Nonsteroidal Anti-inflammatory Drugs Formulations Research Articles

Effectiveness of the Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for Postoperative Pain Management in Patients Undergoing Major Surgical Operations at Manokwari Hospital

Postoperative pain is a common complication in patients undergoing major surgical operations, interfering with comfort and recovery and increasing the risk of further complications. This study aimed to evaluate the effectiveness of NSAIDs in managing postoperative pain at Manokwari Regional Hospital. Utilizing qualitative research methods, data was collected through observation and literature study and analyzed via data reduction, data presentation, and conclusion drawing. The findings indicate that NSAIDs effectively alleviate postoperative pain by inhibiting cyclooxygenase (COX) enzymes responsible for prostaglandin production. However, their use is limited by potential systemic side effects, including gastrointestinal disorders, kidney impairment, increased blood pressure, heart attack, and heart failure. Consequently, topical NSAID formulations are recommended to mitigate these risks. The study suggests that while NSAIDs are effective, clinicians should consider their side effects and prefer topical alternatives. Future research should explore the efficacy and safety of topical NSAIDs and alternative pain management strategies to enhance clinical practice.

A green liquid chromatographic method using ethanol in mobile phase for the determination of nimesulide and naproxen in gel formulations

Dеtеrmination of nonsteroidal anti-inflammatory drugs (NSAIDs) in pharmacеutical formulations hеlps to еnsurе that thеy arе manufacturеd to thе corrеct spеcifications. Consequently, simple, reliable, and environmentally friendly analytical methods are needed for the quality control of NSAID formulations. In this study, a novel and green liquid chromatographic method was developed for the determination of nimesulide (NIM) and naproxen (NAP) in gel formulations by employing ethanol as a green alternative to hazardous methanol and acetonitrile. The high viscosity of ethanol was compensated by employing a Chromolith HighResolution RP18e monolithic column (100 × 4.6 mm) with low flow resistance. Box-Behnken design with desirability function was employed for the optimization of selected significant parameters: pH (2.8-4), ethanol ratio in the mobile phase (35-55%), and flow rate (0.7-1.5 mL/min). Under optimum conditions, satisfactory separation of analytes was achieved within 5 min. Calibration curves for both analytes were linear between 1-50 μg/mL. Accuracies of intra- and inter-day experiments at low-, middle-, and high-quality control levels ranged from 99.0-101.5% with relative standard deviation values lower than 2.3%. The limits of detection were 0.27 and 0.62 µg/mL for NIM and NAP, respectively. The applicability of the method was demonstrated by analyzing gel formulations. The results of this study indicated that monolithic columns in combination with ethanol as a mobile phase component could be considered a desirable and green alternative for the routine analysis of NSAIDs in quality control laboratories.

Thermosensitive Polyurethane-Based Hydrogels as Potential Vehicles for Meloxicam Delivery.

Meloxicam (MX) is a nonsteroidal anti-inflammatory drug (NSAID) used mainly to reduce pain, inflammation, and fever. In the present study, thermosensitive polyurethane (PU)-based hydrogels with various excipients (PEG, PVP, HPC, and essential oil) were prepared and loaded with MX. Rheological investigations were carried out on the PU-based formulations in various shear regimes, and their viscoelastic characteristics were determined. The average size of the PU micelles was 35.8 nm at 37 °C and slightly increased at 37 nm in the presence of MX. The zeta potential values of the hydrogels were between -10 mV and -11.5 mV. At pH = 6 and temperature of 37 °C, the formulated PU-based hydrogels loaded with MX could deliver significant amounts of the active substance, between 60% and 80% over 24-48 h and more than 90% within 2 weeks. It was found that anomalous transport phenomena dominated MX's release mechanism from the PU-based networks. The results are encouraging for further studies aiming to design alternative carriers to commercial dosage forms of nonsteroidal anti-inflammatory drugs.

Parenteral Ready-to-Use Fixed-Dose Combinations Including NSAIDs with Paracetamol or Metamizole for Multimodal Analgesia-Approved Products and Challenges.

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute painful conditions like post-operative and post-traumatic pain. Despite the satisfactory results achieved by oral analgesics, parenteral analgesia remains a key tool in the treatment of painful conditions when the enteral routes of administration are inconvenient. Parenteral ready-to-use fixed-dose combinations of non-opioid analgesics combinations, including NSAIDs and paracetamol or metamizole, could play a central role in the treatment of painful conditions by combining the advantages of multimodal and parenteral analgesia in a single formulation. Surprisingly, only in 2020, a parenteral ready-to-use fixed-dose combination of ibuprofen/paracetamol was launched to the market. This review aims to investigate the current availability of combinations of NSAIDs with paracetamol or metamizole in both European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, we explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. We concluded that, despite the well-recognized utility of combining NSAIDs with paracetamol or metamizole, several randomized clinical trial studies demonstrate no clear advantages concerning their efficacy and safety. Future clinical trials specifically designed to assess the efficacy and safety of pre-formulated fixed-dose combinations are required to generate solid evidence about their clinical advantages.

A prospective comparative randomized trial of the efficacy and safety of topical tenoxicam and diclofenac in knee osteoarthritis

Local forms of non-steroidal anti-inflammatory drugs (NSAIDs) are characterized by a high safety profile due to low systemic absorption. They do not increase the risk of developing class-specific gastrointestinal, cardiovascular and kidney adverse events (AEs), which makes it possible to prescribe them even in severe comorbid pathology, which is typical for patients with osteoarthritis (OA).Objective: to evaluate the efficacy and safety of Artoxan gel (tenoxicam) 1% in comparison with Diclofenac gel 1% in patients with knee OA in a prospective comparative randomized trial.Material and methods. The study included 60 patients with Kellgren–Lawrence stages II–III knee OA, aged 41 to 78 years. The patients were randomly divided into two groups: the 1st group received Artoxan gel 1%, 5 cm 2 times a day for 14 days; 2nd – Diclofenac gel 1% according to the same scheme. During therapy, we assessed pain using a visual analog scale, the WOMAC index, quality of life using the EQ-5D questionnaire, satisfaction with therapy, and time to effect.Results and discussion. It has been demonstrated that local forms of NSAIDs have a positive effect on all clinical manifestations of OA: effectively reduce pain, stiffness, improve the functional state of the joints and quality of life. They also have a good safety profile and a fast symptomatic response. Comparison of the two groups showed that in patients receiving the local form of tenoxicam, there was a tendency to a more rapid and pronounced analgesic effect.Conclusion. The results of the study confirm the good efficacy and safety of local forms of NSAIDs.

The Safety of Celecoxib as an Acute Treatment for Migraine: A Narrative Review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the first-line choice for the acute treatment of migraine attacks for decades; however, the safety of a particular NSAID is related to its treatment dose, duration, and mechanism of action. Although adverse event (AE) risks differ substantially among individual migraine treatments, increased or prolonged exposure to any NSAID elevates risks and severity of AEs. For this narrative review, we conducted a literature search of PubMed until July 2022, focusing on the history, mechanism of action, and treatment guidelines informing the safety and efficacy of celecoxib oral solution for the acute treatment of migraine attacks. Here we discuss the mechanisms of action of nonselective NSAIDs vs. cyclooxygenase-2 (COX-2) inhibitors, and how these mechanisms underlie the AEs associated with these treatments. We review the clinical trials that influenced the regulatory history of NSAIDs, specifically COX-2 inhibitors, the role of traditional and new formulations of NSAIDs including celecoxib oral solution, and special considerations in the acute treatment of migraine attacks. Low-dose formulations of NSAIDs, such as celecoxib oral solution, provide acute migraine analgesia with similar or fewer associated cardiovascular and gastrointestinal events than previous formulations.

Topical nonsteroidal anti-inflammatory drugs for management of osteoarthritis pain: A consensus recommendation.

Osteoarthritis (OA) contributes to significant medical and socioeconomic burden in many populations. Its prevalence is expected to rise continuously owing to the combined effects of aging and increase in risk factors, including obesity, physical inactivity, and joint injuries. Pain is a hallmark presentation of OA. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended by many international guidelines as an early treatment option of the management of osteoarthritic pain. However, the use of topical NSAIDs remains low in Malaysia and appears not to be a preferred agent in managing OA pain by prescribers. There is also limited guidance from local medical bodies on the use of topical NSAIDs to manage OA pain. This consensus recommendation is intended to serve as a practical guide for healthcare practitioners on the use of topical NSAIDs in the management of OA pain. Eight statements and recommendations were finalized covering the areas of OA burden, topical NSAIDs formulations, safety and efficacy of topical NSAIDs, and patient education. Robust evidence is available to support the efficacy and safety of topical NSAIDs, with its benefits further strengthened by ease of use and access. Taking these into consideration, we recommend that healthcare practitioners advocate for the early use of topical NSAIDs over oral NSAIDs for mild-to-moderate OA pain, while engaging in a shared decision-making process with patients for optimal clinical outcomes.

Analgesic and anti-inflammatory effects of diclofenac and ketoprofen patches in two different rat models of acute inflammation

ObjectivesTopical forms of Non-steroidal anti-inflammatory drugs (NSAIDs) used to treat pain, fever and inflammation ensure reduced occurrence of systemic adverse effects that are common with oral application. Compared to the systemic therapy, topical applications of NSAIDs require lower doses to achieve pain relief, and thus pose lower risk of major drug interactions. We aimed to evaluate analgesic and anti-inflammatory effects of diclofenac and ketoprofen patch in the rat model of acute inflammation. MethodsWistar male rats, body weight 220–290 g were randomized into five groups with six rats. Two groups were treated with diclofenac patch at different doses, two with ketoprofen patch at different doses, while a placebo patch was administered to the control group. After patches removal and initial measurements of pain, gait, body temperature, paw temperature, color and paw volume, the models of acute inflammation were applied: yeast-induced hyperalgesia and carrageenan-induced edema. Measurements were repeated one, three and five hours after inflammation induction. ResultsAcute inflammations induced by both used models did not affect the whole-body temperature. However, there were significant (p < 0.05) differences in pain, gait, paw temperature, color and volume between low and high dose diclofenac and ketoprofen groups compared to the control group in different time points, in both models. ConclusionsOur results confirm the analgesic and anti-inflammatory efficacy of diclofenac and ketoprofen patches when used in two well-established rat models of inflammation. These findings suggests that diclofenac patch would be a useful formulation in clinical practice as a novel treatment option. However, new prospective double blind randomized clinical trials are necessary to evaluate analgesic and anti-inflammatory effect of topically applied NSAIDs when used in specific pain and inflammation indications.

Pharmacokinetics, safety and efficacy of intra-articular non-steroidal anti-inflammatory drug injections for the treatment of osteoarthritis: A narrative review.

What is known and ObjectiveOsteoarthritis (OA) is a common cause of joint disease and activity limitation in adults. Common therapies to treat OA‐related pain are oral and topical non‐steroidal anti‐inflammatory drugs (NSAIDs) and intra‐articular (IA) corticosteroids. However, prolonged courses of oral NSAIDs are associated with systemic adverse effects and repeat IA corticosteroid injections may cause cartilage degeneration. IA NSAIDs may be an alternative therapy possibly minimizing systemic side effects while maintaining efficacy. Therefore, we sought to summarize the pharmacokinetics, safety and efficacy of IA NSAIDs to help providers make a more informed decision on the use of IA NSAIDs.MethodsWe searched the National Library of Medicine Database with terms “intraarticular and nsaid”, yielding 1032 results. Only traditional formulations of NSAIDs were considered for inclusion. Animal studies were included if animals were healthy or if the method of arthritis induction was a reasonable model of osteoarthritis. Human studies were included if humans were healthy or if the primary disease studied was osteoarthritis of a large joint. Of 1032 results, 31 research articles met the inclusion criteria and were summarized in this review.Results and DiscussionWe found that single doses of IA NSAIDs provided far less total systemic and synovial exposure compared to a one week course of oral NSAIDs, but maximum concentrations to the synovium with IA administration were much higher. IA NSAIDs had an excellent safety profile in small animals, large animals and humans, although these injections were associated with non‐specific cartilage inflammation in healthy animals. In animal models, IA NSAIDs had similar efficacy to PO NSAIDs in treating OA‐related pain. In humans, IA NSAIDs had similar efficacy to PO NSAIDS and IA corticosteroids in treating OA‐related pain; however, many trials did not have a placebo control and outcome measures were heterogeneous.What is new and ConclusionOverall, single doses of IA NSAIDs appear safe and efficacious across animals and humans. The optimal use of IA NSAIDs is still to be determined and further research is needed. However IA NSAIDs may be an additional beneficial therapy to treat OA‐related pain. Potential uses may be to augment IA corticosteroids injections, to interrupt multiple IA corticosteroid injections or as an alternative in patients that are high risk for corticosteroid‐related adverse events.

Recent advances on transdermal delivery systems for the treatment of arthritic injuries: From classical treatment to nanomedicines.

Arthritic injuries happen frequently during a lifetime due to accidents, sports, aging, diseases, etc. Such injuries can be cartilage/bone injuries, tendon injuries, ligament injuries, inflammation, pain, and/or synovitis. Oral and injective administration of therapeutics are typically used but cause many side effects. Transdermal administration is an alternative route for safe and efficient delivery. Transdermal formulations of non-steroidal anti-inflammatory drugs have been available on market for years and show promising efficacy in pain relieving, inflammation alleviation, infection control, and so on. Innovative transdermal patches, gels/films, and microneedles have also been widely explored as formulations to deliver therapeutics to combat arthritic injuries. However, transdermal formulations that halt disease progression and promote damage repair are translated slowly from lab bench to clinical applications. One major reason is that the skin barrier and synovial capsule barrier limit the efficacy of transdermal delivery. Recently, many nanocarriers, such as nanoparticles, nanolipids, nanoemulsions, nanocrystals, exosomes, etc., have been incorporated into transdermal formulations to advance drug delivery. The combined transdermal formulations show promising safety and efficacy. Therefore, this review will focus on stating the current development of nanomedicine-based transdermal formulations for the treatment of arthritic injuries. The advances, limitations, and future perspectives in this field will also be provided to inspire future studies and accelerate clinical translational studies. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Biology-Inspired Nanomaterials > Lipid-Based Structures.

Місцеве застосування нестероїдних протизапальних засобів: переваги та недоліки

У статті наведені дані літератури щодо ефективності та безпеки декскетопрофену трометамолу у вигляді гелю при місцевому застосуванні та порівняльна характеристика даного фармакологічного засобу з іншими трансдермальними формами нестероїдних протизапальних препаратів. В процесі досліджень було встановлено, що декскетопрофен при місцевому застосуванні у вигляді гелю має високу здатність до накопичення у шкірі, м’язовій і нервовій (нейрони, мієлін та гіпоталамус) тканинах, що обумовлює хороший протизапальний, протинабряковий та аналгезуючий ефект даного лікарського засобу. Декскетопрофен продемонстрував низький рівень накопичення у хрящовій тканині, що не стимулює дегенеративні зміни тканини хряща, оскільки не пригнічує синтез протеогліканів хондроцитами. Разом з тим декскетопрофен показав невисоку здатність до накопичення у клітинах крові та у внутрішніх органах, демонструючи низьку ймовірність системних побічних ефектів.

Prednosti lipozomalnih nesteroidnih antiinflamatornih lekova

Introduction: Liposomes are small, spherical artificial vesicles that can be created from cholesterol and natural non-toxic phospholipids. Due to their size, hydrophobic and hydrophilic character (besides biocompatibility), liposomes are promising drug delivery systems. Topic: Liposomal formulations of non-steroidal anti-inflammatory drugs (NSAIDs) can be used in all population groups (children, adults, and the elderly) which gives them a wide range of applications. NSAIDs oral administration is associated with severe adverse effects in the gastrointestinal tract such as epigastric pain, heartburn, nausea, diarrhea, vomiting, peptic ulcer, and hepatic impairment. It has been observed in clinical trials, that liposomal formulations enhanced the drug permeability and the percentage of accumulated dose in the skin compared to control conventional gel formulations. Liposomal gel controls ibuprofen release and drug permeability in vitro and has shown a permeability pattern conducive to maintaining constant drug levels. Application: So far, liposomes containing sodium diclofenac, indomethacin, aceclofenac, and related NSAIDs have been produced in laboratory conditions. Liposomal technology is most commonly applied in cosmetology, cancer therapy and yet unexplored application possibilities for liposomes, such as therapy for Alzheimer's disease. Although varying in size and structure, they all possess certain common advantages - increased dermal availability of lipophilic drugs and their targeted delivery onto the required location. Liposomes have been proven highly effective in terms of retaining the NSAIDs in the synovial cavity, mostly because of their size and chemical composition. Undesirable therapy effects, fast clearance, and exposure to nontargeted sites could be minimized by administering NSAIDs using liposomes as carriers. Side effects and complications associated with the long-term oral and intramuscular applications of NSAIDs could especially be avoided using their liposomal formulations. Liposomes can be seen as ideal carriers for anti-inflammatory drugs as their ability to (passively) target sites of inflammation and release their content to inflammatory target cells enables them to increase local efficacy with only limited systemic exposure and adverse effects, improving bioavailability and patient compliance. A few NSAIDs are experimentally formulated in liposomes having improved pharmacokinetic characteristics. Further clinical investigations will show their pharmaco-dynamic effects. The in vitro release and ex vivo permeation (permeability) study showed a prolonged diclofenac release with high permeation flux. Conclusion: The use of liposomes as drug carriers becomes a notable positive step in the treatment of inflammatory, pain-causing, and rheumatic diseases. Liposomes present an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address the different delivery considerations. The main objectives for the development of NSAIDs in liposomal carriers are deeper penetration of the active substance, fewer side effects, better and longer effect, the ability to change the characteristics of both the drug and the carrier, and adequate dose adjustment. Despite several challenges that accordingly still need to be addressed, liposomal drug formulations have significant health-promoting potential. Despite the encouragement of NSAID development and research studies, it still takes a long time for liposomal NSAID formulations to become available for everyday use.

Optimization and Evaluation of the In Vitro Permeation Parameters of Topical Products with Non-Steroidal Anti-Inflammatory Drugs through Strat-M® Membrane.

Pharmaceutical products containing non-steroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed topical formulations used for analgesic and antirheumatic properties. These drugs must overcome the skin barrier to cause a therapeutic effect. Human skin has been widely used as a model to study in vitro drug diffusion and permeation, however, it suffers from many limitations. Therefore, to perform in vitro permeation test (IVPT), we used a Strat-M® membrane with diffusion characteristics well-correlated to human skin. This study’s objective was to optimize the IVPT conditions using Plackett–Burman experimental design for bio-predictive evaluation of the in vitro permeation rates of five non-steroidal anti-inflammatory drugs (diclofenac, etofenamate, ibuprofen, ketoprofen, naproxen) across Strat-M® membrane from commercial topical formulations. The Plackett–Burman factorial design was used to screen the effect of seven factors in eight runs with one additional center point. This tool allowed us to set the sensitive and discriminative IVPT final conditions that can appropriately characterize the NSAIDs formulations. The permeation rate of etofenamate (ETF) across the Strat-M® membrane was 1.7–14.8 times faster than other NSAIDs from selected semisolids but 1.6 times slower than the ETF spray formulation.

Therapeutic Recommendations for the Management of Older Adult Patients with Sjögren's Syndrome.

Primary Sjögren's syndrome (SjS) is a systemic autoimmune disease most commonly diagnosed in middle-aged women. Although the disease can occur at all ages, it is diagnosed between 30 and 60years of age in two-thirds of patients. In more than 20% of cases, the people are older than 65years. In this review, we focus on the therapeutic management of primary SjS in older patients, following the recently published 2020 European League Against Rheumatism (EULAR) recommendations for the management of the disease with topical and systemic therapies. These recommendations are applicable to all patients with primary SjS regardless of age at diagnosis, although the therapeutic management in older patients requires additional considerations. Older patients are more likely to have pulmonary, liver, kidney, or heart-related comorbidities (even cognitive disturbances); caution is required when most drugs are used, including muscarinic agents, systemic corticosteroids and synthetic immunosuppressants. It is also important to monitor the use of eye drops containing steroids due to the increased risk of developing cataracts, a frequent ocular complication in the older population. In contrast, the majority of drugs that can be used topically (pilocarpine rinses, eye drops containing topical non-steroidal anti-inflammatory drugs (NSAIDs) or cyclosporine A, topical dermal formulations of NSAIDs) have shown an acceptable safety profile in older patients, as well as rituximab. A rigorous evaluation of the medical history of older patients is essential when drugs included in the EULAR guidelines are prescribed, with special attention to factors frequently related to ageing, such as polypharmacy, the existence of organ-specific comorbidities, or the enhanced susceptibility to infections.

Cost variation analysis of nonsteroidal anti-inflammatory drugs available as single formulation in the Indian market

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed and over the counter (OTC) used drugs worldwide for their analgesic, anti-inflammatory, and anti-pyretic properties. India being a hub for pharmaceutical industries, manufacture large number of branded and generic drugs. Thus, there is wide variation in their cost. Prescribing drug without considering the cost of therapy may result in loss of compliance or imposes economic burden on patient. Aim and Objective: The aim of the study was to evaluate existing price variation of different single NSAIDs formulations available in Indian market. Materials and Methods: Price of NSAIDs manufactured by different pharmaceutical companies in India, in the same strength, was obtained from Current Index of Medical Specialties, January-April 2020, Drug Today October-December 2019, and 1 mg.com. Difference in the maximum to minimum price of the same formulation manufactured by different pharmaceutical companies and percentage cost variation was calculated. Results: price of 14 NSAIDs that are available in 56 different formulations and manufactured by different pharmaceutical companies was obtained and evaluated. Study shows largest variation with Nimesulide 100 mg (5476.74%), piroxicam DT 20 (3071.46%), piroxicam 20 mg (2853.36%), diclofenac 50 mg (2786%), Aceclofenac 100 mg (2345.6%), and ibuprofen 400 mg (1198.70%) and minimum variation was seen with Aspirin 150 mg (90.47%) in oral formulations. All formulations of Diclofenac injection show very high price variation. Diclofenac 1% gel shows maximum price variation of 778.66% while Nimesulide 1% gel shows minimum variation of 159.32%. Conclusion: Our study finding showed significant cost variation in different brand of NSAIDs available in India. The physician must choose the drug on the basis of cost and rationality rather than on the basis of claims done by various pharmaceutical companies. Modifications in pharmaceutical policy with strict control on huge price variations are the need of time.

Comparison of Skin Permeation and Putative Anti-Inflammatory Activity of Commercially Available Topical Products Containing Ibuprofen and Diclofenac.

PurposeThe therapeutic effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs) depends on the drug’s ability to penetrate and permeate the skin and subsequently inhibit cyclo-oxygenase (COX) isoforms responsible for pain and inflammation. Most commercially available topical NSAID formulations are clinically effective, but direct comparisons of anti-inflammatory activity including both skin absorption and inhibitory potency are lacking. This study examined the skin absorption of representative commercially available topical diclofenac- and ibuprofen-based formulations along with published potency values to determine formulations with superior anti-inflammatory activity.Materials and MethodsCumulative absorption and flux profiles of 12 commercially available topical NSAIDs (6 diclofenac-based and 6 ibuprofen-based) were evaluated in vitro using human skin in static Franz diffusion cells. Each formulation was applied as a single dose. In vitro permeation parameters and published COX-2 inhibition values were used to calculate a modified index of topical anti-inflammatory activity (mITAA).ResultsAll diclofenac and ibuprofen formulations permeated human skin in vitro. The rate and degree of absorption differed between diclofenac and ibuprofen formulations and between formulations of the same drug. NSAID concentration within a product was not solely responsible for the permeation flux or degree of absorption. Ibuprofen formulations permeated the skin more rapidly and to a greater degree than diclofenac, but calculated mITAAs were higher for diclofenac.ConclusionDiclofenac exhibited superior anti-inflammatory activity as measured by the index. Differences beyond drug concentration, including excipients, drug salt form, and dosage form, contribute to differences in absorption and thus in anti-inflammatory activity. Both absorption and COX-2 inhibition potency are important for anti-inflammatory activity, but their priority depends upon the products being compared—with the same NSAID, absorption determines superiority; with different NSAIDs, superiority is determined by the balance between absorption and COX-2 potency. These findings should be considered when selecting a topical NSAID for treating patient pain and inflammation.

EP15 A self-limiting symmetrical polyarthritis following COVID-19 infection

Case report - IntroductionWe describe an acute onset self-limiting seronegative non-destructive symmetrical polyarthritis five weeks after laboratory confirmed COVID-19 infection.Case report - Case descriptionA 37-year-old male hospital doctor of presented to the Early Inflammatory Arthritis clinic with a four-week history of acute onset joint pain, swelling and early morning stiffness in excess of two hours. The symptoms began at the left ankle with Achilles’ tendonitis but progressed over the following 72 hours to a symmetrical polyarthritis affecting the wrists, proximal interphalangeal joints, shoulders, elbows, and knees. Approximately five weeks prior to the onset of his joint symptoms he had laboratory confirmed SARS-CoV-2 infection with six days of fever, non-productive cough, and fatigue. He did not require hospitalisation. His past medical history was significant for biopsy proven non-alcoholic fatty liver disease. There was no prior history of inflammatory arthritis and no personal or family history of skin psoriasis, inflammatory bowel disease or uveitis. There was no preceding genitourinary or gastrointestinal upset. His family history was significant for a sister with seronegative rheumatoid arthritis for which she was taking sulfasalazine. Examination revealed a normal BMI, synovitis at the wrists and proximal interphalangeal joints without evidence of joint effusion in the large joints. Blood tests revealed elevations in the ESR (83 mm/hour, reference range 0-10 mm/hour) and CRP (25mg/dL, reference range <5mg/dL). Serology was negative for the rheumatoid factor, anti-CCP antibodies, antinuclear antibodies, and an extractable nuclear antigen panel. Radiographs of the affected joints were unremarkable. Serological testing was positive for anti-SARS-CoV-2 IgG antibodies.He was started on oral Prednisolone 20mg daily and an NSAID with good symptomatic response and normalisation of his ESR (5mm/hour) and CRP (<1mg/dL). The course of prednisolone was tapered over a 6-week period and he is still in steroid free remission with normal inflammatory markers at follow up. The patient was given a diagnosis of a post-viral reactive arthritis which was attributed to the preceding COVID-19 illness. Case report - DiscussionPost infectious inflammatory arthritis has been described with many viral infections including: hepatitis virus, parvovirus B19, enterovirus, rubella, alphavirus (including Chikungunya), flavivirus (including Zika), herpes viruses (including Epstein-Barr virus), varicella, cytomegalovirus and human immunodeficiency virus (HIV). Interestingly, viral arthritis has not been reported in influenza and human coronaviruses (including SARS and MERS). Arthralgia was reported in 14.9% of laboratory confirmed COVID-19 cases in China during the early phases of the pandemic but inflammatory arthritis was not well described. The clinical course of the inflammatory arthritis in this case was self-limiting with enthesitis and synovitis resolving within six weeks of onset with the mainstay of treatment being symptomatic relief in the form of non-steroidal anti-inflammatory drugs and corticosteroids.Patient perspective: When I woke up that Tuesday morning with severe joint pains and stiffness, I knew something was not right. It was not like anything I have felt before in terms of my joints, having had sports injuries in the past. It was to the point where I was even struggling to go from sitting to standing. Without Prednisolone, I feel as if I would not have been able to work and may even have been house bound. I was relieved that this inflammatory arthritis did respond to Prednisolone. After six weeks of taking Prednisolone, the condition seemed to settle. Case report - Key learning pointsA self-limiting episode of inflammatory arthritis may occur following COVID-19 infection.

Myofascial pain syndrome: risk factors, diagnosis and local therapy

One of the main reasons for seeking medical help is myofascial syndrome (MFS), which is manifested by local inflammation with elements of degenerative changes in the affected tissue, pain and muscle spasm due to dysfunctional disorders in the nociceptive system and a decrease in the quality of life. This review discusses etiopathogenesis in detail, taking into account the factors predisposing to the development of MFS, which are divided into anatomical, ergonomic, medical and psychosocial, and also provides diagnostic criteria for pain MFS, including 5 large and 3 small criteria necessary for diagnosis. The second part of the review examines the indications, efficacy, safety, and benefits of topical forms of nonsteroidal anti-inflammatory drugs (NSAIDs), which have a moderate effect on pain, but have a much better safety profile due to reduced systemic absorption. The use of topical drugs allows you to create an effective concentration of the drug directly in the lesion and avoid undesirable systemic effects. Experts strongly recommend prescribing primarily topical, rather than oral, NSAIDs to patients aged 65 years and older who have concomitant cardiovascular and renal pathology, as well as diseases of the gastrointestinal tract. In more detail, the review examines topical forms of diclofenac, which differ in the maximum degree of transdermal penetration compared to other NSAIDs and the effect of slow release of the active substance into the surrounding tissues.

Safe therapy of osteoarthritis: place of topical nonsteroidal anti-inflammatory drugs

The article discusses the social significance of osteoarthritis as a widespread disease that develops mainly in older people, which makes it difficult to carry out anti-inflammatory and analgesic therapy due to the frequent combination of osteoarthritis with other diseases at this age, the need to treat comorbid conditions, which is often poorly combined with systemic therapy with non-steroidal anti-inflammatory drugs. It is noted that osteoarthritis not only worsens the quality of life of patients, but also leads to a decrease in the length of their life, which emphasizes the medical and social importance of conducting the safest possible therapy for this disease. Data on the negative impact of the presence of chronic pain on the progression of osteoarthritis are presented. The negative aspects of the use of oral forms of non-steroidal anti-inflammatory drugs are discussed: the development of adverse events primarily from the gastrointestinal tract and cardiovascular system, the negative effect on the synthesis of glycoaminoglycans («chondronegative effect»). Discusses the place of topical forms of NSAIDs in the treatment of patients with osteoarthritis in accordance with the recommendations of the International society for the use of topical forms of NSAIDs in the management of patients with osteoarthritis of large and small joints. Data on transdermal transport of the topical form of diclofenac, a small molecule with lipophilic properties, are presented. Data on the effectiveness of topical forms of diclofenac in comparison with oral forms are presented according to numerous randomized controlled trials, and the comparable effectiveness of both forms of diclofenac is demonstrated, with maximum safety of the topical form. A special structure of Voltaren® Emulgel (Voltaren® Emulgel), combining the properties of a gel and cream, which provides rapid transdermal penetration and longer retention of the active substance in the area of inflammation, is described, as well as a special prolonged form of Voltaren® Emulgel), which creates additional convenience for use.

Clinical Efficacy and Safety Profile of Topical Etofenamate in the Treatment of Patients with Musculoskeletal Disorders: A Systematic Review

IntroductionNonsteroidal anti-inflammatory drugs (NSAIDs) are, in general, the cornerstone of musculoskeletal pain management; however, systemic adverse events with oral formulations of NSAIDs are common. To address this problem and limit systemic exposure, topical formulations of some NSAIDs have been developed. The aim of this systematic review was to assess the available evidence on the efficacy and safety of the topical formulations of the NSAID etofenamate in patients with musculoskeletal disorders.MethodsA systematic search of PubMed and Web of Science was conducted using the key words “topical etofenamate efficacy” OR “topical etofenamate safety” OR “topical etofenamate effectiveness” to identify studies of etofenamate published from inception to November 2018. Some published manuscripts of interest known by the authors but not identified in the PubMed search were also included to ensure the review article was as comprehensive as possible.ResultsOverall, 12 studies were identified. These studies demonstrate that topical etofenamate [administered either in gel (5 or 10%), cream (10%) or lotion (10%) formulations)] can improve pain and reduce inflammation in patients with musculoskeletal disorders, including blunt injuries and rheumatic diseases. Etofenamate was shown to have an overall efficacy that was superior to other topical NSAIDs, such as 1% indomethacin and 1% diclofenac, and to be as effective as topical formulations of 2.5% ketoprofen gel and 2% ketorolac gel (although ketorolac showed better elimination of pain at some time points). Also, clinical evidence indicates that etofenamate is generally well tolerated in these indications.ConclusionsThe clinical evidence currently available suggests that etofenamate is an effective therapeutic option for the management of musculoskeletal disorders, such as blunt traumas, lumbago or osteoarthrosis. However, larger and well-controlled clinical trials comparing the efficacy and safety of etofenamate with other newer topical NSAIDs are warranted.