Colon targeting of fluticasone propionate inclusion complex: a novel approach in inflammatory bowel disease

Purpose of the present research was to present fluticasone propionate, a glucocorticoid, as a novel formulation exhibiting improved aqueous solubility, and targeting the drug directly to colon for the treatment of inflammatory bowel disease. Inclusion complex of the drug with hydroxypropyl betacyclodextrin were prepared by solvent evaporation and subsequently the granules of the inclusion complex were coated with Eudragit S100, in order to achieve colon targeting. Inclusion complex was characterized by FTIR, DSC, XRD and ¹H-NMR studies. In vitro drug release from coated granules and the drug transport across excised rat colon using modified Ussing chamber were also attempted. The drug was found to be present in amorphous form, when included in HPβCD cavities. Furthermore, intrinsic dissolution of the drug was found to increase by ~18 times. Coated granules exhibited no drug release in 0.01 N HCl as dissolution medium, indicating gastro-resistance, while 92 % of the drug was released in 120 min, in phosphate buffer (pH 7.4) as dissolution medium. The drug transport studies with rat colon led to more drug transport and concentration in target tissue, when presented as inclusion complex. The formulation releases the drug with improved aqueous solubility in colonic region, and thus concentrating the drug at the target tissue itself.     

Cyclodextrin complexation improves aqueous solubility of the antiepileptic drug,rufinamide: solution and solid state characterization of compound-cyclodextrin binary systems

Rufinamide (RUF) was characterized in terms of cyclodextrin (CD) complexation in order to improve its aqueous solubility. Binary systems of RUF with three CDs—β-cyclodextrin (β-CD), randomly methylated-β-cyclodextrin (RAMEB) and sulfobutylether-β-cyclodextrin (SBE-β-CD)—were characterized with a wide variety of analytical techniques. Liquid state characterization was carried out by complementary techniques such as nuclear magnetic resonance spectroscopy (NMR), capillary electrophoresis (CE), mass spectrometry (MS) and phase solubility studies. The latter revealed that the stability of the complexes decreased in the order of RAMEB?>?β-CD?>?SBE-β-CD. A_L-type diagrams were obtained in all cases, characteristic of 1:1 stoichiometry, with a maximum of over 15-fold increase in RUF solubility, when complexed with RAMEB. NMR Job plot and MS studies confirmed phase solubility results, regarding the binding stoichiometry. ¹H NMR and 2D ROESY investigations revealed the inclusion of the triazole moiety of RUF, confirmed by molecular modeling. Solid state complexation in 1:1 molar ratio was carried out by kneading method and investigated by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Comparative dissolution studies indicated an over two-fold improvement in dissolution efficacy of the kneaded products, when compared to the pure drug. Results of the present study might pave the way for a drug formulation with improved bioavailability.     

Characteristic profiles of the inclusion complex of omeprazole/peracylated-β-cyclodextrin formed in supercritical carbon dioxide

Inclusion properties of the drug omeprazole (OMP) with peracetylated-beta-cyclodextrin (PAc-β-CD) prepared by green method, following supercritical carbon-dioxide (scCO₂), were characterized through thermal (TGA and DSC), crystalline (XRD), NMR spectroscopic and dissolution studies. Comparison amongst PAc-β-CD, OMP, physical binary mixture (equimolar ratio of OMP: PAc-β-CD) and the solid inclusion complex (OMP/PAc-β-CD) revealed scCO₂ as a successful technique for inclusion complex formation as well, identified characteristics performances of PAc-β-CD/OMP interactions. For instance, absence of characteristic DSC or XRD peaks of either chemical in the complex was quite noticeable with the shift of proton peaks in ¹H NMR spectra. The formed inclusion complex also showed an important dissolution performance of OMP for controlled release applications partly due to the hydrophobic nature of PAc-β-CD.     

Inclusion Complexation of Anti-HIV Drug with β-Cyclodextrin

The purpose of present investigation was to investigate the effect of complexation of Nelfinavir Mesylate (NM) – an Anti-HIV drug with Beta-cyclodextrin (β-CD) on its dissolution characteristics and subsequent effect on its absorption properties and bioavailability. Phase solubility studies were conducted to find the interaction of NM with β-CD. Physical mixing and milling method were used for complexation. The inclusion complexes were characterized by X-ray diffractometry, FT-IR and NMR studies and further studied by in-vitro dissolution testing. The plain NM and complex was subjected to intestinal absorption studies by using Everted intestinal sac model. Data was treated statistically by Mann–Whitney U test. Pharmacokinetic studies were carried out in rabbits using cross over design and data was treated by Student’s t test. Phase solubility studies confirmed 1:1 complex formation of NM with β-CD with stability constant of 204.84 M⁻¹. In-vitro dissolution studies of inclusion complexes of NM with β-CD prepared by milling method (T ₉₀=60.89 min) showed better dissolution rate kinetics in distilled water in comparison with plain NM (T ₉₀=374.31). The increased solubility with decreased crystallinity is attributed by inclusion of NM in the cavity of β-CD, which was further confirmed by instrumental studies. Intestinal absorption studies further supports these findings by showing 2.13 times enhancement in the absorption rate of complex as compared to plain NM. The percent relative bioavailability of complex in rabbits was 185.37 as compared to the plain NM.     

Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes

In the present study influence of nature of selected cyclodextrins (CDs) and of methods of preparation of drug–CD complexes on the oral bioavailability, in vitro dissolution studies and pharmacodynamic activity of a sparingly water soluble drug rosuvastatin (RVS) was investigated. Phase solubility studies were conducted to find the interaction of RVS with β-CD and its derivatives, which indicated the formation of 1:1 stoichiometric inclusion complex. The apparent stability constant (K_1:1) calculated from phase solubility diagram were in the rank order of β-CD < hydroxypropyl-β-cyclodextrin (HP-β-CD) < randomly methylated-β-cyclodextrin (RM-β-CD). Equimolar drug–CD solid complexes prepared by different methods were characterized by the Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). FTIR study demonstrated the presence of intermolecular hydrogen bonds and ordering of the molecule between RVS and CDs in inclusion complexes. DSC and XRD analysis confirmed formation of inclusion complex by freeze dried method with HP-β-CD and RM-β-CD. Aqueous solubility and dissolution studies indicated improved dissolution rates of prepared complexes in comparison with drug alone. Moreover, CD complexes demonstrated of significant improvement in reducing total cholesterol and triglycerides levels as compared to pure drug. However the in vivo results only partially agreed with those obtained from phase solubility studies.     

Formulation of a Poorly Water-Soluble Drug Sirolimus in Solid Dispersions to Improve Dissolution

An attempt has been made to enhance solubility and dissolution of sirolimus by solid dispersion and complexation technique using various hydrophilic excipients. Sirolimus an immunosuppressant agent has low bioavailability due to its low aqueous solubility. Solid dispersion of sirolimus in PEG-6000, Poloxamer-188, and Mannitol were prepared by fusion and solvent evaporation method. Beta-CD complexation of sirolimus was prepared by kneading method. In vitro dissolution studies were carried out in 0.4% SLS in water, which showed that the solid dispersion containing PEG 6000 (1:1), which was prepared by solvent evaporation method, showed faster dissolution rate than the other formulations and β-cyclodextrin complex. Solid dispersions containing PEG 6000 was further investigated by x-ray powder diffraction, differential scanning calorimetry (DSC), and FTIR. X-ray powder diffraction and DSC patterns suggested that the drug state changed from crystalline to amorphous form in the formulation.     

Preparation & characterization of embelin�Cphospholipid complex as effective drug delivery tool

The aim of the present study was to prepare an embelin?Cphospholipid complex (EPC) formulation in an attempt to enhance the water solubility and to characterize the new developed formulation. Embelin, due to water insolubility causes poor bioavailability by oral route. To improve the bioavailability and prolong its duration in body system, its phospholipid complexes were prepared by a simple and reproducible method. EPC was formulated by mechanical dispersion method using ethanol as a reaction medium, embelin and phospholipids were dissolved into the medium, after that organic solvent was removed under vacuum condition and EPC was formed. The complex formation was confirmed by carrying out FTIR, ¹H-NMR, XRD, DSC and microscopical studies. Solubility and in vitro studies were carried out to ascertain the solubility and dissolution pattern of free and complexed embelin. Content of embelin in EPC was found to be 92.44% (w/w). FTIR, ¹H NMR, DSC and XRD data confirmed the formation of embelin phospholipid complex. Water solubility of embelin was improved from 3 to 42 ??g/mL in the prepared complex. n-Octanol solubility were also altered for free embelin and EPC from 2.3 to 39 ??g/mL. Unlike the free embelin, which showed a total of only 19% drug release at the end of 120 min, EPC showed 99.80% release at the end of 120 min of dissolution study in distilled water. Microscopical characterization of the developed formulation also showed the entrapment of embelin in the lipid core showing complex structure, which was further, supported by change in surface morphology of embelin on microscopical examination. Hence, the present findings demonstrate that complexing embelin with phospholipid can be further explored for improved therapeutic implications.     

Interaction of Valdecoxib with β-cyclodextrin: Experimental and Molecular Modeling Studies

This study aimed to investigate the effect of β-cyclodextrin on aqueous solubility and dissolution rate of valdecoxib and also to get an insight of molecular interactions involved in formation of valdecoxib‐β-cyclodextrin inclusion complex. Phase solubility analysis indicated complex with possible stoichiometry of 1:1 and a stability constant of 234.01 M⁻¹. Thermodynamic studies in water indicated exothermic nature of inclusion complexation.␣Valdecoxib‐β-cyclodextrin complexes (1:1 M) were prepared by kneading method, solution method and␣freeze–drying method. The complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (P-XRD), Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance␣(¹H-NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of β-cyclodextrin with valdecoxib. ¹H-NMR analysis suggested that the unsubstituted phenyl ring of valdecoxib display favorable interaction with the hydrophobic cavity of β-cyclodextrin, which was confirmed by molecular dynamic simulations. An inclusion complex model has been established for explaining the observed enhancement of solubility of valdecoxib in water by β-cyclodextrin. Dissolution studies in water showed that the valdecoxib in freeze-dried complex dissolved much faster than the uncomplexed drug and physical mixture. This improvement in dissolution rate is attributed to the increased solubility and wettability due to encapsulation along with decreased crystallanity caused by complex formation, which is evident by DSC and P-XRD studies.     

Preparation and physicochemical characterization of carbamazepine (CBMZ): para-sulfonated calix[n]arene inclusion complexes

The formation of inclusion complexes with para-sulfonated calix[n]arene (PSC[n]A) was studied for carbamazepine (CBMZ), a poorly water soluble anticonvulsant drug. The effect of PSC[4]A and PSC[6]A on aqueous solubility of carbamazepine was studied extensively. The complete complexation of the drug was achieved after 48 h of shaking with PSC[n]A in water and evaporation of water to get solid complex. The interaction between PSC[n]A and CBMZ in solid state inclusion complexes was accomplished by aqueous phase solubility studies, HPLC, DSC, PXRD, FTIR, UV–Vis, and FT-Raman spectroscopy. The solubility of CBMZ increases as a function of PSC[n]A concentration. The results of the two phase solubility experiments are in good conformity to signify the formation of 1:1 (PSC[6]A:CBMZ) and 2:1 PSC[4]A:CBMZ complexes. The order of dissolution rate of CBMZ is inclusion complex > physical mixture > drug alone. The purpose of this study was to enhance solubility resulting in high dissolution rate and bioavailability of this essentially water insoluble drug.     

Solubility enhancement of kinetin through host–guest interactions with cucurbiturils

We explored the use of cucurbiturils to form inclusion complexes to overcome the solubility problems of kinetin, a plant cytokinin. Inclusion complexes between kinetin and Q[7], TMeQ[6] and HMeQ[6] in aqueous solution and in solid state were investigated by phase solubility studies, ¹H NMR and IR. The effects of pH and temperature on complex stability were also investigated. Phase solubility studies showed that kinetin solubility increased in a linear fashion as a function of Q[7] and TMeQ[6] concentrations. However, kinetin solubility increased first, then decreased as the HMeQ[6] concentration increased, and the maximum solubility of kinetin was achieved at 4.95 mM in HMeQ[6]. The solubility of kinetin as well as the stability constant of its complex with Q[7] were affected by the pH of the medium. The thermodynamic parameters of the complex formation were also determined, and it showed that the formation of the inclusion complexes between kinetin and Q[7] was enthalpy controlled, suggesting that hydrophobic and van der Waals interactions were the main driving forces. Moreover, we found that the size of the cavity of cucurbituril played an important role in the association process. The formation of inclusion complexes between Q[7], TMeQ[6] and HMeQ[6] with kinetin was confirmed by ¹H NMR, and IR spectroscopy showed the presence of inclusion complexes in solid state. Our results demonstrated that the complexation of kinetin with Q[n] could be used to improve the solubility of kinetin in aqueous solution.     

Synthesis of Cyclodextrin and Sugar-Based Oligomers for the Efavirenz Drug Delivery

Summary: In the present work water-soluble lactose based oligomers of β-cyclodextrin were synthesized by a simple and efficient condensation polymerization process. Proposed water-soluble β-cyclodextrin oligomers were prepared by controlled reaction between β-cyclodextrin and a triazine linker and purification by an ultrafiltration process. Similarly, lactose based β-cyclodextrin oligomers were synthesized for enhanced water solubility. The physical and chemical properties of the synthesized polymers were characterized by FT-IR and ¹H NMR spectroscopy, XRD analysis, thermogravimetric analysis (TGA) and aqueous solubility determination.. Molecular weights of these β-cyclodextrin based oligomers were measured by ESI technique. These β-cyclodextrin based water-soluble oligomers polymers were used as supramolecular carriers for efavirenz (an anti HIV drug), improving the inclusion property and aqueous solubility properties of this drug. These synthesized oligomers were found to improve stability and aqueous solubility of efavirenz on their (1:1) inclusion complex through phase solubility and dissolution studies. Reduced cytotoxicity than the parent β-CD was observed in hemolysis test.     

Solubility, dissolution rate and bioavailability enhancement of irbesartan by solid dispersion technique

The objective of present work was to enhance the solubility and bioavailability of poorly aqueous soluble drug Irbesartan (IBS). The solid dispersions were prepared by spray drying method using low viscosity grade HPMC E5LV. Prepared solid dispersions were characterized by dissolution study, fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction studies (XRD). Results of the SEM, DSC and XRD study showed the conversion of crystalline form of IBS to amorphous form. The dissolution rate was remarkably increased in case of solid dispersion compared to pure IBS. Solubility and stability of solid dispersion was increased due to surfactant and wetting property, slowing devitrification and having anti-plasticization effect of HPMC E5LV. In vivo studies were performed in healthy rabbits (New Zealand grey) and compared with plain IBS. Solid dispersions showed increase in relative bioavailability than the plain IBS suspension. In conclusion, the prepared solid dispersions showed remarkable increase in solubility, dissolution rate and hence bioavailability of poorly water soluble drug Irbesartan.     

Improvement of opipramol base solubility by complexation with β-cyclodextrin

Opipramol (OPI), a tricyclic antidepressant and anxiolytic compound, is administered orally in the form of a dihydrochloride. Salt form of the drug has a higher solubility in water and hence bioavailability and stability. A similar effect can be achieved by closing the hydrophobic part of the drug molecule in the cyclodextrin cavity. The paper presents opipramol inclusion complexes with beta-cyclodextrin (β-CD) in 1:1 molar ratio. Studies on the formation of inclusion complexes were carried out both in solution and in the solid state. The formation and physicochemical characterisation of the complexes were determined by UV spectroscopic measurement (UV–vis), Fourier Transform Infrared (FTIR) Spectroscopy, ¹H Nuclear Magnetic Resonance (¹H NMR, 2D NOESY NMR), thermoanalytical methods (TGA – Termogravimetric analysis, DSC – differential scanning calorimetry), X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The phase solubility profile with β-CD was classified as the A_N- type, indicating the formation of the inclusion complex with a drug.     

Inclusion complexes of fluconazole with β-cyclodextrin: physicochemical characterization and in vitro evaluation of its formulation

Fluconazole (FZ) is a triazole antifungal drug administered orally or intravenously. It is employed for the treatment of mycotic infections. However, the efficacy of FZ is limited with its poor aqueous solubility and low dissolution rate. One of the important pharmaceutical advantages of cyclodextrins is to improve pharmacological efficacy of drugs due to increasing their aqueous solubility. The aim of present study was to prepare an inclusion complex of FZ and β-cyclodextrin (β-CD) to improve the physicochemical and biopharmaceutical properties of FZ. The effects of β-CD on the solubility of FZ were investigated according to the phase solubility technique. Complexes were prepared with 1:1 M ratio by different methods namely, freeze-drying, spray-drying, co-evaporation and kneading. For the characterization of FZ/β-CD complex, FZ amount, practical yield %, thermal, aqueous solubility, XRD, FT-IR and NMR (¹H and ¹³C) analysis were performed. In vitro dissolution from hard cellulose capsules containing FZ/β-CD complexes was compared to pure FZ and its commercial capsules and evaluated by f₁ (difference) and f₂ (similarity) factors. Paddle method defined in USP 31 together with high pressure liquid chromatographic method were used in in vitro dissolution experiments. It was found that solubility enhancement by FZ/β-CD complexes depends on the type of the preparation method. High release of active agent from hard cellulose capsules prepared with β-CD complexes compared to commercial capsules was attributed to the interactions between β-CD and active agent, high energetic amorphous state and inclusion complex formation.     

Preparation and evaluation of binary and ternary inclusion complexes of fenofibrate/hydroxypropyl-β-cyclodextrin

This study aimed to investigate the effect of hydroxypropyl methylcellulose on the complexation of fenofibrate and hydroxypropyl-β-cyclodextrin (HP-β-CD). Initially, phase solubility studies with an excess amount of drug in the HP-β-CD solutions with and without hydroxypropyl methylcellulose (HPMC) were investigated. Both of the binary and ternary complexes were prepared by ball-milling. The complexes were characterized by Fourier transform infrared spectroscopy (FI-IR), X-ray powder diffraction (XPRD), differential scanning calorimetry (DSC) and nuclear magnetic resonance spectroscopy (¹H-NMR). The A_L type phase-solubility diagram revealed that the complexes of fenofibrate and HP-β-CD were formed with molecular ratio of 1:1. The results of FT-IR, XPRD, DSC and ¹H NMR analysis show the formulation of inclusion complexes. In conclusion, the interaction occurrs between fenofibrate and HP-β-CD in the complexes, and the existence of HPMC effectively improves the complexation efficiency and stability constant. The in vitro dissolution test suggests ternary complex is superior to binary complex in terms of the release of fenofibrate.     

Eudragit-coated albumin nanospheres carrying inclusion complexes for oral administration of indomethacin

Oral administration of indomethacin (IN) as well as drugs with low aqueous solubility usually results in poor absorption and bioavailability. The aim of this study was to prepare enteric-coated bovine serum albumin (BSA) nanospheres carrying cyclodextrin complex for IN delivery. Inclusion complex composed of IN and ??-cyclodextrin (CD) was prepared by spray-drying. Indomethacin alone and its inclusion complex were incorporated into albumin nanospheres using a coacervation method followed by thermal cross-linking. Then nanosphere suspensions were spray-dried. The inclusion complex and the nanospheres were characterized by FT-IR spectroscopy and DSC analysis. Phase-solubility diagrams and stability constants were determined at pH 2.0 and 7.4 and at different temperatures (10, 25 and 37 °C). Swelling ability of nanospheres were evaluated as well as the in vitro release behaviour at pH 2.0 and 7.4. The nanospheres were coated with Eudragit^® L-100 (EudL) or S-100 (EudS) using spray-drying to give protection in the stomach. The results showed that IN solubility can be increased by complexation with ??-CD or protein/drug interaction with albumin nanospheres. The inclusion complex loaded into BSA nanospheres provided a zero order drug release kinetic. The coating process with EudL and EudS allowed to obtain a negligible release at acidic pH without limiting drug availability at pH 7.4.     

Chrysophanol–phospholipid complex

Delivery of poorly soluble drugs results in poor absorption and low bioavailability to the systemic circulation. Chrysophanol (1,8-dihydroxy 3-methyl anthraquinone) a plant derived herbal drug is well known for its strong anti-inflammatory, anti-mutagenic, and anti-carcinogenic activities but poor aqueous solubility (hence the lower dissolution rate), is a major barrier in its intestinal absorption. To improve the bioavailability and prolong its duration in the body system, its phospholipid complex was prepared and evaluated for various physicochemical parameters like encapsulation efficiency, scanning electron microscopy, differential scanning calorimetry (DSC), X-ray powder diffractometry (X-RPD), IR spectroscopy, aqueous/n-octanol solubility, and dissolution study. The phospholipid complex of chrysophanol was found, fluffy and porous with rough surface morphology. FTIR, DSC, and X-RPD data confirmed the complex formation. The 89.1 % of chrysophanol was encapsulated in the phospholipid complex. The aqueous solubility of chrysophanol was improved from 0.60 to 30.09 μg ml^?1 in the prepared complex. The improved dissolution was shown by the complex (which showed continuous release up to 83.67 % of chrysophanol) at the end of 12 h, in comparison to free drug (which showed a total of only 45.12 % drug release at the end of 12 h of dissolution study).     

Preparation and evaluation of inclusion complexes of diacerein with β-cyclodextrin and hydroxypropyl β-cyclodextrin

The objective of this research was to improve the aqueous solubility, dissolution rate and, consequently, bioavailability of diacerein, along with avoiding its side effect of diarrhea, by complexation with β-cyclodextrin (β-CD) and HP-β-cyclodextrin (HP-β-CD). Phase solubility curve was classified as an A_N type for both the CDs, which indicated formation of complex of diacerein with β-CD and HP-β-CD in 1:1 stoichiometry and demonstrating that both CDs are proportionally less effective at higher concentrations. The complexes were prepared by kneading method and were evaluated to study the effect of complexation on aqueous solubility and rate of dissolution in phosphate buffer (pH 6.8). Based on the dissolution profile HP-β-CD was selected for preparing fast disintegrating tablet of diacerein which was compared with marketed formulation (MF-J). The HP-β-CD complex was probed for Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies which evidenced stable complex formation and increase in amorphousness of diacerein in complex. In brief, the characterization studies confirmed the inclusion of diacerein within the non-polar cavity of HP-β-CD. HP-β-CD complex showed improved in vitro drug release profile compared to pure drug and similar to that of marketed formulation respectively.     

Inclusion complexes of lamotrigine and hydroxy propyl β-cyclodextrin: solid state characterization and dissolution studies

Lamotrigine (LMN) is an antiepileptic drug, with poor aqueous solubility, which might lead to erratic bioavailability. The objective of the present work was to improve the dissolution characteristics of the LMN using Hydroxy propyl β-cyclodextrin (HP β-CD), which might offer reliable bioavailability. The phase solubility profile was classified as A _L -type, revealing 1:1 stoichiometric complexation, with a stability constant (Ks) of 573 M^?1. Binary systems of LMN and HP β-CD were prepared in different molar ratios (1:1, 1:2, 1:3 and 1:4) by kneading method. The binary systems were characterized by Fourier Transform Infrared (FT-IR) Spectroscopy, Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction Analysis (PXRD). Results revealed that in the kneaded products the entire drug was entrapped inside the HP β-CD cavity and reduction in drug crystallinity also took place, which may be responsible for improved dissolution characteristics as compared to that of the pure drug as depicted from the dissolution studies.     

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.