Studies of Ergotamine Tartrate-Caffeine Interactions by Differential Scanning Calorimetry

Differential scanning calorimetry was used to evaluate the interactions between ergotamine tartrate and caffeine. Physical mixtures of ergotamine tartrate and caffeine, as well as mixtures formed by evaporation of ergotamine tartrate and caffeine from a methanol solution, were evaluated. The preparation and characterization of eleven different molar ratios of ergotamine tartrate-caffeine complexes is described. The drug was found to interact with caffeine in the solid state with the formation of complexes. The mixture obtained from the methanol solution showed complexes with ergotamine tartrate-caffeine molar ratios of 2:3 and 2:15, with possible complexes having 1:10, 1:15 and 1:20 molar ratios. A phase diagram was constructed. Physical mixtures of the same molar ratios showed possible complex formation at molar ratios of 1:1, 1:1 and 1:3.     

Differential Scanning Calorimetry of Aspartame-Caffeine Mixture

The possible interaction between aspartame and caffeine was investigated by comparing the thermal behavior, using differential scanning calorimetry, of physical mixtures of aspartame and caffeine along with mixtures, in the same molar ratios, obtained as the co-precipitate. Caffeine was found to form several complexes with aspartame. These complexes were found to be dependent on the molar ratios of aspartame to caffeine. The stoichiometry of the aspartame-caffeine complexes were determined from the enthalpy change of the DSC transitions resulting from the complex formation.     

Differential Scanning Calorimetry of Ampicillin-Aspartame Mixture

Abstract

The possible interaction of anhydrous and trihydrate ampicillin with aspartame, in the solid state, was investigated by comparing the thermal behavior of physical mixtures of the respective original components in different molar ratios, using differential scanning calorimetry. Aspartame was found to form complexes with anhydrous ampicillin and ampicillin trihydrate. These complexes were found to be dependent on the molar ratios of the mixture components. One of the complexes between anhydrous and trihydrate ampicillin and aspartame, as determined from the enthalpy change of the DSC transitions of the mixtures, was found to have a 2:1 molar ratio.     

Differential Scanning Calorimetry of Cephalexin-Dextrose and Cephalexin-Aspartame Mixtures

Abstract

The possible interaction of cephalexin with anhydrous dextrose and with aspartame, in the solid state, was investigaged by comparing the thermal behavior of physical mixtures of the respective original components in different molar ratios, using differential scanning calorimetry. Both anhydrous dextrose and aspartame were found to form complexes with cephalexin. The stoichiometries of these complexes were found to be 1:1 molar complexes between cephalexin and anhydrous dextrose and 4:1 and 1:1 molar complexes between cephalexin and aspartame. Complexed cephalexin was found to decompose at markedly lower temperatures than uncomplexed cephalexin.     

Thermal Analysis of Cimetidine-Caffeine Complexes

The preparation and characterization of cimetidine-caffeine complexes in the solid state is described. Ten different molar ratios were considered. Complexes were obtained as shown on their DSC thermograms. The heat of transition of these complexes was calculated and found to be dependent on the molar ratio of cimetidine to caffeine. A phase diagram was constructed for these complexes from which a 1:3.25 molar ratio of cimetidine to caffeine was found to exhibit optimum complexation characteristics. The cimetidine endotherms for physical mixtures of the same molar ratios show no significant changes as compared to that of cimetidine alone.     

Differential Scanning Calorimetry of Ampicillin-Dextrose Mixture

The possible interaction of anhydrous ampicillin and ampicillin trihydrate with anhydrous dextrose, in the solid state, was investigated by comparing the thermal behavior, using differential scanning calorimetry, of physical mixtures of the respective original components in different molar ratios. Anhydrous dextrose was found to form complexes with anhydrous ampicillin and ampicillin trihydrate. These complexes were found to be dependent on the molar ratios of the mixture components. The stoichiometries of these complexes were determined from the enthalpy change of the DSC transitions of the mixtures and were found to be 1:1, 2:3 and 1:3 molar complexes between ampicillin, anhydrous and trihydrate, and anhydrous dextrose. Complexed ampicillin was found to decompose at markedly lower temperatures than uncomplexed ampicillin.     

Differential Scanning Calorimetry of Ampicillin-Dextrose Mixture

The possible interaction of anhydrous ampicillin and ampicillin trihydrate with anhydrous dextrose, in the solid state, was investigated by comparing the thermal behavior, using differential scanning calorimetry, of physical mixtures of the respective original components in different molar ratios. Anhydrous dextrose was found to form complexes with anhydrous ampicillin and ampicillin trihydrate. These complexes were found to be dependent on the molar ratios of the mixture components. The stoichiometries of these complexes were determined from the enthalpy change of the DSC transitions of the mixtures and were found to be 1:1, 2:3 and 1:3 molar complexes between ampicillin, anhydrous and trihydrate, and anhydrous dextrose. Complexed ampicillin was found to decompose at markedly lower temperatures than uncomplexed ampicillin.     

Differential Scanning Calorimetry of Ampicillin-Aspartame Mixture

The possible interaction of anhydrous and trihydrate ampicillin with aspartame, in the solid state, was investigated by comparing the thermal behavior of physical mixtures of the respective original components in different molar ratios, using differential scanning calorimetry. Aspartame was found to form complexes with anhydrous ampicillin and ampicillin trihydrate. These complexes were found to be dependent on the molar ratios of the mixture components. One of the complexes between anhydrous and trihydrate ampicillin and aspartame, as determined from the enthalpy change of the DSC transitions of the mixtures, was found to have a 2:1 molar ratio.     

Nimesulide and β-Cyclodextrin Inclusion Complexes: Physicochemical Characterization and Dissolution Rate Studies

Complex formation of nimesulide (N) and β-cyclodextrin (βCD) in aqueous solution and in solid state and the possibility of improving the solubility and dissolution rate of nimesulide via complexation with βCD were investigated. Phase solubility studies indicated the formation of a 1:1 complex in solution. The value of the apparent stability constant Kc was 158.98 M^?1. Solid inclusion complexes of N and βCD were prepared by kneading and coevaporation methods. Differential scanning calorimetry (DSC) studies indicated the formation of solid inclusion complexes of N-βCD at a 1:2 molar ratio in both the methods. Solid complexes of N-βD (1:1 and 1:2 M) exhibited higher rates of dissolution and dissolution efficiency values than the corresponding physical mixtures and pure drug. Higher dissolution rates were observed with kneaded complexes than with those prepared by coevaporation. Increases of 25.6- and 38.7-fold in the dissolution rate were observed, respectively, with N-βCD 1:1 and 1:2 kneaded complexes.     

Complexation between risperidone and amberlite resin by various methods of preparation and binding study

Purpose: The purpose of this work was to investigate the effect of preparation methods and the drug-to-resin ratio on complex formation between risperidone and amberlite resin. Methods: The existence of such resin complex may provide taste-masking properties to the dosage forms. It is important to determine when and how the complex forms. Therefore, in this study, the complexes of risperidone and amberlite resin were prepared by granulation, solution, and freeze-drying methods at various drug-to-resin ratios. The physical mixtures of drug–resin were used to compare the results of complexes prepared by granulation, solution, and freeze drying. The complexes were evaluated by various methods of characterization including differential scanning calorimetry, X-ray diffraction, spectroscopy (near infrared, Fourier transform infrared, and Raman), drug release, and binding studies. Results: Complexation between risperidone and amberlite was investigated for various preparation methods. It was found that complexation occurred at lower amounts of amberlite resin (drug-to-resin ratios of 1:1 and 1:2) when solution form of drug was contacted with the resin as in the case of solution and freeze-drying techniques compared with granulation (drug-to-resin ratios of 1:4 and 1:6). Characterization studies such as differential scanning calorimetry, X-ray diffraction, spectroscopic techniques, and drug release studies differentiated complexes from the physical mixtures. Binding studies between them revealed that the binding was linear with solubility of the drug limiting the adsorption capacity. Conclusions: Results of the study highlighted the importance of the preparation methodologies to formulate complexes. When the drug and the resin were simply mixed physically, no complexation occurred. Thus, a careful evaluation of manufacturing procedure would indicate the nature and extent of complexation.     

Differential Scanning Calorimetry of Cephalexin-Dextrose and Cephalexin-Aspartame Mixtures

The possible interaction of cephalexin with anhydrous dextrose and with aspartame, in the solid state, was investigaged by comparing the thermal behavior of physical mixtures of the respective original components in different molar ratios, using differential scanning calorimetry. Both anhydrous dextrose and aspartame were found to form complexes with cephalexin. The stoichiometries of these complexes were found to be 1:1 molar complexes between cephalexin and anhydrous dextrose and 4:1 and 1:1 molar complexes between cephalexin and aspartame. Complexed cephalexin was found to decompose at markedly lower temperatures than uncomplexed cephalexin.     

Enhanced Aqueous Solubility of Phenolic Antioxidants Using Modified β-Cyclodextrins

Abstract

Phenolic antioxidants are useful additives with a possible role in cancer chemoprevention. This study describes inclusion complexation between phenolic antioxidants (butylated hydroxyanisole, BHA; butylated hydroxytoluene, BHT) and hydroxypropyl-β-cyclodextrins (HPB) or hydroxyethyl-β-cyclodextrin (HEB) and their characterization by phase solubility analysis, Xray diffraction and infrared (IR) spectroscopy. The complexes were prepared by shaking an aqueous mixture of the antioxidant with each of the cyclodextrins (1:1 molar) at 40 °C for six days and lyophilizing the resulting clear solution. Each of the complexes dissolved instantaneously in water. Phase solubility analysis indicated a more pronounced increase in the aqueous solubility of BHA compared to that of BHT. Xray diffraction patterns of the antioxidant-cyclodextrin complexes indicated a shift from crystalline pattern of the antioxidant to an amorphous pattern for the complexes. Also, the IR spectra of the BHA-cyclodextrin complexes indicated an almost complete disappearance or at least a shift in the -C-O-C- stretch (1200 cm^-1) compared to the corresponding stretch observed for BHA alone or a physical mixture (1:1) of BHA and each of the cyclodextrins. Furthermore, the sharp -OH absorption (3600 cm^-1) is retained in a physical mixture of BHT with either cyclodextrin (1:1) whereas this stretch is not observed in the IR spectra of either BHT-cyclodextrin complexes. These evidences indicate the formation of an inclusion complex between the antioxidants and each of the cyclodextrins.     

Inclusion Complexes of Tolnaftate with β-Cyclodextrin and Hydroxypropyl β-Cyclodextrin

Abstract

Tolnaftate, an antifungal agent, was found to form inclusion complexes with both β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrins (HPBCDs) with two different degrees of substitution [HPBCD(A)-8% and HPBCD(B)-3%]. Complex formation in the solution state was studied using phase solubility and spectral shift methods. Solid complexes were prepared by the coprecipitation method. Solubilities and dissolution rates were determined for each solid complex, its corresponding physical mixture, and free drug. The increase in solubility of tolnaftate with added HPBCD was found to be significantly greater than with added β-CD. For both HPBCD(A) and HPBCD(B), over the concentration range 0–0.05 M. 1:1 complexes with stability constants of 1460 ± 139 M^-1 and 1860 ± 165 M^-1 were observed, respectively. Over the β-CD concentration range 0–0.02 M, a 1:1 complex with a stability constant of 1190 ± 105 M^-1 was observed. At higher HPBCD concentrations, the increase in solubility was observed to show a positive deviation from linearity (type A_p phase diagram). Using the spectral method, in a 2 5% v/v methanol in water system, the stability constants were determined to be 1020 ± 150 M^-1 1110 ± 120 M^-1 and 1100 ± 260 M^-1 for HPBCD(A), HPBCD(B) and β-CD, respectively. The solid complexes prepared showed improved dissolution over physical mixtures and free drug.     

Preparation of nanoporous silica–zirconia layers by in situ sol–gel method

Abstract

Silica–zirconia membranes were prepared using a sol–gel process, never before used on this system. Thin layers of gel were grown on the outside of porous alumina support tubes using the permeation of water through pores of the tube to control the rate of hydrolysis with a reactive silica–zirconia alkoxide solution. A recipe was developed and optimum coating conditions were found to be the ratios of tetraethylorthosilicate (TEOS) to Zr propoxide to 1-propanol molar ratios (1:0·5:17), with a coating time of 300 s. The method allowed the formation of a membrane in a single step compared with repeated coating and firing. The coatings could be prepared adherent and without cracks when properly prepared.     

Characterization of Cu3SbS4 microflowers produced by a cyclic microwave radiation

Copper antimony sulfide (Cu₃SbS₄) crystals were produced from mixtures of different molar ratios of CuCl, SbCl₃ and thiourea in 40 and 60 ml ethylene glycol (EG) by a 300 W cyclic microwave radiation (CMR) for different lengths of time. In the present research, tetragonal Cu₃SbS₄ microflowers, characterized by X-ray and electron diffraction including electron microscopy and Raman analyses, were successfully produced in the 40 ml solution containing 2:2:4 molar ratio Cu:Sb:S for 40 cycles. Their UV-visible absorption was studied to determine the energy gap (E_g). A formation mechanism was also proposed to relate with the experimental results.     

Coprecipitation of 60Co from aqueous solutions with triethylenediamine complexes of d-element nitrates

Formation of complexes of Co²⁺ with triethylenediamine (CH₂-CH₂)₃N₂ (Q) in aqueous solution and coprecipitation of microamounts of ⁶⁰Co with triethylenediamine complexes of Cu²⁺, Ni²⁺, and Zn²⁺ nitrates were studied. Microamounts of ⁶⁰Co poorly coprecipitate with triethylenediamine complexes of Cu²⁺ and Zn²⁺ nitrates. At practically 100% precipitation of Cu²⁺ and Zn²⁺ from solutions in the form of the corresponding complexes, the degree of coprecipitation of ⁶⁰Co with these complexes does not exceed 15%. With the Ni²⁺ complexes formed from 10⁻¹ M aqueous solutions at the molar ratios Ni²⁺: Q = 1 : 1 and 1 : 2, the degree of coprecipitation of ⁶⁰Co is about 45 and 90%, respectively.     

Nimesulide and beta-cyclodextrin inclusion complexes: physicochemical characterization and dissolution rate studies

Complex formation of nimesulide (N) and β-cyclodextrin (βCD) in aqueous solution and in solid state and the possibility of improving the solubility and dissolution rate of nimesulide via complexation with βCD were investigated. Phase solubility studies indicated the formation of a 1:1 complex in solution. The value of the apparent stability constant Kc was 158.98 M^-1. Solid inclusion complexes of N and βCD were prepared by kneading and coevaporation methods. Differential scanning calorimetry (DSC) studies indicated the formation of solid inclusion complexes of N-βCD at a 1:2 molar ratio in both the methods. Solid complexes of N-βD (1:1 and 1:2 M) exhibited higher rates of dissolution and dissolution efficiency values than the corresponding physical mixtures and pure drug. Higher dissolution rates were observed with kneaded complexes than with those prepared by coevaporation. Increases of 25.6- and 38.7-fold in the dissolution rate were observed, respectively, with N-βCD 1:1 and 1:2 kneaded complexes.     

Influence of Method of Preparation on Inclusion Complexes of Naproxen with Different Cyclodextrins

Abstract

The aim of this study is to increase the solubility of naproxen by inclusion complex formation with α, β, γ, hydroxypropylbeta and dimethylbetacyclodextrin. The apparent stability constants were calculated from the slope and intercept of the AL-solubility diagrams. The solid inclusion complexes of naproxen with cyclodextrins in 1:1 molar ratio were prepared by the kneaded-mix, spray-drying and freeze-drying method. The formation of inclusion complexes in the solid state were confirmed by X-Ray diffractometry I.R. spectroscopy and differential scanning calorimetry. The dissolution rate of naproxen from the inclusion complexes was much more rapid than naproxen alone. The best results were obtained with β-cyclodextrin inclusion complex prepared by the spray-drying method.     

Influence of Tablet Formulation and Size on the in Vztro Sustained-Release Behavior of Metoprolol Tartrate from Hydrophilic Matrices

Abstract

Metoprolol tartrate sustained-release tablets were manufactured in 2.8, 7.0 and 10.0 mm diameters. In order to achieve the sustained release of active ingredients, the hydrophilic cellulose polymers methylcellulose, hydroxypropylcellulose and sodium carboxymethylcellulose were used either alone or in combination. It was investigated, in particular, whether the mini-tablets encased in hard gelatine capsules as multiple units allow for the sustained release of the basic active ingredient, which is highly soluble in the acidic pH.

While a sustained release is possible from the 7.0 and 10.0 mm diameter tablets formulated on the basis of HPC and NaCMC mixtures, tablets with 2.8 mm diameter do not allow for an adequate control of metoprolol tartrate release during the gastrointestinal passage. Active ingredient release in the range of up to 80 % release and the tablet surface area above a minimum of approximately 300 mm² are correlated in a linear manner.     

Synergistic extraction of rare earth elements from HNO<Subscript>3</Subscript> solutions with a mixture of chlorinated cobalt dicarbollide and acidic zirconium salt of dibutyl hydrogen phosphate in a polar diluent

Extraction of La and Ln(III) (except Pm) from HNO₃ solutions with mixtures of acidic zirconium salts of dibutyl hydrogen phosphate (ZS HDBP) with chlorinated cobalt dicarbollide (CCD) in a polar diluent, 1: 1 mixture of о-chloronitrobenzene and CCl₄, was studied. A synergistic effect is observed at definite ratios of CCD and ZS HDBP in the mixture. The magnitude of the synergistic effect increases with an increase in the Zr to HDBP molar ratio. The maximal synergistic effect equal to 360 was reached for Dy in the ZS HDBP (1: 6)–CCD extraction system. The maximal REE distribution ratio (D_max) is observed for elements from La to Dy at the HDBP to CCD molar ratio of 2 in all the extraction systems. For elements of the Ho–Lu series, D_max is observed at the HDBP to CCD molar ratio from 2 to 6. The HDBP to CCD molar ratio at which D_max is reached increases with an increase in the Zr content of the extraction system. For some pairs of elements, the separation factor considerably increases in the extractant mixture relative to the extractants taken separately. The largest increase in the separation factor (by a factor of 8.3) was noted for the Tm–Er pair in the CCD–ZS HDBP (1: 6) system. The synergistic effect in some cases is preserved at least up to the HDBP to CCD molar ratio of 670: 1, and at higher ratios the magnitude of the synergistic effect does not exceed the uncertainty of its determination. This fact suggests the formation of so-called hypercomplexes containing tens and hundreds of HDBP molecules in the CCD–ZS HDBP systems, similarly to the CCD–HDBP system. The largest number of HDBP molecules was noted in the Ln–CCD–[(ZS HDBP (1: 6)]_n complexes. The CCD–ZS HDBP (1: 6) and CCD–ZS HDBP (1: 12) systems are promising for the separation of REE and TPE, and small addition of CCD to the ZS HDBP (1: 6) system in a polar diluent allows the development of a cheap solvent efficiently recovering all the REE and TPE from a 3 M HNO₃ solution.