Alcohol, Tobacco, and Drug Use Disorders and Personality Disorder Symptoms.

In a nonclinical sample of 395 young adults, the authors evaluated the relations between major personality traits, Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) personality disorder symptoms, and DSM-IV alcohol use disorders (AUDs). Consistent with previous findings, traits related to disinhibition and negative affectivity were consistently associated with AUDs, as were Cluster B personality disorder symptoms (especially antisocial and borderline disorder symptoms). Multivariate analyses revealed that Cluster B symptoms were significantly associated with AUDs above and beyond what was accounted for by personality traits. Further, the authors found differential patterns of relations between other substance use disorders (SUDs; i.e., tobacco dependence and drug use diagnoses) and personality disorder symptoms. Overall, these results suggest that personality disorder symptoms predict unique variance in SUDs that reflect maladaptive aspects of personality traits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Properties of Magnetic Nanoparticles about Doped Rare Earth and Its Composites

The magnetic liquid was prepared with ferric salt by inorganic gel technology. The effect of the doped rare earth elements on the properties of magnetic particles was analyzed. The magnetic liquid was composed with clay mineral into magnetic mineral composites. The crystal structure and micro-morphology of the nanoparticles were studied by XRD and TEM. The results show that the crystal structure of the magnetic particles doped 0.5 % of lanthanum is more complete, and the magnetic response capability is higher with doping agent. At the same time, the possibility of the clay mineral magnetic composites as the carrier of target drug was probed.     

Construction and in vitro/in vivo evaluation of 17-allylamino-17-demethoxygeldanamycin (17AAG)-loaded PEGylated nanostructured lipid carriers

In this study, the PEGylated nanostructured lipid carriers (PEG-NLC) were constructed for the intravenous delivery of 17-allylamino-17-demethoxygeldanamycin (17AAG). 17AAG-PEG-NLC was successfully prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature using a mixture of glycerol monostearate and PEG₂₀₀₀-stearate as solid lipids, and medium-chain triglyceride as the liquid lipid. The results revealed that the morphology of the NLC was spheroidal. The particle size, zeta potential and entrapment efficiency for 17AAG-PEG-NLC were observed as 189.4?nm, ?20.2 mV and 83.42%, respectively. X-ray diffraction analysis revealed that 17AAG existed as amorphous structures in the nanoparticles. In the in vitro release study, the 17AAG from 17AAG-PEG-NLC exhibited a biphasic release pattern with burst release initially and sustained release afterwards. In addition, 17AAG-PEG-NLC showed a significantly higher in vitro antitumor efficacy and longer retention time in vivo than 17AAG solution. These results indicated that 17AAG-PEG-NLC may offer a promising alternative to the current 17AAG formulations for the treatment of solid tumors.     

Novel self-assembled mesalamine–sucralfate complexes: preparation,characterization, and formulation aspects

Two well-known active agents, mesalamine (MES) and sucralfate (SUC), were investigated for possible utilization as fixed-dose combination product. The anti-inflammatory action of MES in association with bioadhesiveness and mucosal healing properties of SUC were considered promising for the development of a new compound containing both molecules, aimed as an improved treatment of ulcerative colitis. The present study investigates the capacity of the two active agents to interact and generate a new and stable entity via self-assembling. Spray-drying was used to co-process the two active principles from an aqueous mixture where the ratio MES:SUC was in the range 25:75, 50:50, and 75:25. The structural data (X-Ray, FTIR, SEM, DSC, and ¹H NMR) have shown that MES and SUC are interacting leading to complexes with properties differing from those of each separate active agent and from their physical blends. ¹H NMR results indicated that complexation occurred when the aqueous suspensions of drugs were mixed, prior to spray-drying. Drug–drug self-assembling was the driving mechanism in the formation of the new entity. Based on the structural data, a hypothetical structure of the complex was proposed. Co-processing of MES and SUC represents a simple and useful procedure to prepare new self-assembled compounds by valorizing the ionic interactions between the two entities. Preliminary studies with oral solid dosage forms based on MES–SUC complexes tested in vitro have shown a controlled MES release, opening the perspective of a new colon-targeted delivery system and a novel class of compounds with therapeutic application in inflammatory bowel diseases.     

Drug release from lipid liquid crystalline phases: relation with phase behavior

Introduction: We studied the release of propranolol hydrochloride (PHCl), a water-soluble amphiphilic drug, from monoolein (MO)/water and phytantriol/water systems. Methods: We related the dissolution profiles with phase behavior and viscosity of the different liquid crystalline phases. Diolein has been added aiming to stabilize the cubic phases and thus preventing formation of less viscous (lamellar) phases. Results: Formulations display first-order release rates and diffusion release mechanism. Some formulations (mostly MO) were close to zero-order release in the first 120 minutes. Discussion: Release mechanism can be influenced by phase changes during dissolution. Conclusions: Both MO and phytantriol show good potential to be used for propranolol hydrochloride sustained drug release.     

β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

Abstract

Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous β-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous β-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and β-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on β-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.     

Powdered self-emulsified lipid formulations of meloxicam as solid dosage forms for oral administration

The objectives of this study were to prepare a powdered self-emulsified (SEDDS) formulation of meloxicam and to compare its oral bioavailability against commercial Mobic^® tablets. The SEDDS formulation was prepared by in situ salt formation of meloxicam in a blend of lipid excipients and aqueous tris (hydroxymethyl) aminomethane solution. The liquid SEDDS was subsequently adsorbed on silica powder and was tested for size, flow, and crystal growth. The flowability index of the powdered SEDDS was borderline acceptable. Absence of crystal growth with storage was confirmed by DSC and PXRD studies. Dissolution of meloxicam from the powdered SEDDS was >90% vs. <12% for powdered meloxicam and <80% for the commercial tablets. Stability of the powdered formulations after storage in gelatin and HPMC capsules was also evaluated to study the effect of water migration from the fill into capsule shells. Capsules softened to a different extent as a function of fill material with HPMC capsules showing greater resistance to water migration. Finally, oral bioavailability of the formulations was evaluated in beagle dogs. Powdered meloxicam SEDDS formulation showed a 1.3-fold increase in AUC vs. commercial Mobic^® tablets. Overall, this study described a novel SEDDS formulation of meloxicam and outlined a systematic approach to adsorbing and testing the flow and stability behavior of powdered SEDDS formulations.     

Metronidazole-loaded nanostructured lipid carriers to improve skin deposition and retention in the treatment of rosacea

The objective of the present investigation was to improve the skin deposition and retention of metronidazole (MTZ) in rosacea therapy by incorporating it into nanostructured lipid carriers (NLCs). The main challenge in this endeavor was the partial hydrophilicity of MTZ, which mandated careful selection of excipients, including solid and liquid lipids, surfactants, and their ratios in combination. NLCs were produced by the phase inversion temperature method and finally converted into a gel for topical application. The prepared nanoparticles were evaluated for their particle size, zeta potential, entrapment efficiency, solid-state characteristics, surface morphology, in vitro drug release, and permeation through excised skin. The gel was additionally characterized for its pH, drug content, viscosity, and spreadability. The prepared nanoparticles were spherical in shape and of size less than 300?nm. Incorporation of judiciously chosen excipients made possible a relatively high entrapment efficiency of almost 40%. The drug release was found to be biphasic, with an initial burst release followed by sustained release up to 8?hours. In comparison to the plain drug gel, which had a tissue deposition of 11.23%, the NLC gel showed a much superior and desirable deposition of 26.41%. The lipophilic nature of the carrier, its size, and property of occlusion enabled greater amounts of drug to enter and be retained in the skin, simultaneously minimizing permeation through the skin, i.e. systemic exposure. The results of the study suggest that NLCs of anti-rosacea drugs have the potential to be used in the therapy of rosacea.     

Recent Developments in Drug Delivery to Prolong Allograft Survival in Lung Transplant Patients

Since the discovery of cyclosporine in 1971, calcineurin inhibitors have played a critical role in the therapeutic suppression of the immune response. Patients receiving solid organ transplants rely heavily on these medications to prevent the acute and chronic rejection of allografted tissue. These therapies can prove difficult because of potential toxicity, heightened risk of invasive infection, and erratic oral bioavailability, requiring frequent blood samples for monitoring of systemic levels. Added challenges are presented in immunosuppression of lung transplant patients owing to the increased susceptibility to invasive infection and extensive immune mechanisms inherent in lung tissue. With the introduction of tacrolimus, a more potent calcineurin inhibitor, clinical outcomes of transplants have continued to improve; however, little improvement has been noted in lung transplantation. While very effective upon arrival at the site of action, tacrolimus and cyclosporine present a variety of formulation challenges such as poor solubility, potential systemic toxicity, and extensive first pass metabolism. Initial attempts to improve solubility in both oral and intravenous formulations have resulted in variable drug absorption and increased systemic toxicity, respectfully, creating a need for formulation improvement. Through alternative routes of delivery and novel formulation techniques, researchers have addressed these issues and, in some cases, demonstrated improved clinical outcomes. Through enhanced solubilization, reduction in absorption variability, and more effective drug targeting with reduced systemic levels, improvements in outcomes and overall patient survival in lung and other solid organ transplantation can be expected.