scholarly journals Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b)

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 566 ◽  
Author(s):  
Bart Hens ◽  
Marival Bermejo ◽  
Patrick Augustijns ◽  
Rodrigo Cristofoletti ◽  
Gregory Amidon ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
Buffer Capacity ◽  
Drug Product ◽  
Tap Water ◽  
Systemic Exposure ◽  
Immediate Release ◽  
Release Formulation ◽  
Gastric Emptying Rate ◽  
Physiological Variables ◽  
The Impact

In the present work, we explored if Coca-Cola® had a beneficial impact on the systemic outcome of the weakly basic drug loratadine (Wal-itin®, immediate-release formulation, 10 mg, generic drug product). To map the contribution of underlying physiological variables that may positively impact the intestinal absorption of loratadine, a multi-compartmental and dynamic dissolution device was built, namely the Gastrointestinal Simulator (GIS). The luminal behavior of one immediate-release (IR) tablet of 10 mg of loratadine was tested under four different fasted state test conditions in the GIS: (i) with 250 mL of water and applying a predetermined gastric half-life (t1/2,G) of 15 min; (ii) with 250 mL of water and applying a t1/2,G of 30 min; (iii) with 250 mL of Coca-Cola® and a t1/2,G of 15 min; (iv) with 250 mL of Coca-Cola® and a t1/2,G of 30 min. After initiating the experiments, solution concentrations and solubility were measured in the withdrawn samples, and pH was monitored. To address the impact of the present CO2 in Coca-Cola® on the disintegration time of the tablet, additional disintegration experiments were performed in a single-vessel applying tap water and sparkling water as dissolution media. These experiments demonstrated the faster disintegration of the tablet in the presence of sparkling water, as the present CO2 facilitates the release of the drug. The buffer capacity of Coca-Cola® in the presence of FaSSGF was 4-fold higher than the buffer capacity of tap water in the presence of FaSSGF. After performing the in vitro experiments, the obtained results were used as input for a two-compartmental pharmacokinetic (PK) modeling approach to predict the systemic concentrations. These simulations pointed out that (i) the present CO2 in Coca-Cola® is responsible for the enhancement in drug release and dissolution and that (ii) a delay in gastric emptying rate will sustain the supersaturated concentrations of loratadine in the intestinal regions of the GI tract, resulting in an enhanced driving force for intestinal absorption. Therefore, co-administration of loratadine with Coca-Cola® will highly likely result in an increased systemic exposure compared to co-administration of loratadine with tap water. The mechanistic insights that were obtained from this work will serve as a scientific basis to evaluate the impact of Coca-Cola® on the systemic exposure of weakly basic drugs for patients on acid-reducing agents in future work.

scholarly journals Mechanistic PBPK Modelling to Predict the Advantage of the Salt Form of a Drug When Dosed with Acid Reducing Agents

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1169
Author(s):  
Siri Kalyan Chirumamilla ◽  
Venkatesh Teja Banala ◽  
Masoud Jamei ◽  
David B. Turner
Keyword(s):  
Pbpk Model ◽  
Immediate Release ◽  
Reducing Agents ◽  
Free Base ◽  
Salt Form ◽  
Pbpk Modelling ◽  
Release Formulation ◽  
Drug Products ◽  
Model Drug ◽  
The Impact

Acid reducing agents (ARAs) reduce the dissolution rate of weakly basic drugs in the stomach potentially leading to lower bioavailability. Formulating the API as a rapidly dissolving salt is one strategy employed to reduce the impact of ARAs on dissolution of such drugs. In the present work, a model drug was selected with an immediate release formulation of the free base dosed in both the absence and presence of the ARA famotidine. In the latter case, bioavailability is restricted and several salt formulations were investigated. To simulate these drug products a mechanistic physiologically based pharmacokinetic (PBPK) model was built using the Simcyp Simulator, which illustrates the advantage of formulating an API as a salt compared to the free base form. The simulations use a mechanistic salt model utilising knowledge of the solubility product which was applied to predict the salt advantage. The developed PBPK model exemplifies that it can be critical to account for the surface pH and solubility when modelling the dissolution of low pKa bases and their salts in the gastric environment. In particular, the mechanistic salt model can be used to aid in screening and salt form selection where the aim is to mitigate effects of ARAs.

scholarly journals Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1205
Author(s):  
Teun van Gelder ◽  
Oumaima Etsouli ◽  
Dirk Jan Moes ◽  
Jesse J. Swen
Keyword(s):  
Drug Exposure ◽  
Immediate Release ◽  
Current Data ◽  
Modified Release ◽  
Release Formulation ◽  
Once Daily ◽  
Drug Concentrations ◽  
Presystemic Metabolism ◽  
And Function ◽  
The Impact

Tacrolimus-modified release formulations allow for once-daily dosing, and adherence is better compared to the twice-daily immediate release formulation. When patients are switched from one formulation to another, variable changes in drug concentrations are observed. Current data suggest that the changes in drug exposure are larger in patients who express the CYP3A5 enzyme (CYP3A5 *1/*3 or *1/*1) compared to nonexpressers (CYP3A5*3/*3). Possibly, these differences are due to the fact that in the upper region of the small intestine CYP3A activity is higher, and that this expression of CYP3A decreases towards the more distal parts of the gut. Modified release formulations may therefore be subject to a less presystemic metabolism. However, the full implications of pharmacogenetic variants affecting the expression and function of drug transporters in the gut wall and of enzymes involved in phase I and phase II metabolism on the different formulations are incompletely understood, and additional studies are required. Conclusions: In all patients in whom the formulation of tacrolimus is changed, drug levels need to be checked to avoid clinically relevant under- or overexposure. In patients with the CYP3A5 expresser genotype, this recommendation is even more important, as changes in drug exposure can be expected.

scholarly journals Management of a parenteral opioid shortage using ASHP guidelines

2021 ◽  
Vol 78 (5) ◽  
pp. 426-435
Author(s):  
Peter Vo ◽  
Daniel A Sylvia ◽  
Loay Milibari ◽  
John Ryan Stackhouse ◽  
Paul Szumita ◽  
...  
Keyword(s):  
Electronic Health Record ◽  
Drug Product ◽  
Health Record ◽  
Large Hospital ◽  
Hospital Administrators ◽  
Utilization Data ◽  
Electronic Health ◽  
Opioid Medications ◽  
American Society ◽  
The Impact

Abstract Purpose Management of an acute shortage of parenteral opioid products at a large hospital through prescribing interventions and other guideline-recommended actions is described. Summary In early 2018, many hospitals were faced with a shortage of parenteral opioids that was predicted to last an entire year. The American Society of Health-System Pharmacists (ASHP) has published guidelines on managing drug product shortages. This article describes the application of these guidelines to manage the parenteral opioid shortage and the impact on opioid dispensing that occurred in 2018. Our approach paralleled that recommended in the ASHP guidelines. Daily dispensing reports generated from automated dispensing cabinets and from the electronic health record were used to capture dispenses of opioid medications. Opioid prescribing and utilization data were converted to morphine milligram equivalents (MME) to allow clinical leaders and hospital administrators to quickly evaluate opioid inventories and consumption. Action steps included utilization of substitute opioid therapies and conversion of opioid patient-controlled analgesia (PCA) and opioid infusions to intravenous bolus dose administration. Parenteral opioid supplies were successfully rationed so that surgical and elective procedures were not canceled or delayed. During the shortage, opioid dispensing decreased in the inpatient care areas from approximately 2.0 million MME to 1.4 million MME and in the operating rooms from 0.56 MME to 0.29 million MME. The combination of electronic health record alerts, increased utilization of intravenous acetaminophen and liposomal bupivacaine, and pharmacist interventions resulted in a 67% decline in PCA use and a 65% decline in opioid infusions. Conclusion A multidisciplinary response is necessary for effective management of drug shortages through implementation of strategies and practices for notifying clinicians of shortages and identifying optimal alternative therapies.

scholarly journals Polyphenol Profiling of Chestnut Pericarp, Integument and Curing Water Extracts to Qualify These Food By-Products as a Source of Antioxidants

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2335
Author(s):  
Gabriella Pinto ◽  
Sabrina De Pascale ◽  
Maria Aponte ◽  
Andrea Scaloni ◽  
Francesco Addeo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Negative Impact ◽  
Tap Water ◽  
Time Of Flight ◽  
The Other ◽  
Curing Process ◽  
Flight Mass Spectrometry ◽  
Water Curing ◽  
The Impact ◽  
By Products

Plant polyphenols have beneficial antioxidant effects on human health; practices aimed at preserving their content in foods and/or reusing food by-products are encouraged. The impact of the traditional practice of the water curing procedure of chestnuts, which prevents insect/mould damage during storage, was studied to assess the release of polyphenols from the fruit. Metabolites extracted from pericarp and integument tissues or released in the medium from the water curing process were analyzed by matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray-quadrupole-time of flight-mass spectrometry (ESI-qTOF-MS). This identified: (i) condensed and hydrolyzable tannins made of (epi)catechin (procyanidins) and acid ellagic units in pericarp tissues; (ii) polyphenols made of gallocatechin and catechin units condensed with gallate (prodelphinidins) in integument counterparts; (iii) metabolites resembling those reported above in the wastewater from the chestnut curing process. Comparative experiments were also performed on aqueous media recovered from fruits treated with processes involving: (i) tap water; (ii) tap water containing an antifungal Lb. pentosus strain; (iii) wastewater from a previous curing treatment. These analyses indicated that the former treatment determines a 6–7-fold higher release of polyphenols in the curing water with respect to the other ones. This event has a negative impact on the luster of treated fruits but qualifies the corresponding wastes as a source of antioxidants. Such a phenomenon does not occur in wastewater from the other curing processes, where the release of polyphenols was reduced, thus preserving the chestnut’s appearance. Polyphenol profiling measurements demonstrated that bacterial presence in water hampered the release of pericarp metabolites. This study provides a rationale to traditional processing practices on fruit appearance and qualifies the corresponding wastes as a source of bioactive compounds for other nutraceutical applications.

scholarly journals Photocatalytic Degradation of Sulfolane Using a LED-Based Photocatalytic Treatment System

Catalysts ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 624
Author(s):  
Sripriya Dharwadkar ◽  
Linlong Yu ◽  
Gopal Achari
Keyword(s):  
Photocatalytic Degradation ◽  
Oil And Gas ◽  
Light Emitting Diode ◽  
Tap Water ◽  
Aqueous Media ◽  
Ultrapure Water ◽  
Light Emitting ◽  
Degradation Rates ◽  
Reduced Graphene ◽  
The Impact

Sulfolane is an emerging industrial pollutant detected in the environments near many oil and gas plants in North America. So far, numerous advanced oxidation processes have been investigated to treat sulfolane in aqueous media. However, there is only a few papers that discuss the degradation of sulfolane using photocatalysis. In this study, photocatalytic degradation of sulfolane using titanium dioxide (TiO2) and reduced graphene oxide TiO2 composite (RGO-TiO2) in a light-emitting diode (LED) photoreactor was investigated. The impact of different waters (ultrapure water, tap water, and groundwater) and type of irradiation (UVA-LED and mercury lamp) on photocatalytic degradation of sulfolane were also studied. In addition, a reusability test was conducted for the photocatalyst to examine the degradation of sulfolane in three consecutive cycles with new batches of sulfolane-contaminated water. The results show that LED-based photocatalysis was effective in degrading sulfolane in waters even after three photocatalytic cycles. UVA-LEDs displayed more efficient use of photon energy when compared with the mercury lamps as they have a narrow emission spectrum coinciding with the absorption of TiO2. The combination of UVA-LED and TiO2 yielded better performance than UVA-LED and RGO-TiO2 for the degradation of sulfolane. Much lower sulfolane degradation rates were observed in tap water and groundwater than ultrapure water.

631 Sleep SMART in Adolescents with Neurodevelopmental Disorders

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A247-A248
Author(s):  
Alyson Hanish ◽  
Abbey Jo Klein ◽  
Therese Mathews ◽  
Ann Berger ◽  
Kevin Kupzyk ◽  
...  
Keyword(s):  
Sleep Disturbance ◽  
Neurodevelopmental Disorders ◽  
Sleep Disturbances ◽  
Immediate Release ◽  
Sleep Time ◽  
Normative Values ◽  
Exogenous Melatonin ◽  
Contingency Contracting ◽  
Sleep Questionnaires ◽  
The Impact

Abstract Introduction: Introduction Sleep disturbances are common in adolescents with neurodevelopmental disorders (NDDs). Inclusion of vulnerable populations such as adolescents with NDDs into sleep intervention efforts is essential as they are at high-risk for poor physical/mental health outcomes. The objective of this study is to pilot a sequential, multiple assignment, randomized trial (SMART) design to compare the impact of a sequence of sleep interventions, based on treatment response, to optimize sleep health in adolescents with NDDs. Methods: Methods Recruitment began June 2019 using convenience sampling. The SMART pilot feasibility study includes 1-week of baseline sleep data, and two 4-week periods of a sleep intervention (9-week total study enrollment). Interventions include exogenous melatonin, The Bedtime Bank, and their combination. Exogenous melatonin (liquid, immediate release, 3mg) is administered 30 minutes before bedtime. The Bedtime Bank, a behavioral sleep intervention, is based upon contingency contracting that relies on a credit- or debt-based system to hold adolescents accountable for maintaining a consistent bedtime. At baseline participants completed demographics, PROMIS pediatric sleep questionnaires, the Cleveland Adolescent Sleepiness Questionnaire (CASQ), salivary & urinary endogenous melatonin measurement, and one week of actigraphy. Upon enrollment, participants were randomly assigned to either melatonin or The Bedtime Bank. Participants who respond (nightly increase in total sleep time (TST) ≥18 minutes) remain on the assigned intervention; if non-responsive participants are re-randomized to a different sleep intervention or combination. Results: Results At baseline, participants (n=29, aged 10–18 years) had an average TST of 7 hours 11 minutes. PROMIS Sleep Disturbance (M=64.3, SE=2.5), PROMIS Sleep-Related Impairment scores (M=58.9, SE=2.2), and CASQ scores (M=40.0, SD= 10.5) were higher than reported normative values. Salivary DLMO & urinary 6-sulfatoyxmelatonin analysis is ongoing. For participants who completed the full 9-week trial, nearly 30% (n=7/24) were responsive (increased baseline TST ≥18 minutes) to one of the 4-week interventions. Conclusion: Conclusion Baseline data of the enrolled participants demonstrates poor indicators of TST, sleep disturbance, and sleep related impairment. Preliminary results of this SMART indicate some adolescents are responsive to sleep interventions aimed to improve their TST. Support (if any) Support: This clinical trial is funded by the National Institute of Nursing Research, National Institutes of Health (1K01NR017465-01A1).

scholarly journals Impact of the pan-Canadian Oncology Drug Review on provincial concordance with respect to cancer drug funding decisions and time to funding

2017 ◽  
Vol 24 (5) ◽  
pp. 295 ◽  
Author(s):  
A. Srikanthan ◽  
H. Mai ◽  
N. Penner ◽  
E. Amir ◽  
A. Laupacis ◽  
...  
Keyword(s):  
Linear Models ◽  
Drug Product ◽  
Median Number ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Oncology Drug ◽  
Before And After ◽  
Canadian Provinces ◽  
The Impact ◽  
Drug Review

Background The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 to address uneven drug coverage and lack of transparency with respect to the various provincial cancer drug review processes in Canada. We evaluated the impact of the pcodr on provincial decision concordance and time from Notice of Compliance (noc) to drug funding.Methods In a retrospective review, Health Canada’s Drug Product Database was used to identify new indications for cancer drugs between January 2003 and May 2014, and provincial formulary listings for drug-funding dates and decisions between 1 January 2003 and 31 December 2014 were retrieved. Multiple linear models and quantile regressions were used to evaluate changes in time to decision-making before and after the implementation of the pcodr. Agreement of decisions between provinces was evaluated using kappa statistics.Results Data were available from 9 provinces (all Canadian provinces except Quebec), identifying 88 indications that represented 51 unique cancer drugs. Two provinces lacked available data for all 88 indications at the time of data collection. Interprovincial concordance in drug funding decisions significantly increased after the pcodr’s implementation (Brennan-Prediger coefficient: 0.54 pre-pcodr vs. 0.78 post-pcodr; p = 0.002). Nationwide, the median number of days from Health Canada’s noc date to the date of funding significantly declined (to 393 days from 522 days, p < 0.001). Exploratory analyses excluding provinces with incomplete data did not change the results.Conclusions After the implementation of the pcodr, greater concordance in cancer drug funding decisions between provinces and decreased time to funding decisions were observed.

Presence and formation of disinfection by-products in Cairo residential water supply

2009 ◽  
Vol 9 (2) ◽  
pp. 113-120 ◽  
Author(s):  
E. H. Smith ◽  
K. E. El-Deen
Keyword(s):  
Natural Organic Matter ◽  
Distribution System ◽  
Tap Water ◽  
Residential Community ◽  
Chlorine Disinfection ◽  
Sampling Program ◽  
The Impact ◽  
By Products ◽  
The U.S ◽  
Residential Water

A sampling program was conducted in a residential community in Cairo, Egypt in order to determine the presence of chlorine disinfection by-products (DBPs) in treated water and to observe the impact of the distribution system on DBP levels. Five campaigns were conducted over a 15-month period during 2005–2006. Trihalomethanes (THMs) and haloacetic acids (HAAs) exceeded local and international limits depending upon the season. Tap water concentrations of THMs were considerably higher in summer than during the rest of the year. In the Summer 2005 event, the average for the 20 tap water locations was 158 μg/l Total-THMs, well in excess of the U.S. EPA limit of 80 μg/L and the current Egyptian standard of 100 μg/l; all 20 locations exceeded the 100 μg/l limit. For the following event in late Fall 2005, the average dropped to 84 μg/l with 11 and 6 sites exceeding the U.S. EPA and Egyptian limits, respectively. HAA levels tended to be complementary to Total-THM values in that they were lower in summer but higher during fall and spring. The U.S. EPA limit on a select set of 5 HAAs (HAA5) is 60 μg/l (Egypt does not currently regulate HAAs). The average for HAA5 in the Summer 2005 event was 52 μg/l with 8 of the 20 tap samples equalling or exceeding the 60 μg/l standard. By contrast, in Fall 2005, the HAA5 average increased to 89 μg/l, with 15 of 20 sites exceeding the limit. THM and HAA concentrations generally increased with distance from the WTP along a targeted distribution main, while chlorine and natural organic matter tended to decrease.

scholarly journals Impact of Slope of Growing Trays on Productivity of Wheat Green Fodder by a Nutrient Film Technique System

Water ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3009
Author(s):  
Andrius Grigas ◽  
Aurelija Kemzūraitė ◽  
Dainius Steponavičius ◽  
Aušra Steponavičienė ◽  
Rolandas Domeika
Keyword(s):  
Light Emitting Diode ◽  
Tap Water ◽  
Slope Angle ◽  
Experimental Studies ◽  
Matter Content ◽  
Light Sources ◽  
Dry Matter Content ◽  
Nutrient Film Technique ◽  
Indoor Lighting ◽  
The Impact

Application of hydroponic systems in feed production has not been extensively studied. Therefore, there is insufficient data on the effect of the slope of hydroponic growing trays used in the nutrient film technique on wheat fodder yield and its qualitative parameters. The slope of the trays has only been studied for food crops. This study conducted experimental research using a nutrient film technique hydroponic fodder growing device to evaluate the impact of growing tray slope angle on hydroponic wheat fodder production. The slope angle of the growing trays was changed from 2.0% (1.15°) to 8.0% (4.57°) with increments of 1.5% (0.86°). This research used two different light sources for wheat sprout illumination: indoor lighting (fluorescent lamps) and light-emitting diode illumination. In addition, two nutrient solutions were used for sprout irrigation: tap water and a solution enriched with macro- and microelements. Experimental studies confirmed the hypothesis that the slope angle of growing trays significantly affects the yield of wheat fodder grown for seven days. Analyzing the results, we found that the highest yield of wheat fodder after seven days of cultivation was achieved with growing trays sloped by 6.5% and using indoor lighting. In addition, we achieved the highest wheat fodder dry matter content using a 6.5% slope angle. Experimental studies also confirmed the hypothesis that using macro- and micronutrients in the nutrient solution does not significantly affect the yield of wheat fodder grown hydroponically for seven days.

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