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Heliyon Dec 2023Due to the presence of large surfaces and high blood supply, drug delivery through the nasal route of administration is the appropriate route to administrate drugs with... (Review)
Review
Due to the presence of large surfaces and high blood supply, drug delivery through the nasal route of administration is the appropriate route to administrate drugs with rapid onsets of action. Bypassing first-pass metabolism can increase drug bioavailability. The physicochemical properties of fentanyl led to a need to develop formulations for delivery by multiple routes. Several approved inter-nasal fentanyl products in Europe and the USA have been used in prehospital and emergency departments to treat chronic cancer pain and used to treat severe acute abdominal and flank pain. Analgesia durations and onsets were not significantly different between intranasal and intravenous fentanyl in patients with cancer breakthrough pain and were well-tolerated in the long term. Intranasal Fentanyl (INF) at a 50 μg/ml concentration decreased renal colic pain to the lowest level in 30 min. Possible adverse effects specific to INF are epistaxis, nasal wall ulcer, rhinorrhea, throat irritation, dysgeusia, nausea, and vomiting. However, there is limited available literature about the serious adverse effects of INF in adults and children. Intranasal Fentanyl Spray (INFS) results in significantly higher plasma concentrations and has a lower T than oral transmucosal formulation, and the bioavailability of fentanyl in intranasal formulations is very high (89 %), particularly in pectin-containing formulations such as PecFent and Lazanda.
PubMed: 38144320
DOI: 10.1016/j.heliyon.2023.e23083 -
Drugs in R&D Sep 2023The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual absorption and rate of hepatic metabolism.
OBJECTIVE
The objective of this study is to investigate the bioavailability of melatonin after administration of an oral prolonged-release tablet (PR form) and an immediate-release sublingual spray (IR form). The main metabolite of melatonin, 6-sulfatoxymelatonin (6-SMT), was also measured, which has not been done in previous studies. Its determination is important as an index of the hepatic transformation of melatonin.
METHODS
In this single-center, open-label, randomized, crossover study, 14 healthy male volunteers received one tablet of the PR form (1.9 mg melatonin) or two sprays of the IR form (1 mg melatonin) during two visits separated by a washout period. Blood samples were collected over 7 and 9 h for the IR and PR form, respectively, to determine the main pharmacokinetic parameters.
RESULTS
The observed kinetics were consistent with those expected for immediate and prolonged-release forms. Pulverization of the spray resulted in an early, high plasma melatonin peak (C: 2332 ± 950 pg/mL; T: 23.3 ± 6.5 min), whereas tablet intake produced a lower peak (C: 1151 ± 565 pg/mL; T: 64.2 ± 44.2 min; p < 0.001 for comparison of C and T) followed by a plasma melatonin plateau and a more prolonged decay over time. Plasma melatonin/6-SMT AUC ratio was 0.09 for the PR form and 0.16 for the IR form. Both galenic forms were well tolerated.
CONCLUSIONS
The results suggest that the galenic forms containing melatonin assessed in this study are suitable for the treatment of certain sleep disorders such as sleep onset delay and transient nocturnal awakenings for the IR form and insomnia for the PR form.
TRIAL REGISTRY
Registration number: NCT04574141.
Topics: Humans; Male; Biological Availability; Cross-Over Studies; Melatonin; Tablets; Volunteers; Administration, Oral; Area Under Curve
PubMed: 37438493
DOI: 10.1007/s40268-023-00431-9 -
Materials Horizons Jun 2024Polymeric microspheres (PMs) have attracted great attention in the field of biomedicine in the last several decades due to their small particle size, special... (Review)
Review
Polymeric microspheres (PMs) have attracted great attention in the field of biomedicine in the last several decades due to their small particle size, special functionalities shown on the surface and high surface-to-volume ratio. However, how to fabricate PMs which can meet the clinical needs and transform laboratory achievements to industrial scale-up still remains a challenge. Therefore, advanced fabrication technologies are pursued. In this review, we summarize the technologies used to fabricate PMs, including emulsion-based methods, microfluidics, spray drying, coacervation, supercritical fluid and superhydrophobic surface-mediated method and their advantages and disadvantages. We also review the different structures, properties and functions of the PMs and their applications in the fields of drug delivery, cell encapsulation and expansion, scaffolds in tissue engineering, transcatheter arterial embolization and artificial cells. Moreover, we discuss existing challenges and future perspectives for advancing fabrication technologies and biomedical applications of PMs.
Topics: Microspheres; Polymers; Humans; Tissue Engineering; Drug Delivery Systems; Biocompatible Materials; Tissue Scaffolds; Animals; Microfluidics
PubMed: 38567423
DOI: 10.1039/d3mh01641b -
Cannabis and Cannabinoid Research Aug 2023Spasticity continues to be a very prevalent, highly invalidating, and difficult-to-manage symptom in patients with multiple sclerosis (MS). The aim of this systematic... (Review)
Review
Spasticity continues to be a very prevalent, highly invalidating, and difficult-to-manage symptom in patients with multiple sclerosis (MS). The aim of this systematic review is to evaluate the effectiveness of the use of cannabis and cannabinoids in these patients, evaluating its use as an additional therapy. We performed a systematic review of the literature searching in the major scientific databases (PubMed, Scopus, EMBASE, WOS, and Cochrane Library) for articles from January 2017 to May 2022 containing information about the effectiveness of cannabis and cannabinoids in patients with insufficient response to first-line oral antispastic treatment. A total of five medium high-quality articles were selected to be part of the study and all evaluated the effectiveness of the tetrahydrocannabinol (THC) and cannabidiol (CBD) spray. The effectiveness of this drug and the significant improvements are produced on the patient-related spasticity assessment scales, obtaining improvement up to 45%; and on quality of life, producing a decrease in the appearance of symptoms related to spasticity, as well as an increase in the development of basic activities of daily living. The average dose is 5-7 sprays/day. The discontinuation rate for these treatments is around 40% due to lack of effectiveness and adverse events. All reported adverse effects are mild to moderate in severity and their incidence is ∼17%, although this figure tends to decrease with drug use. Adding the THC:CBD sprays have been shown to be more effective in treating MS spasticity than optimizing the dose of first-line antispastic drugs in selected responders patients. The safety and tolerability profiles remain in line with those obtained in other trials. More patients would benefit from treatment if the initial response search period was extended.
Topics: Humans; Cannabinoids; Quality of Life; Dronabinol; Activities of Daily Living; Multiple Sclerosis; Muscle Spasticity; Cannabidiol; Cannabis
PubMed: 37057959
DOI: 10.1089/can.2022.0254 -
Journal of Applied Toxicology : JAT Oct 2023Cyclodextrins are nanometric cyclic oligosaccharides with amphiphilic characteristics that increase the stability of drugs in pharmaceutical forms and bioavailability,... (Review)
Review
Cyclodextrins are nanometric cyclic oligosaccharides with amphiphilic characteristics that increase the stability of drugs in pharmaceutical forms and bioavailability, in addition to protecting them against oxidation and UV radiation. Some of their characteristics are low toxicity, biodegradability, and biocompatibility. They are divided into α-, β-, and γ-cyclodextrins, each with its own particularities. They can undergo surface modifications to improve their performances. Furthermore, their drug inclusion complexes can be made by various methods, including lyophilization, spray drying, magnetic stirring, kneading, and others. Cyclodextrins can solve several problems in drug stability when incorporated into dosage forms (including tablets, gels, films, nanoparticles, and suppositories) and allow better topical biological effects of drugs at administration sites such as skin, eyeballs, and oral, nasal, vaginal, and rectal cavities. However, as they are nanostructured systems and some of them can cause mild toxicity depending on the application site, they must be evaluated for their nanotoxicology and nanosafety aspects. Moreover, there is evidence that they can cause severe ototoxicity, killing cells from the ear canal even when applied by other administration routes. Therefore, they should be avoided in otologic administration and should have their permeation/penetration profiles and the in vivo hearing system integrity evaluated to certify that they will be safe and will not cause hearing loss.
Topics: Female; Humans; Cyclodextrins; Pharmaceutical Preparations; Biological Availability; Biological Products; Solubility
PubMed: 36579752
DOI: 10.1002/jat.4429 -
Drug Delivery and Translational Research Feb 2024Oral administration is the most commonly used form of treatment due to its advantages, including high patient compliance, convenient administration, and minimal... (Review)
Review
Oral administration is the most commonly used form of treatment due to its advantages, including high patient compliance, convenient administration, and minimal preparation required. However, the traditional preparation process of oral solid preparation has many defects. Although continuous manufacturing line that combined all the unit operations has been developed and preliminarily applied in the pharmaceutical industry, most of the currently used manufacturing processes are still complicated and discontinuous. As a result, these complex production steps will lead to low production efficiency and high quality control risk of the final product. Additionally, the large-scale production mode is inappropriate for the personalized medicines, which commonly is customized with small amount. Several attractive techniques, such as hot-melt extrusion, fluidized bed pelletizing and spray drying, could effectively shorten the process flow, but still, they have inherent limitations that are challenging to address. As a novel manufacturing technique, 3D printing could greatly reduce or eliminate these disadvantages mentioned above, and could realize a desirable continuous production for small-scale personalized manufacturing. In recent years, due to the participation of 3D printing, the development of printed drugs has progressed by leaps and bounds, especially in the design of oral drug dosage forms. This review attempts to summarize the new development of 3D printing technology in oral preparation and also discusses their advantages and disadvantages as well as potential applications.
Topics: Humans; Technology, Pharmaceutical; Drug Industry; Pharmaceutical Preparations; Administration, Oral; Printing, Three-Dimensional
PubMed: 37620647
DOI: 10.1007/s13346-023-01414-8 -
American Journal of Cardiovascular... Sep 2023Patients with arrythmias are at an increased risk of heart-related comorbidities and complications. Specifically, patients with paroxysmal supraventricular tachycardia... (Review)
Review
Patients with arrythmias are at an increased risk of heart-related comorbidities and complications. Specifically, patients with paroxysmal supraventricular tachycardia (PSVT), a type of arrythmia, are at increased risk of lightheadedness or shortness of breath, due to the increased rate of the heartbeat. Most patients are prescribed oral medications to control their heart rates and maintain a normal heart rhythm. Researchers have been tasked with discovering alternative treatment options with new delivery methods to treat arrythmias such as PSVT. A nasal spray was subsequently designed and is currently undergoing clinical studies. This review aims to present and discuss the current clinical and scientific evidence pertaining to etripamil.
Topics: Humans; Tachycardia, Supraventricular; Nasal Sprays; Tachycardia, Paroxysmal; Tachycardia, Ventricular
PubMed: 37278974
DOI: 10.1007/s40256-023-00589-2 -
Annals of Allergy, Asthma & Immunology... Sep 2023The high prescription drug cost in the United States may negatively affect patient prognosis and treatment compliance.
BACKGROUND
The high prescription drug cost in the United States may negatively affect patient prognosis and treatment compliance.
OBJECTIVE
To fill the knowledge gap and inform clinicians regarding rhinology medications price changes by evaluating trends in price changes of highly used nasal sprays and allergy medications.
METHODS
The 2014-2020 Medicaid National Average Drug Acquisition Cost database was queried for drug pricing information for the following classes of medications: intranasal corticosteroids, oral antihistamines, antileukotrienes, intranasal antihistamines, and intranasal anticholinergics. Individual medications were identified by Food and Drug Administration-assigned National Drug Codes. Per unit, drug prices were analyzed for average annual prices, average annual percentage price changes, and inflation-adjusted annual and composite percentage price changes.
RESULTS
Beclometasone (Beconase AQ, 56.7%, QNASL, 77.5%), flunisolide (Nasalide, -14.6%), budesonide (Rhinocort Aqua, -1.2%), fluticasone (Flonase, -6.8%, Xhance, 11.7%), mometasone (Nasonex, 38.2%), ciclesonide (Omnaris, 73.8%), combination azelastine and fluticasone (Dymista, 27.3%), loratadine (Claritin, -20.5%), montelukast (Singulair, 14.5%), azelastine (Astepro, 21.9%), olopatadine (Patanase, 27.3%), and ipratropium bromide (Atrovent, 56.6%) had an overall change in inflation-adjusted per unit cost between 2014 and 2020 (% change). Of 14 drugs evaluated, 10 had an increase in inflation-adjusted prices, for an average increase of 42.06% ± 22.27%; 4 of 14 drugs had a decrease in inflation-adjusted prices, for an average decrease of 10.78% ± 7.36%.
CONCLUSION
The rising cost of highly used medications contributes to increased patient acquisition costs and may pose barriers of drug adherence to particularly vulnerable populations.
Topics: Humans; United States; Fluticasone; Administration, Intranasal; Mometasone Furoate; Adrenal Cortex Hormones; Histamine Antagonists; Loratadine; Beclomethasone
PubMed: 37098404
DOI: 10.1016/j.anai.2023.04.013 -
Virology Journal Jan 2024Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and influenza virus is still a major worldwide health concern. Plants are a good source of...
BACKGROUND
Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and influenza virus is still a major worldwide health concern. Plants are a good source of bioactive compounds to be used as preventive measures for both inhibiting the virus binding and enhancing mucosal innate immunity. Curcumin has been shown to possess antiviral activity and modulate innate immunity. Therefore, the purpose of this study was to develop an oro-nasal film spray containing curcumin and determine its antiviral activity against SARS-CoV-2 and influenza virus infection, as well as its effects on mucosal innate immunity and inflammatory cytokines in vitro.
METHODS
The antiviral activity of the film spray against SARS-CoV-2, influenza A/H1N1, A/H3N2, and influenza B was assessed in vitro by plaque reduction assay. Cytotoxicity of the film spray to oral keratinocytes and nasal epithelial cells was assessed by MTT assay, and cytotoxicity to Vero and MDCK cells was assessed by an MTS-based cytotoxicity assay. Oral and nasal innate immune markers in response to the film spray were determined by ELISA and by a commercial Milliplex Map Kit, respectively.
RESULTS
Our data show that the film spray containing curcumin can inhibit both SARS-CoV-2 and influenza virus infections while maintaining cell viability. Results obtained among 4 viruses revealed that curcumin film spray demonstrated the highest inhibitory activity against SARS-CoV-2 with the lowest EC of 3.15 µg/ml and the highest SI value of 4.62, followed by influenza B (EC = 6.32 µg/ml, SI = 2.04), influenza A/H1N1 (EC = 7.24 µg/ml, SI = 1.78), and influenza A/H3N2 (EC > 12.5 µg/ml, SI < 1.03), respectively. Antimicrobial peptides LL-37 and HD-5, IL-6 and TNF-α produced by oral keratinocytes were significantly induced by the film spray, while hBD2 was significantly reduced.
CONCLUSION
Film spray containing curcumin possesses multiple actions against SARS-CoV-2 infection by inhibiting ACE-2 binding in target cells and enhancing mucosal innate immunity. The film spray can also inhibit influenza virus infection. Therefore, the curcumin film spray may be effective in preventing the viral infection of both SARS-CoV-2 and influenza.
Topics: Animals; Dogs; Humans; SARS-CoV-2; Influenza, Human; Curcumin; Immunity, Mucosal; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; COVID-19; Orthomyxoviridae Infections; Madin Darby Canine Kidney Cells; Antiviral Agents
PubMed: 38263162
DOI: 10.1186/s12985-023-02282-x -
Molecular Pharmaceutics Sep 2023Delamanid (DLM) is a hydrophobic small molecule therapeutic used to treat drug-resistant tuberculosis (DR-TB). Due to its hydrophobicity and resulting poor aqueous...
Delamanid (DLM) is a hydrophobic small molecule therapeutic used to treat drug-resistant tuberculosis (DR-TB). Due to its hydrophobicity and resulting poor aqueous solubility, formulation strategies such as amorphous solid dispersions (ASDs) have been investigated to enhance its aqueous dissolution kinetics and thereby improve oral bioavailability. However, ASD formulations are susceptible to temperature- and humidity-induced phase separation and recrystallization under harsh storage conditions typically encountered in areas with high tuberculosis incidence. Nanoencapsulation represents an alternative formulation strategy to increase aqueous dissolution kinetics while remaining stable at elevated temperature and humidity. The stabilizer layer coating the nanoparticle drug core limits the formation of large drug domains by diffusion during storage, representing an advantage over ASDs. Initial attempts to form DLM-loaded nanoparticles via precipitation-driven self-assembly were unsuccessful, as the trifluoromethyl and nitro functional groups present on DLM were thought to interfere with surface stabilizer attachment. Therefore, in this work, we investigated the nanoencapsulation of DLM via emulsification, avoiding the formation of a solid drug core and instead keeping DLM dissolved in a dichloromethane dispersed phase during nanoparticle formation. Initial emulsion formulation screening by probe-tip ultrasonication revealed that a 1:1 mass ratio of lecithin and HPMC stabilizers formed 250 nm size-stable emulsion droplets with 40% DLM loading. Scale-up studies were performed to produce nearly identical droplet size distribution at larger scale using high-pressure homogenization, a continuous and industrially scalable technique. The resulting emulsions were spray-dried to form a dried powder, and dissolution studies showed dramatically enhanced dissolution kinetics compared to both as-received crystalline DLM and micronized crystalline DLM, owing to the increased specific surface area and partially amorphous character of the DLM-loaded nanoparticles. Solid-state NMR and dissolution studies showed good physical stability of the emulsion powders during accelerated stability testing (50 °C/75% RH, open vial).
Topics: Humans; Tuberculosis, Oral; Emulsions; Nanoparticles; Solubility; Excipients; Water; Particle Size
PubMed: 37578286
DOI: 10.1021/acs.molpharmaceut.3c00240