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Journal of Veterinary Research Jun 2024Chicken bones, a by-product of the poultry industry, can directly or indirectly enter the food chain. Bone meal and bone products could be sources of many contaminants....
INTRODUCTION
Chicken bones, a by-product of the poultry industry, can directly or indirectly enter the food chain. Bone meal and bone products could be sources of many contaminants. Considering the wide range of uses made of bones in the culinary and food industries, this material needs to be safe and antibiotic residue-free. To determine if such is the case, the concentration of doxycycline in chicken bones was investigated, this antimicrobial being one of the most commonly used in poultry production.
MATERIAL AND METHODS
Ross 308 broilers were grouped into three experimental and one control group. Doxycycline was administered in drinking water at therapeutic and sub-therapeutic doses, as well as spray treatment. The concentration of doxycycline in bones was determined post slaughter by ultra-high performance liquid chromatography-tandem mass spectrometry.
RESULTS
Doxycycline was quantified at 135 μg/kg 22 days after the last day of antibiotic administration at therapeutic doses; 2,285 μg/kg after sub-therapeutic treatment for 27 days and 9.62 μg/kg 22 days after the end of spray application.
CONCLUSION
High concentrations and long persistence of doxycycline in bones were found in this study. Doxycycline can contaminate all bone-derived products in the food and fertiliser industries.
PubMed: 38947148
DOI: 10.2478/jvetres-2024-0030 -
Annales Pharmaceutiques Francaises Jun 2024Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known...
OBJECTIVES
Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known for improving solubility and inhibiting drug crystallization in supersaturated conditions of the gastrointestinal tract (GIT). In our previous work, we prepared coamorphous dispersion (COAM) of EDR with sodium taurocholate (NaTC) using spray drying. The optimized EDR COAM exhibited superior in vitro performance compared to plain EDR. EDR is well absorbed in fasted-over-fed conditions.
METHODS
The present work, we conducted a pharmacokinetic study for EDR and EDR COAM in fasted and fed conditions to check effect of food on its oral absorption. The LC-MS/MS-based method was developed and validated to determine the amount of EDR in plasma.
RESULTS
The results suggested that EDR COAM did not show a significant difference in C (p=0.3544) and AUC (p=0.1696) of fasted and fed states. On the other hand, plain EDR showed 2-fold and 3-fold reduced C (p<0.0001) and AUC (p=0.0094) in the fed condition, respectively. The C and AUC of EDR COAM were improved in fasted (AUC:2.56-fold) and fed states (AUC: 5.74-fold) than plain EDR, suggesting better oral absorption of COAM than crystalline EDR without having the effect of food.
CONCLUSIONS
The unique structural attributes of NaTC had the potential to inhibit the recrystallization of EDR in GIT, while concurrently reducing the impact of food on the oral absorption of EDR.
PubMed: 38942078
DOI: 10.1016/j.pharma.2024.06.005 -
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 -
Journal of Periodontal Research Jun 2024To explore the association between periodontitis and olfactory disorders.
AIM
To explore the association between periodontitis and olfactory disorders.
METHODS
Clinical data were collected from 198 individuals between the ages of 18 and 60 years living in Denmark. The exposure was periodontitis, and the outcome was olfactory function (Threshold, Discrimination, Identification - TDI score), both measured clinically. Covariates included sex, age, education level, income, usage of nasal spray, tongue coating, halitosis, xerostomia, smoking, and history of COVID-19. Structural equation modeling was used to estimate the association between periodontitis and olfactory function. Periodontitis was defined using the AAP/EFP classification and dichotomized into "no" (healthy subjects) and "yes" (Stages I, II, and III). Olfactory function was treated as a one-factor latent variable, including the different olfactory scores. In addition, extra models were performed considering each olfactory component as a separate outcome and the TDI Global Score.
RESULTS
The results showed that periodontitis was associated with a lower olfactory function [standardized coefficient (SC) -0.264, 95% CI -0.401, -0.118]. Additionally, periodontitis was also associated with a lower olfactory Threshold (odorant concentration required for detection) (SC -0.207, 95% CI -0.325, -0.089), Discrimination (ability to discriminate between odorants) (SC -0.149, 95% CI -0.270, -0.027), Identification (ability to identify odorants) scores (SC -0.161, 95% CI -0.277, -0.045), and TDI Global Score (SC -0.234, 95% CI -0.370, -0.099).
CONCLUSIONS
This study suggests that periodontitis is associated with olfactory impairment.
PubMed: 38888002
DOI: 10.1111/jre.13315 -
Drug Delivery and Translational Research Jun 2024The fundamental idea underlying the use of amorphous solid dispersions (ASDs) is to make the most of the solubility advantage of the amorphous form of a drug. However,...
The fundamental idea underlying the use of amorphous solid dispersions (ASDs) is to make the most of the solubility advantage of the amorphous form of a drug. However, the drug stability becomes compromised due to the higher free energy and disorder of molecular packing in the amorphous phase, leading to crystallization. Polymers are used as a matrix to form a stable homogeneous amorphous system to overcome the stability concern. The present work aims to design ASD-based formulations under the umbrella of quality by design principles for improving oral drug bioavailability, using celecoxib (CXB) as a model drug. ASDs were prepared from selected polymers and tested both individually and in combinations, using various manufacturing techniques: high-shear homogenization, high-pressure homogenization, microfluidics-on-a-chip, and spray drying. The resulting dispersions were further optimized, resorting to a 3 full-factorial design, considering the drug:polymers ratio and the total solid content as variables. The formulated products were evaluated regarding analytical centrifugation and the influence of the different polymers on the intrinsic dissolution rate of the CXB-ASDs. Microfluidics-on-a-chip led to the amorphous status of the formulation. The in vitro evaluation demonstrated a remarkable 26-fold enhancement in the intrinsic dissolution rate, and the translation of this formulation into tablets as the final dosage form is consistent with the observed performance enhancement. These findings are supported by ex vivo assays, which exhibited a two-fold increase in permeability compared to pure CXB. This study tackles the bioavailability hurdles encountered with diverse active compounds, offering insights into the development of more effective drug delivery platforms.
PubMed: 38861140
DOI: 10.1007/s13346-024-01633-7 -
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