Topical Meloxicam Hydroxypropyl Guar Hydrogels Based on Low-Substituted Hydroxypropyl Cellulose Solid Dispersions.

Meloxicam (MX) is a poorly water-soluble drug with severe gastrointestinal side effects. Topical hydrogel of hydroxypropyl guar (HPG) was formulated using a solid dispersion (SD) of MX with hydroxypropyl cellulose (LHPC) as an alternative to oral administration. The development of a solid dispersion with an adequate MX:LHPC ratio could increase the topical delivery of meloxicam. Solid dispersions showed high MX solubility values and were related to an increase in hydrophilicity. The drug/polymer and polymer/polymer interactions of solid dispersions within the HPG hydrogels were evaluated by SEM, DSC, FTIR, and viscosity studies. A porous structure was observed in the solid dispersion hydrogel MX:LHPC (1:2.5) and its higher viscosity was related to a high increase in hydrogen bonds among the -OH groups from LHPC and HPG with water molecules. In vitro drug release studies showed increases of 3.20 and 3.97-fold for hydrogels with MX:LHPC ratios of (1:1) and (1:2.5), respectively, at 2 h compared to hydrogel with pure MX. Finally, a fitting transition from zero to first-order model was observed for these hydrogels containing solid dispersions, while the n value of Korsmeyer-Peppas model indicated that release mechanism is governed by diffusion through an important relaxation of the polymer.

Development of Chitosan/Sodium Carboxymethylcellulose Complexes to Improve the Simvastatin Release Rate: Polymer/Polymer and Drug/Polymer Interactions' Effects on Kinetic Models.

Simvastatin (SIM) is a potent lipid-lowering drug used to control hyper-cholesterolemia and prevent cardiovascular diseases. SIM presents low oral bioavailability (5%) because of its low aqueous solubility. In this work, polyelectrolyte complexes (PEC) are developed with different chitosan (CS) and carboxymethylcellulose (CMC) ratios that will allow for an increase in the SIM dissolution rate (2.54-fold) in simulated intestinal medium (pH 4.5). Scanning Electron Microscopy (SEM) images revealed highly porous structures. The changes between both complexes, PEC-SIM:CS:CMC (1:1:2) and (1:2:1), were related to the relaxation of the polymer chains upon absorption of the dissolution medium. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRPD) studies were used to evaluate the polymer/polymer and drug/polymer interactions on the different PEC-SIM:CS:CMC ratios. In addition, the PEC-SIM:CS:CMC (1:2:1) complex exhibited a high ratio of protonated amino groups (NH3+) and an increase in intramolecular hydrogen bonds, which were correlated with a high expansion of the interpolymer chains and an increase in the SIM dissolution rate. Different kinetic models such as zero-order, first-order, Higuchi and Korsmeyer-Peppas were studied to evaluate the influence of CS/CMC ionic interactions on the ability to improve the release rate of poorly soluble drugs.

Solid dispersions of atorvastatin with Kolliphor RH40: Enhanced supersaturation and improvement in a hyperlipidemic rat model.

Atorvastatin is a potent lipid-lowering drug with poor solubility and high presystemic clearance that limits its therapeutic efficacy. The aim of this study was to develop solid dispersions and micellar systems to obtain fast-dissolving atorvastatin systems that enhances their anti-hyperlipidemic effect. Solubility and wettability studies allow the development of solid dispersions with low proportions of croscarmellose sodium as hydrophilic carrier. Solid state characterization studies indicated that the addition of Kolliphor® RH40 surfactant to solid dispersions increases intermolecular hydrogen bonding between drug and polymer chains. Dissolution studies in biorelevant Fasted State Simulate Intestinal Fluid (FaSSIF pH 6.5) medium showed for atorvastatin solid dispersion a supersaturation peak of atorvastatin followed by an aggregation/precipitation process. Only the presence of a surfactant such as Kolliphor® RH40 in atorvastatin micellar system, promotes the presence of micelles that achieve delayed recrystallization. Efficacy studies were carried out using a hyperlipidemic model of rats fed with a high- fat diet. The atorvastatin micellar system at doses of 10 mg/kg, revealed a significant improvement in serum levels of total cholesterol, low-density lipoproteins, and triglycerides compared to atorvastatin raw material. This micellar system also exhibited more beneficial effects on liver steatosis, inflammation and ballooning injury.

Multiparticulate Systems of Meloxicam for Colonic Administration in Cancer or Autoimmune Diseases.

The aim of this research is the development of new colonic release systems of meloxicam (MLX) a non-steroidal anti-inflammatory drug (NSAIDs) with pH and time-dependent vehicles for cancer or autoimmune diseases. The colon has a higher pH than the rest of the gastrointestinal tract (GIT) and this can be used as a modified release strategy. Eudragit® polymers are the most widely used synthetic products in the design of colonic release formulations because they might offer mucoadhesiveness and pH-dependent release. Colonic delivery systems produced with pH-dependent and permeable polymers (FS-30D) or with pH-independent and low permeability polymers (NM-30D), must dissolve at a pH range of 6.0-7.0 to delay the release of the drug and prevent degradation in the GIT, before reaching the colon. The conditions prepared to simulate a gastrointestinal transit showed the CNM multiparticulate system, composed of Eudragit® NM and cellulose, as the best release option for MLX with a more sustained release with respect to the other formulations. CNM formulation followed Higuchi and First-order release kinetics, thus MLX release was controlled by a combination of diffusion and polymers swelling/eroding processes.

Trends in Bariatric Surgery in Spain in the Twenty-First Century: Baseline Results and 1-Month Follow Up of the RICIBA, a National Registry.

BACKGROUND: Specific data is needed to safely expand bariatric surgery and to preserve good surgical outcomes in response to the non-stop increase in obesity prevalence worldwide. OBJECTIVE: The aims of this study are to provide an overview of the baseline characteristics, type of surgery, and 30-day postoperative morbidity and mortality in patients undergoing bariatric surgery in Spanish public hospitals, and evaluate changes throughout the 2000-2014 period. MATERIAL AND METHODS: This is a descriptive study using data from the RICIBA, a computerized multicenter and multidisciplinary registry created by the Obesity Group of the Endocrinology and Nutrition Spanish Society. Three periods according to the date of surgery were created: January 2000 to December 2004 (G1), January 2005 to December 2009 (G2), and January 2010 to December 2014 (G3). RESULTS: Data from 3843 patients were available (44.8 ± 10.5 years, a 3:1 female-to-male ratio, 46.9 ± 8.2 kg/m(2)). Throughout the 15-year period assessed, candidate patients for bariatric surgery were progressively older and less obese, with an increase in associated comorbidities and in the prevalence of men. The global trend also showed a progressive decrease in Roux-en-Y gastric bypass, the most performed bariatric procedure (75.1 % in G1, 69.3 % in G2, and 42.6 % in G3; p < 0.001), associated with a parallel increase in sleeve gastrectomy (0.8 % in G1, 18.1 % in G2, and 39.6 % in G3; p < 0.001). An overall mortality rate of 0.3 % was reported. CONCLUSIONS: Data from Spain is similar to data observed worldwide. Information recorded in the National Registries like RICIBA is necessary in order to safely expand bariatric surgery in response to increasing demand.

Enhanced bioavailability and anthelmintic efficacy of mebendazole in redispersible microparticles with low-substituted hydroxypropylcellulose.

BACKGROUND: Mebendazole (MBZ) is an extremely insoluble and therefore poorly absorbed drug and the variable clinical results may correlate with blood concentrations. The necessity of a prolonged high dose treatment of this drug increases the risk of adverse effects. METHODS: In the present study we prepared redispersible microparticles (RDM) containing MBZ, an oral, poorly water-soluble drug, in different proportions of low-substituted hydroxypropylcellulose (L-HPC). We investigated the microparticulate structures that emerge spontaneously upon dispersion of an RDM in aqueous medium and elucidated their influence on dissolution, and also on their oral bioavailability and therapeutic efficiency using a murine model of infection with the nematode parasite Trichinella spiralis. RESULTS: Elevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s) under the curve (AUC)0-∞ values. Likewise, after oral administration of the RDM-1:2.5 and RDM-1:5 the AUC0-∞ were 2.67- and 2.97-fold higher, respectively, compared to those of pure MBZ. Therapeutic activity, assessed on the Trichinella spiralis life cycle, showed that RDM-1:5 was the most effective in reducing the number of parasites (4.56-fold) as compared to pure MBZ, on the encysted stage. CONCLUSION: THE MBZ: L-HPC RDM might be an effective way of improving oral bioavailability and therapeutic activity using low doses of MBZ (5 mg/kg), which implies a low degree of toxicity for humans.

Weight-related quality of life in Spanish obese subjects suitable for bariatric surgery is lower than in their North American counterparts: a case-control study.

BACKGROUND: Obesity impairs quality of life, but the perception of the impairment could be different from one country to another. The purpose was to compare weight-related quality of life (QOL) between cohorts from Spain and North America. METHODS: A cross-sectional case-control study was performed between two populations. Four hundred Spanish and 400 North American obese subjects suitable for bariatric surgery closely matched for race, gender, age, and body mass index (BMI) were included. Two non-obese control groups matched for gender, age, and BMI from each population were also evaluated (n = 400 in each group). The participants completed the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire, a measure of weight-related QOL. RESULTS: Spanish morbidly obese patients showed poorer QOL than their North American counterparts in physical function, sexual life, work, and total score. By contrast, Spanish non-obese control subjects reported better QOL in all domains than their North American counterparts. Women, both in Spain and North America, reported reduced QOL compared to men on the domain of self-esteem. In addition, North American women reported reduced QOL on the sexual life domain compared to men. BMI correlated negatively with all domains of QOL except for self-esteem in both national groups. CONCLUSIONS: Spanish obese subjects suitable for bariatric surgery report poorer weight-related quality of life than their North American counterparts, and obese women, regardless of nationality, perceive a reduced quality of life compared to men.

Social cognition and global functioning in bipolar disorder.

The purpose of this study was to assess the role of social cognition, together with other relevant clinical variables and measures of general cognition, in the global functioning of euthymic bipolar patients. Thirty-nine euthymic outpatients fulfilling DSM-IV-TR criteria for bipolar disorder type I or II were recruited and were divided in two groups: high (n = 19) and low (n = 20) global functioning. Both groups' performance was compared in verbal and nonverbal social cognition (Faux pas test and Facial Emotion Recognition test), sustained attention and executive function. The low-functioning group showed a significant impairment in both verbal and nonverbal measurements of social cognition compared with the high-functioning group. Globally, both bipolar groups showed a significant impairment in facial emotion recognition compared with a similar sample of healthy volunteers. Social cognition may play a significant role in the clinical-functional gap of bipolar patients.

Changed crystallinity of mebendazole solid dispersion: improved anthelmintic activity.

To improve the efficacy of mebendazole (MBZ), a poorly water-soluble drug, MBZ solid dispersions containing different proportions of low-substituted hydroxypropylcellulose (L-HPC) were prepared by lyophilization process. The physical characteristics of recrystallized MBZ, and solid dispersions (SD) at different MBZ:L-HPC proportions were investigated in terms of morphology (scanning electron microscopy, SEM), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution rate. The in vivo performance was assessed by anthelmintic activity studies against enteral (pre-adult) stage of Trichinella spiralis in mice. The XRD, DSC and SEM revealed a characteristic decrease in crystallinity when increasing the L-HPC proportions in the solid dispersions. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with recrystallized drug. The considerable improvement in the dissolution rate of MBZ from solid dispersions was attributed to decreased drug crystallinity and altered surface morphology (major) and to the wetting effect of L-HPC (minor). The in vivo studies revealed that the anthelmintic effects of solid dispersions in mice were significantly increased in comparison with recrystallized MBZ (1.74-fold for SD-1:1, 3.20-fold for SD-1:2.5 and 3.80-fold for SD-1:5). These results have shown the suitability of MBZ:L-HPC solid dispersions for the treatment of enteral helmintic diseases at low doses.

Effects of orlistat on visceral fat after liposuction.

BACKGROUND: Liposuction can aggravate metabolic complications associated with obesity. It has been shown that the recovery of weight lost through these interventions is associated with body fat redistribution toward the visceral cavity, increasing metabolic risk factors for coronary heart disease such as insulin resistance and high triglyceride levels. OBJECTIVES: The aim of this study was to evaluate the consequences of liposuction on body mass redistribution and metabolic parameters 6 months after surgery and to evaluate the use of orlistat treatment (tetrahydrolipstatin) in controlling these parameters. METHODS: A population of 31 women with a mean body mass index of 26.17+/-3.9 kg/m(2) and undergoing liposuction of more than 1,000 cm(3), was studied. Twelve of them were treated postsurgery with 120 mg of orlistat every 8 hours for the following 6 months. Anthropometric, analytical, and radiological (computed tomography) tests were performed to quantify visceral fat area before surgery and 6 months after surgery. RESULTS: Despite weight loss after liposuction, visceral fat was not modified. Patients treated with orlistat showed a greater reduction in visceral fat, although not statistically significant. Orlistat use induced a reduction in low-density lipoprotein cholesterol values of 20.0+/-22.5 mg/dL, compared with an increase of 8.46+/-20.1 mg/dL in controls (p=.07). CONCLUSIONS: Visceral fat does not decrease despite weight loss after liposuction. Orlistat use postliposuction might be a useful tool because it shows a tendency to reduce visceral fat and improve blood lipids profile.