J. M. Ginés

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.

Characterization of Ibuproxam Binary and Ternary Dispersions with Hydrophilic Carriers

This work investigates the possibility of increasing the dissolution properties of ibuproxam (a poorly water‐soluble anti‐inflammatory drug) using hydrophilic carriers such as polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), or urea, alone or in combination. Phase‐solubility studies showed that the carrier solubilizing power was in the order PEG > PVP > urea and evidenced a synergistic effect in drug solubility improvement when using carrier combinations. Binary and ternary systems, at 20/80 or 20/40/40 (w/w) drug/carrier(s) ratios, prepared by coevaporation of their ethanolic solutions or by cogrinding physical mixtures in a high‐energy vibrational micromill, were characterized by differential scanning calorimetry (DSC), hot stage microscopy (HSM), and scanning electron microscopy (SEM) analyses. The results of dissolution tests (USP paddle method), in terms of Dissolution Efficiency, indicated that ternary systems were up to 35% more effective than the corresponding binary preparations and coevaporated products were up to 45% more efficacious than the corresponding coground ones. The IBUX‐PEG‐PVP coevaporated was the best product, allowing a more than three‐times increase in Dissolution Efficiency with respect to drug alone; moreover, t50% ( > 60 min for pure ibuproxam) was < 10 min, and 90% dissolution was achieved after 30 min, whereas only 40% was obtained after 60 min for pure drug. The best performance of this system was attributed to a joined effect of the strong amorphizing power of PVP (as demonstrated by solid state analyses) with the high solubilizing efficacy of PEG (as emerged from phase‐solubility studies). The drug dissolution rate from solid dispersions remained practically unchanged after one‐year storage at room temperature in closed containers.

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.

Solid-state characterization and dissolution characteristics of gliclazide-β-cyclodextrin inclusion complexes

Solid complexes between gliclazide and β-cyclodextrin (β-CD) were prepared by kneading, coprecipitation, neutralization, co-grinding and spray-drying. Characterization of gliclazide-β-CD inclusion complexes was performed using X-ray diffractometry and cross polarizing/magic angle spinning 13C-nuclear magnetic resonance spectroscopy. These techniques have clearly demonstrated the existence of solid-state inclusion compound formation. The complexes, obtained by neutralization and spray-drying methods, showed enhanced dissolution rates of gliclazide.

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.

Thermal study of the effect of several solvents on polymerization of acrylonitrile and their subsequent pyrolysis

The polymerization of acrylonitrile to polyacrylonitrile (PAN) has been studied using several solvents: N,N-dimethylformamide (DMF), hexane, toluene, water, and in bulk form (no solvent). The addition of DMF is the only case where both monomer and polymer are soluble in the solvent. Thermal analyses of the resultant products after polymerization have been performed by differential scanning calorimetry and pyrolysis‐gas chromatography: mass spectrometry. The effect of the solvents employed as media for polymerization is interpreted from the results of the thermal and structural (X-ray diffraction) methods. The polymer samples obtained when using water or toluene as solvents have the greater content of amorphous components compared to the others. The amide molecules are difficult to completely eliminate in the product obtained after the polymerization reaction and even after prolonged heating at 110°C and remain occluded. DMF can be considered to exert a plasticized effect on PAN and is even capable of forming complexes by dipolar bonding. As

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.

Dissolution rate of diazepam from polyethylene glycol 6000 solid dispersions

Abstract A method for the elaboration of solid dispersions, the weight ratios of diazepam to polyethylene glycol 6000 and the particle size of drug in the solid dispersion have been investigated. The preparation method and diazepam-polyethylene glycol 6000 ratio influence the dissolution rate of the drug. It is observed that faster release characteristics were obtained with solid dispersions prepared by the fusion method and by increasing the carrier percentage. The increase in dissolution rate can be considered to result from crystal size reduction and the solubilizing effect of polyethylene glycol 6000. An intrinsic effect of the carrier also increases the dissolution rate of diazepam, since a physical mixture of the same composition dissolves more slowly than the solid dispersions. It is concluded that such a difference must be attributed to a significant reduction of the drug particle size in the carrier matrix.

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.

Development of controlled release formulations of alachlor in ethylcellulose

The herbicide alachlor (2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide) is frequently implicated in groundwater contamination. Microencapsulated alachlor should have reduced potential for leaching in the soil while maintaining effective biological activity. Microspheres of alachlor were prepared using ethylcellulose, according to the solvent evaporation method. The influence of formulation variables affecting the release rate of pesticide, such as the molecular weight of ethylcellulose, the amount of emulsifying agent, the pesticide/polymer ratio and the particle size, were investigated. The results showed that microspheres retarded the release of alachlor in different degrees. Pesticide/polymer ratio and particle size were the more important factors determining the alachlor release. Ethylcellulose microspheres may prove useful for the prolonged release of alachlor.The herbicide alachlor (2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-acetamide) is frequently implicated in groundwater contamination. Microencapsulated alachlor should have reduced potential for leaching in the soil while maintaining effective biological activity. Microspheres of alachlor were prepared using ethylcellulose, according to the solvent evaporation method. The influence of formulation variables affecting the release rate of pesticide, such as the molecular weight of ethylcellulose, the amount of emulsifying agent, the pesticide/polymer ratio and the particle size, were investigated. The results showed that microspheres retarded the release of alachlor in different degrees. Pesticide/polymer ratio and particle size were the more important factors determining the alachlor release. Ethylcellulose microspheres may prove useful for the prolonged release of alachlor.