Bramanti G

Utilization of differential scanning calorimetry as a screening technique to determine the compatibility of ketoprofen with excipients

Abstract Differential scanning calorimetry (DSC) was used as a screening technique for assessing the compatibility of ketoprofen with some excipients currently employed in tablet or capsule formulations. The effect of sample treatment (simple blending, cogrinding, compression, kneading) was also evaluated. On the basis of DSC results, ketoprofen was found to be compatible with hydroxyethylcellulose, hydroxypropylcellulose, microcrystalline cellulose, corn starch, arabic gum, colloidal silica, veegum, lactose, glucose, sorbitol and mannitol. Some drug-excipient interaction was observed with palmitic acid, stearic acid and stearyl alcohol and eutectic formation was found with magnesium stearate. Strong solid-phase interaction with polyethylene glycol 6000, polyvinylpolypyrrolidone and even more with polyvinylpyrrolidone K30 was found.

Evaluation of transcutol as a clonazepam transdermal permeation enhancer from hydrophilic gel formulations.

The influence of diethyleneglycol monoethyl ether (transcutol), alone or in combination with propylene glycol, on clonazepam permeation through an artificial membrane and excised rabbit ear skin from Carbopol hydrogels was investigated. Drug kinetic permeation parameters were determined for both series of experiments and compared. Rheological characteristics, drug solubility and membrane/vehicle partition coefficient for each gel formulation were also determined, and their role in the formulation performance was investigated. Both series of experiments showed an increase of drug permeation as a function of transcutol content in the formulation. The combination of transcutol and propylene glycol resulted in a synergistic enhancement of clonazepam flux. A different trend was found in experiments with gels containing mixtures of the two enhancers, where an increase (in the case of artificial membrane) or a decrease (in the case of rabbit ear skin) of drug permeation was found by increasing the transcutol/propylene glycol ratio in the mixture. Such a result is explained on the basis of the particular mechanism of action demonstrated for transcutol which associates the increase of drug solubility to the potent effect of a depot in the skin.

Properties of Solid Dispersions of Naproxen in Various Polyethylene Glycols

AbstractSolid dispersions of naproxen in polyethylene glycol 4000, 6000, and 20000, aimed at improving the drug dissolution characteristics, were prepared by both the solvent and melting methods. The drug-polymer interaction in the solid state was investigated using differential scanning calorimetry, hot-stage microscopy, Fourier-transform infrared spectroscopy, and x-ray diffraction analysis. Interaction in solution was studied by phase solubility analysis and dissolution experiments. Computer-aided molecular modeling was used to supplement the results from phase solubility studies. No important chemical interaction was found between naproxen and polyethylene glycol, either in solution or in the solid state, apart from the formation of weak drug-polymer hydrogen bonds. The increase of naproxen dissolution rate from its binary systems with polyethylene glycol could be attributed to several factors such as improved wettability, local solubilization, and drug particle size reduction. No influence of polymer...

Compatibility study between ibuproxam and pharmaceutical excipients using differential scanning calorimetry, hot-stage microscopy and scanning electron microscopy.

Differential scanning calorimetry (DSC) was used as a screening technique for assessing the compatibility of ibuproxam with some currently employed pharmaceutical excipients. The influence of processing effects (simple blending, cogrinding or kneading) on drug stability was also evaluated. On the basis of DSC results, ibuproxam was found to be compatible with corn starch, avicel and sodium carboxymethylcellulose. Some drug-excipient interaction was observed with polyethyleneglycol 4000, palmitic acid, stearic acid, Ca and Mg stearate. Actual solid-phase interactions of the drug with polyvinylpolypyrrolidone and polyvinylpirrolidone K30 were induced by mechanical treatments. Hot-stage microscopy (HSM) and scanning electron microscopy (SEM) were of help in interpreting the DSC results and excluding in all cases relevant pharmaceutical incompatibilities.

Thermal Behavior and Dissolution Properties of Naproxen From Binary and Ternary Solid Dispersions

Solid dispersions of 10% w/w naproxen (NAP) in poly(ethylene glycol) (PEG) (4000, 6000, or 20,000) as a carrier with or without incorporation of anionic (sodium dodecyl sulfate; SDS) or nonionic (Tween 80; Tw80) surfactant were prepared by the melting method. Physicochemical characteristics were determined by differential scanning calorimetry (DSC) and X-ray diffraction analysis. The results of dissolution studies showed that drug dissolution properties were better from ternary systems than from binary systems since in the former the wetting and solubilizing effects of surfactant and polymer were additive. No influence of the PEG molecular weight was found. The best performance given by anionic surfactant has been attributed to several factors, such as higher hydrophilicity, better solubilizing power, and most facile interaction with both drug and PEG. No important changes in solid-state characteristics or in drug dissolution properties were found after 30 months storage for dispersions with or without surfactant. Only a slight decrease in initial drug dissolution rate was observed at the highest concentration (10% w/w) of SDS.

Influence of the preparation method on the physicochemical properties of binary systems of econazole with cyclodextrins

Equimolar combinations of econazole, a very poorly water soluble antifungal agent, with beta-cyclodextrin and statistically substituted methyl-beta-cyclodextrin were investigated for both solid state characterization (differential scanning calorimetry, hot-stage microscopy, infrared spectroscopy, scanning electron microscopy) and dissolution properties (dispersed amount method). The influence of the preparation method (physical mixing, ball-milling, kneading, sealed-heating) on the physicochemical properties of the products was evaluated. Kneading and sealed-heating techniques led to amorphous products in the case of systems with methyl-beta-cyclodextrin, whereas crystalline drug was still clearly detectable in all products with beta-cyclodextrin. Independently of the preparation technique, all combinations with methyl-beta-cyclodextrin yielded better performance than the corresponding ones with beta-cyclodextrin. However, the influence of the preparation method was clearly more marked for products with methyl-beta-cyclodextrin and made to be possible to better display the different performance of the examined carriers. In fact, the sealed-heated with the beta-derivative showed an increase of drug dissolution efficiency of 130% with respect to the corresponding physical mixture, in comparison to the 70% increase obtained from that with beta-cyclodextrin. Moreover, whereas the difference in dissolution efficiency values between coground products was only about 8% in favor of the beta-derivative, it reached 80 and 90% between sealed-heated and kneaded products, respectively.

Multicomponent Systems of Econazole with Hydroxyacids and Cyclodextrins

The effect of the type of cyclodextrin (α-, β-, γ-,hydroxypropyl-β-CD) and of hydroxyacid (tartaric, citric, gluconic,malic, lactic) on the solubility enhancement by multicomponent complexationof econazole, a poorly water soluble base-type drug, was studied. A synergisticeffect was found in ternary systems, largely more effective than correspondingbinary complexes and salts. Moreover, the presence of a third component madeeffective the use of γ-CD, which had no solubilizing power in binarysystems. The solubilizing efficiency of multicomponent systems was not relatedto the solubilities of the corresponding salts or binary complexes. Phase-solubility analysis at different temperatures was also used to investigate the interaction of econazole with cyclodextrins, alone or in the presence of hydroxyacid. The best 1 : 1 : 1 molar ratio system was that with α-CD and malic acid which showed the best solubilizing power and the highest stability constant of the ternary complex.Ternary α-CD products, prepared by co-grinding, co-evaporation or colyophilization, were characterized by Differential Scanning Calorimetry and tested for dissolution properties. The higher solubilizing properties of multicomponent systems were reflected in better drug dissolution rates from their solid systems.

Improvement of Econazole Solubility in Multicomponent Systems with Cyclodextrins and Acids

Econazole is an imidazole antifungal agent very poorly water soluble. The combined effects of different acids (nitric, citric, lactic and malic) and cyclodextrins, both natural (α- and γ-) and derivative (statistically-hydroxypropylated s-cyclodextrin), on the enhancement of aqueous solubility of drug was investigated. Multicomponent complex formation was always more effective than salt formation or binary complexation in enhancing the aqueous solubility of econazole. The best result was obtained with the combination of econazole with a-cyclodextrin and lactic acid, in the respective molar ratios 1:1:2.5, which gave an increase of solubility of more than 4200 times in comparison with the pure drug

Pharmaceutical availability of digoxin tablets

Abstract Pharmaceutical availability of two similar formulations of digoxin tablets was compared. A marked difference in drug dissolution rate was found; it was shown that the principal causes of this behaviour come from particle size, crystallinity of active principle and influence of some excipients.