Inclusion Complexes In Solid State Research Articles

Inclusion complexes of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin with 2-hydroxypropyl-(-cyclodextrin: solubility and antimicrobial activity

The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-β-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-β-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-β-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-β-cyclodextrin at 37 oC. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.

Preparation, Solid-State Characterization, Phase Solubility and Dissolution Studies of Azithromycin/Hydroxypropyl-β- Cyclodextrin Host-Guest System

Objectives: Azithromycin has poor aqueous solubility and its dissolution is the rate-limiting step. Therefore the objective of this work to increase the solubility and dissolution of azithromycin. Hence aim of the study was to develop, characterize and evaluate dissolution properties of inclusion complexes of Azithromycin with hydroxypropyl-β-cyclodextrin (HP-β-CD). Methods: Phase solubility was performed by Higuchi and Connors’s method for determination of stoichiometry of AZM/ β-CD and AZM/ HP-β-CD inclusion complex. It again confirmed by Jobs plot. Inclusion complex of Azithromycin with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared by kneading method and solvent evaporation method in molar ratio of 1:1. The inclusion complex in solid state was characterized by FT-IR, DSC, HNMR, SEM. Results: AL type was found in the phase solubility diagram which indicated the development of the inclusion complex in 1:1 stoichiometry with HP-β-CD. The stability constant decrease with increasing temperature. All thermodynamic parameters for the inclusion complex were calculated from Van’t Hoff plots. The highest enhancement in dissolution and solubility were observed in the inclusion complex developed with HPβ-CD using the kneading method. FT-IR spectra exhibited that the hydroxyl group of azithromycin was participate in inclusion process. DSC study supportedamorphization of drug molecule and entrapment of drug in the HP-β-CD cavity. It further confirmed with nuclear magnetic resonance and scanning electron microscopy studies. Conclusion: The solubility was significantly improved by the inclusion complex with HP-β-CD (9 fold). The dissolution of azithromycin was improved with inclusion phenomena using kneading method. The result of studies showed the inclusion of Azithromycin molecule inside HP-β-CD cavities.

Preparation, Characterization, and Properties of Inclusion Complexes of Balofloxacin with Cyclodextrins.

The study mainly aimed to improve the aqueous solubility of Balofloxacin (BLFX) by preparing the inclusion complexes (ICs) of BLFX with cyclodextrins (CDs). In this study, ICs in solid state were obtained by using beta-CD (β-CD), 2-hydroxypropyl-β-CD (HP-β-CD), 2, 6-dimethyl-β-CD (DM-β-CD) through a freeze-drying technique. The formation of ICs was confirmed through Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, nuclear magnetic resonance, and scanning electron microscopy. Results demonstrated that the water solubility and dissolution rates of three ICs were distinctly improved than that of parent BLFX. Bacteriostatic experiment manifested that the antibacterial effect of BLFX was not inhibited after encapsulation in CDs. The damage of BLFX to kidney and liver cells was reduced. Consequently, successful preparation of the ICs of BLFX with CDs provided possibility for devising new dosage form of BLFX, which held great promise for further applications in clinical fields.

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.

A study of the inclusion complex of bioactive thiadiazole derivative with 2‑hydroxypropyl‑β‑cyclodextrin: Preparation, characterization and physicochemical properties

The main aim of this work has been to improve the solubility of bioactive 6-(acetylamino)-N-(5-ethyl-1,3,4-thiadiazol-2-yl)-hexanamide by forming an inclusion complex with 2-hydroxypropyl-β-cyclodextrin. UV–vis spectroscopy was applied to studying the host-guest interaction in the buffer solution pH 7.4. Phase solubility and Job's methods were used to confirm the formation of an inclusion complex with 1:1 stoichiometry and 103 kg·mol−1 stability constant. It has been established that in the presence of 0.069 mol·kg−1 of 2HP-β-CD, the compound solubility is equal to 11.60·10−3 mol·kg−1, which corresponds to a 7-time increase in this parameter compared to the solubility in pure buffer. The thermodynamic functions of complex formation have been determined and it has been found that the inclusion process is spontaneous and thermodynamically advantageous. Data from 1H NMR experiments also provided formation evidence of the inclusion complex between study compound and 2HP-β-CD. The inclusion complex in solid state has been obtained by grinding and characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray diffractometry. The kinetic characteristics of dissolution process for the supramolecular complex have been obtained.

Inclusion complex of antiasthmatic compound with 2-hydroxypropyl-β-cyclodextrin: Preparation and physicochemical properties

This work aims at obtaining 2-hydroxypropyl-β-cyclodextrin inclusion complex with an original antiasthmatic compound in buffer solution and solid state with higher solubility and, hence, bioavailability. The compound solubility with different 2-hydroxypropyl-β-cyclodextrin concentrations has been studied by the phase solubility method. The linearity of the phase solubility diagrams is classified as an AL type and indicates the formation of inclusion complexes with 1:1 stoichiometry. The complex stoichiometry has been confirmed by the Job's method. The solubility of the studied compound in buffer has been considerably increased by complexation with 2-hydroxypropyl-β-cyclodextrin. Complexation stability constants and thermodynamic parameters have been calculated. The obtained inclusion complexes in solid state have been studied by the differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray powder diffraction. The kinetic characteristics of dissolution for the supramolecular complex have been obtained.

Research Advances in Molecular Modeling in Cyclodextrins

Cyclodextrins (CDs), as one type of the novel pharmaceutical excipients, have been widely used in drug delivery and pharmaceutical industry. Over the past decades, a large amount of molecular modeling studies in CDs were reported for profound understanding of structural, dynamic and energetic features of CDs systems. Thus, this review is focused on qualitative and quantitative analysis of research outputs on molecular modeling in CDs. The original data were collected from Web of Science and analyzed by scientific knowledge mapping tools, including Citespace, Science of Science, VOSviewer, GPSvisualizer and Gephi software. Scientific knowledge mapping, as an emerging approach for literature analysis, was employed to identify the knowledge structure and capture the development of the science in a visual way. The results of analysis included research outputs landscape, collaboration patterns, knowledge structure and research frontiers shift with time. China had the largest contributions to the publication number in this area, while USA dominated the high quality research outputs. International collaboration between USA and Europe was much stronger than that within Asia. J American Chemical Society, as one of the most important journals, played a pivotal role in linking different research fields. Furthermore, seven important thematic clusters were identified by the research cluster analysis with visualization tools and demonstrated from three different perspectives including: (1) the mostly-used CD molecules: β-Cyclodextrin, (2) preferred modeling tools: docking calculation and molecular dynamic, (3) hot research fields: structural properties, solubility, chiral recognition and solidstate inclusion complexes. Moreover, research frontier shift in the past three decades was traced by detecting keywords bursts with high citation. The current review provided us a macro-perspective and intellectual landscape to molecular modeling in CDs.

Physicochemical characteristics of the inclusion complexes of biologically active compounds with 2-hydroxypropyl-β-cyclodextrin

Inclusion complexation of 2-hydroxypropyl-β-cyclodextrin with biologically active compounds 2-hydroxybenzaldehyde isonicotinoylhydrazone and 2-hydroxy-3-methoxybenzaldehyde isonicotinoylhydrazone in buffer pH 7.4 solution and in solid state have been investigated. The solubility of compounds at different concentrations 2-hydroxypropyl-β-cyclodextrin was studied by phase solubility method. The profile displayed a typical AL-type, indicating the formation of 1:1 stoichiometric inclusion complex. Solution state complexation in buffer was validated by ultra violet absorption. Stoichiometry of complex was confirmed by Job’s method. The water solubility of compounds studied was significantly increased through complexation with 2-hydroxypropyl-β-cyclodextrin. Complexation stability constants and thermodynamic parameters have been calculated. It has been concluded that inclusion complexation is an exothermal and enthalpy-determined process. The solid state inclusion complex was prepared by the ball-milling method and characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray powder diffraction. The dissolution rate of the active pharmaceutical ingredient of the supramolecular complexes were obtained.

Counterion Anchoring Effect on the Structure of the Solid-State Inclusion Complexes of β-Cyclodextrin and Sodium Perfluorooctanoate

Characterization of the structure and dynamics for the solid inclusion complexes (ICs) between β-cyclodextrin (β-CD; host) and sodium perfluorooctanoate (SPFO; guest) was carried out using 1H/19F/13C NMR spectroscopy. The 1:1 and 2:1 β-CD/SPFO solid complexes were prepared by a modified dissolution method. Evidence for the formation of β-CD/SPFO ICs was provided by 13C DP (direct polarization) and CP (cross-polarization) solid-state NMR spectroscopy with magic angle spinning (MAS) at 20 kHz. The complexation-induced shifts (CIS) of 1H/19F/13C nuclei between solution and the solid state for β-CD/SPFO complexes and the closely related complexes of β-CD/PFOA (perfluorooctanoic acid) were compared. The counterion effect for SPFO and PFOA was observed according to their variable structure and binding as inclusion compounds with β-CD. The effect of sodium versus hydronium counterions on the structure and dynamics of inclusion complexes for these systems was supported by DSC, TGA, FT-IR, and powder X-ray diffrac...

Effect of preparation processes and structural insight into the supermolecular system: Bisacodyl and β-cyclodextrin inclusion complex.

In this study, β-cyclodextrin (β-CD) and bisacodyl were chosen as model host and guest molecule to explore the effect of preparation processes on the physicochemical properties of inclusion complexes (ICs) and to gain an insight into the structure of ICs. The influence of temperature and pH on complexation was studied by multiple temperature-pH phase solubility analysis. The most favorable conformation was predicted by molecular modeling using AutoDock. (1)H nuclear magnetic resonance and rotating frame nuclear Overhauser effect spectroscopy further confirmed the structure. Moreover, bisacodyl · β-CD ICs in solid state were successfully prepared via three different procedures (co-crystallization, co-evaporation, and co-grinding) and fully characterized by several solid-state techniques, namely, Fourier transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, solid-state NMR spectroscopy, and scanning electron microscopy. It was found that acid solution and low temperature were unfavorable for formation of bisacodyl · β-CD. The pyridine moiety was suggested to be enclosed in the hydrophobic cavity of β-CD. The complexes prepared using co-crystallization showed properties similar to those prepared using co-evaporation. Moreover, ICs obtained by co-evaporation and co-grinding had higher loading efficiency, water solubility, and dissolution rate than ICs obtained by co-crystallization.

Preparation and characterization of Trimethoprim inclusion complex with Methyl-β-Cyclodextrin and determination of its antimicrobial activity

The present study focuses on the formation and characterization of inclusion complexes between Trimethoprim (TMP), an inhibitor of bacterial dihydrofolate reductase, and cyclodextrins, namely, methyl-βeta-cyclodextrin (MBCD) and hydroxylpropyl-βeta-cyclodextrin (HBCD) in aqueous solution. MBCD was selected to prepare inclusion complexes in the solid state. These complexes were prepared by different methods: spray drying, kneading and freeze drying. Physical mixtures were prepared as reference. The prepared systems were then characterized by different techniques: Differential scanning calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). The dissolution profile and the antimicrobial activity of Trimethoprim and the inclusion complexes were evaluated using the dissolution test, and the disk diffusion methodology, respectively. An increase of TMP solubility was observed in phase solubility studies. The obtained apparent stability constants (Ks) showed that MBCD formed an inclusion complex more stable with the drug than HPBCD, so it was decided to prepare inclusion complexes in solid state with MBCD. The results obtained with DSC, FTIR and SEM proved the formation of inclusion complexes in solid state. The dissolution profile and the antibacterial activity increased with the complexation process.

Physicochemical Analysis and Molecular Modeling of the Fosinoprilβ-Cyclodextrin Inclusion Complex

This research investigates the interaction between fosinopril sodium (FOS) and beta-cyclodextrin (β-CD) in aqueous solution and in solid state, in order to prove the formation of an inclusion complex between the two components. The stoichiometry of the inclusion complex was found as 1 : 1 by employing continuous variation method in UV. The formation constant was calculated as 278.93 M−1using Benesi-Hildebrand equation. The kneaded product (KP) and the physical mixture (PM) were further experimentally examined, using FTIR, powder X-ray diffractometry, and thermal analysis. The results confirm that the physicochemical properties of the FOS/β-CD KP are different from FOS and that the kneading method leads to formation of solid state inclusion complex between FOS andβ-CD. Structural studies of the FOS/β-CD were carried out using molecular modeling techniques, in order to explain the complexation mechanism and the host-guest geometry.

Characterization and Dynamic Properties for the Solid Inclusion Complexes of β-Cyclodextrin and Perfluorooctanoic Acid

The structural characterization and dynamic properties of solid-state inclusion complexes (ICs) formed between β-cyclodextrin (β-CD; host) and perfluorooctanoic acid (PFOA; guest) were investigated using (13)C NMR spectroscopy. The 1:1 and 2:1 host/guest solid-state complexes were prepared using a modified dissolution method to obtain complexes with high phase purity. These complexes were further characterized using differential scanning calorimetry (DSC), FT-IR spectroscopy, powder X-ray diffraction (PXRD), (19)F directpolarization (DP), and (13)C cross-polarization (CP) with magic-angle spinning (MAS) NMR spectroscopy. The (19)F → (13)C CP results provided unequivocal support for the formation of well-defined inclusion compounds. The phase purity of the complexes formed between β-CD and PFOA were assessed using the (19)F DP NMR technique at variable temperature (VT) and MAS at 20 kHz. The complexes were found to be of high phase purity when prepared in accordance with the modified dissolution method. The motional dynamics of the guest in the solid complexes were assessed using T1/T2/T1ρ relaxation NMR methods at ambient and VT conditions. The relaxation data revealed reliable and variable guest dynamics for the 1:1 versus 2:1 complexes at the VTs investigated. The motional dynamics of the guest molecules involve an ensemble of axial motions of the whole chain and 120° rotational jumps of the methyl (CF3) group at the termini of the perfluorocarbon chain. The axial and rotational dynamics of the guest in the 1:1 and 2:1 complexes differ in distribution and magnitude in accordance with the binding geometry of the guest within the host.

Benznidazole drug delivery by binary and multicomponent inclusion complexes using cyclodextrins and polymers

Benznidazole (BNZ) is the drug of choice for Chagas disease treatment, which affects about 9.8million people worldwide. It has low solubility and high toxicity. The present study aimed to develop and characterize inclusion complexes (IC) in binary systems (BS) with BNZ and randomly methylated-β-cyclodextrin (RMβCD) and in ternary systems (TS) with BNZ, RMβCD and hydrophilic polymers. The results showed that the solid BS had a large increase in dissolution rate (Q>80%). For the solid IC obtained, the kneading method, in ratio of 1:0.17 (77.8% in 60min), appeared to be the most suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and low concentration of CD. The solid TS containing 0.1% of hydroxypropylmethylcellulose (HPMC) showed no significant advantages compared to the binary IC in solid state. The use of cyclodextrins proved to be a viable tool for effective, standardized and safe drug delivery.

A solid-state study of the inclusion of endosulfan in native and derivatised cyclodextrins using X-ray diffraction and thermoanalytical methods

Endosulfan is a highly toxic insecticide used in several countries and known to be relatively persistent in the environment. This recently banned agrochemical is capable of forming solid-state inclusion complexes with both native and derivatised cyclodextrins (CDs). Differential scanning calorimetry and powder X-ray diffraction (PXRD) techniques were used to confirm complexation of β-CD, γ-CD and randomly methylated β-CD (RAMEB) with the technical 7α:3β isomeric sample of endosulfan. The PXRD traces obtained for the inclusion complexes of the native CDs (β-CD and γ-CD) with endosulfan match those of other isostructural CD inclusion complexes. The single crystal X-ray structure of the complex formed between heptakis(2,6-di-O-methyl)-β-CD (DIMEB) and the β-endosulfan isomer is presented and shown to have a novel packing arrangement. The implications of the encapsulation of endosulfan in CDs are discussed with reference to the potential for sequestering the insecticide from contaminated areas.

Formation of Host-Guest Complexes of β-Cyclodextrin and Perfluorooctanoic Acid

Structural characterization and dynamic properties of solid-state inclusion complexes of β-cyclodextrin (β-CD) with perfluorooctanoic acid (PFOA) were investigated by (19)F/(13)C solid-state and (19)F/(1)H solution NMR spectroscopy. The complexes in the solid state were prepared using dissolution and slow cool methods, where thermal analyses (DSC and TGA), PXRD, and FT-IR results provided complementary support that inclusion complexes were formed between β-CD and PFOA with variable stoichiometry and inclusion geometry. (19)F DP (direct polarization) and (13)C CP (cross-polarization) with magic-angle spinning (MAS) solids NMR, along with (19)F/(1)H solution NMR were used to characterize the complexes in the solid and solution phases, respectively. The dynamics of the guest molecules in the inclusion complexes (ICs) were studied using variable temperature (VT) (19)F DP/MAS NMR experiments in the solid state. The guest molecules were observed to be in several different molecular environments, providing strong evidence of variable host-guest stoichiometry and inclusion geometry, in accordance with the preparation method of the complex and the conformational preference of PFOA. It was concluded from PXRD that β-CD and PFOA form inclusion complexes with "channel-type" structures. Variable spin rate (VSR) (19)F DP/MAS NMR was used to assess the phase purity of the complexes, and it was revealed that slow cooling resulted in relatively pure phases. In the solution state, (1)H and (19)F NMR complexation-induced chemical shifts (CISs) of β-CD and PFOA, respectively, provided strong support for the formation of 1:1 and 2:1 β-CD/PFOA inclusion complexes. The dynamics of the guest molecule in the β-CD/PFOA complexes in D(2)O solutions were probed using VT (19)F NMR and revealed some guest conformational and exchange dynamics as a function of temperature and the relative concentrations of the host and guest.

Inclusion of Paracetamol into β-cyclodextrin nanocavities in solution and in the solid state

We report on steady-state UV–visible absorption and emission characteristics of Paracetamol, drug used as antipyretic agent, in water and within cyclodextrins (CDs): β-CD, 2-hydroxypropyl- β-CD (HP- β-CD) and 2,6-dimethyl- β-CD (Me- β-CD). The results reveal that Paracetamol forms a 1:1 inclusion complex with CD. Upon encapsulation, the emission intensity enhances, indicating a confinement effect of the nanocages on the photophysical behavior of the drug. Due to its methyl groups, the Me- β-CD shows the largest effect for the drug. The observed binding constant showing the following trend: Me- β-CD > HP- β-CD > β-CD. The less complexing effectiveness of HP- β-CD is due to the steric effect of the hydroxypropyl-substituents, which can hamper the inclusion of the guest molecules. The solid state inclusion complex was prepared by co-precipitation method and its characterization was investigated by Fourier transform infrared spectroscopy, 1H NMR and X-ray diffractometry. These approaches indicated that Paracetamol was able to form an inclusion complex with CDs, and the inclusion compounds exhibited different spectroscopic features and properties from Paracetamol.

Mechanism of drug dissolution rate enhancement from beta-cyclodextrin-drug systems.

The influence of beta-cyclodextrin on the physicochemical properties of bendrofluazide, chlorothiazide, hydrochlorothiazide and hydroflumethiazide was investigated using solubility, X-ray powder diffraction, differential scanning calorimetry (DSC) and intrinsic dissolution rate methods. The solubility of each drug was enhanced in the presence of beta-cyclodextrin, the effect being greatest with bendrofluazide. X-ray diffraction data on equimolar freeze dried systems indicated the formation of solid state inclusion complex only in the case of bendrofluazide. The relative increase in initial dissolution rate of drug from freeze dried systems varied from sixty fold for bendrofluazide to three fold for hydroflumethiazide. The observed dissolution rates were intermediate between those predicted by the classical two component soluble complex model and a carrier controlled model. It was concluded that the enhanced drug dissolution rates, which are above those predicted by the soluble complex model, are due to an extension of carrier phase dissolution control to higher drug weight fractions than predicted by the soluble complex model and that this was a consequence of the disparate solubilities of the carrier and drug.

Complexation of Haloperidol with a Water‐soluble β‐Cyclodextrin Polymer: Characterization of the Inclusion Complex in Solid State and in Aqueous Solution

Haloperidol, a highly hydrophobic drug, was complexed with a β-cyclodextrin polymer. Its solubility was increased 24 times in the presence of a 10-fold excess of this polymer. The stability constant of the complex was calculated from the phase solubility technique. Differential scanning calorimetry was used to confirm the complexation in solid state and 1H NMR in aqueous solution. The enthalpy and the entropy of the system were calculated by monitoring the isothermic solubility line at four different temperatures, indicating that the complexation of haloperidol with this particular β-cyclodextrin polymer is a favourable procedure. These findings could result in a new, non-acidic water soluble formulation of haloperidol.

Improvement of some pharmaceutical properties of mycophenolate mofetil (MMF) by para sulphonatocalix[4]resorcinarene inclusion complex

As a part of our investigations to unfold the chemistry of calixresorcinarene, we have focused on the formation of inclusion complex of a poorly soluble (43 μg ml−1 at pH 7) drug mycophenolate mofetil (MMF) an immunosuppressive agent and an inosine monophosphate dehydrogenase (IMPDH) inhibitor with para sulphonatocalix[4]resorcinarene (PSC4R). The complete complexation of the drug was achieved after 48 h of stirring with para sulphonatocalix[4]resorcinarene(PSC[4]R) in water and evaporation of water yield the solid complex. The interaction between para sulphonatocalix[4]resorcinarene(PSC[4]R) and MMF in solid state inclusion complexes was accomplished by aqueous phase solubility studies, Thermal Analysis, HPLC, PXRD, FT-IR, and UV–Vis spectroscopy. The results of the phase solubility experiments are in good conformity to signify the formation of 2:1 PSC4R: MMF complexes. The purpose of this study was to enhance solubility and resulting in high dissolution rate and bioavailability of this essentially water insoluble drug. The results of the in vivo study shows that there is a remarkable change in the toxicity of the pure drug MMF and complex did not produce any mortality up to 2200 mg kg−1.