The modes of complexation of benzimidazole with aqueous β-cyclodextrin explored by phase solubility, potentiometric titration, 1H-NMR and molecular modeling studies

The results of rigorous modeling of phase solubility diagrams, pH solubility profiles and potentiometric titrations revealed the following for benzimidazole (BZ) and BZ/β-CD complexation in aqueous solution: (a) the pK _a value of BZ estimated at 5.66 ± 0.08 was reduced to 5.33 ± 0.06 in the presence of 15 mM β-CD at 25 °C, thus indicating inclusion complex formation; (b) BZ forms soluble 1:1 and 2:1 BZ/β-CD complexes with complex formation constants K ₁₁ = 104 ± 8 M⁻¹ and K ₂₁ = 16 ± 6 M⁻¹; (c) protonated BZ forms only 1:1 complex with K ₁₁ = 42 ± 12 M⁻¹; (d) ¹H-NMR studies in D₂O showed significant upfield chemical shift displacements for inner cavity β-CD protons indicating inclusion complex formation, while (e) Molecular modeling of BZ-β-CD interactions in water clearly indicated complete inclusion of one BZ molecule into the β-CD cavity.     

Determining the stoichiometry and binding constants of inclusion complexes formed between aromatic compounds and β-cyclodextrin by solid-phase microextraction coupled to high-performance liquid chromatography

The complexation of native β-cyclodextrin (CD) and seven aromatic compounds, namely, phenetole, toluene, m-xylene, naphthalene, biphenyl, fluorene and phenanthrene, has been studied for first time utilizing a solid-phase microextraction (SPME)–high-performance liquid chromatography (HPLC) method. The stoichiometries of the analyte:β-CD complexes were found to be either 1:1 or 1:2. The formation of 1:2 complexes was confirmed for naphthalene, biphenyl, fluorene, and phenanthrene only when utilizing relatively high concentrations of β-CD (up to 6.6 mM). The 1:2 stoichiometries were confirmed using the classical modified Benesi–Hildebrand (BH) method. The calculated binding constants for 1:1 stoichiometries (K₁) using the SPME method varied from 115.3 M⁻¹ for toluene to 3510 M⁻¹ for phenanthrene, whereas the corresponding values to the 1:2 stoichiometries (K₃) varied from 7.30 × 10⁵ M⁻² for biphenyl to 9.03 × 10⁶ M⁻² for naphthalene.     

Inclusion complexation of diclofenac with natural and modified cyclodextrins explored through phase solubility, 1H-NMR and molecular modeling studies

Guest–host interactions were examined for neutral diclofenac (Diclo) and Diclofenac sodium (Diclo sodium) with each of the cyclodextrin (CD) derivatives: α-CD, β-CD, γ-CD and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), all in 0.05 M aqueous phosphate buffer solution adjusted to 0.2 M ionic strength with NaCl at 20 °C, and with β-CD at different pHs and temperatures. The pH solubility profiles were measured to obtain the acid–base ionization constants (pK _as) for Diclo in the presence and absence of β-CD. Phase solubility diagrams (PSDs) were also measured and analyzed through rigorous procedures to obtain estimates of the complex formation constants for Diclo/CD and Diclo sodium/CD complexation in aqueous solutions. The results indicate that both Diclo and Diclo sodium form soluble 1:1 complexes with α-, β-, and HP-β-CD. In contrast, Diclo forms soluble 1:1 Diclo/γ-CD complexes, while Diclo sodium forms 1:1 and 2:1 Diclo/γ-CD, but the 1:1 complex saturates at 5.8 mM γ-CD with a solubility product constant (pK _sp = 5.5). Therefore, though overall complex stabilities were found to follow the decreasing order: γ-CD > HP-β-CD > β-CD > α-CD, some complex precipitation problems may be faced with aqueous formulations of Diclo sodium with γ-CD, where the overall concentration of the latter exceeds 5.8 mM γ-CD. Both ¹H-NMR spectroscopic and molecular mechanical modeling (MM⁺) studies of Diclo/β-CD indicate the possible formation of soluble isomeric 1:1 complexes in water.     

Effect of self-aggregation of γ-cyclodextrin on drug solubilization

The purpose of this study was to investigate the physicochemical properties of drug-saturated aqueous cyclodextrin (CD) solutions. Phase solubility profiles of different drugs were determined in aqueous solutions containing γ-cyclodextrin (γCD) and/or hydroxypropyl-γ-cyclodextrin (HPγCD) in absence or presence of water-soluble polymers. ¹H-NMR and turbidity analysis were performed as well as permeation studies. Phase solubility diagrams showed that the observed γCD content (1–20% w/v) was only slightly different from the theoretical values for aqueous solutions that had been saturated with indomethacin, diclofenac sodium or amphotericin B, all displayed A-type profiles, while it was less than the theoretical value in solutions that had been saturated with corticosteroids (hydrocortisone and dexamethasone) that displayed B_S-type profiles. In the latter case self-assemble of drug/CD complexes decreased the overall CD solubility. Water-soluble polymers enhanced aqueous solubility of the drugs tested by stabilizing the drug/CD complexes, i.e. enhancing their stability constants, without affecting the observed aqueous γCD solubility. When the drug solubility leveled off (the B_S-type profiles) the amount of dissolved γCD increased and approached the theoretical values. Hydrocortisone formed partial inclusion complex with γCD and HPγCD and no non-inclusion or aggregates could be detected in diluted solutions by ¹H-NMR. Both permeation and turbidity studies showed that formation of dexamethasone/γCD complex promoted CD aggregation. All these observations indicate that CD aggregate formations play a role in CD solubilization of lipophilic and poorly water-soluble drugs and that the water-soluble polymers enhance the complexation efficiency of γCD and HPγCD by stabilizing the self-assembled drug/CD nanoparticles and promote non-inclusion complex formation.     

A POTENTIOMETRIC STUDY OF METAL CHELATES WITH TETRAETHYLENEPENTAAMINEHEPTA-ACETIC ACID

Abstract

The protonation constants of tetraethylenepentaamineheptaacetic acid, TPHA, were determined by potentiometric titration in aqueous solution at an ionic strength of 0.10 M KNO₃ and at 25°C. The formation constants of various metal-TPHA complexes were also obtained by titrating mixtures of metal to ligand in molar ratios of 1 :1 and 2:1. Calculations were performed with the computer program BEST. Individual stability constants are reported for Co(II). Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and Pb(II) with TPHA as well as their related pro-tonated species. The stabilities of the 1:1 complexes parallel to those of similar complexes with DTPA and TTHA. However the 2: 1 complexes have significantly larger log K _ML's than their TTHA counterparts. The extra stability of the 2:1 metal-TPHA complexes is explained in terms of ligand denticity and steric effects. Mercury(II)-TPHA complexes exhibited the highest formation constants and the copper-TPHA complexes had slightly higher log K _ML's than those for Co(II), Ni(II), Zn(II), Cd(II) and Pb(II).     

Extraction of Alkali Metal (Li, Na, K) Picrates with Benzo-15-crown-5 into Various Organic Solvents. Elucidation of Fundamental Equilibria Determining the Extraction-ability and -selectivity

To quantitatively elucidate the effects of the benzo group on the extraction-selectively and -ability of benzo-15-crown-5 (B15C5)for alkali metal ions, the constants of the overall extraction (K_ex), thedistribution for various diluents having low dielectric constants (K_D,MLA), and the aqueousion-pair formation (K_MLA) of B15C5-alkali metal (Li, Na, K) picrate 1:1:1 complexes (MLA) weredetermined at 25 °C. The partition constants of B15C5were also measured at 25 °C. The log K_MLA values for Li⁺, Na⁺, and K⁺ are -0.32 ± 0.22, 2.66 ± 0.19, and 0.71 ± 0.47, respectively. In going from 15-crown-5 (15C5) to B15C5, the benzo group considerably decreasesthe K_MLA value for the same alkali metal ion. The distributionbehavior of B15C5 and its 1:1:1 complexes with the alkali metal picrates closely obeys regularsolution theory, omitting chloroform. Molar volumes and solubility parameters of B15C5and the 1:1:1 complexes were determined. For every diluent, the K_ex valuefor B15C5 increases in the order Li⁺ < K⁺ < Na⁺. K_D,MLA makes anunfavorable contribution to the Na⁺ extraction-selectivity of B15C5 because of the smallest molar volume of the Na(B15C5)A complex. The Na⁺ extraction-selectivity of B15C5 is determined completely by much the highest K_Na(B15C5)A value.The extraction-ability and -selectivity of B15C5 for the alkali metal picrates are compared with those of 15C5on the basis of the underlying equilibrium constants.     

Effect of Chloride Ions on the Hydrolysis of Trivalent Lanthanum,Praseodymium and Lutetium in Aqueous Solutions of 2 <Emphasis Type="Italic">M</Emphasis> Ionic Strength

The solubility product of the solid hydroxides and the first hydrolysis constants of trivalent ions of lanthanum, praseodymium and lutetium, were determined in 2 M NaClO₄(aq) and 2 M NaCl(aq) at 303 K, where M denotes the concentration in mol-L⁻¹. Solubility diagrams (pLn_(aq)−pC_H) were measured by means of a radiochemical method. The pC_H borderlines of precipitation and the solubility products were determined from these diagrams. The fitting of the solubility equation with the experimental values from the pLn_(aq)−pC_H diagrams also allowed the calculation of the first hydrolysis constants and the solubility products. In separate experiments, the stability constants for the first monohydroxide species were determined by means of potentiometric pH titrations, where the data were treated with both the program SUPERQUAD and by fitting of the results to the mean ligand number equation. Values of the log₁₀ < eqid20 > _1,Cl constants for the LnCl²⁺ species were also calculated at 2 M ionic strength and 303 K, using the hydrolysis constants obtained in both perchlorate and chloride media. The quantitative effects of chloride ions on the hydrolysis reactions and solubilities were determined for these three rare-earths spanning the lanthanide series.     

Synthesis,characterization, speciation and biological studies on metal chelates of 1-benzoyl(1,2,4-triazol-3-yl)thiourea

Proton-ligand association constants of 1-benzoyl(1,2,4-triazol-3-yl)thiourea (BTTU) and its complex formation constants with some bivalent metal ions Ni(II), Co(II), Mn(II), Zn(II), and Cu(II), have been determined potentiometrically in 50% EtOH–H₂O and 0.1 M NaNO₃. The complexes formed in solution have a stoichiometry of 1:1 and 1:2 [M:L], where M represents the metal ion and L the BTTU ligand. The corresponding thermodynamic parameters are derived and discussed. The complexes are stabilized by enthalpy changes and the results suggest that complexation is an enthalpy-driven process. The effects of metal ion, ionic radius, electronegativity, and nature of ligand on the formation constants are discussed. The formation constants of the complexes with 3d transition metals follow the order Mn²⁺ < Co²⁺ < Ni²⁺ < Cu²⁺ > Zn²⁺. The metal complexes were synthesized and characterized by elemental analyses, conductance, IR, ¹H NMR, and magnetic measurements. The low magnetic moment of 0.11 BM for the Cu(II) complex is suggestive of dimerization through Cu–Cu interaction. The concentration distribution diagrams of the complexes were evaluated. The ligands and their metal complexes have been screened in vitro against some bacteria and fungi.     

Potentiometric studies of binary and ternary complexes of Zn(II) with triethylenetetramine as primary ligand and selected amino acids and DNA units as secondary ligands

The acid-base equilibria of triethylenetetramine. (Trien) and the formation equilibria of binary and ternary complexes of Zn(II) with Trien as primary ligand and some selected arnino acids and DNA units as secondary ligands have been investigated. The results showed the formation of a 11 Zn (Trien)²⁺ complex. At higher pH, the Zn (Trien)²⁺ complex is hydrolysed to give Zn (Trien) (OH)⁺ and Zn(Trien)(OH)₂ complexes. The fraction of the monohydroxo species attains a maximum of 81.3% at pH 10. The stability constantsK _Zn(Trien)A ^Zn(Trien) for the ternary complexes were determined. Histidine coordinates in a histamine-like way. Lysine and ornithine ligate by the two amino groups. Serine and methionine are bound in a glycine-like mode. However, penicillamine, cysteine and glutathione ligate partly like mercaptoethylamine and partly like mercaptopropionic acid. In the case of DNA complexes, inosine is bound through the n₁ atom. However, uracil, undine, thymine and thymidine ligate through the N₃ atom. The relative stabilities of ternary complexes are compared with those of the corresponding binary complexes in terms of logK values. The concentration distribution diagrams of the complexes are evaluated.     

Stoichiometry, complex stability, molecular size and conformational variations of metal ion crown ether complexes subject to diffusion coefficients in nonaqueous solutions

Both the stoichiometry and complex stability constants of crown ether complexes with metal ions have been determined by examining gradual changes in their diffusional behavior in nonaqueous solution. Diffusion coefficients, D, were evaluated by pulsed field gradient (PFG) NMR titration experiments whilst complex stability constants were determined by nonlinear curve-fitting procedures, D versus c_sol., which also allow the treatment of multiple complexation equilibria (1:1 to 1:2 stoichiometries). Differences in the diffusion coefficients of the various free crown ethers with respect to their metal ion complexes indicate great sensitivity to both conformational changes and changes in molecular size upon complexation.     

Complex forming and extraction properties of oligo benzo-fused crown ethers

The complex forming properties with alkali metal and ammonium ions of a series of oligo benzo-condensed 18-crown-6 ethers1–8 having a different gradation of lipophilicity and of molecular rigidity are investigated by voltammetry at the interface of two immiscible electrolyte solutions (ITIES) and by a liquid-liquid extraction technique. The experimental results obtained in the two phase system H₂O/nitrobenzene are discussed in relation to the structure of the crown and the cation type. The stability constants for the 1 : 1 complexes of Na⁺, K⁺, Rb⁺, Cs⁺ and NH ₄ ⁺ in nitrobenzene have been determined and compared with the extraction constants for the 1: 1 complexes of Na⁺ and K⁺ and for the 1 : 1 and 1 : 2 complexes of Cs⁺, showing the effect of oligo benzo condensation for the 18-crown-6 system.     

Inclusion Complexation of Loratadine with Natural and Modified Cyclodextrins: Phase Solubility and Thermodynamic Studies

The extent and mode of solubility enhancement exerted by the cyclodextrins (α-, β-, γ-, and HP-β-CDs) on loratadine (Lort) have been experimentally measured under controlled conditions in buffered aqueous solutions. Rigorous nonlinear regression analysis of the phase solubility diagrams obtained in 0.1 mol⋅L⁻¹ phosphate buffer at pH=7.0 and 25 °C revealed the following: neutral Lort (pK _a =4.6) tends to form soluble 1:1 and 1:2 Lort/CD complexes with all four of the examined CDs, where complex stability follows the decreasing order β-CD>HP-β-CD>γ-CD>α-CD. The hydrophobic character of Lort constitutes about 66% of the driving force for complex formation whereas specific interactions contribute 11.2 kJ⋅mol⁻¹ towards the stability of the complexes. Thermodynamic studies showed that Lort/CD complex formation was favored by large enthalpic contributions but was impeded by negative entropic changes. Dissolution studies indicate that the dissolution rate of Lort from the freeze-dried Lort/β-CD complex is significantly higher than that of the corresponding physical mixture. Both DSC studies and molecular mechanical modeling of Lort/β-CD interactions were carried out to explore the possible formation of inclusion complexes.     

Mono- and binuclear complexes involving [Pd(N,N-dimethylethylenediamine)(H2O)2]2+, 4,4′-bipiperidine and DNA constituents

The Pd(dmen)Cl₂, where dmen?=?N,N-dimethethylenediamine, was synthesized and characterized by elemental analysis and spectroscopy. The complex-formation equilibria in the reaction of [Pd(dmen)(H₂O)₂]²⁺ with 4,4′-bipiperidine (Bip) and DNA constituents were investigated at 25°C and 0.1?mol?L^?1 ionic strength. The results show the formation of [(H₂O)(dmen)Pd(Bip)Pd(dmen)(H₂O)]⁴⁺. Inosine, uracil, and thymine interact with the previously mentioned complex by the substitution of two-coordinated water molecules. The formation constants of all possible mono- and binuclear complexes were determined and their speciation diagrams were evaluated.     

Speciation studies of mono- and binuclear Pd(II) complexes involving mixed nitrogen–sulfur donor ligand and 4,4′-bipiperidine as a linker

Pd(MME)Cl₂ complex, where MME = methionine methyl ester, was synthesized and characterized by elemental analysis and spectroscopic techniques. [Pd(MME)(H₂O)₂]²⁺ interacts with some DNA constituents giving 1 : 1 and 1 : 2 complexes. The binuclear complexes having 4,4′-bipiperidine as a linker and involving [Pd(MME)(H₂O)₂]²⁺ and DNA constituents were investigated. The results show formation of [(H₂O)(MME)Pd(Bip)Pd(MME)(H₂O)]⁴⁺. Inosine, uracil, and thymine interact with the previously mentioned complex by substitution of the two coordinated water molecules. Formation constants of all possible mono- and binuclear complexes were determined and their speciation diagrams were evaluated.     

Prednisone/Cyclodextrin Inclusion Complexation: Phase Solubility,Thermodynamic, Physicochemical and Computational Analysis

Guest–host interaction of prednisone (PN) with cyclodextrins (CDs) have been investigated using phase solubility diagrams (PSD), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM) and molecular mechanical modeling (MM). Estimates of the complex formation constant (K ₁₁) show that the tendency of PN to complex with CDs follows the order: β-CD>γ-CD>HP-β-CD>α-CD. At the same pH of 7.0, β-CD forms soluble 1:1 and insoluble 1:2 PN/CD complexes (B_S-type PSDs). The thermodynamic functions for 1:1 PN/β-CD estimated at pH = 7.0 (ΔG ₁₁^o=−20.8 kJ⋅mol⁻¹) show that complexation is driven by enthalpy (−30.7 kJ⋅mol⁻¹) but retarded by entropy (ΔS ₁₁^o=−33.1 J⋅mol⁻¹⋅K⁻¹) changes. The MM modeling study indicates the formation of different isomeric 1:1 complexes with CDs. PSD, DSC, XRPD, SEM and MM studies established the formation of inclusion complexes in solution and the solid state.     

Inclusion Complex of 4-Hydroxycoumarin with Cyclodextrins and Its Characterization in Aqueous Solution

The physicochemical properties of 4-hydroxy-7-methoxy-3-phenyl-2H-chromen-2-one (4HC) and β-cyclodextrins (CDs) inclusion complexes were investigated. The phase solubility profile of 4HC with β-cyclodextrin derivatives was classified as A_L-type. Stability constants for complexes with 1:1 molar ratios were calculated from the phase solubility diagrams and indicate the following trend: DMβCD>HPβCD>βCD. The highest value of the binding constant was for 4HC-DMβCD; the binding association constant (K _a) for this complex was determined at different temperatures and the thermodynamic data indicate that 4HC-DMβCD association is mainly an entropically driven process. ¹H NMR and ROESY were carried out, revealing that 4HC is embedded in the apolar cavity of DMβCD with the 4OH group buried in the cyclodextrin cavity with the phenyl group outside, near the primary rim. These results are in agreement with ORAC_FL values; the decrease in the antioxidant activity of 4HC-DMβCD is explained by the effective protection of the hydroxyl group due to complexation.     

Physicochemical characterization of terbinafine-cyclodextrin complexes in solution and in the solid state

Terbinafine (TB) is an allylamine derivative used as oral and topical antifungal agent. The physicochemical properties of the complexes between TB and different cyclodextrins (CDs): α-CD, β-CD, hydroxypropylβ-CD, methylβ-CD and γ-CD, have been studied in pH 12 aqueous solutions at 25 °C and in the solid state. Different phase solubility profiles of TB in the presence of CDs have been obtained: A_L type for TB with hydroxypropylβ-CD and γ-CD, A_P type for the complexes with methylβ-CD and α-CD, while a B_S profile was found for TB-β-CD. The apparent stability constants of the complexes were calculated at 25 °C from the phase solubility diagrams. The higher increase of TB solubility, up to 200-fold, together with the higher value of the stability constant were found for the complex with methylβ-CD. Solid systems of 1:1 drug:CD molar ratio were prepared and characterised using X-ray diffraction patterns, thermal analysis and FTIR spectroscopy. The coevaporation method can be considered the best method in preparing these solid complexes. The complexes of TB with natural CDs, except with α-CD, were crystalline, whereas the methyl and hydroxypropyl derivatives gave rise to amorphous phases. Dissolution rate studies have been performed with TB-β-CD and TB-HPβ-CD complexes, showing a positive influence of complexation on the drug dissolution.     

A Study of Haloperidol Inclusion Complexes with <Emphasis Type="Italic">β</Emphasis>-Cyclodextrin Using Phase Solubility,NMR Spectroscopy and Molecular Modeling Techniques

Guest-host interactions of haloperidol (Halo) with β-cyclodextrin (β-CD) have been investigated using several techniques including phase solubility diagrams (PSD), proton nuclear magnetic resonance (¹H-NMR), X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and molecular mechanical modeling (MM⁺). From an analysis of the PSDs, both protonated and neutral Halo (pK _a=8.5) form soluble 1:1 and 1:2 Halo/β-CD complexes, while the insoluble complex has 1:2 (Halo:β-CD) stoichiometry (B_S-type PSD). Ionization of Halo reduces its tendency to complex with β-CD, where the protonated species at pH=4.6 and 6.0 have K ₁₁ values of 100 L⋅mol⁻¹ and 298 L⋅mol⁻¹, respectively, compared with 2000 L⋅mol⁻¹ for neutral species at pH=10.6. The hydrophobic character of Halo was found to provide 32% of the driving force for complex stability, whereas other factors including specific interactions contribute −15 kJ⋅mol⁻¹. ¹H-NMR and MM⁺ studies indicate the formation of isomeric 1:1 and 1:2 complexes, where the chlorophenyl, flurophenyl, piperidine and butanone moieties become included into separate β-CD cavities. The dominant driving force for complexation is evidently van der Waals with very little electrostatic contribution. PSD, ¹H-NMR, XRPD, DSC and SEM studies indicate the formation of inclusion complexes in solution and in the solid state.     

Lanthanide(III) Complexes of 2‐[4,7,10‐Tris(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecan‐1‐yl]acetic Acid (H7DOA3P): Multinuclear‐NMR and Kinetic Studies

The protonation constants of 2‐[4,7,10‐tris(phosphonomethyl)‐1,4,7,10‐tetraazacyclododecan‐1‐yl]acetic acid (H₇DOA3P) and of the complexes [Ln(DOA3P)]^4? (Ln=Ce, Pr, Sm, Eu, and Yb) have been determined by multinuclear NMR spectroscopy in the range pD 2–13.8, without control of ionic strength. Seven out of eleven protonation steps were detected (pK =13.66, 12.11, 7.19, 6.15, 5.77, 2.99, and 1.99), and the values found compare well with the ones recently determined by potentiometry for H₇DOA3P, and for other related ligands. The overall basicity of H₇DOA3P is higher than that of H₄DOTA and trans‐H₆DO2A2P but lower than that of H₈DOTP. Based on multinuclear‐NMR spectroscopy, the protonation sequence for H₇DOA3P was also tentatively assigned. Three protonation constants (pK_MHL, pK_MH2L, and pK_MH3L) were determined for the lanthanide complexes, and the values found are relatively high, although lower than the protonation constants of the related ligand (pK , pK , and pK ), indicating that the coordinated phosphonate groups in these complexes are protonated. The acid‐assisted dissociation of [Ln(DOA3P)]^4? (Ln=Ce, Eu), in the region c_H+=0.05–3.00 mol dm^?3 and at different temperatures (25–60°), indicated that they have slightly the same kinetic inertness, being the [Eu(H₂O)₉]³⁺ aqua ion the final product for europium. The rates of complex formation for [Ln(DOA3P)]^4? (Ln=Ce, Eu) were studied by UV/VIS spectroscopy in the pH range 5.6–6.8. The reaction intermediate [Eu(DOA3P)]* as ‘out‐of‐cage’ complex contains four H₂O molecules, while the final product, [Eu(DOA3P)]^4?, does not contain any H₂O molecule, as proved by steady‐state/time‐resolved luminescence spectroscopy.     

Complexation of capsaicin with β-cyclodextrins to improve pesticide formulations: effect on aqueous solubility, dissolution rate, stability and soil adsorption

The binary systems of capsaicin (CP) and β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) were investigated in an attempt to improve formulations of this pesticide. UV spectral shift methods indicated guest–host complex formation between CP and the two cyclodextrins (CDs). Phase solubility analysis showed B_s type diagrams with βCD, A_L type with HPβCD indicating the formation of an inclusion complex at 1:1 stoichiometric ratio in solution state. Solubility profiles indicated a 50-fold enhancement of CP solubility could be achieved in the presence of 60 mM HPβCD with respect to CP alone. Solid co-evaporated systems (CES) with 1:0.5–1:5 molar ratios of CP/CDs were physicochemically characterized, revealing that the true inclusion complexes could be formed in the solid CP/βCD systems with 1:5 molar ratio and in the solid CP/HPβCD systems with the molar ratios more than 1:3, respectively. In contrast, crystalline drug was detectable in all other systems. Compared with corresponding physical mixtures (PMs), the CES exhibited significant enhancement with regard to CP dissolution and the protection from CP degradation under the accelerated conditions. It was also revealed that complexation of CP with HPβCD had a pronounced improved effect on the pesticide formulations and greatly reduced the amount of CP adsorbed in the soil. These results demonstrate that HPβCD may be a preferred excipient, enabling more efficient and intelligent use of CP/CDs inclusion complexes in the development of pesticide formulations.