J. I. Pérez-Martínez

Effects of the host cavity size and the preparation method on the physicochemical properties of ibuproxam-cyclodextrin systems

The effect of cyclodextrin (Cd) complexation on ibuproxam (IBUX) dissolution properties was studied by evaluating both the influence of Cd cavity size and the preparation method used for obtaining solid inclusion complexes. Binary systems of IBUX with natural Cds, prepared using different techniques (kneading, sealed-heating, spray-drying), were studied by differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and their dissolution behavior was evaluated according to the dispersed amount method. The nature and the dissolution performance of the end product appeared to be related to both steric factors of host molecule and preparation method of the solid system. The alpha Cd cavity size was less suitable for accommodating the IBUX molecule, whereas spray-drying and sealed-heating methods led to a true inclusion complex of IBUX in the beta Cd and gamma Cd cavity. In contrast, the kneading method did not lead in any case to a real inclusion complex. Spray-dried systems with beta Cd and gamma Cd were the most effective in achieving the enhancement of the IBUX dissolution rate.

Influence of the preparation method of solid dispersions on their dissolution rate: Study of triamterene-d-mannitol system

In this paper, we illustrate the usefulness of spray-drying as a resourceful procedure for preparing solid dispersions. The study in the solid state of the triamterene-D-mannitol system from 10 to 40% w/w drug included scanning electron microscopy (SEM), X-ray diffraction (DRX) and differential scanning calorimetry (DSC). The main finding arising from the former studies was that a strong drug-carrier interaction existed in the systems prepared by spray-drying. In contrast, solid dispersions prepared by the melting carrier method showed only weak interactions between triamterene and D-mannitol. This observation helps to explain the much better dissolution rates obtained for the spray-dried outputs.

Enhanced solubilisation of six PAHs by three synthetic cyclodextrins for remediation applications: molecular modelling of the inclusion complexes

Solubilisation of six polycyclic aromatic hydrocarbons (PAHs) (acenaphthene, anthracene, fluoranthene, fluorene, phenanthrene and pyrene) by three synthetic cyclodextrins (CDs) (2-hydroxypropyl-β-CD, hydroxypropyl-γ-CD and ramdomly methylated-β-CD) was investigated in order to select the CD which presents the greatest increase in solubility and better complexation parameters for its use in contaminated scenarios. The presence of the three cyclodextrins greatly enhanced the apparent water solubility of all the PAHs through the formation of inclusion complexes of 1∶1 stoichiometry. Anthracene, fluoranthene, fluorene and phenanthrene clearly presented a higher solubility when β-CD derivatives were used, and especially the complexes with the ramdomly methylated-β-CD were favoured. On the contrary, pyrene presented its best solubility results when using 2-hydroxypropyl-γ-CD, but for acenaphthene the use of any of the three CDs gave the same results. Complementary to experimental phase-solubility studies, a more in-depth estimation of the inclusion process for the different complexes was carried out using molecular modelling in order to find a correlation between the degree of solubilisation and the fit of PAH molecules within the cavity of the different CDs and to know the predominant driving forces of the complexation.

Inclusion of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) with β-cyclodextrin by different processing methods

Abstract The interaction of the herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) with β-Cyclodextrin produces the formation of a new inclusion compound in solution and in solid state. XRD, MR, DSC and SEM techniques have allowed to investigate the inclusion process of the three processing methods (co-precipitation, spray-drying and kneading) under test. Inclusion of 2,4-D in β-CD in solution was also studied by phase solubility, being determined for the complex an apparent stability constant of 336 Ml. At the solid state, coprecipitation and spray-drying were found to yield an inclusion complex in 1:1 stoichiometry. From these systems, it was attained an increase of 2,4-D aqueous dissolution rate as compared with the uncomplexed herbicide, the spray-dried outcomed being the most effective one. This finding would allow a more rational application of 2,4-D and thus diminish its risks as potential pollutant of ground waters and soils.

β-CD effect on 2,4-D soil adsorption

Abstract The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and the β-Cyclodextrin (β-CD) interact to obtain an inclusion compound in solution and in solid state. The effect of the presence of β-CD on the adsorption-desorption behaviour of the pesticide 2,4-D on soil has been studied by batch equilibration experiments. The removal of 2,4-D previously absorbed on soil has been improved using β-CD solutions, due to the enhancement of 2,4-D solubility as a consequence of formation of water soluble 1:1 inclusion compounds 2,4-D-β-CD. The high complexing capacity of β-CD towards 2,4-D has been demonstrated. On the contrary, the treatment of the soil with β-CD solution before 2,4-D application increases the adsorption capacity of the soil.

Channeling Agent and Drug Release from a Central Core Matrix Tablet

A new oral dosage form for controlled and complete release of drug after a predetermined lag time is described. The system, designed to exploit the relatively constant small intestine transit time, consists of a drug-containing core coated with a polymeric matrix formed by a channeling agent (NaCl, mannitol, and Emdex) and an inert polymer (Eudragit RS100). The lag time was found to be dependent on type and particle size of the channeling substances used. Also, rheological properties of the binary mixtures (channeling substance–polymer) can affect the lag time periods. On the other hand, the release kinetics were found to be influenced significantly by excipient type and particle size. Results obtained from in vitro dissolution testing demonstrated that this device potentially could be used to deliver drugs orally for up to once-a-day dosing at controllable rates.

2,4-D-α-Cyclodextrin Complexes

The aqueous solubility of the pesticide 2,4-D was improved by inclusion complexation with α-CD. The formation of such inclusion compounds was studied via the phase-solubility diagram (solution state) and by DSC and HSM (solid state). 2,4-D presented a typical Bs Higuchi solubility curve, coprecipitating a 1:2 pesticide-α-CD complex. In order to obtain solid complexes, three processing methods were checked: kneading, coprecipitation and spray-drying. DSC and HSM showed that only the last two of these yielded true inclusion compounds. Chemical analysis also revealed that the stoichiometry of such solid complexes corresponds to a 2,4-D-α-CD ratio of 1:2.

H-Nuclear Magnetic Resonance and Phase Solubility Studies of the Stoichiometries in 2,4-D: α- and β-Cyclodextrins Inclusion Complexes

The interaction in solution between2,4-dichlorophenoxyacetic acid with α- andβ-cyclodextrins was evaluated by phasesolubility studies. Association constants werecalculated by this technique. The stoichiometries were1 : 2 and 1 : 1 for the α- and β-cyclodextrincomplexes, respectively. In order to corroborate thecomplexation and the knowledge of structural aspectsof the host : guest interaction, proton nuclearmagnetic resonance (1H-NMR) spectroscopy wasemployed. The application of the continuous variationtechnique corroborated the calculated complexstoichiometries by solubility assays. ComplementaryNOE studies were applied in order to corroborate theproposed complex structures.

Thermal Characterization of Gliclazide/β-Cyclodextrin Inclusion Complexes

Gliclazide/β-CD systems were prepared by various techniques: kneading, co-grinding, spray-drying, coprecipitation and neutralization. The thermal behaviour of these systems was studied by using DSC and TG, in order to find occurrence of the occurrence of solid-state inclusion complexation. The use of a complementary technique, Fourier transform infrared spectroscopy (FTIR), was intended to resolve possible ambiguous conclusions from the thermal study. Both studies demonstrated the existence of inclusion complexation in all cases except the kneading technique, which does not lead to a true inclusion complex.

Preparation and Characterization of 2, 4-D Complexes with α-Cyclodextrin

The interaction of the herbicide 2, 4-D with α-CD investigated by phase solubility, XRD and DSC indicate that 2, 4-D forms an inclusion complex with α-CD by coprecipitation and spray-drying methods. These complexes exist in solution with 1:1 and 1:2 stoichiometry and in the solid phase with 1:2 stoichiometry. The calculated values of stability constant were K1:1 and K1:2 were: K1:1 = 94.5 10−3 mM−1 and K1:2 = 3.48 10−3 mM−2.