INCREASING THE SOLUBILITY OF DIPYRIDAMOLE USING POLYETHYLENE GLYCOLS

Objective: The objective of the present study is a determination of the limiting solubility of dipyridamole in water and optimal ratios of polyethylene glycol:dipyridamole at which formation of solid dispersion is observed. Methods: UV-spectroscopy was used to determine the effect of polymer on limiting solubility of dipyridamole. Using low-temperature differential scanning calorimetry (DSC), it was made possible to obtain solid dispersions of dipyridamole with polyethylene glycols having average molecular weight 1000 and 1400. Results: The optimal ratio of polymer:Drug is 1:1, and is 3:1 for PEG-1000 and PEG-1400 respectively. Joint dissolution of dipyridamole with PEG-1400 and PEG-1000 increases the drug content in the water by up to 8.1 times and up to 175 times, compared with the solution containing only dipyridamole. Conclusion: using systems based on dipyridamole and polyethylene glycol with average molecular weight of 1000, may increase the bioavailability of the drug and consequently reduce the dosages. Wide range of ratios, in which the formation of solid dispersions is possible, enables to adjust the solubility of dipyridamole in neutral aqueous media

New Polymorph of β-Cyclodextrin with a Higher Bioavailability

A new polymorph of anhydrous β-cyclodextrin (polymorph III) was obtained and characterized for the first time using powder X-ray diffraction, infrared spectroscopy, and thermal analysis. The solution enthalpy and time of dissolution in water were determined using solution calorimetry for this polymorph and compared with those of the dried commercial form of β-cyclodextrin (polymorph I), its amorphous form, and 2-hydroxypropyl-β-cyclodextrin. The specific heat capacities of polymorphs I and III were determined using differential scanning calorimetry across a wide range of temperatures, providing enthalpy and Gibbs energy values for the polymorphic transition at 298 K. The affinities of polymorph III and 2-hydroxypropyl-β-cyclodextrin for water were characterized by determining their hydration isotherms, which provided values of hydration Gibbs energy. Being energy-rich, the new-found polymorph of β-cyclodextrin has a significantly higher dissolution rate and an increased affinity for water compared with the dried commercial form of β-cyclodextrin. These properties render the new polymorph promising in industrial applications for guest inclusion in aqueous solutions and pastes, and may be a desirable alternative for water-soluble β-cyclodextrin derivatives

Determination of Melting Parameters of Cyclodextrins Using Fast Scanning Calorimetry

The first evidence of native cyclodextrins fusion was registered using fast scanning calorimetry (FSC) with heating rates up to 40,000 K s−1. The endothermal effects, detected at low heating rates, correspond to the decomposition processes. Upon the increase of the heating rate the onset of these effects shifts to higher temperatures, reaching a limiting value at high heating rates. The limiting temperatures were identified as the melting points of α-, β- and γ-cyclodextrins, as the decomposition processes are suppressed at high heating rates. For γ-cyclodextrin the fusion enthalpy was measured. The activation energies of thermal decomposition of cyclodextrins were determined by dependence of the observed thermal effects on heating rates from 4 K min−1 in conventional differential scanning calorimetry to 40,000 K s−1 in FSC. The lower thermal stability and activation energy of decomposition of β-cyclodextrin than for the other two cyclodextrins were found, which may be explained by preliminary phase transition and chemical reaction without mass loss. The obtained values of fusion parameters of cyclodextrins are needed in theoretical models widely used for prediction of solubility and solution rates and in preparation of cyclodextrin inclusion compounds involving heating

Unusually High Selectivity of Guest Exchange in <i>tert</i>-Butylthiacalix[4]arene Clathrate Producing More Thermostable Inclusion and Memory of Guest

New properties, earlier unknown for calixarenes, were found for <i>tert</i>-butylthiacalix­[4]­arene (<b>1</b>) clathrate with 1,2-dichloroethane (DCE). Guest exchange in <b>1</b>·1.90DCE for vapors of some organic compounds gives clathrates, which are more thermostable at 34–59 °C than those prepared by direct saturation of guest-free <b>1</b> with pure guests. Besides, guest exchange may produce clathrates that cannot be formed by direct saturation in binary host–guest systems. Some compounds, like water, toluene, and trichloroethylene, expel DCE from its clathrate with <b>1</b> but are not included above the trace level. Residual contents of DCE in clathrate may be controlled by variation of water and <b>1</b>·1.90DCE ratio in the studied system. Host <b>1</b> can remember methanol after its elimination from the guest exchange product. This memory can be read as an exoeffect by differential scanning calorimetry. Only methanol and only after guest exchange is remembered giving an example of a genuine molecular recognition

Thermodynamics of dissolution and infrared-spectroscopy of solid dispersions of phenacetin

In this work enthalpies of dissolution in water of polyethylene glycols (PEGs) having an average molecular weight of 1000 and 1400, Pluronic-F127, phenacetin as well as the composites prepared from them were measured using solution calorimetry at 298.15 K. Intermolecular interaction energies of polymer-phenacetin were calculated on the basis of an additive scheme. It was shown that for mixtures with high content of polymer (>90 wt%) Pluronic-F127 has the highest solubilizing effect, while for mixtures with (4–6):1 polymer: phenacetin ratio the best solubilizing agent is PEG-1400. Infrared-spectra showed a decrease of the number of self-associated molecules of phenacetin with increasing of polymer content in the composites. The obtained results enabled us to identify the features of intermolecular interactions of polymers with a model hydrophobic drug and may be used for optimizing the conditions for preparing solid dispersions based on hydrophilic polymers