Further experimentation of inhaled; Lantus,Actrapid and Humulin with todays’ production systems

Background

Several aerosol production systems have been used for aerosol insulin production. However; since the first studies several new models of jet-nebulizers and ultrasound nebulizers have been introduced in the market.

Materials and methods

Three different models of jet-nebulizers (different brands, same properties) and three different ultrasound nebulizers (different brands, same properties). Six residual cups (2 small ≤ 6 ml and 3 large ≤ 8 ml) were used for the jet-nebulizers. The ultrasound nebulizers were used with their facemasks or with their inlets which were included in the purchase package.

Results

Ultrasound nebulizers; LANTUS produces by far the lowest mean droplets (2.44) half the size of the other two drugs (4.43 = 4.97). GIMA nebulizer is the most efficient producing one third of the droplet size of SHIMED and one second of EASYNEB (2.06 < 3.15 < 6.62). Finally, the 4 ml loading concentration is more suitable for supporting the production of smaller droplets (3.65 < 4.24). Drugs and nebulizers act interactively yielding very large droplets when ACTRAPID and HUMULIN are administered in joint with SHIMED nebulizer (9.59 = 7.72). Jet-nebulizers; HUMULIN again is the least preferred insulin since it hardly reaches the low but equal performance of others at the loading level of 6 ml. Residual cups E and B produce uniquely lower mean droplets at loading level 6.

Conclusions

Ultrasound nebulizers; the best suggested combination should be LANTUS insulin, GIMA nebulizer administered at loading dose of 4 ml jet-nebulizers. A global review can give the best combination: the lowest mean droplets are produced when the drugs LANTUS (mostly) and ACTRAPID are administered, applying the SUNMIST nebulizer in concert with residual cup B at loading levels of 6 ml.     

Internal mouthpiece designs as a future perspective for enhanced aerosol deposition. Comparative results for aerosol chemotherapy and aerosol antibiotics

Background

In an effort to identify factors producing a finest mist from Jet-Nebulizers we designed 2 mouthpieces with 4 different internal designs and 1–3 compartments.

Materials and methods

Ten different drugs previous used with their “ideal” combination of jet-nebulizer, residual-cup and loading were used. For each drug the mass median aerodynamic diameter size had been established along with their “ideal” combination.

Results

For both mouthpiece, drug was the most important factor due the high F-values (F_large = 251.7, p < 0.001 and F_small = 60.1, p < 0.001) produced. The design affected the droplet size but only for large mouthpiece (F_large = 5.99, p = 0.001, F_small = 1.72, p = 0.178). Cross designs create the smallest droplets (2.271) so differing from the other designs whose mean droplets were greater and equal ranging between 2.39 and 2.447. The number of compartments in the two devices regarding the 10 drugs was found not statistically significant (p-values 0.768 and 0.532 respectively). Interaction effects between drugs and design were statistically significant for both devices (F_large = 8.87, p < 0.001, F_small = 5.33, p < 0.001).

Conclusion

Based on our experiment we conclude that further improvement of the drugs intended for aerosol production is needed. In addition, the mouthpiece design and size play an important role in further enhancing the fine mist production and therefore further experimentation is needed.     

Lipid nanoparticles for brain targeting III. Long-term stability and in vivo toxicity

Purpose

The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles intended for brain drug delivery.

Methods

Lipid nanoparticles, prepared by high pressure homogenization, were stored at room temperature and 4 °C and monitored for their mean hydrodynamic diameter and Gaussian distribution width over time. Cetylpalmitate and polysorbate^® 80 chemical integrity were investigated by nuclear magnetic resonance on diagnostic signals. Nanoparticle toxicity was assessed in chicken embryos by chorioallantoic membrane assay and in rodents by brain histological evaluation.

Results

Data showed nanoparticle stability at 4 °C over a period of time of 4 years with only a limited particle size increase while at room temperature destabilization was observed after 9 months. Nuclear magnetic resonance investigation confirmed the absence (<5%) of chemical degradation of the lipid matrix and the surfactant after 4 years of storage at 4 °C. Chorioallantoic membrane assay and rat brain histology showed the absence of acute toxicity corroborating previously published data.

Conclusions

Cetylpalmitate nanoparticle long-term physical and chemical stability, together with the in vivo safety, corroborate the existing evidences of the high value of colloidal lipids as parenteral formulations and carriers for brain drug delivery.     

A tale of two stimulants: Mentholated cigarettes may play a role in cocaine,but not methamphetamine,dependence

Background

Research suggests that mentholated cigarettes may play a role in cocaine dependence. The purpose of the present study was to expand upon the research on mentholated cigarettes and cocaine dependence and to evaluate the role of mentholated cigarettes in methamphetamine dependence.

Methods

Secondary analysis of a multisite, randomized trial evaluating the impact of smoking-cessation treatment in stimulant-dependent outpatients (N = 538). Participants’ reasons for concurrent use of cigarettes and illicit stimulants were assessed via self-report. Stimulant-abstinence was measured by self-report and urine drug screens. Smoking cessation was assessed via self-report and carbon monoxide levels.

Results

Of the 301 cocaine-dependent participants, 201 (67%) were menthol and 100 (33%) were non-menthol cigarette smokers. Cocaine-dependent participants who smoked menthol, compared to non-menthol, cigarettes were significantly more likely to report that cigarettes prolong their cocaine high (X²(1) = 16.3, p < .0001, OR = 3.58 [95% CI: 1.88–6.79]) and were less likely to be stimulant abstinent during active treatment (W = 3.6, p < 0.001, d = .39 [95% CI: 0.16–0.62]), at 3-month follow-up (X²(1) = 14.4, p < 0.001, OR = .32 [95% CI: 0.17–0.58]), and at 6-month follow-up (X²(1) = 4.6, p = 0.03, OR = .53 [95% CI: 0.29–0.95]). No parallel differences were found between menthol and non-menthol methamphetamine-dependent smokers. The prevalence of Caucasian menthol smokers was significantly greater in the cocaine-dependent participants (37.2%) than in the methamphetamine-dependent participants (17.61%), (X²(1) = 14.4, p < .001, OR = 2.77 [95% CI:1.62–4.73]). Smoking cessation was not significantly associated with cigarette type for either cocaine- or methamphetamine-dependent participants.

Conclusions

The present results suggest that mentholated cigarettes play a role in cocaine, but not methamphetamine, dependence.     

Alcohol and drug use and related consequences among gay,lesbian and bisexual college students: Role of experiencing violence,feeling safe on campus,and perceived stress

Objective

To examine differences between gay, lesbian, and bisexual (GLB) and non-GLB university students in alcohol and other drug use (AOD) and related consequences as well as the relevance of violence, perceived safety, and stress to any such differences in AOD use and related concerns.

Methods

A random representative sample of university students (n = 988) were recruited via email for an online survey. Linear regression models assessed associations between identifying as GLB and AOD use and related consequences.

Results

Regression models (adjusted for gender) indicated that, in comparison to heterosexual students, GLB students were more likely to report recent illicit drug use (AOR = 2.0; 95% CI: 1.1–3.9), more frequent negative AOD consequences (β = 5.5, SE = 1.4, p < 0.0001), and having seriously thought about/attempted suicide due to AOD use in the past year (AOR = 6.6; 95% CI: 3.0–14.3). Study findings also suggested that violence, safety, and stress variables partially contribute to AOD use and related concerns among GLB students.

Conclusions

Findings highlight the need for future efforts to investigate and address mechanisms, including aspects of campus life, which contribute to AOD related risks among GLB students.     

Latent class analysis of polysubstance use,sexual risk behaviors,and infectious disease among South African drug users

Background

HIV transmission risk among non-injection drug users is high due to the co-occurrence of drug use and sexual risk behaviors. The purpose of the current study was to identify patterns of drug use among polysubstance users within a high HIV prevalence population.

Methods

The study sample included 409 substance users from the Pretoria region of South Africa. Substances used by 20% or more the sample included: cigarettes, alcohol, marijuana and heroin in combination, marijuana and cigarettes in combination, and crack cocaine. Latent class analysis was used to identify patterns of polysubstance use based on types of drugs used. Multivariate logistic regression analyses compared classes on demographics, sexual risk behavior, and disease status.

Results

Four classes of substance use were found: MJ + Cig (40.8%), MJ + Her (30.8%), Crack (24.7%), and Low Use (3.7%). The MJ + Cig class was 6.7 times more likely to use alcohol and 3 times more likely to use drugs before/during sex with steady partners than the Crack class. The MJ + Cig class was 16 times more likely to use alcohol before/during sex with steady partners than the MJ + Her class. The Crack class was 6.1 times more likely to engage in transactional sex and less likely to use drugs before/during steady sex than the MJ + Her class.

Conclusions

Findings illustrate patterns of drug use among a polysubstance using population that differ in sexual risk behavior. Intervention strategies should address substance use, particularly smoking as a route of administration (ROA), and sexual risk behaviors that best fit this high-risk population.     

Dynamics of aerosol size during inhalation: Hygroscopic growth of commercial nebulizer formulations

The size of aerosol particles prior to, and during, inhalation influences the site of deposition within the lung. As such, a detailed understanding of the hygroscopic growth of an aerosol during inhalation is necessary to accurately model the deposited dose. In the first part of this study, it is demonstrated that the aerosol produced by a nebulizer, depending on the airflows rates, may experience a (predictable) wide range of relative humidity prior to inhalation and undergo dramatic changes in both size and solute concentration. A series of sensitive single aerosol analysis techniques are then used to make measurements of the relative humidity dependent thermodynamic equilibrium properties of aerosol generated from four common nebulizer formulations. Measurements are also reported of the kinetics of mass transport during the evaporation or condensation of water from the aerosol. Combined, these measurements allow accurate prediction of the temporal response of the aerosol size prior to and during inhalation. Specifically, we compare aerosol composed of pure saline (150 mM sodium chloride solution in ultrapure water) with two commercially available nebulizer products containing relatively low compound doses: Breath^®, consisting of a simple salbutamol sulfate solution (5 mg/2.5 mL; 1.7 mM) in saline, and Flixotide^® Nebules, consisting of a more complex stabilized fluticasone propionate suspension (0.25 mg/mL; 0.5 mM in saline. A mimic of the commercial product Tobi^© (60 mg/mL tobramycin and 2.25 mg/mL NaCl, pH 5.5–6.5) is also studied, which was prepared in house. In all cases, the presence of the pharmaceutical was shown to have a profound effect on the magnitude, and in some cases the rate, of the mass flux of water to and from the aerosol as compared to saline. These findings provide physical chemical evidence supporting observations from human inhalation studies, and suggest that using the growth dynamics of a pure saline aerosol in a lung inhalation model to represent nebulizer formulations may not be representative of the actual behavior of the aerosolized drug solutions.     

PTSD symptomatology and readiness to quit smoking among women with serious mental illness

Introduction

Posttraumatic stress disorder (PTSD) is a risk factor for tobacco addiction. The majority of research on PTSD and smoking has been conducted with men, particularly combat veterans, and little is known about the association among women. In a clinical sample of women civilian smokers with serious mental illness (SMI), we examined the prevalence of PTSD symptomatology and associations with physical and mental health functioning, co-occurring substance use, nicotine dependence, and readiness to quit smoking.

Methods

376 adult women smokers aged 18–73 were recruited from 7 acute inpatient psychiatry units and screened by diagnostic interview for current PTSD symptomatology (PTSD⁺). In multiple regressions, we examined the associations of screening PTSD⁺ with physical and mental health functioning; past-month drug use; past-year substance use disorders; nicotine dependence and readiness to quit smoking.

Results

Nearly half the sample (43%) screened PTSD⁺, which was significantly associated with the use of stimulants (OR = 1.26) and opiates (OR = 1.98), drug use disorders (OR = 2.01), and poorer mental health (B = − 2.78) but not physical health functioning. PTSD⁺ status was unrelated to nicotine dependence, but predicted greater desire to quit smoking (B = 2.13) and intention to stop smoking in the next month (OR = 2.21). In multivariate models that adjusted for substance use disorders, physical and mental health functioning, and nicotine dependence, screening PTSD⁺ remained predictive of greater desire and intention to quit smoking.

Conclusion

PTSD symptomatology was common in our sample of women smokers with SMI and associated with not only worse substance use and mental health, but also greater readiness to quit smoking, suggesting the need for and potential interest in integrative PTSD-addiction treatment among women.     

Smoking prevalence,cigarette consumption and advice received from physicians: Change between 1996 and 2006 in Geneva,Switzerland

Objective

To assess change between 1996 and 2006 in smoking prevalence, cigarette consumption, quit attempts, motivation to quit and advice received from physicians in Geneva, Switzerland.

Methods

Postal surveys in cross-sectional, representative samples of the general population of Geneva in 1996 and 2006.

Results

There were 742 participants in 1996 (response rate 75%) and 1487 in 2006 (response rate 76%). Smoking prevalence remained stable between 1996 (28.0%, 95% confidence interval: 24.7 to 31.3%) and 2006 (26.5%, 24.3 to 28.7%, p = 0.46). Among smokers, cigarette consumption fell from 15 to 13 cig./day between 1996 and 2006 (p = 0.003). However, tobacco dependence, as measured by the Heaviness of Smoking Index, remained stable (mean = 1.9 vs. 1.7, p = 0.18). The proportion of smokers who made a 24-hour quit attempt in the previous year remained stable (29.2% in 1996, 32.1% in 2006, p = 0.52), but more smokers reported that they intended to quit in the next 6 months in 2006 (39.6%) than in 1996 (29.1%, p = 0.045). The association between smoking prevalence and income was stronger in 2006 (chi² = 53.7, p < 0.001) than in 1996 (chi² = 10.9, p = 0.012). In 2006 (no change since 1996), few smokers reported that, during their last medical visit, their physician told them to quit smoking (27.3%) or offered them help to quit (13.3%).

Conclusions

Over these 10 years, smoking prevalence, nicotine dependence levels and the frequency of quit attempts remained stable, but smokers' motivation to quit increased. We observed a growing social gap in smoking prevalence and cigarette consumption. Smoking cessation advice was seldom received during medical visits.     

Beliefs and attitudes regarding drug treatment: Application of the Theory of Planned Behavior in African-American cocaine users

Background

The Theory of Planned Behavior (TPB) can provide insights into perceived need for cocaine treatment among African American cocaine users.

Methods

A cross-sectional community sample of 400 (50% rural) not-in-treatment African-American cocaine users was identified through respondent-driven sampling in one urban and two rural counties in Arkansas. Measures included self-reports of attitudes and beliefs about cocaine treatment, perceived need and perceived effectiveness of treatment, and positive and negative cocaine expectancies. Normative beliefs were measured by perceived stigma and consequences of stigma regarding drug use and drug treatment. Perceived control was measured by readiness for treatment, prior drug treatment, and perceived ability to cut down on cocaine use without treatment.

Findings

Multiple regression analysis found that older age (standardized regression coefficient β = 0.15, P < 0.001), rural residence (β = − 0.09, P = 0.025), effectiveness of treatment (β = 0.39, P < 0.001), negative cocaine expectancies (β = 0.138, P = 0.003), experiences of rejection (β = 0.18, P < 0.001), need for secrecy (β = 0.12, P = 0.002), and readiness for treatment (β = 0.15, P < 0.001) were independently associated with perceived need for cocaine treatment.

Conclusions

TPB is a relevant model for understanding perceived need for treatment among African-American cocaine users. Research has shown perceived need to be a major correlate of treatment participation. Study results should be applicable for designing interventions to encourage treatment participation.     

Cortical activation deficits during facial emotion processing in youth at high risk for the development of substance use disorders

Background

Recent longitudinal studies demonstrate that addiction risk may be influenced by a cognitive, affective and behavioral phenotype that emerges during childhood. Relatively little research has focused on the affective or emotional risk components of this high-risk phenotype, including the relevant neurobiology.

Methods

Non-substance abusing youth (N = 19; mean age = 12.2) with externalizing psychopathology and paternal history of a substance use disorder and demographically matched healthy comparisons (N = 18; mean age = 11.9) were tested on a facial emotion matching task during functional MRI. This task involved matching faces by emotions (angry, anxious) or matching shape orientation.

Results

High-risk youth exhibited increased medial prefrontal, precuneus and occipital cortex activation compared to the healthy comparison group during the face matching condition, relative to the control shape condition. The occipital activation correlated positively with parent-rated emotion regulation impairments in the high-risk group.

Conclusions

These findings suggest a preexisting abnormality in cortical activation in response to facial emotion matching in youth at high risk for the development of problem drug or alcohol use. These cortical deficits may underlie impaired affective processing and regulation, which in turn may contribute to escalating drug use in adolescence.     

The kinetics of cohesive powder de-agglomeration from three inhaler devices

Purpose

The purpose of the current investigation is to understand the kinetics of de-agglomeration (k_d) of micronised salbutamol sulphate (SS) and lactohale 300 (LH300) under varying air flow rates (30-180 l min⁻¹) from three dry powder inhaler devices (DPIs), Rotahaler^® (RH), Monodose Inhaler^® (MI) and Handihaler^® (HH).

Results

Cumulative fine particle mass vs. time profiles were obtained from the powder concentration, emitted mass and volume percent <5.4 μm, embedded in the particle size distributions of the aerosol at specific times. The rate of de-agglomeration (k_d), estimated from non-linear least squares modelling, increased with increasing air flow rates. The k_dvs. air flow rate profiles of SS and LH300 were significantly different at high air flow rates. The k_d was highest from RH and lowest from MI. Differences in k_d between the devices were related to device mode of operation while the differences between the materials were due to the powder bed structure.

Conclusion

This approach provided a methodology to measure the rate constant for cohesive powder de-agglomeration following aerosolisation from commercial devices and an initial understanding of the influence of device, air flow rate and material on these rate constants.     

Topiramate treatment for alcoholic outpatients recently receiving residential treatment programs: A 12-week,randomized, placebo-controlled trial

Background

Initiation of a relapse prevention medication is crucial at the end of alcohol detoxification. This study aimed to examine the efficacy and safety of topiramate for alcoholism in patients receiving a residential treatment program of alcohol detoxification and post-acute treatment.

Methods

This was a 12-week, randomized, double-blind, placebo-controlled trial of topiramate for alcoholism in patients receiving a residential treatment program. Individuals with DSM-IV alcohol dependence with minimal withdrawal were enrolled. Participants were randomly assigned to receive either 100–300 mg/day of topiramate or placebo. Primary outcomes were given as percentages of heavy drinking days and time to first day of heavy drinking. Other drinking outcomes, craving, and health-related quality of life were evaluated.

Results

A total of 106 participants were randomized to receive topiramate (n = 53) or placebo (n = 53). Twenty-eight participants of the topiramate group (52.8%) and 25 participants of the placebo group (47.2%) completed the study. Averaged over the trial period, there was no significant difference between groups on the mean percentages of heavy drinking days [1.96 (−1.62 to 5.54), p = .28]. Log rank survival analysis found no difference of time to first day of heavy drinking between topiramate and placebo groups (61.8 vs. 57.5 days, respectively; χ² = 0.61, d.f. = 1, p = .81). Other secondary outcomes were not significantly different between groups.

Conclusions

By using a conservative model for data analysis, we could not detect the effectiveness of topiramate in this particular population. As the sensitivity analysis showed a trend of its benefit, further studies in larger sample sizes are still warranted.     

Brief motivational enhancement intervention to prevent or reduce postpartum alcohol use: A single-blinded,randomized controlled effectiveness trial

Aims

The aim of this study is to assess the effect of brief motivational enhancement intervention postpartum alcohol use.

Design

This study is a single-blinded, randomized controlled effectiveness trial in which pregnant women were assigned to receive usual care or up to 5 face-to-face brief motivational enhancement sessions lasting 10–30 minutes each and occurring at study enrollment, 4 and 8 weeks after enrollment, 32 weeks of gestation, and 6 weeks postpartum.

Setting

The setting is in a large, urban, obstetrics clinic.

Participants

Participants were women who were ≥ 18 years old, < 20 weeks of gestation, and consumed alcohol during pregnancy. Of 3438 women screened, 330 eligible women were assigned to usual care (n = 165) or intervention (n = 165). Due to missing data, we analyzed 125 in the intervention group and 126 in the usual care group.

Measurements

The measurements were the proportion of women with any alcohol use and the number of drinks per day, reported via follow-up telephone interviews at 4 and 8 weeks after enrollment, 32 weeks of gestation, and 6 weeks, 6 months, and 12 months postpartum.

Findings

In random effects models adjusted for confounders, the intervention group was less likely to use any alcohol (odds ratio 0.50; 95% confidence interval [CI], 0.23–1.09; P = 0.08) and consumed fewer drinks per day (coefficient − 0.11; 95% CI − 0.23–0.01; P = 0.07) than, the usual care group in the postpartum period but these differences were non-significant. Missing data during the prenatal period prevented us from modeling prenatal alcohol use.

Conclusions

Brief motivational enhancement intervention delivered in an obstetrical outpatient setting did not conclusively decrease alcohol use during the postpartum period.     

Young adult waterpipe smokers: Smoking behaviors and associated subjective and physiological effects

Introduction

The purpose of this pilot study was to investigate smoking behaviors and subjective and physiological effects of nicotine on young adult occasional waterpipe smokers.

Methods

This study utilized a repeated-measures design that included one repeated factor for condition (nicotine and non-nicotine). For each participant, the sequencing of the repeated factor was assigned using random allocation. The two nicotine conditions were nicotine (0.75 g) and non-nicotine (0 g placebo) tobacco. Over the course of two weeks, twenty-two participants completed subjective (Acute Subjective Effects of Nicotine) and physiological (blood pressure, heart rate, and CO level) measures. Additional measures (QSU and MNWS-R) were used to assess for withdrawal symptoms.

Sample

The participants (n = 22) were young adults (23 ± 3.1 years); 71% smoked waterpipe once a month in the past year and 29% smoked waterpipe 1–2 times per week. In addition, 60% reported sharing their waterpipe with friends while smoking. None of the participants reported using any other forms of tobacco products.

Results

Under the nicotine condition, participants tended to smoke longer (i.e. smoking duration, p = 0.004), take more puffs (p = 0.03), take shorter puffs (p = 0.03), and inhale less volume with each puff (p = 0.02). The repeated measures analysis of the factor headrush revealed an effect of the nicotine condition (F = 9.69, p < 0.001, partial η² = 0.31) and time (F = 8.17, p = 0.02, partial η² = 0.30). Heart rate increased significantly across the nicotine condition (F = 7.92, p = 0.01, partial η² = 0.31) and over time (F = 12.64, p = 0.01, partial η² = 0.41).

Conclusions

This study demonstrates how differences between nicotine and non-nicotine waterpipe smoking are associated with changes in smoking behaviors, experiencing a headrush and an increase in heart rate.     

Risk factors for progression to regular injection drug use among street-involved youth in a Canadian setting

Background

Street-involved youth are at high risk for experimenting with injection drug use; however, little attention has been given to identifying the factors that predict progression to on-going injecting.

Methods

Logistic regression was used to identify factors associated with progression to injecting weekly on a regular basis among a Canadian cohort of street-involved youth.

Results

Among our sample of 405 youth who had initiated injecting at baseline or during study observation, the median age was 22 years (interquartile range [IQR] = 21–24), and 72% (293) reported becoming a regular injector at some point after their first injection experience. Of these, the majority (n = 186, 63%) reported doing so within a month of initiating injection drug use. In multivariate analysis, the drug used at the first injection initiation event (opiates vs. cocaine vs. methamphetamine vs. other; all p > 0.05) was not associated with progression; however, younger age at first injection (adjusted odds ratio [AOR] = 1.13), a history of childhood physical abuse (AOR = 1.81), prior regular use of the drug first injected (AOR = 1.77), and having a sexual partner present at the first injection event (AOR = 2.65) independently predicted progression to regular injecting.

Conclusion

These data highlight how quickly youth progress to become regular injectors after experimentation. Findings indicate that addressing childhood trauma and interventions such as evidence-based youth focused addiction treatment that could prevent or delay regular non-injection drug use, may reduce progression to regular injection drug use among this population.     

Anti-Tuberculosis Bacteriophage D29 Delivery with a Vibrating Mesh Nebulizer,Jet Nebulizer,and Soft Mist Inhaler

Purpose

To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices.

Methods

Phage D29 lysate was amplified to a titer of 11.8 ± 0.3 log₁₀(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify phage titer.

Results

Respective titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log₁₀(pfu/mL). Active phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x10⁸ ± 0.8x10⁸ pfu/min) than for the jet nebulizer (5.4x10⁴ ± 1.3x10⁴ pfu/min). The soft mist inhaler delivered 4.6x10⁶ ± 2.0x10⁶ pfu per 11.6 ± 1.6 μL ex-actuator dose.

Conclusions

Delivering active phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing phage D29 under the tested conditions, due to substantial titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.

     

A novel strategy to design sustained-release poorly water-soluble drug mesoporous silica microparticles based on supercritical fluid technique

Background

The organic solvent solution immersion method was often used to achieve the loading of the drugs into mesoporous silica, but the drugs that have loaded into the pores of the mesoporous silica would inevitable migrate from the inside to the external surface or near the outside surface during the process of drying. Hence, it often leads to the pores of mesoporous materials not be fully utilized, and results in a low drug loading efficiency and a fast releasing rate.

Objective

The purpose of this study was to develop a novel drug loading strategy to avoid soluble component migration during the process of drying, then, to prepare poorly water-soluble drug mesoporous silica microparticles with higher drug loading efficiency and longer sustained-release time.

Method

Ibuprofen was used as model drug. The microparticles were prepared by a novel method based on mesoporous silica and supercritical fluid (SCF) technique. The drug-loaded mesoporous silica microparticles prepared by SCF technique were analyzed by thermogravimetric analysis (TGA), N₂ adsorption/desorption, scanning electron microscopy (SEM), powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC). In vitro releasing study was used to evaluate the sustained-release effect of the drug-loaded microparticles.

Results

By virtue of the high diffusibility and the high dissolving capacity of the supercritical carbon dioxide (SCF-CO₂), the poorly water-soluble drugs, ibuprofen, entered the pores of the mesoporous silica. The amount and the depth of ibuprofen entered the pores of the mesoporous silica by SCF technique were both larger than those by the solution immersion method. It was found that ibuprofen loaded into the mesoporous silica by SCF technique was amorphous and the largest amount of the ibuprofen loaded into the mesoporous silica by SCF technique could reach 386 mg/g (w/w, ibuprofen/SiO₂), it was more than that by the solution immersion method. In vitro releasing study showed that the sustained-release effect of ibuprofen in the samples prepared by SCF technique was 50% in 15 min and 90% in 60 min. It was longer than that prepared by the solution immersion method.

Conclusion

Present study showed that sustained-release poorly water-soluble drug mesoporous silica microparticle based on SCF technique has twofold advantages. One is the larger drug loading amount in internal pores of the mesoporous silica, the other is the longer drug releasing time.     

Testing the Cigarette Dependence Scale in 4 samples of daily smokers: Psychiatric clinics,smoking cessation clinics,a smoking cessation website and in the general population

Aim

To assess the properties of the Cigarette Dependence Scale (CDS-12) in various samples of daily smokers and to provide reference scores in a general population sample.

Methods

Surveys in 4 samples of daily cigarette smokers: psychiatric out-patients in Geneva, Switzerland (n = 226), clients of smoking cessation clinics in France (n = 370), visitors of a French-language smoking cessation website (n = 13,697) and a representative sample of the general population of Geneva (n = 292).

Results

In all 4 samples, Cronbach's alpha coefficients were > 0.87 and factor analyses indicated that CDS-12 was unidimensional. CDS-12 was slightly skewed towards higher values, and it was associated with expired carbon monoxide, but this association was not strong (9% of variance explained, p < 0.001). CDS-12 scores were highest in clients of smoking cessation clinics (mean = 47.7, SD = 10.2), followed by psychiatric patients (mean = 44.4, SD = 8.4), visitors of smoking cessation websites (mean = 43.3, SD = 11.6) and the general population sample (mean = 36.9, SD = 12.3). Except for tolerance, each element in the DSM-IV and ICD-10 definitions of dependence is reflected by at least one item in CDS-12, even though the match with these definitions is sometimes indirect.

Conclusions

This paper presents reference scores and validity and reliability tests for CDS-12 in a diversity of samples of daily smokers. This information should be useful to clinicians and researchers.