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Pharmaceutics Jun 2024The present study compared vacuum drum drying (VDD) and conventional spray drying (SD) for solidifying crystalline ABT-199 nanosuspensions into redispersible oral drug...
The present study compared vacuum drum drying (VDD) and conventional spray drying (SD) for solidifying crystalline ABT-199 nanosuspensions into redispersible oral drug products. The aim was to optimize formulation compositions and process conditions to maintain nanoparticle size after tablet redispersion. The impact of drug load (22%, 33%, 44%) and type of drying protectant (mannitol, mannitol/trehalose mix (1:1), trehalose) on redispersibility and material powder properties were investigated. Moreover, compression analysis was performed assessing the influence of compaction pressure on primary nanocrystal redispersibility and tablet disintegration. Higher drug loads and lower drying protectant levels resulted in particle growth, confirming a drug load dependence on redispersibility behavior. Notably, all drying protectants showed similar protection properties at properly chosen drying process parameters (-dependent), except when VDD was used for mannitol formulations. Differences between the applied drying processes were observed in terms of downstream processing and tabletability: mannitol-containing formulations solidified via VDD showed an improved processability compared to formulations with trehalose. In conclusion, VDD is a promising drying technique that offers advantageous downstream processability compared to SD and represents an attractive novel processing technology for the pharmaceutical industry. As demonstrated in the present study, VDD combines higher yields with a leaner manufacturing process flow. The improved bulk properties provide enhanced tabletability and enable direct compression.
PubMed: 38931903
DOI: 10.3390/pharmaceutics16060782 -
Pharmaceutics May 2024Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids...
Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for oral drug delivery, with a focus on powdered formulations. The archaeosomes were negatively charged with a size of approximately 100 nm and a low polydispersity index. To assess their suitability for oral delivery, the archaeosomes were loaded with two model drugs: calcein, a fluorescent compound, and insulin, a peptide hormone. The archaeosomes demonstrated high stability in simulated intestinal fluids, with only 5% of the encapsulated compounds being released after 24 h, regardless of the presence of degrading enzymes or extremely acidic pH values such as those found in the stomach. In a co-culture cell model system mimicking the intestinal barrier, the archaeosomes showed strong adhesion to the cell membranes, facilitating a slow release of contents. The archaeosomes were loaded with insulin in a single-step procedure achieving an encapsulation efficiency of approximately 35%. These particles have been exposed to extreme manufacturing temperatures during freeze-drying and spray-drying processes, demonstrating remarkable resilience under these harsh conditions. The fabrication of stable dry powder formulations of archaeosomes represents a promising advancement toward the development of solid dosage forms for oral delivery of biological drugs.
PubMed: 38931818
DOI: 10.3390/pharmaceutics16060694 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Tuberculosis (TB) is an airborne bacterial infection caused by (), resulting in approximately 1.3 million deaths in 2022 worldwide. Oral therapy with anti-TB drugs...
Tuberculosis (TB) is an airborne bacterial infection caused by (), resulting in approximately 1.3 million deaths in 2022 worldwide. Oral therapy with anti-TB drugs often fails to achieve therapeutic concentrations at the primary infection site (lungs). In this study, we developed a dry powder inhalable formulation (DPI) of clofazimine (CFZ) to provide localized drug delivery and minimize systemic adverse effects. Poly (lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) containing CFZ were developed through a single emulsion solvent evaporation technique. Clofazimine microparticles (CFZ MPs) displayed entrapment efficiency and drug loading of 66.40 ± 2.22 %w/w and 33.06 ± 1.45 µg/mg, respectively. To facilitate pulmonary administration, MPs suspension was spray-dried to yield a dry powder formulation (CFZ SD MPs). Spray drying had no influence on particle size (~1 µm), zeta potential (-31.42 mV), and entrapment efficiency. Solid state analysis (PXRD and DSC) of CFZ SD MPs studies demonstrated encapsulation of the drug in the polymer. The drug release studies showed a sustained drug release. The optimized formulation exhibited excellent aerosolization properties, suggesting effective deposition in the deeper lung region. The in vitro antibacterial studies against H37Ra revealed improved (eight-fold) efficacy of spray-dried formulation in comparison to free drug. Hence, clofazimine dry powder formulation presents immense potential for the treatment of tuberculosis with localized pulmonary delivery and improved patient compliance.
PubMed: 38931422
DOI: 10.3390/ph17060754 -
Frontiers in Neurology 2024Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.g., consumption of food and oral...
INTRODUCTION
Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.g., consumption of food and oral medications), may affect seizure patterns. Specific circadian patterns of seizures have been reported depending on type, onset location, and severity; however, data on patterns for patients with seizure clusters and effectiveness of rescue therapy by time of day are limited.
METHODS
We conducted analyses using patient diary data from the phase 3 safety study of diazepam nasal spray, which is indicated for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Patients were administered age- and weight-based doses; second doses could be administered if needed to control a seizure cluster. We assessed clock timing of seizure-cluster onset along with second-dose use as a proxy for effectiveness. Treatment-emergent adverse events were recorded.
RESULTS
Seizure-cluster onset was observed to be generally highest during mornings and late evenings and lowest in the early evening and middle of the night. Second-dose use was not consistently associated with a specific time of day. The safety profile was consistent with that expected from previous studies of diazepam nasal spray.
CONCLUSION
These results suggest that diazepam nasal spray can be effectively administered at any time of day.
PubMed: 38854958
DOI: 10.3389/fneur.2024.1335421 -
Acta Medica Philippina 2024Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy...
Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy (EBBT) has been shown to provide palliative therapy. It is the insertion of a radioactive material near the mass to reduce tumor size, thereby improving airway obstruction. This is the first case of EBBT done in our institution during the COVID-19 pandemic. A 53-year-old male, 60 kg, ASA Physical Status 2 for hypertension, smoker, malignancy, and previous pulmonary tuberculosis patient, presented with a cough and dyspnea. An endobronchial mass almost obstructing the right mainstem bronchus was seen on a computed tomography (CT) scan. He was diagnosed with squamous cell carcinoma of the lung and underwent radiotherapy and erlotinib chemotherapy. On repeat CT scan, there was no noted decrease in the size of the mass. EBBT was suggested, and a multi-disciplinary team was formed for the planned procedure. Pulmonology, radiation oncology, and anesthesiology teams were identified, and thorough planning was done prior to the actual procedure. Three fractions of EBBT were done under sedation using midazolam, fentanyl, and dexmedetomidine infusion. Lidocaine spray and transtracheal block were also performed as adjuncts prior to sedation. The procedure went as planned, and points for improvement were discussed for subsequent fractions. Due to persistent cough and discomfort from the catheter, additional ipratropium nebulization for minimization of secretions, and oral dextromethorphan for cough suppression were incorporated. After each fraction, the patient was monitored post-procedure for any side effects both from the radiotherapy and anesthetic technique. Qualitative reduction in mass size was noted in subsequent fractions. The patient was able to complete 3 fractions and was advised to follow-up after a month. EBBT is an emerging palliative and treatment modality for lung cancer, especially for intraluminal masses. Anesthetic considerations will depend on each case's characteristics such as airway anatomy, patient comfort and capacity, and procedural requirements. Conscious sedation with topical anesthesia is an adequate and appropriate anesthetic option, especially in cases where severe airway obstruction may compromise ventilation if airway reflexes are blunted. A multidisciplinary approach with different services and stakeholders is important for the proper planning, execution, and management of such patients.
PubMed: 38836083
DOI: 10.47895/amp.v58i9.8839 -
Food Research International (Ottawa,... Jul 2024Oral delivery of larger bioactive peptides (>20 amino acids) to the small intestine remains a challenge due to their sensitivity to proteolytic degradation and chemical...
Oral delivery of larger bioactive peptides (>20 amino acids) to the small intestine remains a challenge due to their sensitivity to proteolytic degradation and chemical denaturation during gastrointestinal transit. In this study, we investigated the capacity of crosslinked alginate microcapsules (CLAMs) formed by spray drying to protect Plantaricin EF (PlnEF) (C-EF) in gastric conditions and to dissolve and release PlnEF in the small intestine. PlnEF is an unmodified, two-peptide (PlnE: 33 amino acids; PlnF: 34 amino acids) bacteriocin produced by Lactiplantibacillus plantarum with antimicrobial and gut barrier protective properties. After 2 h incubation in simulated gastric fluid (SGF) (pH 1.5), 43.39 % ± 8.27 % intact PlnEF was liberated from the CLAMs encapsulates, as determined by an antimicrobial activity assay. Transfer of the undissolved fraction to simulated intestinal fluid (SIF) (pH 7) for another 2 h incubation resulted in an additional release of 16.13 % ± 4.33 %. No active PlnEF was found during SGF or sequential SIF incubations when pepsin (2,000 U/ml) was added to the SGF. To test PlnEF release in C-EF contained in a food matrix, C-EF was mixed in peanut butter (PB) (0.15 g C-EF in 1.5 g PB). A total of 12.52 % ± 9.09 % active PlnEF was detected after incubation of PB + C-EF in SGF without pepsin, whereas no activity was found when pepsin was included. Transfer of the remaining PB + C-EF fractions to SIF yielded the recovery of 46.67 % ± 13.09 % and 39.42 % ± 11.53 % active PlnEF in the SIF following exposure to SGF and to SGF with pepsin, respectively. Upon accounting for the undissolved fraction after SIF incubation, PlnEF was fully protected in the CLAMs-PB mixture and there was not a significant reduction in active PlnEF when pepsin was present. These results show that CLAMs alone do not guard PlnEF bacteriocin peptides from gastric conditions, however, mixing them in PB protected against proteolysis and improved intestinal release.
Topics: Alginates; Bacteriocins; Capsules; Peptides; Intestine, Small; Lactobacillus plantarum; Hydrogen-Ion Concentration; Cross-Linking Reagents; Pepsin A
PubMed: 38823837
DOI: 10.1016/j.foodres.2024.114473 -
BMC Oral Health May 2024Since maintaining oral hygiene is essential in nursing care, the present study was conducted to determine the effect of oral care using Mucosamin artificial saliva spray... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Since maintaining oral hygiene is essential in nursing care, the present study was conducted to determine the effect of oral care using Mucosamin artificial saliva spray to control dry mouth in ICU patients with COVID-19.
MATERIALS AND METHODS
The current semi-experimental research was conducted on eighty patients with COVID-19 selected using the available sampling method. The study tool was a Beck oral assessment scale (BOAS). The case and control groups were selected from two hospitals with relatively similar conditions and treatment procedures. For patients in the intervention group, mucosamin artificial saliva spray was used in addition to the common care, while control group patients received only common care.
RESULTS
Eighty patients were randomly assigned to two groups named control and intervention (40 patients in each group). The intervention was very effective in reducing the BOAS score after four days in comparison with the control group (9.23 vs. 12.05, respectively; p-value < 0.001). Based on the adjusted model, the application of artificial saliva reduced the BOAS score, indicating improvement in mouth dryness. While the BOAS score was increased in the control group, it had a declining trend in the intervention one.
CONCLUSION
The study's results showed that using artificial saliva spray could effectively reduce the symptoms of dry mouth in patients with COVID-19 treated with non-invasive mechanical ventilation.
CLINICAL RELEVANCE
The present study introduced an applicable solution (artificial saliva) to treat mouth dryness in ICU patients under mechanical ventilation.
Topics: Humans; Saliva, Artificial; Xerostomia; COVID-19; Female; Male; Middle Aged; Respiration, Artificial; Adult; Aged; SARS-CoV-2; Oral Hygiene
PubMed: 38822326
DOI: 10.1186/s12903-024-04386-4 -
Psychiatrike = Psychiatriki May 2024Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a...
Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a transient increase in glutamate release, leading to increases in neurotrophic signaling and restoration of synaptic function in brain regions involved in mood regulation and emotional behavior. Several randomized clinical trials have shown its effectiveness in reducing the symptoms of depression in some people, despite its short-term side effects that include mainly disorientation, dizziness, nausea, and increased blood pressure. In 2019, the United States Food and Drug Administration (FDA) as well as the European Medicines Agency approved the use of esketamine nasal spray in combination with an oral antidepressant for treatment-resistant depression in adults. Our study aimed to evaluate the effectiveness of this new therapeutic proposal in a case series of five Greek patients with treatment- resistant depression. Intranasal esketamine was administered under medical supervision in combination with an oral antidepressant. Depressive symptoms were evaluated at three time points (baseline, end of treatment, and one-year post-treatment) using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Patient Health Questionnaire (PHQ-9), the CGI Clinical Global Impression Scale, and the Perceived Deficits Questionnaire for Depression (PDQ-D). Possible side effects were assessed using the Richmond Suppression Agitation Scale (RASS), the Sheehan Disability Scale (SDS), the CADSS Disruptive States Scale, and a predefined list of adverse events (AEs) and serious adverse events (SAEs). Patients followed an individualized treatment plan for seven to twelve months depending on the achievement of an adequate response. Statistical analysis of the results revealed a significant improvement (p<0.05) on all scales used. All participants maintained their level of improvement at follow-up after twelve months. Adverse effects were found to be mild and tolerable. It is worth noting that significant side effects were reported only by the two patients with comorbid personality disorder. The results, despite limited to a small sample, indicate the positive effect of esketamine on the stable reduction of depressive symptoms among patients with resistant depression, even after the completion of treatment.
PubMed: 38814267
DOI: 10.22365/jpsych.2024.006 -
Dentistry Journal Apr 2024Complications such as peri-implantitis could ultimately affect the survival of a dental implant. The prevention and treatment of peri-implant diseases require managing...
Complications such as peri-implantitis could ultimately affect the survival of a dental implant. The prevention and treatment of peri-implant diseases require managing bacterial biofilm and controlling environmental risks, including the presence of pro-inflammatory titanium (Ti) particles in the peri-implant niche. Objectives included the evaluation of the size and quantity of Ti particles released from moderately roughened Ti surfaces during common mechanical surface decontamination methods. One hundred and forty moderately roughened Ti discs were divided into seven groups (n = 20 per group); six groups received mechanical decontamination procedures (ultrasonic scaling (US) with a metal tip and poly-ether-ketone (PEEK) under low and medium power settings, air-polishing with erythritol powder, and Ti brush), and the control group underwent air-water spray using a dental triplex. The rinsing solution was collected for Ti mass analysis using inductively coupled plasma mass spectrometry (ICPMS), as well as for Ti particle size and count analysis under scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS). US metal tip instrumentation generated 34.00 ± 12.54 μg and 34.44 ± 6.08 μg of Ti under low and medium power settings, respectively. This amount of Ti generation was significantly higher than other instrumentation methods. The mean Ti particle size of the US groups ranged from 0.89 ± 0.27 μm to 1.25 ± 0.24 μm. No statistically significant difference was found in the particle size among US groups and Ti brush group (1.05 ± 0.11 μm), except for US with the PEEK tip, where a significantly smaller mean particle diameter was found at the low power setting (0.89 ± 0.27 μm). Mechanical instrumentation can produce Ti particulates and modify the implant surfaces. US using a metal tip generated the highest amount of Ti with smaller Ti size particles compared to all other commonly used mechanical surface instrumentations. The EDS analysis confirmed Ti in PEEK US tips. It can be suggested that deterioration from the PEEK US tip and Ti brush, as observed under SEM, is an additional source of Ti release during Ti surface decontamination.
PubMed: 38786521
DOI: 10.3390/dj12050123