M. J. Arias

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.

Study of the dissolution characteristics of oxazepam via complexation with β-cyclodextrin

Abstract Complex formation of oxazepam and β-cyclodextrin in solution was studied by phase solubility and spectral shift methods. The value of the apparent stability constant, K c , calculated using these techniques, was 205 and 498 M −1 , respectively. Solid complexes of oxazepam and β-CD were prepared using the kneading and spray-drying methods. These complexes led to an improvement in the dissolution rate over free oxazepam, spray-drying being the most efficient technique. These complexes were characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray diffraction.

Thermal investigation of crystallization of polyethylene glycols in solid dispersions containing oxazepam

A critical issue in the processing of solid dispersions is to elucidate the microstructure of the resulting product. Morphological features such as crystallinity degree of both carrier and drug, and particle size of the latter, have a deep effect on the properties of the drug dissolution. In the present paper, Hot Stage Microscopy (HSM) has been employed to investigate the crystallization of polyethylene glycols (PEG) of different molecular weights used in the processing of a benzodiazepine (oxazepam). The results have shown that the crystalline morphology and the radial growth rate were dependent on the polymer molecular weight, crystallization temperature, and also on the molecular state of the drug incorporated into the polymer, forming a solid dispersion and strongly influencing the drug dissolution rate.

Investigation of the triamterene–β-cyclodextrin system prepared by co-grinding

Complex formation of triamterene and β-cyclodextrin in solution was studied by phase solubility and spectral shift methods. The value of the apparent stability constant, Kc, calculated by these techniques, were 340 and 470 M−1, respectively. Binary systems of triamterene and β-CD were prepared using the dry co-grinding method. Their characterization was performed by Fourier transform infrared spectroscopy and scanning electron microscopy. The main conclusion arising from these studies has been a high interaction between drug and carrier, linked to a clear increase in the amorphous nature of the drug in these systems. Finally, as expected, the 1 min co-ground system presented a notable improvement in its dissolution rate: up to five fold dissolution efficiency over the first 60 min over free drug. This might be attributed to the amorphous state, the increased wettability of the drug and the inclusion complex formation at the liquid state.

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.

Study by DSC and HSM of the oxazepam-PEG 6000 and oxazepam-D-mannitol systems : Application to the preparation of solid dispersions

Oxazepam is a drug characterised by its marked hydrophobicity and unsatisfactory wettability on contact with water. These properties lead to incomplete absorption of the drug from the gastrointestinal tract when the pharmaceutical dosage form is not adequately formulated. For this reason, it is of interest to optimise its dissolution properties. For this purpose, the preparation of solid dispersions with hydrophilic carriers has been often employed. In this paper, the possibility of employing two hydrophilic substances (PEG 6000 and D-mannitol) as carriers for solid dispersions, prepared by the co-fusion or the fusion carrier methods, were evaluated by DSC and HSM. The results show, in terms of the miscibility of molten oxazepam in the fused vehicle, that PEG 6000 is the only suitable carrier. D-mannitol yielded non-homogeneous systems.

Effect of Molecular Mass on the Melting Temperature, Enthalpy and Entropy of Hydroxy-Terminated PEO

This paper studies the effect of molecular mass on the melting temperature, enthalpy and entropy of hydroxy-terminated poly(ethylene oxide) (PEO). It aims to correlate the thermal behaviour of PEO polymers and their variation of molecular mass (MW). Samples ranging from 1500 to 200,000 isothermally treated at 373 K during 10 min, were investigated using DSC and Hot Stage Microscopy (HSM). On the basis of DSC and HSM results, melting temperatures were determined, and melting enthalpies and entropies were calculated. Considering the melting temperatures, it was found that the maximum or critical value of MW was found around 4000, and then these remain almost constant. This behaviour was interpreted assuming that lower MW fractions (MW<4000) crystallize in the form of extended chains and higher MW fractions (MW>4000), as folded chains. The melting enthalpies showed a scattering effect at least up to MW 35,000. It was difficult to obtain any relationship between melting enthalpies in J g−1 and MW. These variations seem to be of statistical nature. Corrected enthalpy data on a molar basis (kJ mol−1) exhibited a linear relationship with MW. Considering the solid—liquid equilibrium, the melting entropies (in kJ mol−1) were calculated. These values were more negative as compared with molar enthalpy increases. It was explained because the changes in melting temperatures are much smaller than those observed in the enthalpy values. Linear relationship between enthalpies andentropies as a function of MW was deduced.

The Application of Solid Dispersion Technique with D-mannitol to the Improvement in Oral Absorption of Triamterene

Present paper proposes a new system to administer triamterene, a sparing potassium diuretic which presents absorption problems when administered as a free powder, due to its low solubility in water. To increase the dissolution rate and subsequent oral bioavailability of this drug, it has been formulated as solid dispersion. This method involves preparation by the melting carrier method using D-mannitol as matrix. These systems were subjected to USP XXII dissolution rate determination. The results revealed a marked dissolution rate increase of included triamterene in solid dispersions when compared with micronized drug. Further in vivo assays have demonstrated the absorption efficiency for the proposed systems when referred to pure drug. In vitro-in vivo correlation between the parameter T80% (from dissolution rate studies) and the pharmacokinetic one Ke, has found to be acceptable. All the results obtained make this system suited for further formulation in the pharmaceutical industry.

Dissolution properties and in vivo behaviour of triamterene in solid dispersions with polyethylene glycols

The applicability of the solid dispersion technique as a method for enhancing the GI absorption of a drug has been explored in order to procure better dissolution characteristics and better bioavailability for triamterene. The physicochemical characterization of the systems has shown the absence of chemical reaction between the drug and the polymers during the solid dispersion elaboration process (melting carrier method). In vitro release profiles have been studied and quantified in terms of dissolution efficiency over the first 30 min (DE30) and dissolution percentage over the first 30 min (DP30). The results have shown that there were no significant differences between the three polyethylene glycols (PEGs) under test. The in vivo effectiveness of the different preparations was also investigated by means of the urinary volumetric excretion (UVE)--pharmacologic effect--and by the estimation of Ke, tmax, and MRT-pharmacokinetic parameters. At end, an analysis of the relative bioavailabilities between formulations has been performed.

Dissolution Behavior of Oxazepam in Presence of Cyclodextrins: Evaluation of Oxazepam-Dimeb Binary Systemxs

AbstractThe inclusion complex formation between oxazepam (Ox) and heptakis (2,6-di-O-methyl)-β-cyclodextrin (DIMEB) was studied in solution by solubility and ultraviolet spectroscopy methods, and in the solid state by differential scanning calorimetry, scanning electron microscopy, and powder x-ray diffractometry. The apparent stability constant, Kc, calculated by solubility and spectral data, was estimated as 642 and 588 M-1, respectively. The solid complexes have been prepared by kneading and spray-drying techniques. The dissolution rate studies reveal that the better dissolution behavior corresponded to the spray-dried systems.