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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 -
Epilepsia Mar 2020The study assesses the bioavailability of diazepam after intranasal administration (diazepam nasal spray) in healthy volunteers. Comparative agents were diazepam rectal... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The study assesses the bioavailability of diazepam after intranasal administration (diazepam nasal spray) in healthy volunteers. Comparative agents were diazepam rectal gel, which served as the regulatory reference product; and oral diazepam, a product with decades of clinical use. Tolerability of diazepam nasal spray was also assessed.
METHODS
This was a phase 1, open-label, randomized, single-dose, three-treatment, three-period, six-sequence crossover study in 48 healthy adult subjects that consisted of a screening period, a baseline period, and an open-label treatment period. Interperiod intervals were at least 28 days.
RESULTS
Forty-eight healthy volunteer subjects were enrolled, two of whom discontinued before receiving study medication. For all routes of administration, the onset of diazepam absorption was rapid, with measurable concentrations of drug present by the first sample time point. The t (time to reach maximum plasma concentration) was similar for diazepam nasal spray and diazepam rectal gel, both of which were slower than oral diazepam in fasted individuals. Variability (as defined by % coefficient of variation of geometric mean) in peak plasma concentration and area under the curve was lowest with oral diazepam, followed by diazepam nasal spray, with diazepam rectal gel showing the greatest variability. Overall, 131 treatment-emergent adverse events (TEAEs) were considered mild (42 subjects, 91.3%), four TEAEs were considered moderate (four subjects, 8.3%), and no TEAEs were considered severe. The most commonly reported TEAE was somnolence at 56.5% (26/46) during diazepam nasal spray treatment, 89.1% (41/46) with the rectal diazepam gel treatment, and 82.6% (38/46) with oral diazepam treatment. No nasal irritation was observed for the majority of the subjects at any time point after administration, with no score higher than 2 ("minor bleeding that stops within 1 minute").
SIGNIFICANCE
Diazepam nasal spray shows predicable pharmacokinetics and represents a potential novel therapeutic approach to control bouts of increased seizure activity (cluster seizures, acute repetitive seizures).
Topics: Administration, Intranasal; Administration, Oral; Administration, Rectal; Adolescent; Adult; Biological Availability; Diazepam; Female; Gels; Healthy Volunteers; Humans; Male; Middle Aged; Nasal Sprays; Sleepiness; Young Adult
PubMed: 32065672
DOI: 10.1111/epi.16449 -
Pharmaceutics Nov 2020Novel-antibiotics are urgently needed to combat an increase in morbidity and mortality due to resistant bacteria. The preclinical candidate corallopyronin A (CorA) is a...
Novel-antibiotics are urgently needed to combat an increase in morbidity and mortality due to resistant bacteria. The preclinical candidate corallopyronin A (CorA) is a potent antibiotic against Gram-positive and some Gram-negative pathogens for which a solid oral formulation was needed for further preclinical testing of the active pharmaceutical ingredient (API). The neat API CorA is poorly water-soluble and instable at room temperature, both crucial characteristics to be addressed and overcome for use as an oral antibiotic. Therefore, amorphous solid dispersion (ASD) was chosen as formulation principle. The formulations were prepared by spray-drying, comprising the water-soluble polymers povidone and copovidone. Stability (high-performance liquid chromatography, Fourier-transform-infrared spectroscopy, differential scanning calorimetry), dissolution (biphasic dissolution), and solubility (biphasic dissolution, Pion's T3 apparatus) properties were analyzed. Pharmacokinetic evaluations after intravenous and oral administration were conducted in BALB/c mice. The results demonstrated that the ASD formulation principle is a suitable stability- and solubility-enhancing oral formulation strategy for the API CorA to be used in preclinical and clinical trials and as a potential market product.
PubMed: 33217948
DOI: 10.3390/pharmaceutics12111105 -
Forensic Sciences Research 2022Forensic odontology majorly focuses on the identification of victims through the analyses of oral and para-oral structures. Exposure to high temperatures and trauma can...
Forensic odontology majorly focuses on the identification of victims through the analyses of oral and para-oral structures. Exposure to high temperatures and trauma can occur in mass disasters and may lead to the fracturing and fragmentation of teeth. These fragments may become very fragile and easily damaged while handling. Conventional methodologies such as the use of transparent nail polish, hair spray, cyanoacrylate or adhesives have been used to stabilize the fragmented pieces. This study introduces a new and innovative digital technique that utilizes three-dimensional surface scanning (3DSS) and rapid prototyping techniques to reconstruct fractured portions of the teeth. The results of qualitative congruency analysis suggest that over all variance of morphological error (0.0526 ± 0.05) mm. These results imply that the reconstructed 3D model can be used for various morphometric analyses.
PubMed: 35341125
DOI: 10.1080/20961790.2020.1737462 -
Pharmaceutics Jan 2023The taste-masking of bitter-tasting active pharmaceutical ingredients is key to ensuring patient compliance when producing oral pharmaceutical formulations. This is...
The taste-masking of bitter-tasting active pharmaceutical ingredients is key to ensuring patient compliance when producing oral pharmaceutical formulations. This is generally achieved via the incorporation of pH-responsive, reverse enteric polymers, that prevent the dissolution of the formulation in the oral environment, but rapidly mediate it within the gastric environment. Reverse enteric polymers are commonly applied as coatings on oral dosage forms via spray atomisation (e.g., fluidised-bed spray coating), and generally exhibit the most efficient taste-masking. However, currently used reverse enteric coatings require high mass gains (% /) during coating to mediate taste-masking, and thereby exhibit delayed release within the gastric environment. Therefore, there remains a need for the development of new reverse enteric coatings, that can efficiently taste-mask at low mass gains and maintain rapid release characteristics within the gastric environment. Herein we report the synthesis and evaluation of a series of addition copolymers of 2-vinylpyridine and butyl methacrylate, methyl methacrylate and isobornyl methacrylate. The thermal, solubility, and water absorption properties of the copolymers were effectively tuned by altering the mol% fraction of the constitutive monomers. Based on their physical properties, selected copolymers were preliminarily evaluated for their compatibility with fluidised-bed spray coating, and effectiveness as taste-masking reverse enteric coatings. The copolymers poly[(2-vinylpyridine)-co-(butyl methacrylate)] (mol% ratio 40:60) and poly[(2-vinylpyridine)-co-(butyl methacrylate)-co-(methyl methacrylate)] (mol% ratio 40:50:10) were found to exhibit excellent taste-masking properties following fluidised-bed spray coating onto Suglets sugar spheres. Suglets bearing a film coating of either copolymer (5.2-6.5% / mass gain) were found to effectively impede the release of a model drug formulation for up to 72 h in a simulated salivary environment, and rapidly release it (<10 min) within a simulated gastric environment. The results demonstrated the potential of poly[(2-vinylpyridine)-co-(butyl methacrylate)] copolymers to form effectively taste-masked, reverse enteric dosage forms, and suggested that these copolymers may provide improved performance compared to currently available polymers.
PubMed: 36839776
DOI: 10.3390/pharmaceutics15020454 -
International Journal of Molecular... Jul 2019Episodes of hypoglycemia are frequent in patients with diabetes treated with insulin or sulphonylureas. Hypoglycemia can lead to severe acute complications, and, as... (Review)
Review
Episodes of hypoglycemia are frequent in patients with diabetes treated with insulin or sulphonylureas. Hypoglycemia can lead to severe acute complications, and, as such, both prevention and treatment of hypoglycemia are important for the well-being of patients with diabetes. The experience of hypoglycemia also leads to fear of hypoglycemia, that in turn can limit optimal glycemic control in patients, especially with type 1 diabetes. Treatment of hypoglycemia is still based on administration of carbohydrates (oral or parenteral according to the level of consciousness) or of glucagon (intramuscular or subcutaneous injection). In 1983, it was shown for the first time that intranasal (IN) glucagon drops (with sodium glycocholate as a promoter) increase blood glucose levels in healthy volunteers. During the following decade, several authors showed the efficacy of IN glucagon (drops, powders, and sprays) to resolve hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. Only in 2010, based on evaluation of patients' beliefs and patients' expectations, a canadian pharmaceutical company (Locemia Solutions, Montreal, Canada) reinitiated efforts to develop glucagon for IN administration. The project has been continued by Eli Lilly, that is seeking to obtain registration in order to make IN glucagon available to insulin users (children and adolescents) worldwide. IN glucagon is as effective as injectable glucagon, and devoid of most of the technical difficulties associated with administration of injectable glucagon. IN glucagon appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both children and adults.
Topics: Administration, Intranasal; Animals; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucagon; Humans; Hypoglycemia; Risk; Treatment Outcome
PubMed: 31349701
DOI: 10.3390/ijms20153646 -
Expert Opinion on Drug Delivery 2016Nanosuspensions combine the advantages of nanotherapeutics (e.g. increased dissolution rate and saturation solubility) with ease of commercialisation. Transformation of... (Review)
Review
INTRODUCTION
Nanosuspensions combine the advantages of nanotherapeutics (e.g. increased dissolution rate and saturation solubility) with ease of commercialisation. Transformation of nanosuspensions to solid oral and inhalable dosage forms minimises the physical instability associated with their liquid state, enhances patient compliance and enables targeted oral and pulmonary drug delivery.
AREAS COVERED
This review outlines solidification methods for nanosuspensions. It includes spray and freeze drying as the most widely used techniques. Fluidised-bed coating, granulation and pelletisation are also discussed as they yield nanocrystalline formulations with more straightforward downstream processing to tablets or capsules. Spray-freeze drying, aerosol flow reactor and printing of nanosuspensions are also presented as promising alternative solidification techniques. Results regarding the solid state, in vitro dissolution and/or aerosolisation efficiency of the nanocrystalline formulations are given and combined with available in vivo data. Focus is placed on the redispersibility of the solid nanocrystalline formulations, which is a prerequisite for their clinical application.
EXPERT OPINION
A few solidified nanocrystalline products are already on the market and many more are in development. Oral and inhalable nanoparticle formulations are expected to have great potential especially in the areas of personalised medicine and delivery of high drug doses (e.g. antibiotics) to the lungs, respectively.
Topics: Administration, Inhalation; Chemistry, Pharmaceutical; Dry Powder Inhalers; Excipients; Freeze Drying; Nanoparticles; Solubility; Tablets
PubMed: 26764574
DOI: 10.1517/17425247.2016.1142524 -
Journal of Pharmacy & Bioallied Sciences Feb 2019The aim of the current study was to evaluate the efficacy of nasal spray midazolam by collating it with conventional intravenous midazolam for conscious sedation in...
AIM
The aim of the current study was to evaluate the efficacy of nasal spray midazolam by collating it with conventional intravenous midazolam for conscious sedation in minor oral surgeries.
MATERIALS AND METHODS
Sixty patients were selected randomly and divided into two groups: group A for intranasal midazolam atomized spray ( = 30) and group B for intravenous midazolam ( = 30). Physiological parameters, anxiety score, sedation rating, patient's cooperation score, and retrograde and anterograde amnesia were recorded for each patient during preoperative, intraoperative, and postoperative period. Final evaluation of safety and efficacy in the nasal and intravenous routes of midazolam drug during minor oral surgery was compared.
RESULTS
In this study, both intranasal and intravenous groups showed decrease in systolic blood pressure and diastolic blood pressure intraoperatively but within physiological limits and increase in the average pulse rates in both the groups. The average oxygen saturation levels were maintained to normal range in both the groups. The average respiratory rate decreased in both intranasal and intravenous groups during surgical procedure. The preoperative to postoperative anxiety scores were decreased significantly in the both groups and there was no significant difference in pre- to postoperative anxiety scores between the groups.
CONCLUSION
Both intravenous and intranasal administration of midazolam showed better patient cooperation, satisfaction, and clinical effectiveness. Intranasal midazolam spray is effective in the reduction of subjective stress, reliable anxiolysis while preserving protective reflexes.
PubMed: 30923430
DOI: 10.4103/jpbs.JPBS_199_18 -
Integrated Pharmacy Research & Practice 2017Patients suffering from allergic rhinitis often attempt to self-manage their symptoms and may seek advice from pharmacists about nonprescription product choices. Several... (Review)
Review
Patients suffering from allergic rhinitis often attempt to self-manage their symptoms and may seek advice from pharmacists about nonprescription product choices. Several drug classes, both prescription and over-the-counter (OTC), are available, including intranasal corticosteroids (INCSs); oral, intranasal, and ocular antihistamines; leukotriene antagonists; and topical and systemic decongestants, as well as immunotherapies. Selection of the optimal treatment approach depends on the temporal pattern, frequency, and severity of symptoms as well as the patient's age. Nasal congestion is typically the most bothersome symptom, although rhinorrhea, postnasal drip, and ocular symptoms are also problematic. Together, these symptoms may adversely impact the quality of life, work productivity, sleep quality, and the ability to perform daily activities, particularly when uncontrolled. Practice guidelines recognize that INCSs are the most effective medications for controlling allergic rhinitis symptoms, including nasal congestion. Available INCS products have comparable safety and efficacy profiles, but they differ in formulation characteristics and sensory attributes. Several barriers can impede the use of INCSs, including concerns about safety, misperceptions regarding the loss of response from frequent use, and undesirable sensations associated with intranasal administration. Given the increasing number of INCSs available OTC, pharmacists can help allay these concerns by discussing treatment expectations, recommending INCS products with favorable formulation characteristics, and reviewing proper use and technique for the administration of the selected product. These steps can help to foster a collaborative relationship between the patient and the pharmacist in the treatment of allergic rhinitis.
PubMed: 29354557
DOI: 10.2147/IPRP.S129544 -
Pharmaceutics Jan 2023Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was...
Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was nano-spray-dried using three mucoadhesive polymers and four cyclodextrin species to form composite powders for nasal administration. The product was composed of hydroxypropyl methylcellulose polymer, including LC as a zwitterion, after neutralization by NaOH, and XRD investigations verified its amorphous state. This and a sulfobutylated-beta-cyclodextrin sodium salt-containing sample showed crystal peaks due to NaCl content as products of the neutralization reaction in the solutions before drying. The average particle size of the spherical microparticles was between 2.42 and 3.44 µm, except for those containing a polyvinyl alcohol excipient, which were characterized by a medium diameter of 29.80 µm. The drug was completely and immediately liberated from all the samples at pH 5.6 and 32 °C; i.e., the carriers did not change the good dissolution behavior of LC. A permeability test was carried out by dipping the synthetic cellulose ester membrane in isopropyl myristate using modified horizontal diffusion cells. The spray-dried powder with β-cyclodextrin showed the highest permeability (188.37 µg/cm/h), as this additive was the least hydrophilic. Products prepared with other cyclodextrins (randomly methylated-beta-cyclodextrin, sulfobutylated-beta-cyclodextrin sodium salt and (hydroxypropyl)-beta-cyclodextrin) showed similar or slightly higher penetration abilities than LC. Other polymer excipients resulted in lower penetration of the active agent than the pure LC.
PubMed: 36839640
DOI: 10.3390/pharmaceutics15020317