Biomechanical and histological evaluation of aspirin in rotator cuff tear rat model.

Background: Aspirin is a representative non-steroidal anti-inflammatory drug (NSAIDs) and has been commonly used for the treatment of tendinopathy in clinical practice. In this study, we aimed to evaluate the biomechanical and histological healing effects of aspirin on the healing of the tendon-to-bone interface after rotator cuff tear repair. Methods: A total of 20 male Sprague-Dawley rats were randomly divided into two groups of 10 rats each. Group-C performed repaironly, and group-aspirin treated with aspirin after tendon repair. Group-aspirin rat were intraperitoneally injected with aspirin at 10 mg/kg every 24 h for 7 days. Eight weeks after surgery, the left shoulder of each rat was used for histological analysis and the right shoulder for biomechanical analysis. Results: In the biomechanical analysis, there was no significant difference in load-to-failure (group-C: 0.61 ± 0.32 N, group-aspirin: 0.74 ± 0.91 N; p = .697) and ultimate stress (group-C: 0.05 ± 0.01 MPa, group-aspirin: 0.29 ± 0.43 MPa; p = .095). For the elongation (group-C: 222.62 ± 57.98%, group-aspirin: 194.75 ± 75.16%; p = .028), group-aspirin confirmed a lower elongation level than group-C. In the histological evaluation, the Bonar score confirmed significant differences in collagen fiber density (group-C: 1.60 ± 0.52, group-aspirin: 2.60 ± 0.52, p = .001) and vascularity (group-C: 1.00 ± 0.47, group-aspirin: 2.20 ± 0.63, p = .001) between the groups. Conclusions: Aspirin injection after rotator cuff tear repair may enhance the healing effect during the early remodeling phase of tendon healing.

Early administration of ketorolac after cardiac surgery and postoperative complications: Analysis of the MIMIC-IV database.

Inflammation may contribute to postoperative cardiac complications and ketorolac, an anti-inflammatory agent inhibiting cyclooxygenase (COX), shows promise in enhancing cardiac graft patency by suppressing endothelial cell proliferation in animal studies. However, the safety of postoperative ketorolac use remains controversial. This study investigates the association between early ketorolac application and complications following cardiac surgery. Data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database fueled this retrospective cohort study. The primary outcome is a composite of mortality, pulmonary insufficiency, severe acute kidney injury (AKI), hemorrhage or hematoma, infection, cardiogenic shock, and cerebrovascular infarction postcardiac surgery. Propensity score matching (PSM; 1:1 match, caliper 0.2), multivariate logistic regression, interaction stratification analysis, pairwise algorithmic, and overlap weight model analyses were employed. Following inclusion and exclusion criteria, 7143 patients who underwent valvular surgery or coronary artery bypass grafting (CABG) were included. PSM created a balanced cohort of 3270 individuals (1635 in the ketorolac group). The matched cohort exhibited an 8.1% overall rate of postoperative complications, with a lower composite outcome rate in patients receiving ketorolac within 48 h of surgery compared with those without (PSM, OR 0.70 [95% CI, 0.54-0.90]). Consistent associations were observed in total cohort analyses, sensitivity, and subgroup analyses. Early ketorolac use within 48 h post-CABG or valvular procedures in adults is independently associated with a lower incidence of composite postoperative adverse events. Prospective trials are warranted to assess causality.

Progress and Challenges of Topical Delivery Technologies Meditated Drug Therapy for Osteoarthritis.

Osteoarthritis (OA) is a degenerative disease commonly seen in middle-aged and elderly people. Multiple cytokines are involved in the local tissue damage in OA. Currently, non-pharmacologic and surgical interventions are the main conventional approaches for the treatment of OA. In terms of pharmaceutical drug therapy, NSAIDs and acetaminophen are mainly used to treat OA. However, it is prone to various adverse reactions such as digestive tract ulcer, thromboembolism, prosthesis loosening, nerve injury and so on. With the in-depth study of OA, more and more novel topical drug delivery strategies and vehicles have been developed, which can make up for the shortcomings of traditional dosage forms, improve the bioavailability of drugs, and significantly reduce drug side effects. This review summarizes the immunopathogenesis, treatment guidelines, and progress and challenges of topical delivery technologies of OA, with some perspectives on the future pharmacological treatment of OA proposed.

Refining pain management in mice by comparing multimodal analgesia and NSAID monotherapy for neurosurgical procedures.

While neurosurgical interventions are frequently used in laboratory mice, refinement efforts to optimize analgesic management based on multimodal approaches appear to be rather limited. Therefore, we compared the efficacy and tolerability of combinations of the non-steroidal anti-inflammatory drug carprofen, a sustained-release formulation of the opioid buprenorphine, and the local anesthetic bupivacaine with carprofen monotherapy. Female and male C57BL/6J mice were subjected to isoflurane anesthesia and an intracranial electrode implant procedure. Given the multidimensional nature of postsurgical pain and distress, various physiological, behavioral, and biochemical parameters were applied for their assessment. The analysis revealed alterations in Neuro scores, home cage locomotion, body weight, nest building, mouse grimace scales, and fecal corticosterone metabolites. A composite measure scheme allowed the allocation of individual mice to severity classes. The comparison between groups failed to indicate the superiority of multimodal regimens over high-dose NSAID monotherapy. In conclusion, our findings confirmed the informative value of various parameters for assessment of pain and distress following neurosurgical procedures in mice. While all drug regimens were well tolerated in control mice, our data suggest that the total drug load should be carefully considered for perioperative management. Future studies would be of interest to assess potential synergies of drug combinations with lower doses of carprofen.

Real-world evidence evaluation on consumer experience and prescription journey of diclofenac gel in Sweden.

OBJECTIVES: The aim of this study was to understand profiles of topical Voltaren gel diclofenac (VGD) 2.32 and 1.16% consumers through analyzing prescription patterns and to characterize treatment satisfaction, functional impairment, and pain relief after over-the-counter (OTC) VGD use in Sweden under real-world conditions. METHODS: This observational, real-world study conducted in Sweden had retrospective and prospective segments. The retrospective secondary data segment utilized 12-month diclofenac gel prescription data from the Swedish eHealth Agency (E-hälsomyndigheten). The prospective segment included electronic surveys completed at baseline and weeks 4 and 12 by adult consumers who purchased OTC VGD to treat their pain. RESULTS: Secondary data analyses (n = 12,145) showed that 56.7% of patients receiving diclofenac gel were females ≥70 years old. Most patients did not switch pain treatments; the mean time between diclofenac gel refills was about 2.5 months. From the surveys (n = 264), VGD provided pain relief, indicated by improvement in 11-point pain numeric rating scale scores. Average pain severity at baseline was 5.8 - improving by a mean of 1.3 and 1.9 points at weeks 4 and 12, respectively. The majority of consumers reported improvement in daily functioning (i.e., health-related quality of life [HRQoL]), and most were at least somewhat satisfied with VGD treatment results. CONCLUSIONS: This real-world study provides important insights into the prescription patterns of diclofenac gel and the consumer experience with OTC VGD in Sweden. Patients rarely switched to other topical nonsteroidal anti-inflammatory drugs, and VGD consumers reported pain relief and improved HRQoL compared to baseline - resulting in treatment satisfaction.

Topical bromfenac in VEGF-driven maculopathies: topical review and meta-analysis.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies. METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac. RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported. CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.

Nitroglycerin combined with NSAIDs for prevention of post-ERCP pancreatitis: A meta-analysis of prospective, randomized, controlled trials.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. OBJECTIVE: A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. METHODS: Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. RESULTS: A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. CONCLUSION: GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.

Combination of Indomethacin with Nanostructured Lipid Carriers for Effective Anticancer Therapy.

Purpose: The anticancer potential of indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, in vivo, and in clinical trials is well known and widely reported in the literature, along with their side effects, which are mainly observed in the gastrointestinal tract. Here, we present a strategy for the application of the old drug indomethacin as an anticancer agent by encapsulating it in nanostructured lipid carriers (NLC). We describe the production method of IND-NLC, their physicochemical parameters, and the results of their antiproliferative activity against selected cancer cell lines, which were found to be higher compared to the activity of free indomethacin. Methods: IND-NLC were fabricated using the hot high-pressure homogenization method. The nanocarriers were physicochemically characterized, and their biopharmaceutical behaviour and therapeutic efficacy were evaluated in vitro. Results: Lipid nanoparticles IND-NLC exhibited a particle size of 168.1 nm, a negative surface charge (-30.1 mV), low polydispersity index (PDI of 0.139), and high encapsulation efficiency (over 99%). IND-NLC were stable for over 60 days and retained integrity during storage at 4 °C and 25 °C. The potential therapeutic benefits of IND-NLC were screened using in vitro cancer models, where nanocarriers with encapsulated drug effectively inhibited the growth of breast cancer cell line MDA-MB-468 at dosage 15.7 µM. Conclusion: We successfully developed IND-NLC for delivery of indomethacin to cancer cells and confirmed their antitumoral efficacy in in vitro studies. The results suggest that indomethacin encapsulated in lipid nanoparticles possesses high anticancer potential. Moreover, the presented strategy is highly promising and may offer a new alternative for future therapeutic drug innovations.

Safety of Oral and Topical Nonsteroidal Anti-Inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to manage mild to moderate pain. While limited use is appropriate for many patients, there are safety concerns with use in certain patient populations or with long-term use of these agents. Topical NSAIDs may provide analgesic benefits while decreasing the overall risks of adverse effects. This article will review safety information for both oral and topical NSAIDs.

Thermo-activated in situ rectal gel preparation for Ibuprofen using eutectic mixture.

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.

Estimating the economic effect of harm associated with high risk prescribing of oral non-steroidal anti-inflammatory drugs in England: population based cohort and economic modelling study.

OBJECTIVES: To quantify prevalence, harms, and NHS costs in England of problematic oral non-steroidal anti-inflammatory drug (NSAID) prescribing in high risk groups. DESIGN: Population based cohort and economic modelling study. SETTING: Economic models estimating patient harm associated with NSAID specific hazardous prescribing events, and cost to the English NHS, over a 10 year period, were combined with trends of hazardous prescribing event to estimate national levels of patient harm and NHS costs. PARTICIPANTS: Eligible participants were prescribed oral NSAIDs and were in five high risk groups: older adults (≥65 years) with no gastroprotection; people who concurrently took oral anticoagulants; or those with heart failure, chronic kidney disease, or a history of peptic ulcer. MAIN OUTCOME MEASURES: Prevalence of hazardous prescribing events, by each event and overall, discounted quality adjusted life years (QALYs) lost, and cost to the NHS in England of managing harm. RESULTS: QALY losses and cost increases were observed for each hazardous prescribing event (v no hazardous prescribing event). Mean QALYs per person were between 0.01 (95% credibility interval (CI) 0.01 to 0.02) lower with history of peptic ulcer, to 0.11 (0.04 to 0.19) lower with chronic kidney disease. Mean cost increases ranged from a non-statistically significant £14 (€17; $18) (95% CI -£71 to £98) in heart failure, to a statistically significant £1097 (£236 to £2542) in people concurrently taking anticoagulants. Prevalence of hazardous prescribing events per 1000 patients ranged from 0.11 in people who have had a peptic ulcer to 1.70 in older adults. Nationally, the most common hazardous prescribing event (older adults with no gastroprotection) resulted in 1929 (1416 to 2452) QALYs lost, costing £2.46m (£0.65m to £4.68m). The greatest impact was in people concurrently taking oral anticoagulants: 2143 (894 to 4073) QALYs lost, costing £25.41m (£5.25m to £60.01m). Over 10 years, total QALYs lost were estimated to be 6335 (4471 to 8658) and an NHS cost for England of £31.43m (£9.28m to £67.11m). CONCLUSIONS: NSAIDs continue to be a source of avoidable harm and healthcare cost in these five high risk populations, especially in inducing an acute event in people with chronic condition and people taking oral anticoagulants.

Chondrotoxicity of Intra-Articular Injection Treatment: A Scoping Review.

The purpose of this scoping review was to identify possible chondrotoxic effects caused by drugs usually used for intra-articular injections. PubMed, Scopus, Web of Science and Cochrane were searched. Inclusion criteria required randomized controlled trials written in English that evaluate the toxic effect that damages the cartilage. The literature search resulted in 185 unique articles. 133 full-text articles were screened for inclusion, of which 65 were included. Corticosteroids, with the exception of triamcinolone, along with local anaesthetics, potentially excluding ropivacaine and liposomal bupivacaine, and nonsteroidal anti-inflammatory drugs, exhibited insufficient safety profiles to warrant casual use in clinical settings. Hyaluronic acid, on the other hand, appears to demonstrate safety while also mitigating risks associated with concurrent compounds, thereby facilitating therapeutic combinations. Additionally, there remains a paucity of data regarding platelet-rich plasma, necessitating further evaluation of its potential efficacy and safety. Overall, it seems that results are significantly influenced by the dosage and frequency of injections administered, observed in both human and animal studies.

Alternatives to Conventional Topical Dosage Forms for Targeted Skin Penetration of Diclofenac Sodium.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

Low-Dose Aspirin and Progression of Age-Related Hearing Loss: A Secondary Analysis of the ASPREE Randomized Clinical Trial.

Importance: Age-related hearing loss is common in an aging population, affecting communication and contributing to a worsened quality of life. It occurs as a result of cochlear degeneration and may be further exacerbated by inflammation and microvascular changes, as observed in animal models. Objective: To compare the effect of daily low-dose aspirin vs placebo on the progression of age-related hearing loss in healthy older adults. Design, Setting, and Participants: A prespecified secondary analysis was conducted of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial. Participants were 279 healthy community-dwelling individuals living in Australia who were aged 70 years or older and free of overt cardiovascular diseases, dementia, and life-limiting illnesses. Participants were recruited between January 1, 2010, and December 31, 2014, and followed up over 3 years. Statistical analysis was completed from June to December 2023. Intervention: A 100-mg daily dose of enteric-coated aspirin or matching placebo. Main Outcomes and Measures: Hearing measures were air conduction audiometry and binaural speech perception in noise. Assessments were conducted at baseline, 18 months, and 3 years. The change from baseline hearing measures were analyzed using an intention to treat approach. Aspirin and placebo were compared using mixed linear regression models adjusting for age, sex, diabetes, and smoking. Results: Of 279 participants, 154 (55%) were male, and the median age at baseline was 73.1 years (IQR, 71.5-76.2 years). A total of 98 of 138 participants (71%) in the aspirin group and 94 of 141 participants (67%) in the placebo group reported experiencing hearing loss at baseline. Compared with placebo, aspirin did not affect the changes in mean (SD) 4-frequency average hearing threshold from baseline to year 3 (aspirin: baseline, 27.8 [13.3] dB; year 3, 30.7 [13.7] dB; difference, 3.3 [3.9] dB; placebo: baseline, 27.5 [12.6] dB; year 3, 30.9 [13.8] dB; difference, 3.0 [4.8] dB; P = .55) nor any other tested frequencies. An increase in air conduction threshold indicates a deterioration in hearing. Similarly, for the mean (SD) speech reception threshold, there was no significant difference observed between the aspirin and placebo group at the year 3 follow-up assessment (aspirin: baseline, -9.9 [3.8] dB; year 3, -9.1 [3.8] dB; difference, 0.9 [2.9] dB; placebo: baseline, -10.5 [7.1] dB; year 3, -9.6 [4.1] dB; difference, 0.9 [5.9] dB; P = .86). The findings were consistent across sex, age groups, diabetic and smoking status. Conclusions and Relevance: In this secondary analysis of the ASPREE randomized clinical trial, low-dose aspirin did not affect the progression of age-related hearing loss. More investigation is warranted on whether a longer follow-up or the use of a more powerful anti-inflammatory agent might prove beneficial. Trial Registration: anzctr.org.au Identifier: ACTRN12614000496617.

Eudragit S100 coated iron oxide-chitosan nanocomposites for colon targeting of 5-aminosalicylic acid ameliorate ulcerative colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome.

The therapeutic effect of 5-amino salicylic acid (5-ASA), a first-line therapeutic agent for the treatment of ulcerative colitis (UC), is limited by the modest bioavailability afforded by its oral administration. In this study, a 5-ASA oral delivery system was developed using Eudragit S100-coated iron oxide-chitosan nanocomposites (ES-IOCS/5-ASA) to address this issue. According to drug release studies in vitro, ES-IOCS/5-ASA only released a small amount of drug in simulated gastric fluid with a pH of 1.2. However, in a medium with a pH of 7.5, a relatively rapid and complete release was noted. 5-ASA-loaded iron oxide-chitosan nanocomposites (IOCS/5-ASA) could be effectively taken up by NCM460 cells and performed better anti-inflammatory effects than free 5-ASA. At the same time, IOCS/5-ASA improved barrier damage in DSS-induced NCM460 cells. In vivo models of dextran sulphate sodium (DSS)-induced colitis were used to assess the therapeutic efficacy of oral administration of ES-IOCS/5-ASA. ES-IOCS/5-ASA significantly relieved DSS-induced colitis and enhanced the integrity of the intestinal epithelial barrier. ES-IOCS/5-ASA also reduced the expression of NLRP3, ASC and IL-1ß. Additionally, iron oxide nanoparticles used as nanozymes could alleviate inflammation. In summary, this study indicates that ES-IOCS/5-ASA exert anti-inflammatory effects on DSS-induced colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome expression, presenting a viable therapeutic choice for the treatment of UC.

Formulation Development, Optimization and Evaluation of Flurbiprofen Microsponge Tablet for the Treatment of Rheumatoid Arthritis (RA) by using Box- Behnken Design.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, autoimmune and inflammatory disease that mostly impacts the joints. Chronotherapeutics refers to a treatment method in which in-vivo drug availability is timed to match rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Flurbiprofen is a non-steroidal anti-inflammatory drug, indicated for the relief of inflammation. OBJECTIVES: The aim of the present study was to develop & optimize the microsponges based of Flurbiprofen tablet for Chronotherapeutics for enhanced therapeutic effect. METHODS: Microsponges were developed by Quasi Emulsion solvent diffusion method. Prepared microsponges were optimized in order to analyze the effects of independent variables like concentration of PVA (X1), Volume of Dichloromethane (X2) & stirring speed (X3) on the Entrapment Efficiency (Y1), Mean particle size (Y2) and Drug release at 8 hr (Y3) using box Behnken design. The optimized formulation was subjected to in vitro study and Comparison with marketed formulation. With release kinetics study. RESULT: The optimized formulation Batch (F-18) Show particle size of 49.12µm, entrapment efficiency of 87.46%, and drug release at 8 h 70.49%, which is under the acceptance criteria, which is more effective compared with Marketed tablet. CONCLUSION: The results showed that, as stirring speed increases, the particle size decreases and entrapment efficiency increases. While volume of dichloromethane increases, particle size decreases. Morphology was found to be porous and spherical. Optimized batch of Flurbiprofen microsponge was further formulated in future for invivo study and clinical trials.

Formulation and Evaluation of Meloxicam Hybrid nano Particles.

The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders.

Adjuvant Treatment with Celecoxib after Collagenase Injection for Dupuytren Contracture: A Double-Blind Randomised Controlled Trial.

Background: In patients with a high recurrence risk after treatment for Dupuytren contracture (DC) by Collagenase Clostridium histolyticum (CCH), adjuvant medical therapy may improve the outcome. Non-steroidal anti-inflammatory drugs have been used in the treatment of similar fibroproliferative processes. The aim of this study was to investigate if adjuvant anti-inflammatory medication could improve the outcome of CCH treatment for DC. Methods: In a prospective double blinded randomised trial, the effect of adjuvant peroral celecoxib on the outcome of DC treated with CCH was investigated in 32 patients with a high fibrosis diathesis. Primary outcome was the increase in Total Passive Extension Deficit (TPED)/ray. Secondary outcomes were the TPED of the individual finger joints, Tubiana index, Disability of Arm, Shoulder and Hand score (DASH) and visual analogue scale (VAS) for pain and satisfaction. Results: A significantly greater improvement in the celecoxib group for TPED and metacarpophalangeal contracture was found. For the proximal interphalangeal joint, the effect was much less pronounced. The VAS for pain and satisfaction were better at 6 and 12 weeks in the celecoxib group. The other outcome parameters did not significantly differ between both groups. Conclusions: Adjuvant peroral administration of celecoxib might improve the gain in TPED after treatment with CCH in patients with DC and a high fibrosis diathesis, with a beneficial effect up to 24 months. Level of Evidence: Level II (Therapeutic).