[Factors associated with success of a smoking cessation program]. / Factores asociados con el éxito de la terapia antitabaco en pacientes tratados con vareniclina: 10 años de experiencia en un programa multidisciplinario.

BACKGROUND: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. AIM: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. PATIENTS AND METHODS: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. RESULTS: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). CONCLUSIONS: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.

Factores asociados con el éxito de la terapia antitabaco en pacientes tratados con vareniclina: 10 años de experiencia en un programa multidisciplinario / Factors associated with success of a smoking cessation program

Background: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. Aim: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. Patients and Methods: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. Results: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). Conclusions: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.

[Results of a multidisciplinary program to quit smoking]. / Resultados de un programa multidisciplinario para el control del hábito tabáquico.

BACKGROUND: Therapies to quit smoking are based on counseling, psychological therapy (PT), nicotine replacement therapy, bupropion or varenidine. AIM: To report the results of a multidisciplinary program to quit smoking. MATERIAL AND METHODS: Patients aged l8 years or more, motivated to quit smoking were admitted in a program based in counseling and PT, with or without pharmacological therapy. They were assessed by telephone during one year of follow up. Patients with unstable psychiatric diseases were excluded. Results were considered as "successful" when patients maintained abstinence during the year of follow up. A logistic regression analysis was done to identify factors associated with treatment success. RESULTS: Between 2005 and 2011, 198 patients aged 45 ± 11 years (56% males), who smoked 31.5 ± 20.6 packages/year, were treated. Of these, 155 (78%) were treated with varenidine, 26 (13%) with bupropion and 17 (9%>) did not receive pharmacological therapy. One hundred sixty eight patients completed the year of follow up. In 82 (49%>), treatment was successful and was negatively associated with a history of depression (odds ratio = 4 (95% confidence intervals 1.23-38.33). The main side effeets associated to varenidine and bupropion were nausea in 37 and 23%o, sleep disorders in 20 and 19%o and headache in 12 and 0%>, respectively. CONCLUSIONS: A multidisciplinary program to quit smoking achieved a 49%> of abstinence during a year of follow up.

Resultados de un programa multidisciplinario para el control del hábito tabáquico / Results of a multidisciplinary program to quit smoking

Background: Therapies to quit smoking are based on counseling, psychological therapy (PT), nicotine replacement therapy, bupropion or varenidine. Aim: To report the results of a multidisciplinary program to quit smoking Material and Methods: Patients agedl8years or more, motivated to quit smoking were admitted in a program based in counseling and PT, with or without pharmacological therapy. They were assessed by telephone during one year offollow up. Patients with unstable psychiatric diseases were excluded. Results were considered as "successful" when patients maintained abstinence during the year offollow up. A logistic regression analysis was done to identify factors associated with treatment success. Results: Between 2005 and 2011, 198 patients aged 45 ± 11 years (56% males), who smoked 31.5 ± 20.6 packages/year, were treated. Ofthese, 155 (78%) were treated with varenidine, 26 (13%) with bupropion and 17 (9%>) did not receive pharmacological therapy. One hundred sixty eightpatients completed the year offollow up. In 82 (49%>), treatment was successful and was negatively associated with a history of depression (odds ratio = 4 (95% confidence intervals 1.23-38.33). The main side effeets associated to varenidine and bupropion were nausea in 37 and 23%o, sleep disorders in 20 and 19%o and headache in 12 and 0%>, respectively Conclusions: A multidisciplinary program to quit smoking achieved a 49%> of abstinence during a year offollow up.

Solubility behavior and prediction for antihelmintics at several temperatures in aqueous and nonaqueous mixtures.

A model based on solubility parameters is proposed to predict the solubility curves of antihelmintic drugs at several temperatures, including aqueous and non-aqueous mixtures. The solubility of the drugs was measured in ethanol-water and ethanol-ethyl acetate mixtures at 15-35 degrees C (mebendazole) and at 25 degrees C (thiabendazole and metronidazole). The solid phases were analyzed by differential scanning calorimerty. The polymorphic form A of mebendazole was also characterized from infrared spectroscopy. Markedly different solubility profile shapes were obtained against the solubility parameter of the mixtures: two symmetrical peaks (metronidazole), two maxima of different height (mebendazole) and a single peak (thiabendazole). The solubility parameter of the drugs was related to the co-solvent action of both mixtures and to the solubility peaks. The single equation proposed was able to predict solubility profiles of different shape, including both mixtures and all temperatures, providing reasonable physical meaning for the regression coefficients. The model was successfully tested for its predictive capability using a limited number of experimental data. More than 100 solubilities were predicted at several temperatures using 20 data point for each drug.

Influence of temperature on the solubilization of thiabendazole by combined action of solid dispersions and co-solvents.

Co-solvents and solid dispersions with polyvinyl pyrrolidone were tested to increase solubility of thiabendazole. Solid dispersions were prepared by the solvent method and analyzed by differential scanning calorimetry. The solubility was measured at 15-35 degrees C in aqueous (ethanol-water) and non-aqueous (ethanol-ethyl acetate) mixtures. Combination of solid dispersions with cosolvents increased the water solubility of thiabendazole in a larger extent that each method separately. The effect of the solid dispersions is greatest in water and it decreases nonlinearly as the volume fraction of ethanol-in water increases. The solubility enhancement is smaller in ethanol-ethyl acetate and is uncorrelated with co-solvent concentration. Solubility parameters delta were used to predict drug/carrier compatibility and related to solubility profiles. Thiabendazole shows an intermediate behaviour between solubility curves with two peaks (more polar drugs with larger delta values) and a single peak (less polar drugs with lower delta values). The solid dispersions increase the solubility parameter of thiabendazole from delta=24 to delta=25.7 MPa(1/2). The model of Bustamante et al. allowed solubility prediction including jointly both mixtures whereas the equation of Jouyban et al. was able to predict the solubility at several temperatures in each binary mixture separately, using a few experiments.

Relationship between swelling of hydroxypropylmethylcellulose and the Hansen and Karger partial solubility parameters.

A model that relates the equilibrium swelling of hydroxypropylmethylcellulose to the partial solubility parameters of both the polymer and the solvents is proposed to interpret and correlate the experimental data. The non-specific interactions are expressed as the dispersion delta(d) and polar delta(p) solubility parameters of Hansen, or as a combination of both. Hydrogen bonding is represented by the acidic delta(a) and the basic delta(b) Karger solubility parameters. The results are compared with models including the same parameters for non-specific interactions (delta(d) and delta(p)) and the Hansen hydrogen bonding parameter delta(h). Equilibrium swelling of this hydrophilic polymer that is widely used in drug formulation is measured in pure solvents covering a wide polarity range. In a qualitative way, swelling increases in solvents with higher Hildebrand solubility parameters and stronger hydrogen bonding capability, and it decreases in non-polar solvents. Single polarity indexes, such as the Hildebrand solubility parameter or the partition coefficient (PC), do not fit well the overall experimental data. The best correlations were obtained with the proposed model, providing at the same time an interpretation consistent with the physical meaning of the terms included in the equation. Swelling increases as the non-specific interactions of the polymer and the solvents become alike, and as the Lewis acid-base interactions of the polymer (1) and the solvent (2) represented by the products delta(1a)delta(2b) and delta(1b)delta(2a) become greater. Conversely, hydrogen bonding self association of the solvents (the product delta(1a)delta(1b)) lowers swelling. The results show that the Karger hydrogen bonding parameters provide a better approach than the Hansen hydrogen bonding parameter to correlate the swelling behavior of a hydrophilic polymer.

A new method to determine the partial solubility parameters of polymers from intrinsic viscosity.

A modification of the extended Hansen method, formerly used to determine the partial solubility parameters of drugs and non-polymeric excipients is tested with a polymer for the first time. The proposed method relates the logarithm of the intrinsic viscosities of the polymer in a series of solvents and solvent mixtures with the Hansen (three parameter model) and Karger (four parameter model) partial solubility parameters. The viscosity of diluted solutions of hydroxypropyl methylcellulose (HPMC) was determined in pure solvents and binary mixtures of varying polarity. The intrinsic viscosity was obtained from the common intercept of the Huggins and Kraemer relationships. The intrinsic viscosity tends to increase with increasing the solubility parameter of the medium. The results show that hydrogen bonding and polarity of the polymer largely determine polymer-solvent interactions. The models proposed provided reasonable partial and total solubility parameters for the polymer and enable one to quantitatively characterize, for the first time, the Lewis acid-base ability of a polymer thus, providing a more realistic picture of hydrogen bonding for solvent selection/compatibility and to predict drug-polymer interactions. Combination of the dispersion and polar parameters into a single non-specific solubility parameter was also tested. The results extend earlier findings and suggest that the models are quite versatile and may be applied to drugs, non-polymeric and polymeric excipients.

Solubility and phase separation of benzocaine and salicylic acid in 1,4-dioxane-water mixtures at several temperatures.

The solubilities of benzocaine and salicylic acid were determined in water-dioxane mixtures at several temperatures (5-40 degrees C for benzocaine and 10-40 degrees C for salicylic acid). The solubility curves as a function of dioxane ratio showed a maximum at 90% dioxane at all temperatures. Above 25 degrees C, the homogeneous mixture splits into two liquid immiscible phases. For benzocaine, the initial dioxane concentration range at which phase separation takes place increased with temperature (50-60% at 25 degrees C, 50-70% at 30-35 degrees C and 40-70% at 40 degrees C). For salicylic acid, the dioxane concentration required for phase separation (40-60% dioxane) did not change with temperature. Phase separation was not related to solid phase changes (polymorphism or solvates). The phase composition and drug extraction at the drug-rich phase were determined. The apparent enthalpies of the solution process were a nonlinear function of the dioxane ratio for both drugs. The apparent enthalpy of solution of benzocaine was larger than that expected at the upper limit of phase separation (70% dioxane), whereas for salicylic acid the apparent enthalpy of solution decreased abruptly at the region corresponding to phase separation (40-70% dioxane). Both drugs showed a nonlinear pattern of enthalpy-entropy compensation.

Deviation from linearity of drug solubility in ethanol/water mixtures.

A new empirical function that describes the deviation from linearity of solubility of a drug in an ethanol/water matrix is applied to the experimental data for 51 compounds. The proposed model is a more accurate predictor of the co-solvent solubility profile than a general third order polynomial with the same number of parameters. Both the root mean square error and average absolute error for the proposed model are significantly lower than those of existing models. The model also accurately predicts the fraction of co-solvent that gives maximum solubility (fmax).

Influence of solvent composition on the solid phase at equilibrium with saturated solutions of quinolones in different solvent mixtures.

The dissolution profiles and solubilities of three quinolonic drugs (oxolinic, pipemidic, and nalidixic acids) in different solvent mixtures were studied. The behavior of the solid phase, during solubility experiments was in-depth investigated with the aim of detecting possible crystalline modifications, such as polymorphic transitions or solvate formations, that might modify drug stability and/or solubility properties. In order to test the influence of both the nature and polarity of the co-solvents, aqueous and non-aqueous binary mixtures have been prepared by using Lewis base (dioxane and ethyl acetate) and amphiprotic co-solvents (ethanol and water). Differential scanning calorimetry (DSC), hot stage microscopy, IR spectroscopy and X-ray powder diffraction were used in combination with solubility and dissolution studies to characterize and investigate the solid state properties of the original powders and the corresponding ones at equilibrium with the different pure solvents and solvent mixtures examined. The solid phases of nalidixic and oxolinic acids did not show any change after equilibration with the various pure solvents or binary solvent mixtures, regardless the chemical nature of the examined solvents. On the contrary, in the case of pipemidic acid, the different analytical techniques used to characterize the drug solid state enabled identification of a solvated form at equilibrium with pure dioxane and a trihydrated form in aqueous mixtures of water with both ethanol (amphiprotic) or dioxane (Lewis base) in a concentration range from 10 to 100% water.

A cosolvency model to predict solubility of drugs at several temperatures from a limited number of solubility measurements.

A cosolvency model to predict the solubility of drugs at several temperatures was derived from the excess free energy model of Williams and Amidon. The solubility of oxolinic acid, an antibacterial drug, was measured in aqueous (water+ethanol) and non-aqueous (ethanol+ethyl acetate) mixtures at several temperatures (20, 30, 35, 40 degrees C). Oxolinic acid displays a solubility maximum in each solvent mixture at solubility parameter values of 32 and 22 MPa(1/2). The temperature and heat of fusion were determined from differential scanning calorimetry. The solvent mixtures do not produce any solid phase change during the solubility experiments. The experimental results and those from the literature were employed to examine the accuracy and prediction capability of the proposed model. An equation was obtained to represent the drug solubility changes with cosolvent concentration and temperature. The model was also tested using a small number of experimental solubilities at 20 and 40 degrees C showing reasonably accurate predictions. This is important in pharmaceutics because it save experiments that are often expensive and time consuming.

Thermodynamic origin of the solubility profile of drugs showing one or two maxima against the polarity of aqueous and nonaqueous mixtures: niflumic acid and caffeine.

The purpose of this work was to investigate the origin of the different solubility profiles of drugs against the polarity of solvent mixtures with a common cosolvent. Niflumic acid and caffeine where chosen as model drugs. The solubilities were measured at five or six temperatures in aqueous (ethanol-water) and nonaqueous (ethyl acetate-ethanol) mixtures. The enthalpies of solution were obtained at the harmonic mean of the experimental temperature. Solid phase changes were analyzed using differential scanning calorimetry and thermomicroscopy. A single solubility maximum was obtained for niflumic acid against the solubility parameter of both mixtures that is not related to solid phase changes. In contrast, caffeine displays two maxima and anhydrous-hydrate transition occurs at the solubility peak in the amphiprotic mixture. The apparent enthalpies of solution of both drugs show endothermic maxima against solvent composition that are related to hydrophobic hydration. A general explanation for the cosolvent action in aqueous mixtures is proposed. The dominant mechanism shifts from entropy to enthalpy at a certain cosolvent ratio dependent on the hydrophobicity and the solubility parameter of the drug. Niflumic acid and caffeine show enthalpy-entropy compensation in ethanol-water, and this relationship is demonstrated for the first time in nonaqueous mixtures. The results support that enthalpy-entropy compensation is a general effect for the solubility of drugs in solvent mixtures. The shape of the solubility curves is correlated with the compensation plots. The solubility peaks separate different enthalpy-entropy relationships that also differentiate the solubility behavior of the hydrate and the anhydrous forms of caffeine.