Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties,Blending and In Vitro Performance

Pharmaceutical Research - Traditionally, α-lactose monohydrate is the carrier of choice in dry powder inhaler (DPI) formulations. Nonetheless, other sugars, such as D-mannitol, have emerged as...     

Validity of Teacher-Based Vision Screening and Factors Associated with the Accuracy of Vision Screening in Vietnamese Children

Purpose: To assess validity of teacher-based vision screening and elicit factors associated with accuracy of vision screening in Vietnam.

Methods: After brief training, teachers independently measured visual acuity (VA) in 555 children aged 12–15 years in Ba Ria – Vung Tau Province. Teacher VA measurements were compared to those of refractionists. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for uncorrected VA (UVA) and presenting VA (PVA) 20/40 or worse in either eye. Chi-square, Fisher’s exact test and multivariate logistic regression were used to assess factors associated with accuracy of vision screening. Level of significance was set at 5%.

Results: Trained teachers in Vietnam demonstrated 86.7% sensitivity, 95.7% specificity, 86.7% positive predictive value and 95.7% negative predictive value in identifying children with visual impairment using the UVA measurement. PVA measurement revealed low accuracy for teachers, which was significantly associated with child’s age, sex, spectacle wear and myopic status, but UVA measurement showed no such associations.

Conclusions: Better accuracy was achieved in measurement of VA and identification of children with visual impairment using UVA measurement compared to PVA. UVA measurement is recommended for teacher-based vision screening programs.     

Sleep-disordered breathing and urinary albumin excretion in older men

Purpose  

Sleep-disordered breathing(SDB) may be deleterious to the cardiovascular system and other organs, including the kidney. Although older men are at increased risk for both kidney disease and SDB, it is unknown whether SDB is associated with higher urinary albumin excretion in this population.     

Association between depressive symptoms and sleep disturbances in community-dwelling older men

OBJECTIVES: To examine the association between depressive symptoms and subjective and objective measures of sleep in community-dwelling older men.
DESIGN: Cross-sectional.
SETTING: Six U.S. clinical centers.
PARTICIPANTS: Three thousand fifty-one men aged 67 and older.
MEASUREMENTS: Depressive symptoms assessed using the 15-item Geriatric Depression Scale and categorized as 0 to 2 (normal, referent group), 3 to 5 (some depressive symptoms), and 6 to 15 (depressed); objective sleep measures ascertained using wrist actigraphy (mean duration 5.2 nights); and subjective sleep measures assessed using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale.
RESULTS: There was a strong multivariable-adjusted association between level of depressive symptoms and subjective sleep disturbances ( P -trend <.001). For example, the odds of reporting poor sleep quality were 3.7 times (95% confidence interval (CI)=2.5–5.3) higher for depressed men as for normal men, and 2.1 times (95% CI=1.7–2.6) higher for men with some depressive symptoms. For objectively measured sleep disturbances, men with more depressive symptoms had greater odds of sleep latency of 1 hour or more ( P -trend=.006). There was no association between level of depressive symptoms and sleep efficiency, awakening after sleep onset, multiple long-wake episodes, or total sleep time. Excluding 384 men taking antidepressants, benzodiazepines, or other anxiolytic or hypnotics did not alter the results.
CONCLUSION: Depressive symptoms have a strong, graded association with subjective sleep disturbances and are moderately associated with objectively measured prolonged sleep latency. Future studies should address temporality of depression and sleep disturbances.     

Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: Formulation and process considerations

Spray drying is an efficient technology for solid dispersion manufacturing since it allows extreme rapid solvent evaporation leading to fast transformation of an API-carrier solution to solid API-carrier particles. Solvent evaporation kinetics certainly contribute to formation of amorphous solid dispersions, but also other factors like the interplay between the API, carrier and solvent, the solution state of the API, formulation parameters (e.g. feed concentration or solvent type) and process parameters (e.g. drying gas flow rate or solution spray rate) will influence the final physical structure of the obtained solid dispersion particles. This review presents an overview of the interplay between manufacturing process, formulation parameters, physical structure, and performance of the solid dispersions with respect to stability and drug release characteristics.     

An Investigation into the Effect of Spray Drying Temperature and Atomizing Conditions on Miscibility,Physical Stability,and Performance of Naproxen–PVP K 25 Solid Dispersions

The present study investigates the effect of changing spray drying temperature (40°C–120°C) and/or atomizing airflow rate (AR; 5–15 L/min) on the phase structure, physical stability, and performance of spray-dried naproxen–polyvinylpyrrolidone (PVP) K25 amorphous solid dispersions. The modulated differential scanning calorimetry, attenuated total internal reflectance-Fourier transform infrared, and powder X-ray diffractometry (pXRD) studies revealed that higher inlet temperature (IT) or atomization airflow leads to the formation of amorphous-phase-separated dispersions with higher strongly H-bonded and free PVP fractions, whereas that prepared with the lowest IT was more homogeneous. The dispersion prepared with the lowest atomization AR showed trace crystallinity. Upon exposure to 75% relative humidity (RH) for 3 weeks, the phase-separated dispersions generated by spray drying at higher temperature or higher atomization airflow retained relatively higher amorphous drug fraction compared with those prepared at slow evaporation conditions. The humidity-controlled pXRD analysis at 98% RH showed that the dispersion prepared with highest atomization AR displayed the slowest kinetics of recrystallization. The molecular-level changes occurring during recrystallization at 98% RH was elucidated by spectroscopic monitoring at the same humidity. The rate and extent of the drug dissolution was the highest for dispersions prepared at the highest atomizing AR and the lowest for that prepared with the slowest atomizing condition.     

A rare case of pancreatic mediastinal pseudocyst.

Pancreatic pseudocysts are the most common cystic lesions of the pancreas, accounting for 75-80% of such masses. Pancreatic pseudocyst with mediastinal extension is a rare clinical entity and only a handful cases report on dysphagia associated with mediastinal pseudocyst formation.1 We present a case of pancreatic mediastinal pseudocyst that presented with palpitations and dysphagia. Demonstration of cystic lesion in relation to the pancreas on ultrasound and mediastinal extension of the cyst on CT suggested the diagnosis. Key words: pseudocyst, mediastinal cyst, pancreas.     

Circadian Activity Rhythms and Mortality: The Study of Osteoporotic Fractures

OBJECTIVES: To determine whether circadian activity rhythms are associated with mortality in community‐dwelling older women. DESIGN: Prospective study of mortality. SETTING: A cohort study of health and aging. PARTICIPANTS: Three thousand twenty‐seven community‐dwelling women from the Study of Osteoporotic Fractures cohort (mean age 84). MEASUREMENTS: Activity data were collected using wrist actigraphy for a minimum of three 24‐hour periods, and circadian activity rhythms were computed. Parameters of interest included height of activity peak (amplitude), midline estimating statistic of rhythm (mesor), strength of activity rhythm (robustness), and time of peak activity (acrophase). Vital status, with cause of death adjudicated through death certificates, was prospectively ascertained. RESULTS: Over an average of 4.1 years of follow‐up, there were 444 (14.7%) deaths. There was an inverse association between peak activity height and all‐cause mortality rates, with higher mortality rates observed in the lowest activity quartile (hazard ratio (HR)=2.18, 95% confidence interval (CI)=1.63–2.92) than in the highest quartile after adjusting for age, clinic site, race, body mass index, cognitive function, exercise, instrumental activity of daily living impairments, depression, medications, alcohol, smoking, self‐reported health status, married status, and comorbidities. A greater risk of mortality from all causes was observed for those in the lowest quartiles of mesor (HR=1.71, 95% CI=1.29–2.27) and rhythm robustness (HR=1.97, 95% CI=1.50–2.60) than for those in the highest quartiles. Greater mortality from cancer (HR=2.09, 95% CI=1.04–4.22) and stroke (HR=2.64, 95% CI=1.11–6.30) was observed for later peak activity (after 4:33 p.m.; >1.5 SD from mean) than for the mean peak range (2:50–4:33 p.m.). CONCLUSION: Older women with weak circadian activity rhythms have higher mortality risk. If confirmed in other cohorts, studies will be needed to test whether interventions (e.g., physical activity, bright light exposure) that regulate circadian activity rhythms will improve health outcomes in older adults.