Development of effervescent tablets containing benzonidazole complexed with cyclodextrin

Objectives 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). Method 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 3² factorial design. The effects of the concentration of CD and effervescent mixture on the dissolution rate and physical stability of tablets were evaluated. Key findings 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. Conclusions 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.     

Influence of hydroxypropyl-β-cyclodextrin and dimethyl-β-cyclodextrin on diphenhydramine intestinal absorption in a rat in situ model

The influence of complexation of diphenhydramine (DPHA) with hydroxypropyl-β-cyclodextrin (HPβCD) and dimethyl-β-cyclodextrin (DMβCD) on intestinal absorption of DPHA has been investigated on an in situ model in rats. The mean apparent stability constants of the complexes formed at 23°C between DPHA and the cyclodextrins DMβCD and HPβCD were 4988 and 1635 M⁻¹, respectively. At 37°C, the apparent stability constants were smaller: 895 and 494 M⁻¹ for the complexes formed between DPHA and the cyclodextrins DMβCD and HPβCD, respectively. Complexation of DPHA with DMβCD led to a significant decrease (−36%) in the percentage of DPHA absorbed (30.6±12.0 vs. 22.5±6.9%, P=0.018). On the other hand, complexation of DPHA with HPβCD only slightly decreased (−8%) the extent of absorption (43.2±9.0 vs. 40.0±7.7%, P=0.16). These data suggest that the magnitude of the apparent stability constant of drug–cyclodextrin complexes should be considered when complexes are used to increase the oral absorption of drugs.     

Improved in vitro dissolution parameters and in vivo hypolipidemic efficiency of atorvastatin calcium through the formation of hydrophilic inclusion complex with cyclodextrins

An aim of the present study was to improve the dissolution of the inherently low water solubility hypolipidemic agent, Atorvastatin calcium (ATC), through the preparation and characterization of ATC with cyclodextrins (CDs) inclusion complexes employing different techniques. A second goal was to study the in vivo hypolipidemic efficacy of ATC‐complexes with enhanced dissolution characteristics. Inclusion complexation of ATC with β‐cyclodextrin (β‐CD) and hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) was evaluated in aqueous and solid states. ATC formed inclusion complexes with β‐CD and HP‐β‐CD depending to a great extent upon ATC ionization state. Evaporation and freeze‐drying were the most efficient techniques to achieve complexation. In contrast, kneading was an inefficient tool to create true inclusion complexes, which could reflect the hindrance of drug–CDs interactions in the semisolid medium. The ATC:CD ratio of 1:2 showed better dissolution characteristics compared to a 1:1 ratio. Moreover, the in vivo hypolipidemic activities of ATC‐CDs (β‐CD and HP‐β‐CD) complexes were greater (P<0.05) than the other investigated formulations. Thus the nature of the carrier did not play a critical role in the dissolution characteristics of the inclusion system. In contrast, the carrier molar ratio, and the employed complexation technique were found to be key factors in enhancing the ATC dissolution rate, yielding performances as well as the in vivo hypolipidemic efficacies. Drug Dev Res 72: 379–390, 2011. © 2011 Wiley‐Liss, Inc.     

Controlled-release drug delivery system based on fluocinolone acetonide–cyclodextrin inclusion complex incorporated in multivesicular liposomes

Abstract

Multivesicular liposomes (MVLs) have been widely studied for encapsulation of hydrophilic drugs due to their structural properties and large aqueous inner cavities. In this study, to investigate MVLs and their potential application for incorporation of hydrophobic drugs, new drug delivery system for fluocinolone acetonide (FA), as a lipophilic model drug, was developed combining the advantages of cyclodextrin inclusion complexes (CD-IC) and multivesicular liposomes. FA was complexed with several CDs to form inclusion complex (FA–CD-IC) and then FA–CD-IC was incorporated into MVLs by reverse-phase evaporation method. Physicochemical characterization of drug–CD-IC, at a molar ratio of 1:1 (drug to CD) was studied using ¹HNMR, FT-IR, DSC and UV spectroscopy. The influence of various types of CDs on the aqueous solubility of FA, encapsulation efficiency and release profile in MVLs was studied. The results revealed the formation of inclusion complexes between the drug and CDs. Both the CD's type and proportion played an important role in the physicochemical properties of the systems. The inclusion complex of the drug with hydroxypropyl-β-cyclodextrin exhibited the most appropriate loading and sustained-release profile over prolonged periods. The results reveal the promising potential of MVLs as a stable drug delivery system to release the drug in a sustained manner for the treatment of ocular inflammatory disease.     

Evaluation of cholesterol depletion as a marker of nephrotoxicity in vitro for novel β-cyclodextrin derivatives

Cyclodextrins (CDs) have been shown to improve physicochemical and biopharmaceutical properties of drugs when low solubility and low safety limit their use in the pharmaceutical field. Recently, we have developed new multi-substituted-β-CDs, hydroxypropyl-sulfobutyl ether-β-cyclodextrin (HPn-SBEm-β-CD). HPn-SBEm-β-CD exhibit low hemolysis, good solubility, strong inclusion ability, and an appropriate average molecular weight. In this study, we chose two products of HPn-SBEm-β-CD (HP₃-SBE₂-β-CD and HP₂-SBE₃-β-CD) and compared their effects to sulfobutyl ether-β-cyclodextrin (SBE₇-β-CD), methyl-β-cyclodextrin (M-β-CD) and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD). We evaluated viability, membrane damage, induction of apoptosis and necrosis, cholesterol depletion, and morphological changes in human embryonic kidney 293A cells (HEK293A) in vitro. CDs caused a reduction of cell viability and increased LDH levels in a concentration-dependent manner. The effect of HP₃-SBE₂-β-CD or HP₂-SBE₃-β-CD on cell viability, membrane damage, and the induction of apoptosis and necrosis resembled that of SBE₇-β-CD, whereas the effects were significantly lower for M-β-CD or DM-β-CD. HP₃-SBE₂-β-CD and HP₂-SBE₃-β-CD exhibited morphological changes at high concentrations. In conclusion, the results showed that cholesterol depletion may be as a marker for evaluating the cytotoxicity of novel β-CD derivatives. These results will provide useful information for HPn-SBEm-β-CD as a promising safe adjuvant for intravenous administration in the future.     

Phase solubility behavior of hydrophilic polymer/cyclodextrin/lansoprazole ternary system studied at high polymer concentration and by response surface methodology

Evaluation of polymer/cyclodextrin (CD)/drug ternary systems has been performed at low polymer levels to date, and the cross-interaction of polymers and CDs has not been well studied. In this study, the effects of PVP K30 and PEG 6000 on the complexation ability of β-CD and 2-hydroxypropyl-β-cyclodextrin (HPCD) with lansoprazole (LSP) was investigated. The phase solubility of polymer/CD/LSP ternary systems was first studied at polymer levels of 0%, 2% and 6%, respectively. A response surface methodology was then employed to investigate the cross-interaction of polymers/CDs on phase solubility at polymer levels up to 10%. Results indicated A_L-type inclusion for both β-CD and HPCD. Increase in PEG concentration leads to improved complexation efficiency, whereas increase of PVP lead to decreased CE, which is attributable to the strong interaction between PVP and LSP. Second-order polynomial equations were well employed to estimate the relationship between LSP solubility and the two independent variables. The response surface showed that PVP and PEG had no significant effects on LSP/CD complexation, while a synergistic effect on LSP solubility was observed at higher concentrations of HPCD and PEG. It is concluded that high levels of polymer lead to increased LSP solubility but not significant increase in CE.     

Reused cyclodextrin as a new way to deliver and enhance drug loading onto ion exchange resin

Abstract

Context: Cyclodextrins could improve drug solubility and drug loading onto ion exchange resins. Moreover, the remaining cyclodextrin in the solution might be reused for drug solubility enhancement and drug loading onto resin.

Objectives: To investigate the application of fresh and reused cyclodextrin to improve drug solubility and drug loading onto resin.

Methods: The inclusion complexes were prepared and characterized using β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD). The drug solution was loaded onto resin with and without cyclodextrin. Then, the remaining cyclodextrin was reused for the complex and the drug loading process.

Results and discussion: Improved drug solubility was observed when using cyclodextrins. The complex was successfully formed with 1:1 stoichiometry. The increase in drug solubility with cyclodextrins improved drug loading onto resin. The cyclodextrins delivered drug to bind with resin, forming resinate, and did not bind with the resinate themselves, which was confirmed by quantification of the amount of cyclodextrin in drug loading solution before and after drug loading process. Therefore, cyclodextrins were available to reuse for drug loading without affecting the percentage of drug loading.

Conclusions: Reused cyclodextrin is a novel way to deliver and enhance drug loading onto resin for development of an ion exchange-based drug delivery system.     

Cyclodextrin and phospholipid complexation in solubility and dissolution enhancement: a critical and meta-analysis

Introduction: Poor solubility and dissolution of drugs are the major challenges in drug formulation and delivery. In order to improve the solubility and dissolution profile of drugs, various methods have been investigated so far. The cyclodextrin (CD) complexation and phospholipid (PL) complexation are among the exhaustively investigated methods employed for more precise improvement of the solubility and dissolution of poorly water-soluble drugs.

Areas covered: The article discusses the CD and PL complexation techniques of solubility and dissolution enhancement. Various studies reporting the CD and PL complexation as the potential approaches to improve the dissolution, absorption and the bioavailability of the drugs have been discussed. The article critically reviews the physicochemical properties of CDs and PLs, eligibility of drugs for both the complexation, thermodynamics of complexation, methods of preparation, characterization, advantages, limitation and the meta-analysis of some studies for both the techniques.

Expert opinion: The CD and PL complexation techniques are very useful in improving solubility and dissolution (and hence the bioavailability) of biopharmaceutical classification system Class II and Class IV drugs. The selection of a particular kind of complexation can be made on the basis of eligibility criteria (of drugs) for the individual techniques, cost, stability and effectiveness of the complexes.     

The interaction of nifedipine with selected cyclodextrins and the subsequent solubility–permeability trade-off

The purpose of this study was to investigate the interaction of 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 2,6-dimethyl-β-cyclodextrin (DMβCD) with the lipophilic drug nifedipine and to investigate the subsequent solubility–permeability interplay. Solubility curves of nifedipine with HPβCD and DMβCD in MES buffer were evaluated using phase solubility methods. Then, the apparent permeability of nifedipine was investigated as a function of increasing HPβCD/DMβCD concentration in the hexadecane-based PAMPA model. The interaction with nifedipine was CD dependent; significantly higher stability constant was obtained for DMβCD in comparison with HPβCD. Moreover, nifedipine displays different type of interaction with these CDs; a 1:1 stoichiometric inclusion complex was apparent with HPβCD, while 1:2 stoichiometry was apparent for DMβCD. In all cases, decreased apparent intestinal permeability of nifedipine as a function of increasing CD level and nifedipine apparent solubility was obtained. A quasi-equilibrium mass transport analysis was developed to explain this solubility–permeability interplay; the model enabled excellent quantitative prediction of nifedipine’s permeability as a function of CD concentrations. This work demonstrates that when using CDs in solubility-enabling formulations, a trade-off exists between solubility increase and permeability decrease that must not be overlooked. This trade-off was found to be independent of the type of CD–drug interaction. The transport model presented here can aid in striking the appropriate solubility–permeability balance in order to achieve optimal overall absorption.     

Competitive displacement of drugs from cyclodextrin inclusion complex by polypseudorotaxane formation with poloxamer: implications in drug solubilization and delivery

The competitive interactions between the poly-[propylene oxide] (POO)-poly-[ethylene oxide] (PEO) block copolymer poloxamer 407 (Pluronic F127) and two drugs, triamcinolone acetonide and ciclopirox olamine, by the formation of inclusion complexes with two cyclodextrin hydrophilic derivatives, hydroxypropyl-β-cyclodextrin (HPβCD; molar substitution (MS) 0.65) and partially methylated-β-cyclodextrin (MβCD; MS 0.57), were studied by means of one-dimensional (1)H NMR, 2D ROESY experiments, solubility studies and drug release studies. 1D and 2D NMR and solubility studies indicate that both triamcinolone acetonide and ciclopirox olamine form stable inclusion complexes with the cyclodextrin derivatives. In the case of ciclopirox olamine the complex was more stable at pH 1. Effective complexation of poloxamer with the two cyclodextrins (CDs) was also evidenced by NMR analysis, and competitive displacement of the drugs from the CD cavity by the polymer was observed. Drug solubility in CD solutions was not modified by the addition of polymers, indicating that a decrease in solubility due to the competitive displacement is probably compensated by the solubilizing effect of polymer micellization. Finally, polypseudorotaxanes formation has a significant influence on the release of the drugs studied. Changes in the release rate depend on the stability of drug-CD inclusion complex and on cyclodextrin concentration in the bulk solution; so polypseudorotaxane formation can be employed to modulate drug controlled release from thermosensitive hydrogels.     

Inhibition of Agitation‐Induced Aggregation of an IgG‐Antibody by Hydroxypropyl‐β‐Cyclodextrin

In order to provide an alternative to nonionic surfactants as excipients for protein formulations, cyclodextrin‐derivatives (CDs) were examined for their potential to inhibit agitation‐induced aggregation of an IgG in aqueous solution. Loss of monomeric protein and protein aggregation were monitored throughout the agitation experiments by size exclusion chromatography. Hydroxypropyl‐β‐cyclodextrin (HPβCD) completely suppressed IgG‐aggregation at a remarkably low concentration (2.5 mM) and in contrast to other CDs it also did not negatively affect IgG‐stability during storage in nonagitated solution. Further agitation experiments demonstrated the superiority of HPβCD to other common excipients in protein formulation, such as sugars and sugar alcohols or polysorbate 80 in low concentrations. Spectroscopic (fluorescence spectroscopy and Fourier transform infrared spectroscopy), thermodynamic (microcalorimetry), and physical investigations (surface tension measurements) were carried out to elucidate the mechanism of stabilization of the IgG. In contrast to other studies with HPβCD, protein stabilization could not be attributed to direct interaction between hydrophobic amino acids on the IgG and this excipient. Competition with the protein for the air–water interface appears to be the dominating mechanism of stabilization. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1193–1206, 2010     

New prostaglandin analog formulation for glaucoma treatment containing cyclodextrins for improved stability,solubility and ocular tolerance

Latanoprost is a practically insoluble prostaglandin F2α analog considered a first-line agent for glaucoma treatment. From a pharmaceutical point of view, latanoprost is challenging to be formulated as an eye drop due to its poor water solubility and the presence of an ester bond that needs to be cleaved in vivo but maintained unchanged during storage. Cyclodextrins (CDs) are known to form complexes with hydrophobic drugs, influencing their stability, availability, solubility, and tolerance in a non-predictable manner. A variety of CDs including native α, β, and γCDs as well as substituted hydroxypropylβCD, hydroxypropylγCD, dimethylβCD, sulphatedβCD, and propylaminoβCD were screened and the most appropriate CD for the formulation of latanoprost for an ocular topical application was selected. Among the tested CDs, propylaminoβCD had the best trade-off between latanoprost stability and availability, which was confirmed by its complex constant value of 3129 M⁻¹. Phase-solubility and NMR investigations demonstrated that the propylaminoβCD effectively formed a complex involving the ester group of latanoprost providing protection to its ester bond, while ensuring proper latanoprost solubilization. Furthermore, in vivo experiments demonstrated that the latanoprost-propylaminoβCD formulation led to lower ocular irritation than the commercial latanoprost formulation used as a reference. The latanoprost-propylaminoβCD formulation was demonstrated to successfully address the main stability, solubility, and tolerance limitations of topical ocular latanoprost therapy for glaucoma.     

Utility of cyclodextrins in the formulation of genistein: Part 1. Preparation and physicochemical properties of genistein complexes with native cyclodextrins

Isoflavones are suitable guest molecules for inclusion complex formation with cyclodextrins (CDs). The molecular encapsulation with CDs results in a solid, molecularly dispersed form and in a significantly improved aqueous solubility of isoflavones. Genistein, a key isoflavone constituent of Ononidis spinosae radix was found to form a supramolecular, non-covalent inclusion complex with both β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD), while it did not form a stable complex with α-CD. The guest genistein was found to spatially located in the less polar cavity of cyclodextrin. The isolated binary genistein/CD complexes appeared novel crystalline lattices. The in vitro dissolution of genistein entrapped into both β- and γ-CD, significantly surpassed that of the plain isoflavone.     

Novel non-acidic formulations of haloperidol complexed with β-cyclodextrin derivatives

Haloperidol (Hal), a highly hydrophobic drug, was complexed with two β-cyclodextrin (β-CD) derivatives. Hal solubility was increased 20-fold in the presence of a 10-fold excess of methyl β-CD (Meβ-CD) and 12-fold in the presence of a 10-fold excess of 2-hydroxypropyl β-CD (HPβ-CD). The stoichiometries and stability constants of Hal–Meβ-CD (1:1 and 2345 M⁻¹ at 27°C) and Hal–HPβ-CD (1:1 and 2112 M⁻¹ at 27°C) complexes were calculated by the continuous variation and phase solubility methods respectively. Differential scanning calorimetry and ¹H-NMR were used to confirm the formation of inclusion complexes. Moreover, the enthalpy and entropy of the complexation process were calculated for both complexes in order to obtain such information as the main `driving force' and whether or not complex formation is thermodynamically favoured. This was achieved by monitoring the isothermic solubility lines at various temperatures.     

Preparation and characterization of mosapride citrate inclusion complexes with natural and synthetic cyclodextrins

The aim of this work was to investigate the inclusion complexes between mosapride citrate and SBE₇β-CD in comparison with the natural β-CD to enhance its bioavailability by improving the solubility and dissolution rate. The complexation efficiency value of SBE₇β-CD was higher than that for β-CD. Solid binary systems of mosapride citrate with CDs were prepared by physical mixing, kneading and freeze-drying techniques at molar ratio of 1:1(drug:CD). Physicochemical characterization of the prepared systems was studied using X-ray diffractometry, differential scanning calorimetry, Fourier-transform infrared spectroscopy and scanning electron microscopy (SEM). Amorphous drug was detectable to large extent in inclusion complexes prepared using the freeze-drying technique. From the dissolution study of different inclusion complexes in simulated saliva solution (pH 6.8), we could concluded that irrespective of the preparation technique, the systems prepared using SBE₇β-CD showed better performance than the corresponding ones prepared using β-CD. In addition, the freeze-drying technique showed superior dissolution enhancement than other methods especially when combined with the SBE₇β-CD     

Improved dissolution and bioavailability of phenytoin by sulfobutylether-β-cyclodextrin ((SBE)7m-β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) complexation

The inclusion complexation of phenytoin with charged and neutral water-soluble cyclodextrins (CDs), (SBE)_7m-β-CD and HP-β-CD, was studied in order to improve the low aqueous solubility and incomplete oral bioavailability of phenytoin. Effects of CDs on the aqueous solubility of phenytoin were determined by phase-solubility method at pH 7.4 and 11.0. Solubility of phenytoin increased as a function of CD concentration, showing A_L type diagrams for both (SBE)_7m-β-CD and HP-β-CD which indicate a formation of 1:1-complexes. Solid inclusion complexes of phenytoin with (SBE)_7m-β-CD and HP-β-CD were prepared by freeze-drying. Dissolution rate of phenytoin was increased with inclusion complexes as well as with phenytoin/HP-β-CD physical mixture in vitro. Also the freeze-drying of phenytoin tended to enhance the dissolution of phenytoin in vitro. However, plain phenytoin (300.0 mg) pharmacokinetics after oral administration as a crystal form and as a freeze-dried form were comparable in dogs. CD-based formulations of phenytoin increased peak plasma concentration of phenytoin about 1.6-fold and bioavailability (AUC_{0–24 h}) of phenytoin about 2-fold compared to plain phenytoin. Oral pharmacokinetics were not statistically different among various CD formulations. This study indicates that increased bioavailability of phenytoin in the presence of CDs was due to an increased extent of drug dissolution.     

Drug-in-cyclodextrin-in-liposomes: a promising delivery system for hydrophobic drugs

Introduction: Recently, the entrapment of hydrophobic drugs in the form of water-soluble drug–cyclodextrin (CD) complex in liposomes has been investigated as a new strategy to combine the relative advantages of CDs and liposomes into one system, namely drug-in-CD-in-liposome (DCL) systems.

Areas covered: For DCLs preparation, an overall understanding of the interaction between CDs and lipid components of liposomes is necessary and valuable. The present article reviews the preparation, characterization and application of DCLs, especially as antitumor or transdermal carriers. Double-loading technique, an interesting strategy to control release and increase drug-loading capacity, is also discussed.

Expert opinion: DCL approach can be useful in increasing drug solubility and vesicles stability, in controlling the in vivo fate of hydrophobic drugs and in avoiding burst release of drug from the vesicles. To obtain stable DCL, the CDs should have a higher affinity to drug molecules compared with liposomal membrane lipids. DCLs prepared by double-loading technique seem to be a suitable targeted drug delivery system because they have a fast onset action with prolonged drug release process and the significantly enhanced drug-loading capacity. In particular, DCLs are suitable for the delivery of hydrophobic drugs which also possess volatility.     

Interaction of Omeprazole with a Methylated Derivative of β-Cyclodextrin: Phase Solubility,NMR Spectroscopy and Molecular Simulation

Purpose Cyclodextrins are known to be good solubility enhancers for several drugs, improving bioavailability when incorporated in pharmaceutical formulations. In this work we intend to assess and characterize the formation of inclusion complexes between omeprazole (OME) and a methylated derivative of β-cyclodextrin, methyl-β-cyclodextrin (MβCD). A comparison with results obtained from the most commonly used natural cyclodextrin, β-cyclodextrin (βCD) is also presented in most cases. Materials and Methods The interaction of OME with the mentioned cyclodextrins in aqueous solutions was studied by phase solubility studies, 1D ¹H and 2D rotating frame nuclear overhauser effect NMR spectroscopy (ROESY) and Molecular Dynamics. Results The solubility of OME was significantly increased by formation of inclusion complexes with each cyclodextrin. Phase solubility studies and continuous variation plots revealed that OME forms an inclusion complex in a stoichiometry of 1:1 with both cyclodextrins. ¹H NMR and ROESY spectra of the inclusion complexes indicated that the benzimidazole moiety is included within the cyclodextrins cavities. Molecular dynamics showed that OME is more deeply included in the MβCD than in βCD cavity, in agreement with a larger apparent stability constant (K _S) obtained for the inclusion complex with MβCD. Conclusions MβCD proved to be an efficient enhancer of OME solubility, thus possessing characteristics for being an useful excipient in pharmaceutical formulations of this drug.     

Analysis of triclosan inclusion complexes with β-cyclodextrin and its water-soluble polymeric derivative

Interaction in solution and in the solid state of triclosan (TR), a practically water-insoluble antimicrobial agent, with parent β-cyclodextrin (βCD) and its water-soluble epichlorohydrin polymer (EPI-βCD) was investigated by several analytical techniques, to evaluate the role of the carrier features on the physicochemical properties of the drug-cyclodextrin complex. Phase-solubility studies showed the higher solubilizing and complexing ability of EPI-βCD (K(s) =1 1,733 M(-1)) than parent βCD (K(s) = 2526 M(-1)). Actual inclusion complex formation between TR and both cyclodextrins tested was confirmed by 2D (1)H NMR studies (ROESY), which also gave insight into some different drug/cyclodextrin binding modes between polymeric and parent βCD. Addition of hydrophilic polymers (hydroxypropylcellulose, hypromellose or amidated pectin) to TR/βCD systems increased βCD solubilizing efficacy, but, unexpectedly, decreased its complexing ability towards the drug. Solid binary and ternary samples prepared by co-grinding of components in high energy mills were carefully characterised by Differential Scanning Calorimetry, X-ray powder diffractometry and Fourier transform infrared spectroscopy. The results pointed out the higher affinity of EPI-βCD than βCD for the interaction with TR even in the solid state, resulting in the formation of completely amorphous products with superior dissolution properties. Addition of hydrophilic polymers failed to effectively promote solid-state interactions between TR and βCD, while their positive influence on drug solubility, observed in phase-solubility studies, was absent in solid TR/βCD/polymer products. Finally, the time-kill analysis, used to evaluate the TR antimicrobial activity against Streptococcus mutans, demonstrated the significantly (p < 0.001) superior performance of both cyclodextrin complexes than drug alone, and confirmed the higher effectiveness (p < 0.05) of TR/EPI-βCD than TR/βCD complex.