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Substance Abuse and Rehabilitation 2024Nalmefene hydrochloride was first discovered as an opioid antagonist derivative of naltrexone in 1975. It is among the most potent opioid antagonists currently on the... (Review)
Review
Nalmefene hydrochloride was first discovered as an opioid antagonist derivative of naltrexone in 1975. It is among the most potent opioid antagonists currently on the market and is differentiated from naloxone and naltrexone by its partial agonist activity at the kappa-opioid receptor which may benefit in the treatment of alcohol use disorder. Oral nalmefene has been approved in the European Union for treatment of alcohol use disorder since 2013. As of 2023, nalmefene is available in the United States as an intranasal spray for reversal of opioid overdose but is not approved for alcohol or opioid use disorder as a maintenance treatment. The substantially longer half-life of nalmefene and 5-fold higher binding affinity to opioid receptors makes it a superior agent over naloxone in the reversal of high potency synthetic opioids like fentanyl and the emerging nitazenes. Nalmefene presents with a comparable side effect profile to other opioid antagonists and should be considered for further development as a maintenance treatment for opioid and other substance use disorders.
PubMed: 38585160
DOI: 10.2147/SAR.S431270 -
BMC Oral Health Apr 2024Many instruments used in dentistry are rotary, such as handpieces, water syringes, and ultrasonic scalers that produce aerosols. The spray created by these instruments... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many instruments used in dentistry are rotary, such as handpieces, water syringes, and ultrasonic scalers that produce aerosols. The spray created by these instruments can carry, in addition to water, droplets of saliva, blood, and microorganisms, which can pose a risk of infections for healthcare professionals and patients. Due to the COVID-19 pandemic, this gained attention.
OBJECTIVE
The aim was to carry out a systematic review of the evidence of the scope of the aerosol produced by ultrasonic scaler in environmental contamination and the influence of the use of intraoral suction reduction devices.
DESIGN
Scientific literature was searched until June 19, 2021 in 6 databases: Pubmed, EMBASE, Web of science, Scopus, Virtual Health Library and Cochrane Library, without restrictions on language or publication date. Studies that evaluated the range of the aerosol produced by ultrasonic scaler during scaling/prophylaxis and the control of environmental contamination generated by it with the use of low (LVE) and high (HVE) volume evacuation systems were included.
RESULTS
Of the 1893 potentially relevant articles, 5 of which were randomized controlled trials (RCTs). The meta-analysis of 3 RCTs showed that, even at different distances from the patient's oral cavity, there was a significant increase in airborne bacteria in the dental environment with the use of ultrasonic scaler. In contrast, when meta-analysis compared the use of HVE with LVE, there was no significant difference (P = 0.40/CI -0.71[-2.37, 0.95]) for aerosol produced in the environment.
CONCLUSIONS
There is an increase in the concentration of bioaerosol in the dental environment during the use of ultrasonic scaler in scaling/prophylaxis, reaching up to 2 m away from the patient's mouth and the use of LVE, HVE or a combination of different devices, can be effective in reducing air contamination in the dental environment, with no important difference between different types of suction devices.
Topics: Humans; Ultrasonic Therapy; Ultrasonics; Respiratory Aerosols and Droplets; Aerosols; Water; Dental Scaling
PubMed: 38580933
DOI: 10.1186/s12903-024-03996-2 -
Translational Medicine @ UniSa 2024This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate...
AIMS
This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed.
METHODS
From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD).
RESULTS
The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs.
CONCLUSION
Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.
PubMed: 38560616
DOI: 10.37825/2239-9747.1047 -
The Medical Journal of Malaysia Mar 2024Acne is a common skin disease with a high psychosocial burden, affecting mostly adolescents and youth worldwide. Management of acne is often challenged by cutaneous side... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Acne is a common skin disease with a high psychosocial burden, affecting mostly adolescents and youth worldwide. Management of acne is often challenged by cutaneous side effects that leads to therapeutic intolerance, poor compliance and impaired efficacy.
MATERIALS AND METHODS
This was a single-centre, evaluatorblinded, split-face, randomised study investigating the effects of thermal spring water (TSW) in improving efficacy and tolerability of standard acne therapy. Total of 31 participants with mild-to-moderate acne were recruited and subjected to TSW spray to one side of the face 4 times daily for 6 weeks in addition to standard therapy. The other side received standard therapy only.
RESULTS
Six (19.4%) males and 25 (80.6%) female with mean age 25.1±6.13 participated, 15 (48.4%) had mild acne while 16 (51.6%) had moderate acne. Seven (22.6%) were on oral antibiotics, 25 (80.6%) used adapalene, 6 (19.4%) tretinoin and 21 (67.7%) benzoyl peroxide. Skin hydration improved and better on spring water treated side with mean difference12.41±30.31, p = 0.04 at the forehead, 39.52±65.14, p < 0.01 at the cheek and 42.172±71.71, p < 0.01 at the jaw at week 6. Participants also report significant reduction in dryness at the treated side at week 6, mean difference 0.93±0.10, p < 0.001. TEWL, sebum and pH were comparable on both sides with no significant differences. Tolerability towards standard therapy improved as early week 2 with reduction of stinging following application of topical therapy (mean difference 0.62±1.43, p = 0.03), increase in skin feeling good (-1.79±1.70, p < 0.001) and skin suppleness (0.62±1.43, p < 0.001). These improvements were significantly maintained till week 6. Cardiff acne disability index significantly improved at week 6 (p<0.001) despite no significant changes in Comprehensive Acne Severity Scale score before and after treatment.
CONCLUSION
TSW may have a role as an adjunct to standard acne therapy by improving hydration, acne disability index and tolerability towards standard topical treatment.
Topics: Adolescent; Adult; Female; Humans; Male; Young Adult; Acne Vulgaris; Adapalene; Benzoyl Peroxide; Hot Springs; Prospective Studies; Treatment Outcome
PubMed: 38553920
DOI: No ID Found -
Pharmaceutics Mar 2024Alginate is a natural biopolymer widely studied for pharmaceutical applications due to its biocompatibility, low toxicity, and mild gelation abilities. This review... (Review)
Review
Alginate-Based Encapsulation Fabrication Technique for Drug Delivery: An Updated Review of Particle Type, Formulation Technique, Pharmaceutical Ingredient, and Targeted Delivery System.
Alginate is a natural biopolymer widely studied for pharmaceutical applications due to its biocompatibility, low toxicity, and mild gelation abilities. This review summarizes recent advances in alginate-based encapsulation systems for targeted drug delivery. Alginate formulations like microparticles, nanoparticles, microgels, and composites fabricated by methods including ionic gelation, emulsification, spray drying, and freeze drying enable tailored drug loading, enhanced stability, and sustained release kinetics. Alginate microspheres prepared by spray drying or ionic gelation provide gastric protection and colon-targeted release of orally delivered drugs. Alginate nanoparticles exhibit enhanced cellular uptake and tumor-targeting capabilities through the enhanced permeation and retention effect. Crosslinked alginate microgels allow high drug loading and controlled release profiles. Composite alginate gels with cellulose, chitosan, or inorganic nanomaterials display improved mechanical properties, mucoadhesion, and tunable release kinetics. Alginate-based wound dressings containing antimicrobial nanoparticles promote healing of burns and chronic wounds through sustained topical delivery. Although alginate is well-established as a pharmaceutical excipient, more extensive in vivo testing is needed to assess clinical safety and efficacy of emerging formulations prior to human trials. Future opportunities include engineered systems combining stimuli-responsiveness, active targeting, and diagnostic capabilities. In summary, this review discusses recent advances in alginate encapsulation techniques for oral, transdermal, and intravenous delivery, with an emphasis on approaches enabling targeted and sustained drug release for enhanced therapeutic outcomes.
PubMed: 38543264
DOI: 10.3390/pharmaceutics16030370 -
Pharmaceutics Feb 2024The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research over the last few decades due, most... (Review)
Review
The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research over the last few decades due, most notably, to its reported involvement in promoting social cognition and motivation, reducing anxiety, and relieving pain. It is also increasingly being considered as an important therapeutic intervention in a variety of disorders with social dysfunction as a symptom. While, in recent years, studies in humans have administered oxytocin primarily via an intranasal route, since it may partly enter the brain directly this way via the olfactory and trigeminal nerves, there is increasing evidence that many of its functional effects can be peripherally mediated via increasing its concentration in the blood. This has opened up an oromucosal administration route as an alternative, which is beneficial since the oral consumption of peptides is problematic due to their rapid breakdown in the acidic environment of the gastrointestinal system. In this review we will discuss both the methodologies we have developed for administering oxytocin via lingual application and medicated lollipops, 'oxipops', in terms of increasing blood concentrations and the bioavailability of the peptide, and also their validation in terms of functional effects on the brain and behavior. While areas under the curve are significantly greater in terms of plasma oxytocin concentrations following intranasally relative to oromucosally administered oxytocin, with the estimated absolute bioavailability of the latter being around 4.4% compared with 11.1% for intranasal administration, the time to peak concentrations (around 30 min) and functional effects on the brain and behavior are broadly similar. We will also discuss potential therapeutic advantages of the oromucosal administration of oxytocin in different clinical contexts and its wider application for other peptides which are increasingly being developed for therapeutic use.
PubMed: 38543227
DOI: 10.3390/pharmaceutics16030333 -
Journal of Pain Research 2024Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023... (Review)
Review
BACKGROUND
Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023 American Geriatrics Society Beers Criteria for potentially inappropriate medication use in older adults. In our geriatric practice, off-label use of tizanidine as preemptive analgesia drove us to find recent advances in its pharmacology and therapeutics. An update review of tizanidine was thus presented, aiming to bring the latest knowledge to clinicians and promote further research and practical exploration.
METHODS
Relevant literature up to December 2023 was identified through searches of PubMed, Web of Science, and Embase.
RESULTS
Tizanidine, a centrally acting alpha-2 adrenoceptor agonist with both antispastic and antispasmodic activity, shows efficacy in the common indications for all SMRs. From the perspective of drug safety, tizanidine has lower incidences of adverse events (injury, delirium, encephalopathy, falls, and opioid overdose) compared to baclofen, no association with risk of Alzheimer's disease as with orphenadrine, no risk of serotonin syndrome like metaxalone when comedicated with serotonergic drugs, no significant pharmacokinetic changes in CYP2C19 poor metabolizers unlike diazepam and carisoprodol, and no physically addictive or abuse properties like carisoprodol and diazepam. From the perspective of new and potential therapeutic uses, tizanidine has additional benefits (eg, gastroprotection that can improve patient tolerance to nonsteroidal anti-inflammatory agents, anti-neuropathic pain, a key component of multimodal analgesia strategy to reduce early postoperative pain, and anti-tumor effects). New delivery systems of tizanidine are developing to improve the pharmacokinetics of oral products, including buccal patches, transdermal delivery systems, nasal spray, and in situ rectal gel.
CONCLUSION
Tizanidine is an SMR with unique features and may be an optimal initial choice for older adults. There would be more scientific studies, wider therapeutic applications, and new drug formulations in the future.
PubMed: 38529017
DOI: 10.2147/JPR.S461032 -
European Journal of Pharmaceutical... May 2024Poorly water-soluble drugs present a significant challenge in the development of oral solid dosage forms (OSDs). In formulation development the appropriate use of...
The challenge of downstream processing of spray dried amorphous solid dispersions into minitablets designed for the paediatric population - A sustainable product development approach.
Poorly water-soluble drugs present a significant challenge in the development of oral solid dosage forms (OSDs). In formulation development the appropriate use of excipients to adjust solubility, and the choice of manufacturing method and pharmaceutical processes to obtain a dosage form to meet the needs of the patient group, is crucial. Preparing an amorphous solid dispersion (ASD) is a well-established method for solubility enhancement, and spray drying (SD) a common manufacturing method. However, the poor flowability of spray dried materials poses a significant challenge for downstream processing. Promoting sustainability in OSD development involves embracing a versatile formulation design, which enables a broader spectrum of patients to use the product, as opposed to altering existing dosage forms retrospectively. The objective of the current study was to develop a formulation of spray dried indomethacin ASD suited to the production, by direct compression, of instant release paediatric minitablets. Excipients evaluated were PVP or HPMCAS in solid dispersions at the preformulation phase, and MCC and lactose as a filler in direct compression. From the studied formulations, a 3:1 ratio blend of Vivapur 200/Pharmatose 200 M (MCC/lactose) with 0.5% (w/w) magnesium stearate was found to be the most promising in tableting, and minitablets containing a 6.22% content of spray-dried ASD of indomethacin/PVP K 29-32 could be obtained with desired tablet hardness and pharmaceutical quality, complying with tests of weight variation and fast disintegration in an aqueous environment. As a case example, this study provides a good foundation for further studies in harnessing a sustainable approach to the development of pharmaceutical formulations that can appropriately serve different patient sub-populations.
PubMed: 38518998
DOI: 10.1016/j.ejps.2024.106752 -
International Journal of Pharmaceutics Apr 2024Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal...
Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.
Topics: Animals; Angiotensin-Converting Enzyme 2; COVID-19; Pharmaceutical Preparations; Powders; SARS-CoV-2
PubMed: 38493838
DOI: 10.1016/j.ijpharm.2024.124009 -
Cureus Feb 2024Effective implant placement depends critically on the implant's level of osseointegration with the alveolar bone. To increase osseointegration during implant placement,...
BACKGROUND
Effective implant placement depends critically on the implant's level of osseointegration with the alveolar bone. To increase osseointegration during implant placement, research has concentrated on the surface modification of implants, and morphological analyses have looked at the thread pattern in close interaction with the bone's surface.
AIM
This study aimed to assess and compare the extent of oral implant osseointegration in different surface modification techniques.
MATERIALS AND METHODS
In this study, 12 healthy adult dogs aged 18-24 months were used. Tooth extractions were performed on both sides of the mandible, and wounds were closed with sutures. Two months later, the right mandible of each dog underwent local anesthesia and general anesthesia. Four different implant types were placed based on their surface treatments: resorbable blast media (RBM)-treated implants, hydroxyapatite (HA) implants with an ultra-thin HA film, hydrothermal-treated HA implants coated with HA, and sandblasting combined acid etching (SLA) implants treated with plasma spray and acid etching. A total of 48 implants were divided into two- and four-week groups, with identical dimensions. Each dog received two implants from each group, for a total of eight implants per dog. The implants were securely placed into the superior alveolar bone with a torque greater than 35-N up to a depth of 1 mm. Periotest M (Medizintechnik Gulden e.K., Modautal, Germany) was used to calculate the periotest value (PTV) as a typical value on the buccal side of each implant immediately following placement and sacrifice to test the main fixation and stability of the implants. Resonance frequency analysis (RFA) was utilised by Osstell Mentor (Osstell AB, Gothenburg, Sweden) to simultaneously assess the implant stability quotient (ISQ) on the medial, distal, buccal, and lingual sides of the implant. The rotational torque in one of the sacrificed dogs was calculated using the MGT 50 (ELECTROMATIC Equipment Co., Inc., New York, USA) torque analyzer. The histomorphometric evaluation was performed using an optical microscope (Olympus Corporation, Tokyo, Japan). The upper half's bone-implant contact (BIC), which was found to be more important for implant stability, was studied together with the ratio of the new bone formation area (NBFA) to the complete implant.
RESULTS
The maximum stability was observed in HA-treated implants in the fourth week. The minimum stability was observed in hydrothermal-treated HA implants in the fourth week. The stability in each group was greater in the four-week evaluation as compared to the two-week evaluation. The stability was satisfactory in almost all implants at two- and three-week evaluations. The maximum value of the percentage area of newly formed bone at the two- and four-week evaluations was observed in HA-treated implants. The minimum value of the percentage of the area of newly formed bone at two- and four-week evaluations was observed in SLA and RBM-treated implants respectively. The difference was significant statistically (p ≤ 0.05).
CONCLUSION
All implant surface modifications, in general, produced satisfactory osseointegration. Excellent osseointegration was seen in the upper portion of the implant with hydrothermally treated HA.
PubMed: 38476793
DOI: 10.7759/cureus.54014