Short-term Dual Therapy or Mono Therapy With Acetaminophen and Ibuprofen for Fever: A Network Meta-Analysis.

CONTEXT: There is uncertainty whether acetaminophen and ibuprofen are similar in their effects and safety when used as single or dual (alternating or combined) therapies. OBJECTIVE: To assess the comparative efficacy of acetaminophen, ibuprofen alone, alternating, or combined through a systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, and CENTRAL from inception to September 20, 2023. STUDY SELECTION: Randomized trials comparing acetaminophen, ibuprofen, both alternating, and both combined, for treating children with fever. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model. RESULTS: We included 31 trials (5009 children). We found that combined (odds ratio [OR], 0.19; confidence interval [CI], 0.09-0.42) and alternating therapies (OR, 0.20; CI, 0.06-0.63) may be superior to acetaminophen, whereas ibuprofen at a high dose may be comparable (OR, 0.98; CI, 0.63-1.59) in terms of proportion of afebrile children at the fourth hour. These results were similar at the sixth hour. There were no differences between ibuprofen (low or high dose), or alternating, or combined with acetaminophen in terms of adverse events. LIMITATIONS: We only evaluated the efficacy and safety during the first 6 hours. CONCLUSIONS: Dual may be superior to single therapies for treating fever in children. Acetaminophen may be inferior to combined or alternating therapies to get children afebrile at 4 and 6 hours. Compared with ibuprofen, acetaminophen was also inferior to ibuprofen alone at 4 hours, but similar at 6 hours. PROSPERO registration: CRD42016035236.

Quercetin and ibuprofen combination displayed anti-inflammatory effects and also extenuates the enteric neurons damage of arthritic rats.

This study aimed to investigate the antioxidant and anti-inflammatory properties of quercetin on the cellular components of the Enteric Nervous System in the ileum of rats with arthritis. Rats were distributed into five groups: control (C), arthritic (AIA), arthritic treated with ibuprofen (AI), arthritic treated with quercetin (AQ) and arthritic treated with both ibuprofen and quercetin (AIQ). The ileum was processed for immunohistochemical techniques for HuC/D, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. Measurements in histological sections, chemiluminescence assays, and total antioxidant capacity were also performed. Rheumatoid arthritis resulted in a decrease in neuronal density, yet neuroplasticity mechanisms were evident through observed changes in varicosities size and neuronal area compared to the control group. Reduced paw edema and neuroprotective effects were predominantly noted in both plexuses, as evidenced by the increased density preservation of HuC/D-IR neurons in the AIQ group. The increase of lipoperoxidation levels and paw edema volume in the AQ group was observed compared to the arthritic, whereas the AIQ group mainly showed similar results to those observed in the control. The enteropathy associated with arthritis proved to be significant in the field of gastroenterology, and the combination of quercetin and ibuprofen demonstrated promising anti-inflammatory and neuroprotective effects.

Mapping trends in preemptive analgesia related to oral surgery with the use of Ibuprofen: a comprehensive quantitative and qualitative analysis of bibliometric parameters.

PURPOSE: This study aims to conduct a thorough analysis, both quantitative and qualitative, of bibliometric parameters related to preemptive analgesia (PA) in oral surgical procedures (OSP). METHODS: Research trends on PA in OSP using ibuprofen were reviewed through bibliometric analysis of 68 journal articles published from 1991 to 2022 in the Web of Science database. Bibliometric indicators were applied to analyze the journal article data, including the annual distribution of publications and literature growth, document types, citation indicators to measure qualitative research performance, and keyword mapping to identify research trends. The results were imported into RStudio, and the Bibliometrix package was used to prepare and analyze the metadata. RESULTS: The 68 included articles received a total of 900 citations, ranging from 1 source to 72 citations with some fluctuations. The papers on PA in OSP using ibuprofen had an average of 16.85 citations per paper. These publications were originated from 25 countries, with the highest contributions from Brazil (n = 17), the USA (n = 13), and Turkey (n = 8). The top five major contributing journals were the International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, Journal of Cranio-Maxillo-Facial Surgery, Journal of Periodontology, and Acta Odontologica Scandinavica, representing more than half of all selected papers. CONCLUSION: Papers focused on PA in OSP received numerous citations. The citation per article correlated with the number of publications at the affiliation, author, country, and journal levels. However, there is still a scarcity of studies in this field.

Comparative effectiveness of preemptive administration of ibuprofen and ibuprofen-arginine on the anesthetic success of inferior alveolar nerve block in teeth with symptomatic irreversible pulpitis - A double-blind randomized clinical trial.

OBJECTIVES: This study examined the impact of premedication with ibuprofen and ibuprofen-arginine and the influence of preoperative pain and anxiety on inferior alveolar nerve block (IANB) efficacy in cases of symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study involved 150 SIP patients who were randomly assigned to receive ibuprofen (600 mg), ibuprofen-arginine (1,155 mg), or a placebo 30 min before IANB. Preoperative anxiety and pain levels were assessed using the Modified Dental Anxiety Scale and the Heft-Parker visual scale. IANB efficacy was determined by the absence of or mild pain during the procedure. Statistical analysis included chi-square, z-tests, Analysis of Variance, and Student's t tests. RESULTS: The ibuprofen and ibuprofen-arginine groups exhibited significantly higher IANB success rates (62% and 78%, respectively) compared to the placebo group (34%). However, no significant difference was observed between the ibuprofen and ibuprofen-arginine groups. Patients with successful IANB in the ibuprofen and ibuprofen-arginine groups displayed lower median anxiety scores (8) than those with failed blocks (15) and lower mean preoperative pain scores (118.3). CONCLUSION: In cases of symptomatic irreversible pulpitis the preemptive medication with ibuprofen-arginine effectively increased the efficacy of the inferior alveolar nerve block The inferior alveolar nerve block efficacy was influenced by preoperative anxiety levels and the intensity of pain. CLINICAL RELEVANCE: This research underscores the potential benefits of oral premedication with ibuprofen and ibuprofen-arginine in improving anesthesia outcomes in cases of symptomatic irreversible pulpitis.

Investigating the pharmacological potential of phytol on experimental models of gastric ulcer in rats.

Phytol is a diterpene constituent of many essential oils, belonging to the group of unsaturated acyclic alcohols. Although phytol possesses antimycobacterial and anti-inflammatory effects, no reports of a gastrointestinal action are available from the literature. Due to the well-known shortcomings of classical anti-ulcer drugs (e.g. side effects or relapses), natural products may offer an attractive alternative. In this study, a potential gastroprotective activity of phytol was evaluated using acute and chronic ulcer models in rats. Phytol 12.5, 25 and 50 mg/kg, administered orally 1 h prior to induction of gastric lesions by absolute ethanol, inhibited the lesion area by 96, 90 and 95%, respectively. When lesions were induced by ischemia and reperfusion, phytol 12.5 and 25 mg/kg per os decreased the lesion areas by 89 and 46%, respectively. In the third acute ulcer model (lesions induced by ibuprofen), phytol 12.5 mg/kg reduced the lesion area by 55%. Phytol restored the decreased level of reduced glutathione, the increased levels of myeloperoxidase and malondialdehyde and the decreased levels of catalase and superoxide dismutase in rats with gastric ulcer induced by ethanol to levels obtained in vehicle group. Finally, in a chronic model in which gastric ulcer was induced by acetic acid directly instilled into the stomach, phytol administered orally over a time period of 7 days at 12.5, 25, 50 and 100 mg/kg reduced lesion areas by 84, 81, 83 and 68%. Our data suggest a gastroprotective and cicatrizing effect of phytol, possibly associated with its antioxidant effect.

Unveiling the potential of machine learning in cost-effective degradation of pharmaceutically active compounds: A stirred photo-reactor study.

In this study, neural networks and support vector regression (SVR) were employed to predict the degradation over three pharmaceutically active compounds (PhACs): Ibuprofen (IBP), diclofenac (DCF), and caffeine (CAF) within a stirred reactor featuring a flotation cell with two non-concentric ultraviolet lamps. A total of 438 datapoints were collected from published works and distributed into 70% training and 30% test datasets while cross-validation was utilized to assess the training reliability. The models incorporated 15 input variables concerning reaction kinetics, molecular properties, hydrodynamic information, presence of radiation, and catalytic properties. It was observed that the Support Vector Regression (SVR) presented a poor performance as the ε hyperparameter ignored large error over low concentration levels. Meanwhile, the Artificial Neural Networks (ANN) model was able to provide rough estimations on the expected degradation of the pollutants without requiring information regarding reaction rate constants. The multi-objective optimization analysis suggested a leading role due to ozone kinetic for a rapid degradation of the contaminants and most of the results required intensification with hydrogen peroxide and Fenton process. Although both models were affected by accuracy limitations, this work provided a lightweight model to evaluate different Advanced Oxidation Processes (AOPs) by providing general information regarding the process operational conditions as well as know molecular and catalytic properties.

UiO-66(Zr) as drug delivery system for non-steroidal anti-inflammatory drugs.

The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile accessibility to the population. New drug delivery systems (DDS) are necessary to overcome the bioavailability and toxicity related to NSAIDs. In this context, UiO-66(Zr) metal-organic framework (MOF) shows high porosity, stability, and load capacity, thus being a promising DDS. However, the adsorption and release capability for different NSAIDs is scarcely described. In this work, the biocompatible UiO-66(Zr) MOF was used to study the adsorption and release conditions of ibuprofen, naproxen, and diclofenac using a theoretical and experimental approximation. DFT results showed that the MOF-drug interaction was due to an intermolecular hydrogen bond between protons of the groups in the defect sites, (µ3 - OH, and - OH2) and a lone pair of oxygen carboxyl functional group of the NSAIDs. Also, the experimental results suggest that the solvent where the drug is dissolved affects the adsorption process. The adsorption kinetics are similar between the drugs, but the maximum load capacity differs for each drug. The release kinetics assay showed a solvent dependence kinetics whose maximum liberation capacity is affected by the interaction between the drug and the material. Finally, the biological assays show that none of the systems studied are cytotoxic for HMVEC. Additionally, the wound healing assay suggests that the UiO-66(Zr) material has potential application on the wound healing process. However, further studies should be done.

Environmental risk assessment of pharmaceutical pollutants in the Oro River Sub-basin (Colombia).

Pharmaceuticals and Personal Care Compounds (PPCPs) are contaminants present in wastewater and in the receiving surface waters, which have no regulations and can bring on environmental risks. In this study, we evaluated the presence of six PPCPs in the Oro River Sub-basin (Colombia) and the environmental risk associated with them. We have verified that the monitored rivers show the presence of Ibuprofen, Cephalexin and Carbamazepine; the first ones (Ibuprofen and cephalexin) were those that presented higher concentrations since they are widely prescribed in Colombia. Pharmaceutical compound concentrations in the rivers downstream of the wastewater treatment plants from Floridablanca were higher than in other monitoring sites being a significant point source of contamination. This wastewater treatment plant receives hospital discharges from the city, including internationally recognized clinics accepting patients from different parts of the country. The environmental risk assessment showed that ibuprofen and Cephalexin have a higher impact on aquatic organisms.

Role for Carboxylic Acid Moiety in NSAIDs: Favoring the Binding at Site II of Bovine Serum Albumin.

The molecular structures of nonsteroidal anti-inflammatory drugs (NSAIDs) vary, but most contain a carboxylic acid functional group (RCOOH). This functional group is known to be related to the mechanism of cyclooxygenase inhibition and also causes side effects, such as gastrointestinal bleeding. This study proposes a new role for RCOOH in NSAIDs: facilitating the interaction at the binding site II of serum albumins. We used bovine serum albumin (BSA) as a model to investigate the interactions with ligands at site II. Using dansyl-proline (DP) as a fluorescent site II marker, we demonstrated that only negatively charged NSAIDs such as ibuprofen (IBP), naproxen (NPX), diflunisal (DFS), and ketoprofen (KTP) can efficiently displace DP from the albumin binding site. We confirmed the importance of RCOO by neutralizing IBP and NPX through esterification, which reduced the displacement of DP. The competition was also monitored by stopped-flow experiments. While IBP and NPX displaced DP in less than 1 s, the ester derivatives were ineffective. We also observed a higher affinity of negatively charged NSAIDs using DFS as a probe and ultrafiltration experiments. Molecular docking simulations showed an essential salt bridge between the positively charged residues Arg409 and Lys413 with RCOO-, consistent with the experimental findings. We performed a ligand dissociation pathway and corresponding energy analysis by applying molecular dynamics. The dissociation of NPX showed a higher free energy barrier than its ester. Apart from BSA, we conducted some experimental studies with human serum albumin, and similar results were obtained, suggesting a general effect for other mammalian serum albumins. Our findings support that the RCOOH moiety affects not only the mechanism of action and side effects but also the pharmacokinetics of NSAIDs.

Effects of major analgesics on male fertility: A systematic literature review.

OBJECTIVE: To verify, based on a systematic literature review, the effects of the main analgesics on male fertility. DATA SOURCES: The studies were analyzed from the PubMed, SciELO and LILACS databases. STUDY SELECTION: The articles selected for the present review included: cohort studies; cross-sectional studies, clinical trials; complete studies; studies with animal models that addressed the proposed theme and that were published within the stipulated period from March 1, 2013, to March 31, 2023, in English, Portuguese and Spanish. These would later have to go through inclusion stages such as framing the type of study and exclusion criteria. DATA COLLECTION: Author's name, year of publication, study population, number of patients, analgesic, administration time, dose, and effect. CONCLUSIONS: There are in vitro and in vivo studies that link paracetamol and ibuprofen to endocrine and seminal changes that are harmful to male fertility. However, more clinical research is needed to determine the doses and timing of administration that affect fertility. The effects of aspirin on male fertility are still unclear due to the lack of studies and consistent methodologies. There is not enough research on dipyrone and its relationship with male fertility, requiring more studies in this area.

Prednisone and ibuprofen conjugate Janus dendrimers and their anticancer activity.

Drug release from hyperbranched Janus dendrimer-drug conjugates and their subsequent activity are influenced by the different drugs in each dendron and the linker. To understand these effects, we synthetized new Janus-type dendrimers of first and second generation. One dendron with 2,2-Bis(hydroxymethyl)propionic acid functionalized with ibuprofen and the second dendron was obtained with 3-aminopropanol-amidoamine and prednisone. The dendrimers were obtained by copper(I)-catalyzed Click azide-alkyne cycloaddition for the formation of a triazole as a dendrimeric nucleus of Janus dendrimer conjugates are reported. The influence of ibuprofen, prednisone, and spacer on cancer activity of Janus dendrimers conjugates is reported. The IC50 values of the anticancer activity on cancer cell lines the Janus dendrimer of second generation was higher in comparison to the first generation dendrimer. Similarly, the anticancer activity was higher compared to the dendron conjugates. Also, no cytotoxic effects of dendrons and dendrimers on non-cancerous kidney COS-7 cell line was observed. The interesting anticancer activity of the prepared prednisone-ibuprofen Janus dendrimer conjugates suggest that the dendrimers could be of potential use as new anticancer drug.

Effect of topical application of ibuprofen/arginine on the in-office bleaching-induced tooth sensitivity: A randomized, triple-blind controlled trial.

OBJECTIVE: The application of anti-inflammatories as topical desensitizers before dental bleaching is an approach to reduce bleaching-induced tooth sensitivity (TS). This randomized controlled trial compared the risk and intensity of TS and the color change resulting from in-office dental bleaching after using an experimental desensitizing gel containing ibuprofen and arginine. METHODS: Sixty-two participants with upper canine shades A2 or darker were randomly assigned to either the ibuprofen-arginine desensitizing group or the placebo group. The desensitizing gel was applied for 15 min before in-office bleaching with 35 % hydrogen peroxide gel for 50 min (2 sessions). To assess the absolute risk and intensity of TS, visual (0-10) and numeric rating (0-5) scales were used, and group comparisons were made using the McNemar test, Wilcoxon test, and paired Student t-test (α = 0.05). Color change was evaluated using Vita Classical, Vita Bleachedguide (ΔSGU), and Vita EasyShade (ΔEab, ΔE00, and ΔWID) before and one month after the bleaching procedure. Group comparisons for color change were done using a paired t-test (α = 0.05). RESULTS: The odds ratio for TS was 0.14 [95 % CI 0.02 to 0.6], meaning lower odds of TS for the desensitizing gel. A lower intensity of TS was also observed for the experimental group (p < 0.005) up to 48 h after bleaching. All color evaluation tools demonstrated effective and similar whitening for both groups (p > 0.05). CONCLUSIONS: Using the experimental desensitizing gel containing ibuprofen and arginine effectively reduced the risk and intensity of TS without compromising the bleaching efficacy. CLINICAL RELEVANCE: The topical application of ibuprofen/arginine on the in-office bleaching reduced risk and intensity of bleaching-induced tooth sensitivity.

Compounds Consisting of Quinazoline, Ibuprofen, and Amino Acids with Cytotoxic and Anti-Inflammatory Effects.

In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) and cyclooxygenase-2 (COX-2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A-431, MCF-7, MDA-MB-231) and epithelial non-tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC50) than gefitinib (reference drug) on three cancer cell lines (0.034 µM in A-431, 2.67 µM in MCF-7, and 3.64 µM in AGS) without showing activity on the non-tumorigenic cell line (>100 µM). Furthermore, assessment of EGFR-TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an in vivo anti-inflammatory assay using the 12-O-tetradecanoylphorbol-3-acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR-TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX-2, involving S531. The RMSD graph indicated that the ligand remained stable in 50 ns.

Activated carbon from avocado seed as sorbent phase for microextraction technologies: activation, characterization, and analytical performance.

According to green analytical chemistry principles, the use of agricultural byproducts as sorbent phases is an interesting topic due to their lignocellulosic origin, as they are biodegradable and inexpensive. To the best of our knowledge, this is the first study in which avocado seed and avocado seed activated carbon are proposed as sustainable sorbents for solid-phase microextraction technologies, which were used to assess the proof of concept. Rotating disk sorptive extraction (RDSE) was used as a model technology and ibuprofen (Ibu) and 1-hydroxy-ibuprofen (1-OH-Ibu) as representative analytes. It was found that activated carbon (AC) prepared at 600 °C with an impregnation ratio (raw material/activating agent (ZnCl2), w/w) of 1:1.2 had better extraction efficiency than other ACs obtained at different temperatures, impregnation ratios, and activating agents (K2CO3). Characterization revealed several differences between natural avocado seed, biochar prepared at 600 °C, and selected AC since the typical functional groups of the natural starting material begin to disappear with pyrolysis and increasing the surface area and pore volume, suggesting that the main interactions between analytes and the sorbent material are pore filling and π-π stacking. By using this AC as the sorbent phase, the optimal extraction conditions in RDSE were as follows: the use of 50 mg of sorbent in the disk, 30 mL of sample volume, pH 4, 90 min of extraction time at a rotation velocity of the disk of 2000 rpm, and methanol as the elution solvent. The extracts were analyzed via gas chromatography coupled to mass spectrometry (GC-MS). The method provided limits of detection of 0.23 and 0.07 µg L-1 and recoveries of 81% and 91% for Ibu and 1-OH-Ibu, respectively. When comparing the extraction efficiency of the selected activated carbon with those provided by Oasis® HLB and C18 in RDSE, nonsignificant differences were observed, indicating that avocado seed activated carbon is a suitable alternative to these commercial materials.

Neuromodulation of Acid-Sensitive Ion Channels (ASICs) and Anti-Inflammatory Potential by Lichenxanthone in Adult Zebrafish (Danio rerio): Experimental and Docking Studies.

The xanthone lichenxanthone did not show toxic effects (LC50>1.0 mg/mL). lichenxanthone prevented nociceptive behavior induced by acidic saline, and its analgesic effect was blocked by amiloride, highlighting the involvement of neuromodulation of acid-sensitive ion channels (ASICs). In the analysis of anti-inflammatory activity, concentrations of 0.1 and 0.5 mg/mL of lichenxanthone reduced the edema induced by k-carrageenan 3.5 %, observed from the fourth hour of analysis. This effect was similar to that observed with ibuprofen (positive control). No leukocyte infiltrates were observed in lichenxanthone, suggesting that the compound acts in the acute inflammatory response. The results of the molecular docking study revealed that lichenxanthone exhibited better affinity energy when compared to the ibuprofen control against the two targets evaluated.

Green Synthesis of Er-Doped ZnO Nanoparticles: An Investigation on the Methylene Blue, Eosin, and Ibuprofen Removal by Photodegradation.

We present a study on the green synthesis of undoped and Er-doped ZnO compounds using Mangifera indica gum (MI). A set of tests were conducted to assess the structure of the material. The tests included X-ray diffraction, Raman, and Fourier-transform infrared spectroscopy. Optical properties were studied using diffuse reflectance and photoluminescence. Morphological and textural investigations were done using SEM images and N2 adsorption/desorption. Furthermore, photocatalytic tests were performed with methylene blue (MB), yellow eosin (EY), and the pharmaceutical drug ibuprofen (IBU) under UV irradiation. The study demonstrated that replacing the stabilizing agent with Mangifera indica gum is an effective method for obtaining ZnO nanoparticles. Additionally, the energy gap of the nanoparticles exhibits a slight reduction in value. Photoluminescence studies showed the presence of zinc vacancies and other defects in both samples. In the photocatalytic test, the sample containing Er3+ exhibited a degradation of 99.7% for methylene blue, 81.2% for yellow eosin, and 52.3% for ibuprofen over 120 min. In the presence of methyl alcohol, the degradation of MB and EY dyes is 16.7% and 55.7%, respectively. This suggests that hydroxyl radicals are responsible for the direct degradation of both dyes. In addition, after the second reuse, the degradation rate for MB was 94.08%, and for EY, it was 82.35%. For the third reuse, the degradation rate for MB was 97.15%, and for EY, it was 17%. These results indicate the significant potential of the new semiconductor in environmental remediation applications from an ecological synthesis.

Nociceptive and histomorphometric evaluation of the effects of ozone therapy on the rat masseter muscle in a carrageenan model of myofascial pain.

OBJECTIVE: This study evaluated the effects of intramuscular ozone therapy on nociception, inflammation, and tissue damage caused by the injection of carrageenan in the masseter muscle of rats. DESIGN: Rat masseter muscles were injected with saline or carrageenan. Seventy-seven adult male rats were divided into six groups: Sal, saline; Car, carrageenan; Ibup + Sal, ibuprofen and saline; Ibup + Car, ibuprofen and carrageenan; O3 + Sal, ozone and saline; and O3 + Car, ozone and carrageenan. The mixture of 5% ozone and 95% oxygen (20 µg/mL) was administered three times in the course of a week. Nociceptive responses in the masseter muscles were measured using a head withdrawal threshold, determined by an electronic von Frey anesthesiometer. The animals were euthanized one or eight days after the carrageenan injection, and the masseters were submitted to histological and histomorphometric analyses. RESULTS: Mechanical allodynia and inflammation levels were reduced in the Ibup + Car group compared to the other groups. Myonecrosis was similar among carrageenan-treated groups. Picrosirius red stained sections showed more collagen fibers and more regenerating myofibers in the O3 + Car group compared to the other groups. Eight days after carrageenan injection, the O3 + Car group showed neutrophils close to the regenerating myofibers. CONCLUSIONS: Intramuscular ozone therapy did not alleviate mechanical allodynia, and it did not protect the masseter muscle against the deleterious effects produced by carrageenan, probably due to the mode of administration of this therapeutic agent.

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients.

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning process was performed using 3.0 kg of Prosolv® and 3.0 kg of Tablettose® 70. The impact of different volumetric feed rates of the cleaning excipient was assessed. The displacement of API and blend residues was evaluated with in-line near infrared (NIR) spectroscopy. Principal component analysis (PCA) was performed to evaluate the cleaning progress as the Prosolv® flowed through the feeder, mixer and stream sampler. In-place Raman spectra were acquired from the material sticking to detect the ibuprofen residues. The study showed that Prosolv® and Tablettose® can remove ibuprofen residues effectively from the hopper, feeder screw, mixer paddles, shaft and stream sampler. The Process Analytical Technology (PAT) system can be utilized to detect API displacement during the cleaning process. However, dismantling and manual cleaning was required to remove material sticking at the surfaces adjacent to the rotating feeder screws and mixer paddles.

Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network.

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.