Search

Our work aimed at evaluating the use of permeability glycoprotein (P-gp) inhibiting nanoparticles (NPs) as a part of a suitable oral solid dosage to improve bioavailability. Famotidine (Pepcid®), a stomach acid production inhibitor, was used as a drug model to test our hypothesis. Famotidine-loaded NPs were prepared by solvent emulsion evaporation using PEG grafted on a polylactide acid (PLA) polymer backbone (PLA-g-PEG), with a 5% molar ratio of PEG versus lactic acid monomer and PEG of either 750 or 2000 Da molecular weight. Tablet formulation was composed of 40% Famotidine-loaded NPs, 52.5% microcrystalline cellulose as filler, 7% pre-gelatinized starch as binder/disintegrant, and 0.5% magnesium stearate as lubricant. Tablets containing 1.6 mg of Famotidine were prepared at an average weight of 500 mg, thickness of 6.2-6.5 mm, hardness of 5-8 kp, and disintegration time of <1 min. Our results suggest that Famotidine-loaded NPs using grafted PEG-g-PLA polymers can be formulated as an oral solid dosage form while effectively inhibiting P-gp mediated Famotidine efflux, irrespective of PEG molecular weights. This could therefore represent an attractive formulation alternative to enhance oral permeability and bioavailability of drugs that are P-gp substrates. [ABSTRACT FROM AUTHOR]

Background:The Geriatric Anxiety Inventory (GAI) and a short form of this instrument (GAI-SF) were developed to assess the severity of anxiety symptoms in older adults in order to compensate for the lack of validated screening tools adapted to the elderly population. This study examined the psychometric properties of the French Canadian version of the GAI, in its complete (GAI-FC) and short form (GAI-FC-SF). Method:A total of 331 community-dwelling seniors between 65 and 92 years old participated in this study. Results:Both the GAI-FC and the GAI-FC-SF have sound psychometric properties with, respectively, a high internal consistency (α = .94 and .83), an adequate convergent validity (r= .50 to .86 with instruments known to evaluate constructs similar to the GAI or related to anxiety), a good test–retest reliability (r= .89 and .85), in addition to a single-factor structure. Conclusions:The results support the use of both the GAI-FC and the GAI-FC-SF. The GAI-FC-SF seems to be an interesting alternative to the GAI-FC as a screening tool when time available for assessment is limited. [ABSTRACT FROM PUBLISHER]

Bioavailability of oral drugs can be limited by an intestinal excretion process mediated by P-glycoprotein (P-gp). Polyethylene glycol (PEG) is a known P-gp inhibitor. Dispersion of Famotidine (a P-gp substrate) within PEGylated nanoparticles (NPs) was used to improve its oral bioavailability. In this work, we evaluated the potential impact of NPs prepared from a grafted copolymer of polylactic acid and PEG on P-gp function by studyingin vitropermeability of Famotidine across Caco-2 cells. Copolymers of PEG grafted on polylactic acid (PLA) backbone (PLA-g-PEG) were synthesised with 1 mol% and 5 mol% PEG vs. lactic acid monomer using PEG 750 and 2000 Da. The polymers were used to prepare Famotidine-loaded NPs and testedin vitroon Caco-2 cells. Significant decrease in basolateral-to-apical transport of Famotidine was observed when Famotidine was encapsulated in NPs prepared from PLA-g-PEG5%. NPs prepared from PLA-g-PEG5% are promising to improve oral bioavailability of P-gp substrates. [ABSTRACT FROM PUBLISHER]

Objective: The main objective of this study was to examine the efficacy of a guided self-help treatment based on cognitive behavioral principles (CBT-GSH) for generalized anxiety disorder (GAD) in older adults. Methods: Three older adults aged from 66 to 70 and diagnosed with GAD were included in a single-case experimental multiple-baseline protocol. Data were collected using daily self-monitoring, standardized clinician ratings, and self-report questionnaires at pretest, posttest, and 6-month and 12-month follow-ups. Treatment consisted of awareness training, worry interventions, relaxation training, pleasant activities scheduling, and relapse prevention. Participants used a manual presenting weekly readings and at-home practice exercises. They also received weekly supportive phone calls from a therapist. Results: At posttest, participants showed improvement on worries and GAD severity, on psychological process variables targeted by treatment (intolerance of uncertainty, negative problem orientation, cognitive avoidance, and perceived usefulness of worry), and on secondary variables associated with GAD (anxiety, depression, sleep difficulties, cognitive functioning, and disability). These results were generally maintained at 12 months after the end of treatment. Participants had favorable opinions toward the treatment. Conclusion: The results of this study suggest that CBT-GSH is both feasible and effective for the treatment of GAD in older adults. [ABSTRACT FROM AUTHOR]

Purpose. To compare the physical and physicochemical characteristics of carbamazepine microparticles prepared using two different methods: (1) the rapid expansion of supercritical solutions (RESS) and (2) the spray-drying process. METHODS: For both processes, microparticles were produced over a range of different temperatures (35 to 100°C). For the RESS method, carbon dioxide was the solvent used over a pressure range of 2500 to 3500 psi. As for the spray-drying method, different organic solvents were used at atmospheric pressure. Comparison was based on morphology, crystalline structure, mean particle size, and size distribution of processed particles. The influence of process parameters on microparticles' characteristics was also investigated. Particles were analyzed using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), thermogravimetric analyzer (TGA), and differential scanning calorimetry (DSC). RESULTS: The carbamazepine particles used as unprocessed starting material had a mean diameter of approximately 85 μm with a size distribution range between 15 and 336 μm. Microparticles produced by either the RESS or spray-drying method had a mean diameter smaller than 2 μm and a narrower size distribution range between 0.25 and 2.5 μm. SEM photomicrographs, X-ray diffractograms, and DSC spectra revealed that modification of crystal morphology was dependent on the operating conditions. CONCLUSIONS: Significant reduction in mean particle size and size distribution range of carbamazepine particles was observed by RESS and spray-drying methods. The results also demonstrate that the crystalline nature of carbamazepine particles depends on the method of production and on the operating parameters of pressure and temperature. [ABSTRACT FROM AUTHOR]