True Inclusion Complexes Research Articles

Cyclodextrin Inclusion Complexes for Improved Drug Bioavailability and Activity: Synthetic and Analytical Aspects.

Many active pharmaceutical ingredients show low oral bioavailability due to factors such as poor solubility and physical and chemical instability. The formation of inclusion complexes with cyclodextrins, as well as cyclodextrin-based polymers, nanosponges, and nanofibers, is a valuable tool to improve the oral bioavailability of many drugs. The microencapsulation process modifies key properties of the included drugs including volatility, dissolution rate, bioavailability, and bioactivity. In this context, we present relevant examples of the stabilization of labile drugs through the encapsulation in cyclodextrins. The formation of inclusion complexes with drugs belonging to class IV in the biopharmaceutical classification system as an effective solution to increase their bioavailability is also discussed. The stabilization and improvement in nutraceuticals used as food supplements, which often have low intestinal absorption due to their poor solubility, is also considered. Cyclodextrin-based nanofibers, which are polymer-free and can be generated using environmentally friendly technologies, lead to dramatic bioavailability enhancements. The synthesis of chemically modified cyclodextrins, polymers, and nanosponges based on cyclodextrins is discussed. Analytical techniques that allow the characterization and verification of the formation of true inclusion complexes are also considered, taking into account the differences in the procedures for the formation of inclusion complexes in solution and in the solid state.

Fluorescent Bis-Calix[4]arene-Carbazole Conjugates: Synthesis and Inclusion Complexation Studies with Fullerenes C60 and C70.

Supramolecular chemistry has become a central theme in chemical and biological sciences over the last decades. Supramolecular structures are being increasingly used in biomedical applications, particularly in devices requiring specific stimuli-responsiveness. Fullerenes, and supramolecular assemblies thereof, have gained great visibility in biomedical sciences and engineering. Sensitive and selective methods are required for the study of their inclusion in complexes in various application fields. With this in mind, two new fluorescent bis-calix[4]arene-carbazole conjugates (4 and 5) have been designed. Herein, their synthesis and ability to behave as specific hosts for fullerenes C60 and C70 is described. The optical properties of the novel compounds and their complexes with C60 and C70 were thoroughly studied by UV-Vis and steady-state and time-resolved fluorescence spectroscopies. The association constants (Ka) for the complexation of C60 and C70 by 4 and 5 were determined by fluorescence techniques. A higher stability was found for the C70@4 supramolecule (Ka = 5.6 × 104 M−1; ΔG = −6.48 kcal/mol). Evidence for the formation of true inclusion complexes between the host 4 and C60/C70 was obtained from NMR spectroscopy performed at low temperatures. The experimental findings were fully corroborated by density functional theory (DFT) models performed on the host–guest assemblies (C60@4 and C70@4).

Docetaxel/dimethyl-β-cyclodextrin inclusion complexes: preparation, in vitro evaluation and physicochemical characterization

Despite the development in novel drug delivery techniques and synthesis of multifunctional excipients, oral delivery of hydrophobic drug like docetaxel (DTX) is still challenging. The present work investigates the inclusion complexation of DTX, and dimethyl-β-cyclodextrin (DM-β-CD) to improve the solubility, dissolution and permeability of the drug. Amongst the native and modified β-cyclodextrins, DM-β-CD showed the highest solubility of DTX. Solid binary inclusion complex (IC) of DTX with DM-β-CD was prepared by solvent evaporation technique and thoroughly characterized for solubility, dissolution, permeability, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (1H NMR). The aqueous solubility and in vitro dissolution rate of DTX/DM-β-CD IC were markedly increased by 76.04- and 3.55-fold compared to free DTX powder. The permeability of DTX/DM-β-CD IC showed similar absorptive permeability but decreased efflux from the absorbed DTX, compared to pure DTX. Further, physicochemical studies of IC revealed the change of crystalline state DTX to its amorphous form. Moreover, FT-IR and 1H NMR results indicate the formation of true inclusion complex between DTX and DM-β-CD at 1:1 molar ratio. Collectively, solid inclusion complexes prepared by spray drying method can be an effective strategy to enhance the biopharmaceutical performance of a highly hydrophobic drug DTX.

Comparative studies of directly loaded and cyclodextrin-mediated release of Theophylline and evaluation of biodegradation studies of HPNs

Theophylline, also known as 1,3-dimethylxanthine, is a bronchodilator used to cure respiratory problems. With a view to improve drug solubility, therapeutic index, stability and controlled drug delivery of Theophylline, the Host–Guest, solid inclusion compounds of Theophylline and beta-cyclodextrin were prepared through traditional methods and microwave-prompted technique. All the characterization techniques like FESEM, FTIR, PXRD 1HNMR and DSC confirmed the MW irradiation method is the best method to form true inclusion complexes of beta-cyclodextrin and drug Theophylline. The drug release of directly loaded TP was compared with inclusion loaded hybrid polymer networks (HPNs) of chitosan and gelatin synthesized in air conditions. It was found that TP was released in a controlled manner as compare to the HPNs loaded with TP directly. Secondly, the drug release through the differently prepared ICs was also compared and found that the microwave-triggered synthesis of ICs is a brilliant method for the sustained release of the TP. It is a competent, green, quick and environment friendly in comparison to the traditional methods. In drug release kinetics, the values of n were found as 1.143, 0.501 and 0.797 at pH of 2, 7 and 7.4, respectively, which confirmed the non-Fickian diffusion at pH of 7 and 7.4, but at acidic pH conditions, the value of diffusion exponent was found to be greater than one, and it is the non-Fickian super case II diffusion. The continuous development of biodegradation at diverse steps was inspected by weight loss and with different characterization techniques like FTIR and FESEM, which revealed the hydrogel networks prepared in air conditions are biodegradable and the composting process of biodegradation was established as a more efficient method than soil burial approach.

Synthesis and biological evaluation of β-lapachone and nor-β-lapachone complexes with 2-hydroxypropyl-β-cyclodextrin as trypanocidal agents.

We study βLAP and its derivative nor-β-Lapachone (NβL) complexes with 2-hydroxypropyl-β-cyclodextrin to increase the solubility and bioavailability. The formation of true inclusion complexes between βLAP or NβL in 2-HP-β-CD in solid solution was characterization by FT-IR, DSC, powder X-ray was and was confirmed by one- and two-dimensional 1H NMR experiments. Additionally, the biological activities of βLAP, NβL, ICβLAP, and ICNβL were investigated through trypanocidal assays with T. cruzi and cytotoxicity studies with mouse peritoneal macrophages. Originally, we tested these complexes against T. cruzi viability and observed higher biological activities and lower cytotoxicity when compared to βLAP and NβL. Thus, the complexation of βLAP and NβL with 2-HP-β-CD increases the drug solubility, in addition vectorization was observed, increasing the biological activity against epimastigotes and trypomastigotes T. cruzi forms. Reduced the toxicity of the compounds against mammalian cells. In addition, the selectivity indices higher of the inclusion complexes comparing to substance free and those of benznidazole.

Synthesis, characterization and studies on host-guest interactions of inclusion complexes of metformin hydrochloride with β–cyclodextrin

In this research paper, we describe a study on the inclusion complex formation between Metformin hydrochloride (MF) and beta-cyclodextrin (β-CD) in order to improve the sustained release, dissolution and oral bioavailability of the drug MF. Metformin hydrochloride is a drug used for treating non-insulin-dependent diabetes mellitus and for polycystic ovary syndrome. The host-guest solid inclusion complex of MF with β-CD is prepared by Microwave irradiation method along with conventional methods such as physical mixture, kneading method and co-precipitation method. The phase solubility studies suggested the 1:1 stoichiometry and revealed the solubility of MF is enhanced during the inclusion complex formation between MF and β-CD. The value of the apparent stability constant was found to be 61.11 M−1. The rate of dissolution of the drug was found to be highest (95% in 60 min) for the inclusion complex prepared by microwave irradiation method. Inclusion complexes were characterized by using FTIR, FESEM, PXRD, DSC and 1HNMR techniques. All the instrumentation techniques revealed that microwave and co-precipitation methods form true inclusion complexes. Different parameters such as apparent molar volume (Vϕ), partial molar volume at infinite dilution (Vϕ0) have been determined by using the experimental density data. Apparent molar and partial molar parameters concerning volumetric predict that the host-guest interactions prevailed in the ternary system of MF, β-CD and distilled water. Microwave irradiation completes the process of inclusion complex formation in a very short duration of time and is a more environment-friendly method. Thus microwave irradiation can be utilized as an advanced, time-saving and cost-effective method for the generation of MF/β-CD inclusion complexes.

Thermal analysis used to guide the production of thymol and Lippia origanoides essential oil inclusion complexes with cyclodextrin

This study aimed to use thermal analysis and other analytical tools to guide the production of thymol (TML) and essential oil of Lippia origanoides (EO) solid inclusion complexes from a screening of different cyclodextrins (CDs) types and production methods (freeze drying, spray drying, rotary evaporation and supercritical CO2). According to the phase solubility diagrams, the best complexation efficiency of TML was achieved using hydroxypropyl-β-cyclodextrin (~ 0.7), comparing to the natives CDs, which showed values below 0.5. Thermogravimetry was effective in evaluating the amount of drug inclusion complexes in each solid sample by measuring the evaporation of TML, which was dependent of its degree of interaction with the CD. Freeze drying was the most effective method in originating true inclusion complexes in solid state producing the encapsulation of nearly 70% of available TML which were stable at temperature ranges from 200 to 280 °C. Indeed, according to the stability assay, the shelf-life increase achieved for the TML standard was 354%, while the EO had a stability increase of around 45%. Finally, the antifungal effect against Candida albicans (ATCC 14053) was increased in complexed forms in about 1.5 times and 5.4 times for EO and TML, respectively, while the antifungal activity for Trichophyton mentagrophytes (ATCC 11481) was increased with TML and EO encapsulated with CD in more than 22 times and 45 times, respectively, compared to their free forms. Thus, the optimized inclusion complexes seem to be promising in pharmaceutical field for a future development of topical preparations containing TML and its natural substrates.

Preparation and Evaluation of Nateglinide-Cyclodextrin Inclusion Complex

A physicochemical characterization of nateglinide (NT) - hydroxy propyl s-cyclodextrin (HPsCD) inclusion complex both in solution state and solid state were studied to improve the solubility and dissolution properties of nateglinide. Inclusion complex were prepared by micro wave irradiation and kneading method at 1:1M, 1:2M ratios. The prepared inclusion complex were investigated in solution state by drug content, phase solubility studies and solid state by differential scanning calorimetry (DSC), Fourier transformation-infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and in vitro dissolution studies. Phase solubility studies revealed 1:1M stoichiometry inclusion complex, a true inclusion complex was observed at 1:1 and 1:2M ratios it was confirmed by FTIR, DSC, XRD studies. In vitro dissolution data suggests the dissolution properties of nateglinide was dependent on method and ratio, the inclusion complex of both methods shows superior dissolution properties when compare to corresponding physical mixture and pure nateglinide.

ENHANCEMENT OF SOLUBILITY OF RILPIVIRINE BY INCLUSION COMPLEXATION WITH CYCLODEXTRINS

Rilpivirine having lowest water solubility indicates class II drugs of BCS. These classes of drugs could potentially exhibit dissolution rate limited absorption. The objective of the present study is to improve the solubility and dissolution of Rilpivirine through inclusion complexation with βCD and HPβCD. Solid binary systems of Rilpivirine with βCD and HPβCD were prepared by solvent evaporation and kneading methods at 1:1 and 1:2 M ratios. The prepared solid binary systems were studied in solution state by phase solubility, in vitro dissolution rate and solid state by FTIR and XRD. The dissolution parameters were studied by using dissolution software PCP Disso V3. The drug content was uniform in all the solid binary systems with low SD and CV values. The apparent stability constant indicates there is a 1:1 stochiometric complex with βCD and HPβCD. The formation of inclusion complexes with βCD and HPβCD in the solid state were confirmed by FTIR, XRD. The dissolution data clearly suggest drug release was method dependent and type of cyclodextrin. The dissolution of solid binary systems obeyed first-order kinetics and model fitted with Hixon crowel. A true inclusion complex of Rilpivirine was observed with βCD and HPβCD. Dissolution properties of solid binary systems were superior then rilpivirine alone and its corresponding physical mixtures. Overall dissolution rate was solvent evaporation > kneaded binary systems > physical mixture > pure drug. One-way ANOVA results suggest the DE30 and DE60 values were significantly higher (P<0.05) in solid binary systems when compared to physical mixture and pure drug.

Diloxanide furoate binary complexes with β-, methyl-β-, and hydroxypropyl-β-cyclodextrins: inclusion mode, characterization in solution and in solid state and in vitro dissolution studies

The purpose of this study was to investigate the effect on solubility and dissolution rate of binary complexes of β-(βCD), methyl-(MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) with diloxanide furoate (DF). The complexation in solution was evaluated by phase solubility studies and 1H nuclear magnetic resonance (NMR). Enhanced water solubility of DF was obtained with the DF:MβCD system (61-fold). The mode of inclusion was supported by NMR experiments, which indicated that real inclusion complexes were formed between DF and MβCD or HPβCD. Solid state analysis was performed using infrared and thermal methods, which suggested the formation of true inclusion complexes of DF with two derivatized cyclodextrins, MβCD and HPβCD, and an exclusion complex with βCD when the systems were prepared by freeze-dried technique. Dissolution studies conducted in simulated gastric fluid (2 h) and subsequent simulated intestinal fluid (next 4 h) showed increased dissolution rate of DF from the freeze-dried systems with βCD, MβCD, and HPβCD (85; 77 and 75% of dissolved drug at 5 min, respectively) and 100% of the drug dissolved at 150 min for the three systems. The enhancement of the solubility and the dissolution of DF observed make these complexes promising candidates for the preparation of oral pharmaceutical formulations.

Characterisation and anti-inflammatory evaluation of the inclusion complex of ellagic acid with hydroxypropyl-β-cyclodextrin

The aim of the present work was to examine ellagic acid hydroxypropyl-β-cyclodextrin complex (EA-HP-β-CD) obtained through the freeze-drying method via FTIR, XRD, SEM, NMR and molecular modeling, as well as to investigate it’s antioxidant and anti-inflammatory activity on carrageenan-induced paw oedema in rats. Phase-solubility study showed that ellagic acid (EA) formed 1:2 stoichiometric inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD). The XRD and SEM analysis were confirmed true inclusion complex formation of EA with HP-β-CD by freeze-drying method when compared with a physical mixture. The FTIR, NMR and molecular modeling studies suggested that the carbonyl groups and hydroxyl groups of EA were involved in the inclusion complexation with HP-β-CD. EA-HP-β-CD exhibited better protection from protein denaturation and lysis of erythrocyte membrane as compared to positive controls. In vivo anti-inflammatory evaluation of EA-HP-β-CD in rats showed significant anti-inflammatory and antioxidant activity on carrageenan-induced rat paw oedema. The present findings suggest that EA-HP-β-CD inclusion complex enhances the anti-inflammatory and antioxidant effect of EA in experimental animal models.

Recognition of nitrate by the ammonium derivative of a 20-membered dioxadiaza-calix[4]arene analog—solution and solid-state study of the anion binding properties

A 20-membered dioxadiaza-calix[4]arene analog (1) was combined with a series of inorganic acids to explore the anion-inclusion properties of the corresponding ammonium dication [1-H2]2+. The neutral calix[4]arene analog 1 and six salts of the receptor in the mono- or diprotonated form, [1-H2]Cl2 (2), [1-H2]Br2 (3), [1-H2][MeOSO3]2 (4), [1-H2][NO3]2 (5), [1-H2][ClO4]2 (6), and [1-H][ClO4] (6b), were structurally characterized by single-crystal X-ray diffraction analysis, which enabled a detailed comparative analysis of the non-covalent interactions. The structural comparison showed that the different anions induce conformational changes of the macrocyclic structure, but only NO3− gave a true inclusion complex. Additionally, the tetramethylammonium derivative of 1, [1-Me4]I2 (7), was prepared and structurally characterized.1H NMR titration studies of [1-H2]2+ in an aqueous–polar solvent mixture (H2O/MeOH, 9:1 v/v, pH 5.5) with a series of organic and inorganic anions gave association constants varying from 1.4 to 84.6 M−1.

Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement.

The aims of this study were to enhance the solubility and dissolution rate of nimodipine (ND) by preparing the inclusion complexes of ND with sulfobutylether-b-cyclodextrin (SBE-β-CD) and 2-hydroxypropyl-b-cyclodextrin (HP-β-CD) and to study the effect of the preparation method on the in vitro dissolution profile in different media (0.1 N HCl pH 1.2, phosphate buffer pH 7.4, and distilled water). Thus, the inclusion complexes were prepared by kneading, coprecipitation, and freeze-drying methods. Phase solubility studies were conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were investigated with differential scanning calorimetry (DSC), X-ray diffractometry (X-RD), and Fourier transform infrared spectroscopy (FT-IR). Stable complexes of ND/SBE-β-CD and ND/HP-β-CD were formed in distilled water in a 1:1 stoichiometric inclusion complex as indicated by an AL-type diagram. The apparent stability constants (Ks) were 1334.4 and 464.1 M(-1) for ND/SBE-β-CD and ND/HP-β-CD, respectively. The water-solubility of ND was significantly increased in an average of 22- and 8-fold for SBE-β-CD and HP-β-CD, respectively. DSC results showed the formation of true inclusion complexes between the drug and both SBE-β-CD and HP-β-CD prepared by the kneading method. In contrast, crystalline drug was detectable in all other products. The dissolution studies showed that all the products exhibited higher dissolution rate than those of the physical mixtures and ND alone, in all mediums. However, the kneading complexes displayed the maximum dissolution rate in comparison with drug and other complexes, confirming the influence of the preparation method on the physicochemical properties of the products.

Breaking Down the Interdigitated Dimeric Structure of Calix[4]arenediphosphonic Acid: the Structures of the Complexes with Piroxicam and 9-Aminoacridine

The solid-state structures of the complexes of calix[4]arenediphosphonic acid with piroxicam and 9-aminoacridine are described, in both cases, the classical interdigitated dimer formed by calix[4]arenediphosphonic acid is no longer present. For the 9-aminoacridine complex, a π–π stacked dimer of 9-aminoacridine is surrounded by calix[4]arenediphosphonic acid molecules with dimethyl sulfoxide included in the calix arene cavity. In the case of the piroxicam complex the piroxicam molecule forms a true inclusion complex and the pyridinium ring projects out to hydrogen bond to an opposing calix[4]arenediphosphonic acid, thus spanning the bilayer. The structures of the complexes of calix[4]arenediphosphonic acid with piroxicam and 9-aminoacridine show a breakdown in the classical interdigated calix-arene dimer with formation of trus inclusion complexes and exo-complexation.

Formulation and In Vivo Evaluation of Orally Disintegrating Tablets of Clozapine/Hydroxypropyl-β-cyclodextrin Inclusion Complexes

The aim of this study was to improve the solubility and oral bioavailability of clozapine (CLZ), a poorly water-soluble drug subjected to substantial first-pass metabolism, employing cyclodextrin complexation technique. The inclusion complexes were prepared by an evaporation method. Phase solubility studies, differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy were used to evaluate the complexation of CLZ with hydroxypropyl-β-cyclodextrin (HP-β-CD) and the formation of true inclusion complexes. Characterization and dissolution studies were carried out to evaluate the orally disintegrating tablets (ODTs) containing CLZ/HP-β-CD complexes prepared by direct compression. Finally, the bioavailability studies of the prepared ODTs were performed by oral administration to rabbits. The ODTs showed a higher in vitro dissolution rate and bioavailability compared with the commercial tablets. It is evident from the results herein that the developed ODTs provide a promising drug delivery system in drug development, owing to their excellent performance of a rapid onset of action, improved bioavailability, and good patient compliance.

Development of orally disintegrating tablets of Perphenazine/hydroxypropyl-β-cyclodextrin inclusion complex

The aim of the present work was to prepare perphenazine (PPZ) orally disintegrating tablets (ODTs) based on the use of hydroxypropyl-β-cyclodextrin (HP-β-CD) forming inclusion complex with PPZ to improve the solubility and dissolution of this practically insoluble drug. Phase solubility studies were performed to evaluate the complexation of PPZ with HP-β-CD in three aqueous systems. The inclusion complex prepared by evaporation method was characterized by different physicochemical techniques, including the dissolution studies. The prepared complex was incorporated into ODTs containing different fillers and disintegrants. The ODTs prepared by direct compression were evaluated for drug content, hardness, porosity, friability, in vitro disintegration time (DT), wetting time (WT) and dissolution profiles. The solubility and dissolution rate were substantially improved compared with that of PPZ. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) analyses suggested that PPZ could form true inclusion complex with HP-β-CD. The optimized formulation F6 exhibited short DT (15.5 ± 1.9 s) and WT (34.2 ± 2.3 s), sufficient hardness (30.4 ± 1.6 N/mm) and rapid drug dissolution. The developed tablet formulation could be a promising drug delivery system with improvements in PPZ bioavailability and patient compliance.

Modulated dissolution rate from the inclusion complex of antichagasic benznidazole and cyclodextrin using hydrophilic polymer

Benznidazole (BNZ) is the primary chemotherapeutic agent for treating Chagas’ disease; however, its poor water solubility and irregular oral absorption lead to the treatment failure in the chronic phase. The aim of this work was to investigate the utility of the polymer hydroxypropyl methylcellulose (HPMC) in controlling the release of BNZ from solid inclusion complexes with cyclodextrin to overcome the problem of its bioavailability. Preliminary studies of solubility were conducted in solution using selected β-cyclodextrin derivatives according to an experimental mixture design. The best cyclodextrin composition was used to produce solid-state systems by kneading in the presence or absence of HPMC. The formulations were characterized by different physico-chemical techniques, including the dissolution rate. Hydroxypropyl-β-cyclodextrin (HPβCD) produced the greatest improvement in drug solubility and was selected for the development of solid systems. Assays confirmed the production of true inclusion complexes between BNZ and HPβCD. The dissolution rate of the BNZ-HPβCD system was markedly increased, while the presence of HPMC retarded drug release. An optimal formulation obtained by the combination of kneading systems developed in appropriate ratios could be a promising drug delivery system with a prolonged therapeutic effect coupled with more balanced bioavailability. The produced systems present interesting perspectives for Chagas’ therapy.

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 Bs type diagrams with βCD, AL 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.

Development of effervescent tablets containing benznidazole complexed with cyclodextrin

Benznidazole (BNZ), the primary chemotherapy agent used to treat Chagas disease, has poor aqueous solubility, which results in low bioavailability. The purpose of this work was to develop stable effervescent tablets using an inclusion complex of BNZ with cyclodextrin (CD). In the first phase, different CDs were evaluated according to their ability to improve the aqueous solubility of BNZ. Then, inclusion complexes of BNZ in the solid state were produced by the kneading method and the complexes were evaluated using several physical-chemical assays. Finally, effervescent tablets were prepared according to a complete 3(2) factorial design. The effects of the concentration of CD and effervescent mixture on the dissolution rate and physical stability of tablets were evaluated. Hydroxypropyl-β-cyclodextrin produced the greatest improvement in the aqueous solubility of BNZ, almost 20-times greater than the water system. Solid systems produced with BNZ and CD showed physical-chemical interactions and increased the drug dissolution rate, suggesting the formation of a true solid inclusion complex. Moreover, the effervescent matrix of the tablets was effective in improving the dissolution behaviour of BNZ complexed with CD. Effervescent tablets produced using an inclusion complex of BNZ with CD suggest a possible improvement in the bioavailability of BNZ, and this could represent a relevant advance in Chagas therapy.

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. Phase 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 with 1:0.5∼1:5 molar ratios of CP/CDs were physicochemically characterized, revealing true inclusion complexes could be formed at specific molar ratios. Compared with corresponding physical mixtures, the co-evaporated systems 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 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.