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Yakugaku Zasshi : Journal of the... 2019Dynamic light scattering (DLS) is used for measuring average particle diameter and particle diameter distribution of nano-sized particles dispersed in liquid. The... (Review)
Review
Dynamic light scattering (DLS) is used for measuring average particle diameter and particle diameter distribution of nano-sized particles dispersed in liquid. The parameters are important characteristics mainly for drug delivery system (DDS) formulations, such as solid in oil (S/O) formulations, liposome formulations, suspension formulations, and emulsion formulations. Herein are described a measurement method and measurement case of particle diameter analysis of medical products using laser light.
Topics: Drug Compounding; Drug Delivery Systems; Dynamic Light Scattering; Emulsions; Liposomes; Nanoparticles; Oils; Particle Size; Pharmacopoeias as Topic; Suspensions
PubMed: 30713234
DOI: 10.1248/yakushi.18-00171-1 -
Clinical Gastroenterology and... Jul 2022We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
We evaluated treatment withdrawal, long-term outcomes, and safety of budesonide oral suspension (BOS) 2.0 mg twice daily in patients with eosinophilic esophagitis who completed a 12-week induction study.
METHODS
Induction full responders (≤6 eosinophils per high-power field [eos/hpf] and ≥30% reduction in the Dysphagia Symptom Questionnaire score) to BOS 2.0 mg twice daily (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS-BOS) or withdraw to placebo (BOS-PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial responders and nonresponders, and patients who received induction placebo, received BOS for 36 weeks. The primary end point was the proportion of BOS-BOS and BOS-PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia [Dysphagia Symptom Questionnaire] over 2 weeks) by week 36. The key secondary end point was the proportion of induction partial responders and nonresponders who fully responded after 52 weeks of total BOS therapy. Other secondary end points included the proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes.
RESULTS
The randomized withdrawal period enrolled 48 patients (BOS-BOS, n = 25; BOS-PBO, n = 23); 106 induction partial responders and nonresponders, and 65 induction placebo patients received BOS. More BOS-PBO than BOS-BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P = .131) and had histologic responses at week 12 of therapy (P < .001). Overall, 13.2% of induction partial responders and nonresponders fully responded at week 36. BOS was well tolerated; therapy duration was not associated with new safety concerns.
CONCLUSIONS
For induction full responders, continuing BOS numerically improved maintenance of efficacy vs withdrawal. A longer therapy duration did not raise safety concerns. (ClinicalTrials.gov: NCT02736409.).
Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Deglutition Disorders; Double-Blind Method; Enteritis; Eosinophilia; Eosinophilic Esophagitis; Gastritis; Humans; Suspensions; Treatment Outcome
PubMed: 34182150
DOI: 10.1016/j.cgh.2021.06.020 -
Academic Pediatrics Aug 2022Individual-, school-, and neighborhood-level support and connectedness may help to mitigate against school suspensions, which have profound health and social...
INTRODUCTION
Individual-, school-, and neighborhood-level support and connectedness may help to mitigate against school suspensions, which have profound health and social consequences. Most research on social connectedness and suspension has focused only on school connectedness, and much less is known about the effects of individual social support and neighborhood-level connectedness on suspension.
METHODS
We examined associations between all three levels of connectedness and suspension in a cross-sectional analysis of a population-based youth sample in Allegheny County, Pennsylvania. The Healthy Allegheny Teen Survey, a county-wide survey of 1813 male and female youth ages 14 to 19, assessed health risk/protective behaviors through random-digit-dialing in 2014. This survey included validated items evaluating each type of support as well as items assessing lifetime history of suspension. Logistic regression models examined associations between suspension and social support, school connectedness, and neighborhood-level cohesion.
RESULTS
In fully adjusted logistic regression models examining associations between suspension and each type of support, youth with high social support had 0.38 times the odds of school suspension compared to youth with low social support (95% confidence interval [CI] 0.19-0.74). High levels of school connectedness and neighborhood-level cohesion were also associated with significantly lower odds of suspension (odds ratio [OR] 0.31, 95% CI 0.18-0.53; OR 0.28, 95% CI 0.16-0.47, respectively). Examining all 3 types of support jointly, school connectedness and neighborhood-level cohesion were significantly inversely related to suspension (OR 0.41, 95% CI 0.24-0.71; OR 0.41, 95% CI 0.23-0.74, respectively).
CONCLUSIONS
Programs that foster connectedness at the individual-, school-, and neighborhood-level may help reduce school suspension.
Topics: Adolescent; Cross-Sectional Studies; Female; Humans; Male; Schools; Social Support; Students; Suspensions; Young Adult
PubMed: 34929388
DOI: 10.1016/j.acap.2021.12.016 -
Asia-Pacific Journal of Ophthalmology...Retinal pigment epithelium (RPE) transplants rescue photoreceptors in selected animal models of retinal degenerative disease. Early clinical studies of RPE transplants... (Review)
Review
Retinal pigment epithelium (RPE) transplants rescue photoreceptors in selected animal models of retinal degenerative disease. Early clinical studies of RPE transplants as treatment for age-related macular degeneration (AMD) included autologous and allogeneic transplants of RPE suspensions and RPE sheets for atrophic and neovascular complications of AMD. Subsequent studies explored autologous RPE-Bruch membrane-choroid transplants in patients with neovascular AMD with occasional marked visual benefit, which establishes a rationale for RPE transplants in late-stage AMD. More recent work has involved transplantation of autologous and allogeneic stem cell-derived RPE for patients with AMD and those with Stargardt disease. These early-stage clinical trials have employed RPE suspensions and RPE monolayers on biocompatible scaffolds. Safety has been well documented, but evidence of efficacy is variable. Current research involves development of better scaffolds, improved modulation of immune surveillance, and modification of the extracellular milieu to improve RPE survival and integration with host retina.
Topics: Angiogenesis Inhibitors; Animals; Humans; Retinal Pigment Epithelium; Suspensions; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration
PubMed: 36041145
DOI: 10.1097/APO.0000000000000521 -
Advanced Healthcare Materials Apr 2022The extrusion printing of inks into suspension baths is an exciting tool, as it allows the printing of diverse and soft hydrogel inks into 3D space without the need for...
The extrusion printing of inks into suspension baths is an exciting tool, as it allows the printing of diverse and soft hydrogel inks into 3D space without the need for layer-by-layer fabrication. However, this printing process is complex and there have been limited studies to experimentally and computationally characterize the process. In this work, hydrogel inks (i.e., gelatin methacrylamide (GelMA)), suspension baths (i.e., agarose, Carbopol), and the printing process are examined via rheological, computational, and experimental analyses. Rheological data on various hydrogel inks and suspension baths is utilized to develop computational printing simulations based on Carreau constitutive viscosity models of the printing of inks within suspension baths. These results are then compared to experimental outcomes using custom print designs where features such as needle translation speed, defined in this work as print speed, are varied and printed filament resolution is quantified. Results are then used to identify print parameters for the printing of a GelMA ink into a unique guest-host hyaluronic acid suspension bath. This work emphasizes the importance of key rheological properties and print parameters for suspension bath printing and provides a computational model and experimental tools that can be used to inform the selection of print settings.
Topics: Baths; Bioprinting; Computer Simulation; Gelatin; Hydrogels; Ink; Printing, Three-Dimensional; Suspensions
PubMed: 34699689
DOI: 10.1002/adhm.202101679 -
Journal of Pediatric Gastroenterology... Dec 2023The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE).
OBJECTIVES
The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE).
METHODS
This post hoc analysis pooled data from two 12-week, randomized, double-blind, placebo-controlled studies of BOS 2.0 mg twice daily (b.i.d.) (phase 2, NCT01642212; phase 3, NCT02605837) in patients aged 11-17 years with EoE and dysphagia. Efficacy endpoints included histologic (≤6, ≤1, and <15 eosinophils per high-power field [eos/hpf]), dysphagia symptom (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] scores from baseline), and clinicopathologic (≤6 eos/hpf and ≥30% reduction in DSQ scores from baseline) responses at week 12. Change from baseline to week 12 in peak eosinophil counts, DSQ scores, EoE Histology Scoring System (EoEHSS) grade (severity) and stage (extent) total score ratios (TSRs), and total EoE Endoscopic Reference Scores (EREFS) were assessed. Safety outcomes were also examined.
RESULTS
Overall, 76 adolescents were included (BOS, n = 45; placebo, n = 31). Significantly more patients who received BOS than placebo achieved histologic responses (≤6 eos/hpf: 46.7% vs 6.5%; ≤1 eos/hpf: 42.2% vs 0.0%; <15 eos/hpf: 53.3% vs 9.7%; P < 0.001) and a clinicopathologic response (31.1% vs 3.2%; P = 0.003) at week 12. More BOS-treated than placebo-treated patients achieved a dysphagia symptom response at week 12 (68.9% vs 58.1%; not statistically significant P = 0.314). BOS-treated patients had significantly greater reductions in EoEHSS grade and stage TSRs ( P < 0.001) and total EREFS ( P = 0.021) from baseline to week 12 than placebo-treated patients. BOS was well tolerated, with no clinically meaningful differences in adverse events versus placebo.
CONCLUSIONS
BOS 2.0 mg b.i.d. significantly improved most efficacy outcomes in adolescents with EoE versus placebo.
Topics: Adolescent; Humans; Budesonide; Deglutition Disorders; Eosinophilic Esophagitis; Esophagoscopy; Suspensions; Treatment Outcome; Child; Randomized Controlled Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic
PubMed: 37718471
DOI: 10.1097/MPG.0000000000003948 -
Antimicrobial Agents and Chemotherapy Jul 2023Invasive fungal infections are a major cause of morbidity and mortality for immunocompromised patients. Posaconazole is approved for treatment and prophylaxis of...
Model Based Estimation of Posaconazole Tablet and Suspension Bioavailability in Hospitalized Children Using Real-World Therapeutic Drug Monitoring Data in Patients Receiving Intravenous and Oral Dosing.
Invasive fungal infections are a major cause of morbidity and mortality for immunocompromised patients. Posaconazole is approved for treatment and prophylaxis of invasive fungal infection in adult patients, with intravenous, oral suspension, and gastroresistant/delayed-released tablet formulations available. In Europe, until very recently, posaconazole was used off-label in children, although a new delayed-release suspension approved for pediatric use is expected to become available soon. A population pharmacokinetic model was developed which uses posaconazole therapeutic drug monitoring data following intravenous and oral dosing in hospitalized children, thus enabling estimation of pediatric suspension and tablet oral bioavailability. In total, 297 therapeutic drug monitoring plasma levels from 104 children were included in this analysis. The final model was a one-compartment model with first-order absorption and nonlinear elimination. Allometric scaling on clearance and volume of distribution was included . Tablet bioavailability was estimated to be 66%. Suspension bioavailability was estimated to decrease with increasing doses, ranging from 3.8% to 32.2% in this study population. Additionally, concomitant use of proton pump-inhibitors was detected as a significant covariate, reducing suspension bioavailability by 41.0%. This is the first population pharmacokinetic study to model posaconazole data from hospitalized children following intravenous, tablet, and suspension dosing simultaneously. The incorporation of saturable posaconazole clearance into the model has been key to the credible joint estimation of tablet and suspension bioavailability. To aid rational posaconazole dosing in children, this model was used alongside published pharmacodynamic targets to predict the probability of target attainment using typical pediatric dosing regimen.
Topics: Adult; Humans; Child; Antifungal Agents; Child, Hospitalized; Biological Availability; Drug Monitoring; Administration, Oral; Invasive Fungal Infections; Tablets; Suspensions
PubMed: 37260401
DOI: 10.1128/aac.00077-23 -
International Journal of Pharmaceutical... 2021Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be... (Review)
Review
Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be individualized in the treatment of trichomoniasis, in patients with hepatic impairment, and in pediatric as well as geriatric patients. A review of the therapeutic uses of metronidazole reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of metronidazole currently exists. Metronidazole is commercially available only as 250-mg and 500-mg film-coated tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded metronidazole suspensions in PCCA SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two metronidazole concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatographic assay for the determination of the chemical stability of metronidazole in PCCA SuspendIt was developed and validated. Suspensions of metronidazole were prepared in PCCA SuspendIt at 25-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5ÆC and 25ÆC). Samples were assayed initially and on the following time points (days): 7, 14, 28, 42, 59, 90, 122, and 180. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was also tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that metronidazole concentrations did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values also did not change significantly. This study demonstrates that metronidazole is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for metronidazole in a liquid dosage form, with an extended beyond-use-date to meet patient needs.
Topics: Administration, Oral; Aged; Child; Chromatography, High Pressure Liquid; Chromones; Drug Compounding; Drug Stability; Drug Storage; Humans; Metronidazole; Suspensions
PubMed: 33798117
DOI: No ID Found -
Proceedings of the National Academy of... Aug 2022Airborne transmission occurs through droplet-mediated transport of viruses following the expulsion of an aerosol by an infected host. Transmission efficiency results...
Airborne transmission occurs through droplet-mediated transport of viruses following the expulsion of an aerosol by an infected host. Transmission efficiency results from the interplay between virus survival in the drying droplet and droplet suspension time in the air, controlled by the coupling between water evaporation and droplet sedimentation. Furthermore, droplets are made of a respiratory fluid and thus, display a complex composition consisting of water and nonvolatile solutes. Here, we quantify the impact of this complex composition on the different phenomena underlying transmission. Solutes lead to a nonideal thermodynamic behavior, which sets an equilibrium droplet size that is independent of relative humidity. In contrast, solutes do not significantly hinder transport due to their low initial concentration. Realistic suspension times are computed and increase with increasing relative humidity or decreasing temperature. By uncoupling drying and suspended stages, we observe that enveloped viruses may remain infectious for hours in dried droplets. However, their infectivity decreases with increasing relative humidity or temperature after dozens of minutes. Examining expelled droplet size distributions in the light of these results leads to distinguishing two aerosols. Most droplets measure between 0 and 40 µm and compose an aerosol that remains suspended for hours. Its transmission efficiency is controlled by infectivity, which decreases with increasing humidity and temperature. Larger droplets form an aerosol that only remains suspended for minutes but corresponds to a much larger volume and thus, viral load. Its transmission efficiency is controlled by droplet suspension time, which decreases with increasing humidity and decreasing temperature.
Topics: Humans; Humidity; Respiratory Aerosols and Droplets; Suspensions; Virus Diseases; Water
PubMed: 35930663
DOI: 10.1073/pnas.2204593119 -
BioMed Research International 2021Management of diarrhea has evolved over the years from relatively inadequate interventions in the early years to more successful physiological approaches. The use of...
Management of diarrhea has evolved over the years from relatively inadequate interventions in the early years to more successful physiological approaches. The use of herbal medicinal products and supplements has grown significantly over the past three decades, with more than half of the global population depending on it for some aspect of their primary health care needs. This study is aimed at formulating solid and liquid oral dosage forms of the ethanolic extract of seeds for the treatment of diarrhea. The flow property of the dried ethanolic extract was determined and subsequently formulated into granules for encapsulation. The ethanolic extract was also used in formulating an oral suspension. Pharmacopeia tests such as uniformity of weight, disintegration, drug content, and dissolution were carried out on the formulated capsules. The formulated suspension was also assessed using the following parameters; viscosity, flow rate, drug content, dissolution, sedimentation rate, and sedimentation volume. The dried ethanolic extract and formulated granules exhibited good flow properties. The formulated capsules exhibited optimal release of extract (>90% after 45 minutes) and passed the uniformity of weight, disintegration, and drug content tests. The formulated suspension also passed the drug content test and had a good sedimentation rate, sedimentation volume, and flow rate. The formulated suspension also exhibited pseudoplastic flow, optimal viscosity, and a good release profile (>90% after 45 minutes). Capsules and suspension of the ethanolic extract of seeds have been successfully formulated and can be used as standard dosage forms for the management of diarrhea.
Topics: Administration, Oral; Capsules; Cola; Diarrhea; Drug Compounding; Ethanol; Hydrogen-Ion Concentration; Plant Extracts; Rheology; Rotation; Seeds; Suspensions; Time Factors; Viscosity
PubMed: 34307662
DOI: 10.1155/2021/6630449