- Effects of Formulation Variables on Lung Dosimetry of Albuterol Sulfate Suspension and Beclomethasone Dipropionate Solution Metered Dose Inhalers. [Journal Article]
- APAAPS PharmSciTech 2018 Jun 01
- The performance of pressurized metered dose inhalers (MDIs) is affected by formulation and device variables that impact delivered dose, aerodynamic particle size distribution, and consequently lung d...
The performance of pressurized metered dose inhalers (MDIs) is affected by formulation and device variables that impact delivered dose, aerodynamic particle size distribution, and consequently lung deposition and therapeutic effect. Specific formulation variables of relevance to two commercially available products-Proventil® HFA [albuterol sulfate (AS) suspension] and Qvar® [beclomethasone dipropionate (BDP) solution]-were evaluated to determine their influence on key performance attributes measured experimentally with in vitro cascade impaction studies. These commercial MDIs, utilized as model systems, provided mid-points for a design of experiments (DoE) plan to manufacture multiple suspension and solution MDI formulations. The experimental results were utilized as input variables in a computational dosimetry model to predict the effects of MDI formulation variables on lung deposition. For the BDP solution DoE MDIs, increased concentrations of surfactant oleic acid (0-2% w/w) increased lung deposition from 24 to 46%, whereas changes in concentration of the cosolvent ethanol (7-9% w/w) had no effect on lung deposition. For the AS suspension DoE MDIs, changes in oleic acid concentration (0.005-0.25% w/w) did not have significant effects on lung deposition, whereas lung deposition decreased from 48 to 26% as ethanol concentration increased from 2 to 20% w/w, and changes in micronized drug volumetric median particle size distribution (X50, 1.4-2.5 μm) increased deposition in the tracheobronchial airways from 5 to 11%. A direct correlation was observed between fine particle fraction and predicted lung deposition. These results demonstrate the value of using dosimetry models to further explore relationships between performance variables and lung deposition.
- Significant Lactic Acidosis from Albuterol. [Journal Article]
- CPClin Pract Cases Emerg Med 2018; 2(2):128-131
- Lactic acidosis is a clinical entity that demands rapid assessment and treatment to prevent significant morbidity and mortality. With increased lactate use across many clinical scenarios, lactate val...
Lactic acidosis is a clinical entity that demands rapid assessment and treatment to prevent significant morbidity and mortality. With increased lactate use across many clinical scenarios, lactate values themselves cannot be interpreted apart from their appropriate clinical picture. The significance of Type B lactic acidosis is likely understated in the emergency department (ED). Given the mortality that sepsis confers, a serum lactate is an important screening study. That said, it is with extreme caution that we should interpret and react to the resultant elevated value. We report a patient with a significant lactic acidosis. Though he had a high lactate value, he did not require aggressive resuscitation. A different classification scheme for lactic acidosis that focuses on the bifurcation of the "dangerous" and "not dangerous" causes of lactic acidosis may be of benefit. In addition, this case is demonstrative of the potential overuse of lactates in the ED.
- The Effect of Different Closed Suction Catheter Designs and pMDI Adapters on Aerosol Delivery in Simulated Adult Mechanical Ventilation With and Without Exhaled Humidity. [Journal Article]
- RCRespir Care 2018 May 29
- CONCLUSIONS: Closed suction catheter, pMDI spacer/adapters, and exhalation conditions have an impact on drug delivery during simulated adult mechanical ventilation. Aerosol delivery without exhaled humidity appears to report unrealistically high values in comparison to the more accurate values with simulated exhalation humidity.
- Post-discharge outcomes of failed car seat tolerance screens: A case-control and follow-up study. [Journal Article]
- JNJ Neonatal Perinatal Med 2018 May 23
- CONCLUSIONS: This is the first study to evaluate longer term post-discharge outcomes of subjects having undergone CSTS. Subjects who failed CSTS had significantly increased incidence of respiratory diagnoses such as OSA and asthma than matched controls by 2- 3 years after discharge. Larger studies are necessary to further evaluate these findings, but this does provide data that CSTS may be useful in identifying at risk neonates.
- Post-radiotherapy maintenance treatment with fluticasone propionate and salmeterol for lung cancer patients with grade III radiation pneumonitis: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(21):e10681
- CONCLUSIONS: This maintenance therapy of FP/Salm for patient with grade III RP may help avoid relapse when steroid therapy is tapered, particularly for patients with a history of COPD. It may also reduce risk of steroid-associated adverse effects. Based on the results observed with our patient, we intend to design a prospective trial to assess the efficacy of FP/Salm when used as preventive treatment for patients at high risk of RP, and when used as maintenance treatment for patients with grade III RP.
- Molecular Tension Probes to Investigate the Mechanopharmacology of Single Cells: A Step toward Personalized Mechanomedicine. [Journal Article]
- AHAdv Healthc Mater 2018 May 22; :e1800069
- Given that dysregulation of mechanics contributes to diseases ranging from cancer metastasis to lung disease, it is important to develop methods for screening the efficacy of drugs that target cellul...
Given that dysregulation of mechanics contributes to diseases ranging from cancer metastasis to lung disease, it is important to develop methods for screening the efficacy of drugs that target cellular forces. Here, nanoparticle-based tension sensors are used to quantify the mechanical response of individual cells upon drug treatment. As a proof-of-concept, the activity of bronchodilators is tested on human airway smooth muscle cells derived from seven donors, four of which are asthmatic. It is revealed that airway smooth muscle cells isolated from asthmatic donors exhibit greater traction forces compared to the control donors. Additionally, the mechanical signal is abolished using myosin inhibitors or further enhanced in the presence of inflammatory inducers, such as nicotine. Using the signal generated by the probes, single-cell dose-response measurements are performed to determine the "mechano" effective concentration (mechano-EC50) of albuterol, a bronchodilator, which reduces integrin forces by 50%. Mechano-EC50 values for each donor present discrete readings that are differentially enhanced as a function of nicotine treatment. Importantly, donor mechano-EC50 values varied by orders of magnitude, suggesting significant variability in their sensitivity to nicotine and albuterol treatment. To the best of the authors' knowledge, this is the first study harnessing a piconewton tension sensor platform for mechanopharmacology.
- Ohio Pediatric Asthma Repository: Opportunities to Revise Care Practices to Decrease Time to Physiologic Readiness for Discharge. [Journal Article]
- HPHosp Pediatr 2018; 8(6):305-313
- CONCLUSIONS: Substantial variation in care practices for inpatient asthma treatment exists among children's hospital systems in Ohio. We found several modifiable, system-level factors and therapies that contribute to PRD that warrant further investigation to identify the best and safest care practices. We also found that there was no standardized measure of exacerbation severity used across the hospitals. The development of such a tool is a critical gap in current practice and is needed to enable definitive comparative effectiveness studies of the management of acute asthma exacerbation.
- Multicenter Study of Albuterol Use Among Infants Hospitalized with Bronchiolitis. [Journal Article]
- WJWest J Emerg Med 2018; 19(3):475-483
- CONCLUSIONS: Variation in pre-admission albuterol use suggests that local practice had a strong influence on use, but that patient characteristics also influenced the decision. While we agree with current guidelines in recommending against albuterol for all infants with bronchiolitis, our understanding of possible subgroups of responders may improve through investigation of infants with the identified characteristics.
- Enantiomeric impurity analysis using circular dichroism spectroscopy with United States Pharmacopeia liquid chromatographic methods. [Journal Article]
- JPJ Pharm Biomed Anal 2018 Jul 15; 156:366-371
- Over 300 chiral drug substances lack official United States Pharmacopeia (USP) methods for the enantiomeric purity determination. Because enantiomeric analysis typically requires specialized methods ...
Over 300 chiral drug substances lack official United States Pharmacopeia (USP) methods for the enantiomeric purity determination. Because enantiomeric analysis typically requires specialized methods for each drug compound, developing protocols for each of these 300+ substances would be an expensive and laborious endeavor. Alternatively, if a detector capable of determining the enantiomeric composition without chiral separation could be used with certain drug compounds, this could be implemented relatively rapidly into official testing monographs. Circular dichroism (CD) detection following HPLC (HPLC-CD) has been proposed for this purpose but studies performed thus far have not prioritized its compatibility with validated regulatory methods. In this study, HPLC-CD was evaluated for enantiomeric purity determinations of 13 drug substances using HPLC methods consistent with assay protocols described in United States Pharmacopeia (USP) monographs. Of these selected substances, three (sitagliptin, timolol, and levalbuterol) showed no CD activity and one other (levofloxacin) could not be analyzed due to incompatibility of the mobile phase with the CD detector. For the remaining 9 substances, method validation was performed to determine the linearity, accuracy, precision and limits of quantitation of enantiomer impurities, which was compared to limits established by USP. It was found that enantiomeric impurities for four substances (pramipexole, levocetirizine, (S)-citalopram, and tolterodine) could be quantitatively determined at levels suitable to USP specifications. This analysis demonstrated that HPLC-CD does provide an effective enantiomeric characterization strategy for compatible chiral compounds, and can be implemented quickly and economically compared to traditional column-dependent chiral separation or derivatization methods.
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- Case study: A Combination of Mepolizumab and Omaluzimab injections for severe asthma. [Journal Article]
- JAJ Asthma 2018 May 07; :1-3
- CONCLUSIONS: Combination of omalizumab and mepolizumab could become the gold standard for severe asthma patients that have elevated IgE levels and an eosinophilic phenotype.