Becher ◽  
...  
Keyword(s):  
Water Solubility ◽  
Pharmaceutical Research ◽  
Water Soluble ◽  
Complexing Agents ◽  
Cyclodextrin Complex ◽  
Scanning Calorimetry ◽  
In Vivo Experiments ◽  
Strong Candidate

AbstractThe chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for in vivo experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling in vivo administration. Cyclodextrins were used as water-soluble and nontoxic complexing agents, and the complex of Xanthohumol C and 2-hydroxypropyl-β-cyclodextrin was characterized using HPLC, HPLC-MS, NMR, and differential scanning calorimetry. The water solubility of Xanthohumol C increases with increasing concentrations of cyclodextrin. Using 50 mM 2-hydroxypropyl-β-cyclodextrin, solubility was increased 650-fold. Furthermore, in vitro bioactivity of Xanthohumol C in free and complexed form did not significantly differ, suggesting the release of Xanthohumol C from 2-hydroxypropyl-β-cyclodextrin. Finally, a small-scaled in vivo experiment in a rat model showed that after i. p. administration of the complex, Xanthohumol C can be detected in serum, the brain, and the cerebrospinal fluid at 1 and 6 h post-administration. Mean (± SD) Xanthohumol C serum concentrations after 1, 6, and 12 h were determined as 463.5 (± 120.9), 61.9 (± 13.4), and 9.3 (± 0.8) ng/mL upon i. v., and 294.3 (± 22.4), 45.5 (± 0.7), and 13 (± 1.0) ng/mL after i. p. application, respectively. Accordingly, the formulation of Xanthohumol C/2-hydroxypropyl-β-cyclodextrin is suitable for further in vivo experiments and further pharmaceutical research aiming for the determination of its neuroregenerative potential in animal disease models.

scholarly journals Characterization, in Vitro and in Vivo Evaluation of Naringenin-Hydroxypropyl-β-Cyclodextrin Inclusion for Pulmonary Delivery

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 554 ◽  
Author(s):  
Minyi Guan ◽  
Rui Shi ◽  
Yuying Zheng ◽  
Xuan Zeng ◽  
Weiyang Fan ◽  
...  
Keyword(s):  
Pulmonary Delivery ◽  
Pharmacokinetic Profile ◽  
Proton Nuclear Magnetic Resonance ◽  
Flavonoid Compound ◽  
Phase Solubility ◽  
Local Concentration ◽  
Nmr Studies ◽  
Solubility Study ◽  
Phase Solubility Study

Naringenin, a flavonoid compound which exists abundantly in Citrus fruits, is proven to possess excellent antitussive and expectorant effects. However, the clinical applications of naringenin are restricted by its poor solubility and low local concentration by oral administration. The aim of the present study is to prepare a naringenin-hydroxypropyl-β-cyclodextrin (naringenin-HPβCD) inclusion as an inhalation solution for pulmonary delivery. The naringenin-HPβCD inclusion was characterized by phase solubility study, XRD, differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1HNMR), and two-dimensional rotating frame Overhauser effect spectroscopy (2D ROESY). The in vitro permeability of the inclusion was evaluated on Calu-3 cells and the pharmacokinetic profile of pulmonary delivery was investigated in Sprague-Dawley (SD) rats. Based on the linear model of phase solubility study, the relationship between naringenin and HPβCD was identified as AL type with a 1:1 stoichiometry. XRD, DSC, and NMR studies indicated that the entire naringenin molecule is encapsulated into the cavity of HPβCD. HPβCD could increase the concentration of naringenin in the epithelium-lining fluid (ELF) of Calu-3 cells and act as a sustained release system for naringenin. The pharmacokinetic profile of naringenin-HPβCD inclusion showed rapid response and higher local concentration by pulmonary delivery. In conclusion, pulmonary delivery of naringenin-HPβCD inclusion is a promising formulation strategy, which could provide a new possibility for the clinical application of naringenin.

scholarly journals Inclusion Complex of Fexofenadine Hydrochloride with Cyclodextrins

2021 ◽  
Vol 11 (3) ◽  
pp. 282
Author(s):  
Melita Huremovic ◽  
Majda Srabovic ◽  
Mirsada Salihovic ◽  
Ekrem Pehlic
Keyword(s):  
Bathochromic Shift ◽  
Aqueous Solubility ◽  
Taste Masking ◽  
Solid Inclusion ◽  
Phase Solubility ◽  
Covalent Bonds ◽  
Molar Ratios ◽  
Solubility Study ◽  
Phase Solubility Study ◽  
Vis Spectroscopy

<p>Fexofenadine hydrochloride (FFN), (±)-4-[1-hydroxy-4[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl] α,α-dimethylbenzeneacetic acid hydrochloride, is a second-generation antihistamine that is used to treat allergies. The drug is highly hydrophobic and slightly soluble in water. Cyclodextrins are widely used to improve the physicochemical and pharmaceutical properties such as solubility, stability, and bioavailability of poorly soluble drug molecules.Cyclodextrins can molecularly encapsulate various drugs into their hydrophobic cavity without forming any covalent bonds. Cyclodextrin (CDs), especially ß-Cyclodextrin (ß-CD), are widely used in the pharmaceutical field due to its ability to stabilize drug molecules and taste masking purposes.<strong> </strong></p><p>The phase solubility study was performed according to the method of Higuchi and Connors by adding the fexofenadine hydrochloride in excess to different concentrations of cyclodextrin solutions. Phase solubility study records show that the stability constant and complex stoichiometry of FFN-CD complexes increases linearly with CD concentration. Also, an increase in the concentration of β-cyclodextrin leads to an increase in the aqueous solubility of FFN. Complexes were analyzed by UV-VIS spectroscopy using the calibration curve of FFN. Also, UV-VIS spectra indicate a bathochromic shift which proves that complex formation has occurred.</p><p>Solid inclusion complexes of fexofenadine/β-cyclodextrin and its derivatives were prepared at the molar ratios of 1:1 by the physical mixing method. Characterization of the complexes was performed by using infrared spectroscopy. </p>

scholarly journals Improved water solubility of quercetin by preparing complexation with cyclodextrins in binary solvent

2021 ◽  
Vol 18 (4) ◽  
pp. 701-708
Author(s):  
Pham Thi Lan ◽  
Pham Long Khanh ◽  
Nguyen Thi Ngoan ◽  
Le Hai Khoa ◽  
Vu Xuan Minh ◽  
...  
Keyword(s):  
Water Solubility ◽  
Biological Effects ◽  
Pure Water ◽  
Phase Solubility ◽  
Binary Solvent ◽  
Complexation Reaction ◽  
Cyclodextrin Complex ◽  
Pharmaceutical Industries

The antioxidant capacity of polyphenols have been widely used in food and pharmaceutical industries. Quercetin (Quer) is a polyphenolic flavonoid that shows several biological effects such as antioxidant, antitumor, antibacterial and antiproliferative effects both in-vitro and in-vivo. However, the solubility of quercetin in water is poor. Thus, it is essential to improve solubility of quercetin in pharmaceuticals by making its complexation with other compounds. In this study, the synthesis of the 2-hydroxypropyl-β-cyclodextrin complex with quercetin (Quer-HPβCD) in the form of nanoparticles in water-ethanol solvents has been carried out. The results showed that the obtained yield of (Quer-HPβCD) complexation in binary solvent was greater than that in pure water. The highest Y value was 80% in a binary solvent with 20% v/v of ethanol. The composition, morphology, structural and thermodynamic properties of the nanoparticles Quer-HPβCD have been determined. This study demonstrated that using mixed water- ethanol solvent and lyophilization technique was able to produce quercetin nanoparticles with significantly smaller particle size. The nanoparticles have a spherical shape with an average size of about 40-60 nm. The results of the phase solubility diagram showed that in water the solubility of quercetin increased and linearly depended on the concentration of host’s molecule while Quer and HP-βCD obtained a 1:1 stoichiometric complex. The stability constant of (Quer-HPβCD) complex was found to be logK = 2.56. The Gibbs energy change of the complexation reaction was found to be -14.60 kJ/mol.

scholarly journals Dissolution Enhancement of Flurbiprofen by Solid Dispersion Adsorbate Technique

2021 ◽  
Vol 69 (2) ◽  
Author(s):  
Sohansinh S. Vaghela ◽  
Samkit M. Shah ◽  
Sanjesh G. Rathi ◽  
Shrenik K. Shah
Keyword(s):  
Solid Dispersion ◽  
Aqueous Solubility ◽  
Dissolution Enhancement ◽  
Phase Solubility ◽  
Fusion Method ◽  
Poloxamer 188 ◽  
X Ray ◽  
Solubility Study ◽  
Phase Solubility Study

Flurbiprofen solid dispersion Adsorbate (SDA) has been prepared using PEG 4000 and Poloxamer 188 as carrier and Neusilin as adsorbent material. The SDA of Flurbiprofen was prepared by using Fusion method in various drugs to carrier ratios. The phase solubility study concludes that both polymers have ability to improve the aqueous solubility of flurbiprofen. Pure API Flurbiprofen and final formulation samples of SDA are characterized by FTIR, DSC and X-ray diffraction spectroscopy. X-ray powder diffraction and DSC study indicated that the drug was present in amorphous form. FTIR study revealed that the characteristic peaks in spectra of pure Flurbiprofen are also present in spectra of SDA’s. Drug found compatible with the excipients. The highest improvement in solubility and in-vitro drug release were observed in solid dispersion prepared with Poloxamer 188 (F14) by fusion method. The increased dissolution rate of drug from solid dispersion adsorbates may be due to surface tension lowering effect of polymer to the medium and increased wettability and dispersibility of drug. Hence, F14 Solid dispersion adsorbates with the Poloxamer carrier in 1:2 ratio considered as most satisfactory among all solid dispersion adsorbates.

Systematic Development of Bicalutamide Immediate Release Pellets using Aeroperl and Non-MCC Extruder aid

2020 ◽  
Vol 15 ◽  
Author(s):  
Hardik Rana ◽  
Hussain Hasan ◽  
Mukesh Gohel ◽  
Vaishali Thakkar ◽  
Tejal Gandhi
Keyword(s):  
Drug Release ◽  
Propylene Glycol ◽  
Microcrystalline Cellulose ◽  
Immediate Release ◽  
Phase Solubility ◽  
Disintegration Time ◽  
Solubility Study ◽  
Short Period ◽  
Phase Solubility Study ◽  
Pellet Formulation

Background: The Microcrystalline Cellulose is called as a gold standard for the manufacture of pellets. The poor disintegration leads to incomplete drug release restricts the use of MCC in the immediate-release formulation. Objective: The present work aims to explore non-MCC extruder aid for pellet formulation and solubility modulation potential of Aeroperl® 300 Pharma. Methods: Bicalutamide (BCL) was selected as a model BCS class-II drug. The solubility of BCL was assessed in different vehicles like polyethylene glycol, propylene glycol, and Tween by carrying out phase solubility study. The suitable vehicle was selected based on the higher solubility of BCL. The vehicle was further adsorbed on newer adsorbent Aeroperl® 300 Pharma to formulate liquisolid granules. The liquisolid granules were further incorporated into the pellet using mannitol and microcrystalline cellulose as an extruder aid. Box-Behnken design was adopted for optimization of formulation considering MCC: mannitol ratio, concentration of HPMC and spheronizer speed as independent factors whereas drug release at 30 min, disintegration time and aspect ratio were selected as dependent variables. The pellets were evaluated for different evaluation parameters. Results: Propylene glycol was selected for the formulation of liquisolid technique based on the results of the phase solubility study. Propylene glycol containing BCL was adsorbed on Aeroperl 300 Pharma. The optimized batch was selected exploring the Design-Expert software by considering limits of different responses. Pellet had excellent flowability. Friability was found to be within the range (<1%). Pellets were found to be spherical and had pores on the surfaces. Conclusion: Liquisolid granules containing newer solubilizer Aeroperl was found to be a promising approach for the improvement in the solubility of the drug. The use of mannitol with MCC has a profound effect on disintegration time, without altering flow property and other parameters. No patents were reported on the combination of Bicalutamide, mannitol and Aeroperl. The critical finding of the present work is to use mannitol as an extruder aid to fasten the disintegration leads to complete drug release within a short period of time. Aeroperl and Mannitol, MCC: mannitol ratio, concentration of HPMC and spheronizer speed was found to be significant and had the potential effect in pellet formulation.

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