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European Journal of Pharmaceutics and... Aug 2023Low oral absorption and extensive first pass metabolism of progesterone is reported for many oral formulations which warrants investigation into other routes of...
Low oral absorption and extensive first pass metabolism of progesterone is reported for many oral formulations which warrants investigation into other routes of administration. It is the aim of this study to investigate the generation of inhaled formulations of progesterone though a spray drying approach with a focus on how spray drying impacts the physicochemical properties of progesterone. Formulations of progesterone with L-leucine and hydroxypropyl methylcellulose acetate succinate (HPMCAS) are reported to this aim. X-ray diffraction, spectroscopy and thermal analysis were used to characterise these formulations and confirmed that progesterone crystallises as the Form II polymorph during spray drying regardless of the solvent used. The resultant formulations showed higher aqueous solubility than progesterone Form I starting material and the addition of HPMCAS was shown to temporarily enable a supersaturated state. Thermal analysis was used to show that the Form II polymorph was sensitive to transformation to Form I during heating. The addition of L-leucine to the formulations reduced the temperature for the polymorphic transformation by ∼ 10 °C. However, when HPMCAS was added to the formulation, the Form II polymorph was prevented from transforming to the Form I polymorph. Cascade impaction was used to determine the aerosol performance of the spray dried powders and showed promising lung deposition profiles (mass median aerodynamic diameter 5 µm) with significant variation depending on the organic solvent used and the ratio of organic to aqueous phase in the feedstock. However, further optimisation of formulations was required to direct more progesterone into the alveolar regions. The addition of HPMCAS was seen to increase the alveolar deposition and therefore formed a formulation with a lower fine particle fraction and mass median aerodynamic diameter. The most suitable formulation for inhalation was formed from a 50:50 acetone:water mixture and showed an ED, FPF and FPD of 81.7%, 44.5% and 7.3 mg respectively. Therefore, HPMCAS is suggested as a suitable excipient to increase solubility, prevent polymorphic transformation and improve inhalation properties of spray dried progesterone formulations. This study highlights the use of spray drying to form inhalable progesterone powders with higher solubility which may broaden the application of this medicine.
Topics: Powders; Progesterone; Leucine; Excipients; Administration, Inhalation; Aerosols; Solvents; Particle Size; Dry Powder Inhalers
PubMed: 37392870
DOI: 10.1016/j.ejpb.2023.06.018 -
International Dental Journal Dec 2023Dental restorative procedures remain a cornerstone of dental practice, and for many decades, dental amalgam was the most frequently employed material. However, its use... (Review)
Review
Dental restorative procedures remain a cornerstone of dental practice, and for many decades, dental amalgam was the most frequently employed material. However, its use is declining, mainly driven by its poor aesthetics and by the development of tooth-coloured adhesive materials. Furthermore, the Minamata Convention agreed on a phase-down on the use of dental amalgam. This concise review is based on a FDI Policy Statement which provides guidance on the selection of direct restorative materials as alternatives to amalgam. The Policy Statement was informed by current literature, identified mainly from PubMed and the internet. Ultimately, dental, oral, and patient factors should be considered when choosing the best material for each individual case. Dental factors include the dentition, tooth type, and cavity class and extension; oral aspects comprise caries risk profiles and related risk factors; and patient-related aspects include systemic risks/medical conditions such as allergies towards certain materials as well as compliance. Special protective measures (eg, a no-touch technique, blue light protection) are required when handling resin-based materials, and copious water spray is recommended when adjusting or removing restorative materials. Cost and reimbursement policies may need to be considered when amalgam alternatives are used, and the material recommendation requires the informed consent of the patient. There is no single material which can replace amalgam in all applications; different materials are needed for different situations. The policy statement recommends using a patient-centred rather than purely a material-centred approach. Further research is needed to improve overall material properties, the clinical performance, the impact on the environment, and cost-effectiveness of all alternative materials.
PubMed: 38071154
DOI: 10.1016/j.identj.2023.11.004 -
British Journal of Clinical Pharmacology Nov 2023Nalbuphine is a synthetic opioid with comparable analgesic activity to morphine but with a better safety profile. Nalbuphine is only available in injectable form due to... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Nalbuphine is a synthetic opioid with comparable analgesic activity to morphine but with a better safety profile. Nalbuphine is only available in injectable form due to low oral bioavailability. Nasal nalbuphine spray provides advantages in drug safety, avoids hepatic first-pass metabolism, is non-invasive and is convenient for patient-controlled analgesia by self-administration. This study aimed to evaluate the safety and pharmacokinetics (PK) of the newly developed nalbuphine nasal spray in comparison with a solution for injections.
METHODS
Twenty-four healthy Caucasian volunteers were enrolled in this randomized, open-label, cross-over study. Subjects were administered one of the drugs: nasal spray 7.0 mg/dose, nalbuphine hydrochloride solution for injection 10 mg/dose intravenously (IV) or intramuscularly (IM). High-performance liquid chromatography-tandem mass spectrometry was used to determine nalbuphine concentrations.
RESULTS
A comparison of PK profiles for IV, IM and intranasal (IN) routes of nalbuphine administration revealed a close similarity of absorption phases for nasal spray and IM injection. Differences between the mean T and dose-adjusted C values for nasal spray and IM injection were statistically insignificant. The median values of the elimination rate constants and the terminal elimination half-life following IV, IM and IN nalbuphine administration were similar. The mean absolute bioavailability of the nasal spray equalled 65.04%.
CONCLUSIONS
The similarity of PK parameters of IM-injected nalbuphine solution and the nasal spray allows us to assume the latter is a feasible alternative to intramuscular nalbuphine injections appropriate for self-administration and field environments for managing moderate and severe pain of various aetiologies.
Topics: Humans; Nalbuphine; Nasal Sprays; Healthy Volunteers; Cross-Over Studies; Analgesics, Opioid; Biological Availability
PubMed: 37328144
DOI: 10.1111/bcp.15828 -
Journal of Dental Research Aug 2023Oral cryotherapy is used in dentistry as a safe, simple, and low-cost treatment for a variety of oral lesions. It is well known for its ability to aid in the healing...
Oral cryotherapy is used in dentistry as a safe, simple, and low-cost treatment for a variety of oral lesions. It is well known for its ability to aid in the healing process. However, its effect on oral biofilms is unknown. As a result, the purpose of this study was to assess the effects of cryotherapy on in vitro oral biofilms. In vitro multispecies oral biofilms were grown on the surface of hydroxyapatite discs in symbiotic or dysbiotic states. CryoPen X+ was used to treat the biofilms, whereas untreated biofilms served as control. One set of biofilms was collected for study immediately after cryotherapy, whereas another group was reincubated for 24 h to permit biofilm recovery. Changes in biofilm structure were analyzed with a confocal laser scanning microscope (CLSM) and a scanning electron microscope (SEM), while biofilm ecology and community compositional changes were analyzed with viability DNA extraction and quantitative polymerase chain reaction (v-qPCR) analysis. One cryo-cycle immediately reduced biofilm load by 0.2 to 0.4 log Geq/mL, which increased with additional treatment cycles. Although the bacterial load of the treated biofilms recovered to the same level as the control biofilms within 24 h, the CLSM detected structural alterations. Compositional alterations were also detected by SEM, corroborating the v-qPCR findings that showed ≈≤10% incidence of pathogenic species compared to nontreated biofilms that encompassed ≈45% and 13% pathogenic species in dysbiotic and symbiotic biofilms, respectively. Spray cryotherapy showed promising results in a novel conceptual approach to the control of oral biofilms. Acting selectively by targeting oral pathobionts and retaining commensals, spray cryotherapy could modify the ecology of in vitro oral biofilms to become more symbiotic and prevent the evolution of dysbiosis without the use of antiseptics/antimicrobials.
Topics: Anti-Infective Agents; Bacterial Load; Biofilms; Cryotherapy
PubMed: 37278360
DOI: 10.1177/00220345231172688 -
Cureus Apr 2024Xerostomia, commonly known as dry mouth, presents a significant challenge for individuals wearing complete dentures, affecting their oral health and quality of life.... (Review)
Review
Xerostomia, commonly known as dry mouth, presents a significant challenge for individuals wearing complete dentures, affecting their oral health and quality of life. This review explores the relationship between saliva and complete dentures, highlighting the varied management strategies for xerostomia. Saliva plays a critical role in denture retention, lubrication, and oral environment buffering. Complete denture wearers often experience reduced salivary flow, aggravating symptoms of xerostomia. Various management approaches are discussed, including general measures such as hydration and salivary stimulation techniques which aim to boost saliva production naturally. The use of salivary substitutes provides artificial lubrication and moisture to alleviate dry mouth discomfort. Oral lubricating devices, such as sprays, gels, and lozenges, offer relief by mimicking saliva's lubricating properties, thereby improving denture stability and comfort. This review addresses the etiology of xerostomia in complete denture wearers and explores preventive measures to reduce its impact. A comprehensive approach has been discussed for the management of xerostomia which will help to improve the oral health and well-being of complete denture wearers experiencing dry mouth.
PubMed: 38770459
DOI: 10.7759/cureus.58564 -
Dentistry Journal Apr 2024Soft drinks may have a deleterious effect on dental health due to a high titratable acidity and a low pH that could be sufficient to induce tooth demineralization. The...
Soft drinks may have a deleterious effect on dental health due to a high titratable acidity and a low pH that could be sufficient to induce tooth demineralization. The use of oral care products immediately after acidic challenge may diminish the erosive potential of soft drinks. We assessed the effect of oral care foams and a spray on salivary pH changes after exposure to Coca-Cola in young adults. Thirty-three consenting eligible patients were recruited in this double-blind, randomized, crossover study performed in six visits. Baseline examination included unstimulated salivary flow rate, stimulated salivary buffer capacity, and the simplified oral hygiene index (OHI-S) assessment. Salivary pH and time for pH recovery were registered after exposure to Coca-Cola alone or that followed by the application of each of the studied products (an oral foam containing hydroxyapatite and probiotics, an oral foam containing amino fluoride, an alkaline oral spray, and tap water). Thirty-two patients completed the entire study protocol and were included in the final analysis. The mean minimum salivary pH and the mean oral clearance rate after rinsing with Coca-Cola were 6.3 and 27 min, respectively. Further rinsing with any one of the tested solutions, including tap water, resulted in a significant improvement in these parameters. When the pH curves were plotted, the oral care products demonstrated a lower area under the curve that differed significantly from the area under the curve for Coca-Cola; tap water did not differ significantly from Coca-Cola and oral care products. Minimum salivary pH correlated positively with salivary buffer capacity and salivation rate, while salivary clearance correlated with OHI-S plaque scores. In conclusion, the effect of oral care foams and a spray on minimum salivary pH and salivary clearance after exposure to Coca-Cola did not differ significantly among the tested products and tap water. Trial registration NCT06148662. Funding: none.
PubMed: 38668005
DOI: 10.3390/dj12040093 -
In Vivo (Athens, Greece) 2023The aim of this study was to evaluate the safety and efficacy of AFree oral spray, in combination with Standard of Care, in treating mild to moderate COVID-19 patients.... (Randomized Controlled Trial)
Randomized Controlled Trial
A Prospective Study of AFree Oral Spray as an Adjuvant Therapy for Mild and Moderate COVID-19 in Community Health Stations: Clinical Progression and Viral Clearance Outcomes.
BACKGROUND/AIM
The aim of this study was to evaluate the safety and efficacy of AFree oral spray, in combination with Standard of Care, in treating mild to moderate COVID-19 patients. This was an open-label, single-blinded, and controlled randomized clinical trial.
PATIENTS AND METHODS
The study involved 1,252 patients, who were randomly assigned to either the control or study group, with 626 patients in each group. Patients in the control group were treated with Standard of Care recommended by the Ministry of Health of Vietnam, while patients in the study group received AFree oral spray in addition to Standard of Care for a period of 10 days. The clinical progression and outcomes of both groups were compared.
RESULTS
The results showed that the proportion of patients with clinical symptoms on the 5, 7 and 10 days were significantly lower in the study group (45.05%, 3.19% and 0%, respectively) compared to the control group (86.10%, 67.73% and 22.84%, respectively). Additionally, the rate of Real-time PCR test positivity for COVID-19 was significantly lower in the study group compared to the control group on the 4, 7, and 10 days (82.75% vs. 98.72%, 9.27% vs. 92.97%, and 1.12% vs. 50.48%, respectively). Furthermore, no side effects or complications related to AFree oral spray were recorded in the study group.
CONCLUSION
The use of AFree oral spray resulted in significant improvements in clinical symptoms, recovery time, and viral clearance in COVID-19 patients with mild to moderate symptoms. This therapy has been shown to be safe and can be used as an adjuvant treatment for COVID-19 as well as other respiratory viral infections.
Topics: Humans; COVID-19; Prospective Studies; Oral Sprays; SARS-CoV-2; Public Health; Disease Progression; Treatment Outcome
PubMed: 37652493
DOI: 10.21873/invivo.13313 -
Journal of Materials Chemistry. B Dec 2023Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in treating type 2 diabetes (T2D). However, owing to their limited oral bioavailability, most... (Review)
Review
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in treating type 2 diabetes (T2D). However, owing to their limited oral bioavailability, most commercially available GLP-1 RAs are administered through frequent subcutaneous injections, which may result in poor patient compliance during clinical treatment. To improve patients' compliance, sustained-release GLP-1 RA-loaded microspheres have been explored. This review is an overview of recent progress and research in GLP-1 RA-loaded microspheres. First, the fabrication methods of GLP-1 RA-loaded microspheres including the coacervation method, emulsion-solvent evaporation method based on agitation, premix membrane emulsification technology, spray drying, microfluidic droplet technology, and supercritical fluid technology are summarized. Next, the strategies for maintaining GLP-1 RAs' stability and activity in microspheres by adding additives and PEGylation are reviewed. Finally, the effect of particle size, drug distribution, the internal structure of microspheres, and the hydrogel/microsphere composite strategy on improved release behavior is summarized.
Topics: Humans; Diabetes Mellitus, Type 2; Microspheres; Glucagon-Like Peptide-1 Receptor; Delayed-Action Preparations; Glucagon-Like Peptide 1; Research
PubMed: 37975420
DOI: 10.1039/d3tb02207b -
PloS One 2023The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from...
Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies.
BACKGROUND
The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from the decreased pleasure of eating to impaired quality of life. This research aimed to provide a comprehensive understanding of the effects of corticosteroid treatments by comparing that to other currently available treatments and interventions.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist's 27-point checklist was used to conduct this review. PubMed (Public/Publisher MEDLINE), PubMed Central and EMBASE (Excerpta Medica Database) databases were conveniently selected and Boolean search commands were used for a comprehensive literature search. Five core search terms were "effects of treatments", " COVID-19-related olfactory dysfunction", "corticosteroids", "treatments" and "interventions". The reporting qualities of the included studies were appraised using JBI (Joanna Briggs Institute) appraisal tools. The characteristics of the 21 experimental studies with a total sample (of 130,550) were aggregated using frequencies and percentages and presented descriptively. The main interventions and their effects on the duration of the COVID-19-related olfactory dysfunction were narratively analyzed.
RESULTS
Among patients with COVID-19, the normal functions of the olfactory lobe were about 23 days earlier to gain with the treatments of fluticasone and triamcinolone acetonide nasal spray compared with that of mometasone furoate nasal spray and oral corticosteroid. The smell loss duration was reduced by fluticasone and triamcinolone acetonide nasal spray 9 days earlier than the inflawell syrup and 16 days earlier than the lavender syrup. The nasal spray of corticosteroids ended the COVID-19-related smell loss symptoms 2 days earlier than the zinc supplementation, about 47 days earlier than carbamazepine treatment and was more effective than palmitoylethanolamide (PEA) and luteolin and omega-3 supplementations and olfactory training. Treatment with oral corticosteroid plus olfactory training significantly improved Threshold, Discrimination and Identification (TDI) scores compared with olfactory training alone. A full dose of the COVID-19 vaccination was not uncertain to reduce the COVID-19-related smell loss duration.
CONCLUSION
Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.
Topics: Humans; Nasal Sprays; Anosmia; Quality of Life; Triamcinolone Acetonide; COVID-19; Randomized Controlled Trials as Topic; Steroids; Adrenal Cortex Hormones; Fluticasone
PubMed: 37531338
DOI: 10.1371/journal.pone.0288285 -
Molecular Pharmaceutics Sep 2023Tuberculosis (TB), caused by (), remains a leading cause of death with 1.6 million deaths worldwide reported in 2021. Oral pyrazinamide (PZA) is an integral part of...
Tuberculosis (TB), caused by (), remains a leading cause of death with 1.6 million deaths worldwide reported in 2021. Oral pyrazinamide (PZA) is an integral part of anti-TB regimens, but its prolonged use has the potential to drive the development of PZA-resistant . PZA is converted to the active moiety pyrazinoic acid (POA) by the pyrazinamidase encoded by , and mutations in are associated with the majority of PZA resistance. Conventional oral and parenteral therapies may result in subtherapeutic exposure in the lung; hence, direct pulmonary administration of POA may provide an approach to rescue PZA efficacy for treating -mutant PZA-resistant . The objectives of the current study were to (i) develop novel dry powder POA formulations, (ii) assess their feasibility for pulmonary delivery using physicochemical characterization, (iii) evaluate their pharmacokinetics (PK) in the guinea pig model, and (iv) develop a mechanism-based pharmacokinetic model (MBM) using PK data to select a formulation providing adequate exposure in epithelial lining fluid (ELF) and lung tissue. We developed three POA formulations for pulmonary delivery and characterized their PK in plasma, ELF, and lung tissue following passive inhalation in guinea pigs. Additionally, the PK of POA following oral, intravenous, and intratracheal administration was characterized in guinea pigs. The MBM was used to simultaneously model PK data following administration of POA and its formulations via the different routes. The MBM described POA PK well in plasma, ELF, and lung tissue. Physicochemical analyses and MBM predictions suggested that POA maltodextrin was the best among the three formulations and an excellent candidate for further development as it has: (i) the highest ELF-to-plasma exposure ratio (203) and lung tissue-to-plasma exposure ratio (30.4) compared with POA maltodextrin and leucine (75.7/16.2) and POA leucine salt (64.2/19.3) and (ii) the highest concentration in ELF (: 171 nM) within 15.5 min, correlating with a fast transfer into ELF after pulmonary administration (: 22.6 1/h). The data from the guinea pig allowed scaling, using the MBM to a human dose of POA maltodextrin powder demonstrating the potential feasibility of an inhaled product.
Topics: Humans; Animals; Guinea Pigs; Pyrazinamide; Leucine; Powders; Body Fluids
PubMed: 37590399
DOI: 10.1021/acs.molpharmaceut.3c00199