Effect of Cyclodextrin Complexation on the Aqueous  Solubility of Diazepam and Nitrazepam: Phase-Solubility Analysis, Thermodynamic Properties

The content of this investigation was to study the influence of β-cyclodextrin and hydroxy propyl-β-cyclodextrin complexation on enhancement of solubility and dissolution rate of isradipine. Based on preliminary phase solubility studies, solid complexes prepared by freeze drying method in 1:1 molar ratio were selected and characterized by DSC for confirmation of complex formation. Prepared solid dispersions were evaluated for drug content, solubility and in vitro dissolution. The physical stability of optimized formulation was studied at refrigerated and room temperature for 2 months. Solid state characterization of optimized complex performed by DSC and XRD studies. Dissolution rate of isradipine was increased compared with pure drug and more with HP-β-CD inclusion complex than β-CD. DSC and XRD analyzes that drug was in amorphous form, when the drug was incorporated as isradipine β-CD and HP-β-CD inclusion complex. Stability studies resulted in low or no variations in the percentage of complexation efficiency suggesting good stability of molecular complexes. The results conclusively demonstrated that the enhancement of solubility and dissolution rate of isradipine by drug-cyclodextrin complexation was achieved.

Download Full-text

Improving the Solubilization and Bioavailability of Arbidol Hydrochloride by the Preparation of Binary and Ternary β-Cyclodextrin Complexes with Poloxamer 188

Pharmaceuticals ◽

10.3390/ph14050411 ◽

2021 ◽

Vol 14 (5) ◽

pp. 411

Author(s):

Md. Khalid Anwer ◽

Muzaffar Iqbal ◽

Mohammad Muqtader Ahmed ◽

Mohammed F. Aldawsari ◽

Mohd Nazam Ansari ◽

...

Keyword(s):

Antiviral Agent ◽

Aqueous Solubility ◽

Phase Solubility ◽

Pharmacokinetic Studies ◽

Solubility Curve ◽

Cyclodextrin Complexes ◽

Poloxamer 188 ◽

The Stability

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188.

Download Full-text

Evaluation the effect of cyclodextrin complexation on aqueous solubility of fluorometholone to achieve ophthalmic solution

Journal of Inclusion Phenomena and Macrocyclic Chemistry ◽

10.1007/s10847-009-9590-1 ◽

2009 ◽

Vol 65 (3-4) ◽

pp. 335-340 ◽

Cited By ~ 2

Author(s):

Bizhan Malaekeh-Nikouei ◽

Sayyed A. Sajadi Tabassi ◽

Hossein Ashari ◽

Ali Gholamzadeh

Keyword(s):

Ophthalmic Solution ◽

Aqueous Solubility ◽

Cyclodextrin Complexation

Download Full-text

Cyclodextrin inclusion complexes of the antioxidant α-lipoic acid

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s205327331409007x ◽

2014 ◽

Vol 70 (a1) ◽

pp. C992-C992 ◽

Cited By ~ 1

Author(s):

Mino Caira ◽

Susan Bourne ◽

Buntubonke Mzondo

Keyword(s):

Inclusion Complex ◽

Inclusion Complexes ◽

Lipoic Acid ◽

Aqueous Solubility ◽

Phase Solubility ◽

Monoclinic System ◽

Space Group ◽

Racemic Form ◽

Native Host

Owing to its potent antioxidant activity,α-lipoic acid (1,2-dithiolane-3-pentanoic acid) is widely used as a supplement and is recommended for treating a number of conditions including chronic liver disease and diabetes. The poor aqueous solubility of the acid (~0.003 M at 250C) has prompted studies of its interaction with cyclodextrins (CDs) as a possible route to improving its solubility. However, relatively few studies have focused on the isolation of solid CD inclusion complexes of the antioxidant, and in most cases the racemic form of the acid was employed. In the comprehensive study reported here, the bioactive (R)-(+)-enantiomeric form of the molecule was used exclusively, resulting in the isolation and structural characterization of its inclusion complexes with each of the native host CDs (α-, β- and γ-CD) as well as permethylated α-CD (TRIMEA), permethylated β-CD (TRIMEB) and 2,6-dimethylated-β-CD (DIMEB). The α-CD complex crystallizes in the trigonal system, space group R32, with three independent CD molecules in the asymmetric unit and is not isostructural with any known CD complex while the β-CD complex crystallizes in the monoclinic system (C2). With the host γ-CD, an orthorhombic (pseudo-tetragonal) inclusion complex was identified, an unusual result as γ-CD complexes generally crystallize in the tetragonal space group P4212. The complexes with TRIMEA and TRIMEB crystallize in the orthorhombic system (P212121), the modes of inclusion of the (R)-(+)-α-lipoic acid molecule in the respective hosts being reversed: the guest molecule is fully encapsulated by the former host with the dithiolane ring located at the secondary rim, while in the latter host, the dithiolane ring rests on the concave surface of the host cavity at the primary side. A significant level of guest disorder was detected in the inclusion complex with DIMEB (P21). Thermal and phase-solubility analyses complemented the X-ray structural studies.

Download Full-text

Inter-molecular physiochemical characterization for etodolac-hydroxypropyl-β-cyclodextrin polymeric systems in solid and liquid state

Open Chemistry ◽

10.2478/s11532-010-0066-3 ◽

2010 ◽

Vol 8 (4) ◽

pp. 953-962 ◽

Cited By ~ 2

Author(s):

Vivek Sinha ◽

Renu Chadha ◽

Honey Goel ◽

Keyword(s):

Solid State ◽

Inclusion Complexes ◽

Liquid State ◽

Chemical Properties ◽

Aqueous Solubility ◽

Phase Solubility ◽

Scanning Calorimetry ◽

Polymeric Systems ◽

Hydrophobic Molecule ◽

Physical And Chemical

AbstractThe purpose of this study was to explore the utility of hydroxypropyl-β-cyclodextrin (HP-β-CD) systems in forming inclusion complexes with the anti-rheumatic or anti-arthritic drug, etodolac (EDC), in order to overcome the limitation of its poor aqueous solubility. This inclusion system achieved high solubility for the hydrophobic molecule. The physical and chemical properties of each inclusion compound were investigated. Complexes of EDC with HP-β-CD were obtained using the kneading and co-evaporation techniques. Solid state characterization of the products was carried out using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and Scanning electron microscopy (SEM). Studies in the solution state were performed using UV-Vis spectrophotometry and 1H-NMR spectroscopy. Phase solubility profiles with HP-β-CD employed was found to be AL type. Stability constants (Kc) from the phase solubility diagrams were calculated indicating the formation of 1:1 inclusion complex. Stability studies in the solid state and in liquid state were performed; the possible degradation by RP-HPLC was monitored. The dissolution studies revealed that EDC dissolution rate was improved by the formation of inclusion complexes.

Download Full-text

Effect of hydroxypropyl-β-cyclodextrin complexation on the aqueous solubility, structure, thermal stability, antioxidant activity, and tyrosinase inhibition of paeonol

Journal of Inclusion Phenomena and Macrocyclic Chemistry ◽

10.1007/s10847-011-0003-x ◽

2011 ◽

Vol 72 (3-4) ◽

pp. 405-411 ◽

Cited By ~ 20

Author(s):

Jung-Ying Tsao ◽

Chien-Pang Wu ◽

Hsieh-Ho Tsai ◽

Kuang-Chia Peng ◽

Pi-Yun Lin ◽

...

Keyword(s):

Thermal Stability ◽

Antioxidant Activity ◽

Aqueous Solubility ◽

Tyrosinase Inhibition ◽

Cyclodextrin Complexation

Download Full-text

A Comprehensive Review on Cyclodextrin-Based Carriers for Delivery of Chemotherapeutic Cytotoxic Anticancer Drugs

BioMed Research International ◽

10.1155/2015/198268 ◽

2015 ◽

Vol 2015 ◽

pp. 1-15 ◽

Cited By ~ 166

Author(s):

Bina Gidwani ◽

Amber Vyas

Keyword(s):

Anticancer Drugs ◽

Delivery System ◽

Antineoplastic Agents ◽

Aqueous Solubility ◽

Chemotherapeutic Agents ◽

Review Article ◽

Administration Routes ◽

Cyclodextrin Complexation ◽

Important Approach ◽

Biopharmaceutical Properties

Most of the cytotoxic chemotherapeutic agents have poor aqueous solubility. These molecules are associated with poor physicochemical and biopharmaceutical properties, which makes the formulation difficult. An important approach in this regard is the use of combination of cyclodextrin and nanotechnology in delivery system. This paper provides an overview of limitations associated with anticancer drugs, their complexation with cyclodextrins, loading/encapsulating the complexed drugs into carriers, and various approaches used for the delivery. The present review article aims to assess the utility of cyclodextrin-based carriers like liposomes, niosomes, nanoparticles, micelles, millirods, and siRNA for delivery of antineoplastic agents. These systems based on cyclodextrin complexation and nanotechnology will camouflage the undesirable properties of drug and lead to synergistic or additive effect. Cyclodextrin-based nanotechnology seems to provide better therapeutic effect and sustain long life of healthy and recovered cells. Still, considerable study on delivery system and administration routes of cyclodextrin-based carriers is necessary with respect to their pharmacokinetics and toxicology to substantiate their safety and efficiency. In future, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents.

Download Full-text

Inclusion Complex of Fexofenadine Hydrochloride with Cyclodextrins

Mediterranean Journal of Chemistry ◽

10.13171/mjc02112181597huremovic ◽

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

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. 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.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.

Download Full-text

Dissolution Enhancement of Flurbiprofen by Solid Dispersion Adsorbate Technique

International Journal of Pharmaceutical Sciences Review and Research ◽

10.47583/ijpsrr.2021.v69i02.014 ◽

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.

Download Full-text

Development of Starch-Based Antifungal Coatings by Incorporation of Natamycin/Methyl-β-Cyclodextrin Inclusion Complex for Postharvest Treatments on Cherry Tomato against Botrytis cinerea

Molecules ◽

10.3390/molecules24213962 ◽

2019 ◽

Vol 24 (21) ◽

pp. 3962 ◽

Cited By ~ 6

Author(s):

Yuexi Yang ◽

Chen Huan ◽

Xianrui Liang ◽

Sheng Fang ◽

Jian Wang ◽

...

Keyword(s):

Inclusion Complex ◽

Botrytis Cinerea ◽

Corn Starch ◽

Tomato Fruit ◽

Aqueous Solubility ◽

Phase Solubility ◽

Waxy Corn Starch ◽

Reduce Weight Loss ◽

Postharvest Treatments

The application of natamycin as a natural fungicide in edible coatings is challenging because of its low aqueous solubility. In this study, the natamycin/methyl-β-cyclodextrin (N/ME-β-CD) inclusion complex was fabricated and incorporated into waxy corn starch-based coatings for postharvest treatments. The phase solubility of natamycin in the presence of ME-β-CD at 293.2 K, 303.2 K, and 313.2 K is determined and used to calculate the process thermodynamic parameters. The N/ME-β-CD inclusion complex was confirmed and characterized by FTIR and 1H NMR spectroscopy. The results indicated that the inclusion complex was formed and the hydrophobic part (C16-C26) of natamycin might be partially inserted into the cavity of ME-β-CD form the wide rim. The effects of N/ME-β-CD incorporated starch-based coatings (N/ME-β-CD S coatings) on postharvest treatments of cherry tomatoes were evaluated in vivo. The N/ME-β-CD S coatings could reduce weight loss, delay fruit ripening, and inhibit fruit decay caused by Botrytis cinerea in tomato fruit during storage.

Download Full-text