Fixed-dose Combination Research Articles

Eco-friendly second derivative synchronous fluorescence spectroscopic method for simultaneous determination of rosuvastatin and ezetimibe in pharmaceutical capsules

The fixed dose combination of Rosuvastatin and ezetimibe has recently received approval from the FDA for the treatment of elevated levels of low-density lipoprotein cholesterol in adults. Herein, an eco-friendly and highly sensitive spectrofluorimetric method was developed and validated for simultaneous determination of rosuvastatin and ezetimibe in commercial capsules. The developed method involved synchronous fluorescence spectroscopy combined with second derivative spectroscopy to resolve the overlapping fluorescence spectra of rosuvastatin and ezetimibe. The studied drugs were measured in synchronous mode at Δλ of 40 and their recorded synchronous fluorescence spectra were derivatized into second-order spectra, enabling the selective quantification of rosuvastatin and ezetimibe at 370 nm and 312 nm, respectively. Optimization studies regarding to the influence of buffer pH, incorporation of surfactant, choice of diluting solvent, and synchronous Δλ were carried out. The method was validated using the validation characteristics listed in ICH Q2(R1). The calibration curves displayed satisfactory linear relationships across the calibration range of 0.1–2 µg/mL for rosuvastatin and 0.05–3 µg/mL for ezetimibe. The methodology demonstrated robustness to minor modifications in the procedural parameters and selectivity in quantifying the studied drugs in synthetic mixed solutions and commercial capsules without interference. Furthermore, the level of environmental friendliness and sustainability of the suggested spectrofluorimetric approach was assessed in relation to two previously documented methodologies utilizing the AGREE metric. The findings indicated that the suggested method demonstrated a notably superior level of sustainability in comparison to the documented methods.

Abstract MP09: Characteristics of Antihypertension Medication Adherence Among Patients with Resistant Hypertension in the RADIANCE HTN-TRIO Ultrasound Renal Denervation Trial

Background: About 50% of patients are nonadherent to antihypertensive medications (AHM), impairing blood pressure (BP) management. The RADIANCE-HTN TRIO trial screened patients with resistant hypertension by first placing them on a fixed-dose combination triple pill (ARB+amlodipine+HCTZ). Ambulatory BP measurement 4 weeks later found 43% had controlled BP and were thus ineligible for enrollment. A total of 136 patients with uncontrolled BP were randomized to ultrasound renal denervation (uRDN) or sham-control. This analysis assessed adherence characteristics among patients in the trial. Method: TRIO patients consented to have chemical adherence testing that detected AHM or their metabolites in spot urine samples at baseline, 2 and 6 months. Full adherence (FA) was defined by all prescribed drugs detected in the sample. Results: Adherence data were available at any timepoint for 129 and all timepoints for 91 patients. Among patients with data at all timepoints, 66% (60/91) were FA and 34% (31/91) were partially- or fully nonadherent (PA/NA) to any of their prescribed medications. Adherence rates did not differ between treatment groups or geographies. Women were less likely to be FA (p<0.001) (Table). PA/NA patients had higher rates of peripheral and cerebrovascular disease, and higher BP before and after triple pill. Adherence to triple pill was 81% at baseline, 85% at 2-months, and 83% at 6-months. Medications were titrated after 2-months. At 6-months, adherence to additional medication classes prescribed was: aldosterone antagonist 71%, beta blockers 62%, and centrally-acting alpha-2 agonists 60%. Conclusions: The stringent TRIO study design uncovered significant medication nonadherence that translated into a high rate of apparent resistant HTN. It also showed high adherence to a fixed-dose triple pill. One third of enrolled patients were not fully adherent to medications, and these patients had higher BP and higher rates of vascular disease. Understanding clinical features associated with medication adherence may improve hypertension management.

Applying the SeDeM Expert Diagram System for Characterization of Multiple Component Powder Mixtures for Fixed-dose Combination Matrix-type Tablet Formulations

Background: The SeDeM Expert Diagram System (SeDeM EDS) is an innovative formulation tool that provides an index of compressibility, which can be used to predict a pow-der’s suitability for direct compression to produce acceptable tablets. Objective: This study investigated the application of this tool to evaluate multiple component powder formulation mixtures for direct compression of tablets. The SeDeM EDS was specifically used to characterize powder mixtures for fixed-dose combination (FDC) matrix-type tablets that contained multiple active ingredients, which has not been done previously with SeDeM EDS. Methods: The FDC matrix-type tablets contained diclofenac sodium and vitamins B1, B6 and B12 in fixed ratios, intended for the management of peripheral neuropathy. The parameters of the SeDeM EDS were determined for the multiple-component powder mixtures and the indices were calculated to predict direct compressibility. The FDC tablets were subsequently manufactured uti-lizing direct compression and subjected to pharmacotechnical test evaluations to measure the ac-curacy of the SeDeM EDS’s predictions. Results: This study proved the versatility of the SeDeM EDS and its utility to adequately charac-terize FDC powder mixtures for matrix-type tablets manufactured by direct compression. Addi-tionally, a new calculation was suggested to determine the percentage of corrective excipients re-quired in the case when multiple incidence factor values are below the value of 5. Prediction of the correct quantity of corrective excipient to be added is important to obtain an acceptable direct compressible formulation. Conclusion: The results obtained confirmed that the SeDeM EDS correctly predicted the performance of all formulations.

Dexamethasone-Sparing Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting in Highly and Moderately Emetogenic Chemotherapy: The SHEILD Study.

Chemotherapy-induced nausea and vomiting (CINV) significantly impacts patient's quality of life and treatment adherence. This study investigated the efficacy of Generic Netupitant and Palonosetron tablets (Nykron) with dexamethasone single dose for CINV prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).Additionally, this approach aligns with the principles of the SHIELD study (Sparing High Efficacy Intervention for Low Dose Dexamethasone), which focuses on maximizing antiemetic effectiveness while minimizing dexamethasone use. This multicenter retrospective study evaluates data from patients who received HEC/MECand were administered a fixed-dose combination of Generic NEPA (Netupitant 300 mg and Palonosetron 0.5 mg tablets, Nykron combi-pack) along with a single dose of dexamethasone (12 mg/8 mg) before chemotherapy. The data were collected from September 2022 till September 2023. Outcomes measuredincluded complete response (no vomiting and no need for rescue medications), complete protection (no significant nausea (<2.5 cm on VAS), no vomiting, and no use of rescue medication), and complete control (no emetic episodes, no rescue therapy, and no nausea [0 cm on VAS])during the acute phase (0-24 hours) and delayed phase (24-120 hours) post-chemotherapy. The data of 372 patients was evaluated in which breast cancer was the most common cancer with 223 (59.95%) patients for which doxorubicin and cyclophosphamide (192, 51.61%) was the most administered chemotherapy combination. The second most common cancer was gastrointestinal (GI) cancer with stomach cancer in 47 (12.6%), colorectal cancer in 4 (1%), and pancreatic cancer in 2 (0.54%). A total of 360 (96.8%) patients received an HEC regimen across the cycle, while only 5 (1.3%) received an MEC regimen. The regimen demonstrated exceptional efficacy with a 96.9% overall response rate across all cycles. Complete control rates for acute CINV were 92% and 90% for delayed CINV across chemotherapy cycles. Complete response rates remained consistently high (94%-98%) across all cycles and overall phases. Only 3% of patients experienced anticipatory CINV. This dexamethasone-sparing Generic NEPA regimen showed remarkable efficacy in CINV management for HEC/MEC regimen-receiving patients, maintaining high response rates in both acute and delayed across all cycles. These findings indicate a potential paradigm shift in CINV prophylaxis, necessitating further investigation through prospective, randomized controlled trials to validate long-term safety and efficacy.

Abstract MP07: Efficacy and safety of aprocitentan in patients with resistant hypertension and elevated NT-proBNP

Background and Objectives: The endothelin ETA/ETB receptor antagonist aprocitentan (APRO) decreased blood pressure (BP) in patients with confirmed resistant hypertension (RHT) in the PRECISION study. 19.6% of the overall population (143 subjects) had a reported history of Heart Failure (HF). It is well known that in subjects with RHT, HF is often underdiagnosed. In PRECISION, NT-proBNP (a marker of HF) was measured. Here we report the efficacy and safety of APRO in patients with increased NT-proBNP. Methods: 730 patients with RHT were switched to a standardized fixed-dose combination of amlodipine/valsartan/hydrochlorothiazide from their existing anti-hypertensive and diuretic medication and then randomized to APRO (12.5 mg or 25 mg) or placebo in PRECISION. This analysis considers subjects with baseline blood levels of NT-proBNP &gt;125 pg/mL. Change in BP, incident cases of edema/fluid retention and change in body weight were assessed. Descriptive statistics are presented. Results: 236 enrolled subjects (32.3%) had NT-proBNP levels from 125–1125 pg/mL. At Week 4, APRO 12.5 mg decreased trough sitting systolic BP (SiSBP) by mean (SD) 14.2 (16.7) mm/Hg, APRO 25 mg by 15.8 (13.5) mm/Hg and placebo by 9.9 (18.0) mm/Hg, confirming that the effect was greater for APRO than placebo with no apparent difference between 12.5 and 25 mg, as observed in the overall population enrolled in PRECISION. The effect was maintained with APRO 25 mg at Week 36 with a decrease of 18.4 (15.2) mm/Hg versus baseline. Adverse events of edema/fluid retention were reported with an incidence of 13.4%, 25.7% and 1.2% in the 12.5 mg, 25 mg and placebo group, respectively, at Week 4. During the SB part up to 36 weeks edema/fluid retention was reported by 26.1% of subjects with 25 mg. Body weight change at Week 4 was +0.5, +0.7 and -0.2 Kg with 12.5 mg, 25mg and placebo, respectively. This weight increase was reversible: a subsequent decrease resulted in a difference versus baseline of 0.4 kg at Week 36. NT-proBNP ratio vs baseline (geometric mean) was 0.94, 0.86 and 0.78 with 12.5 mg, 25 mg and placebo, respectively, at Week 4. There was no increase over time, the ratio vs baseline was still below 1 (0.91) at Week 36. Conclusion: Aprocitentan is effective in patients with RHT and elevated NT-proBNP. Edema and fluid retention are more common in this sub-group compared with the overall population included in PRECISION, but it is not linked to significant weight gain or increase of NT-proBNP.

Safety and Efficacy of Fixed-Dose Combination of Adapalene and Benzoyl Peroxide in Acne Vulgaris Treatment: A Systematic Review of Clinical Trials.

The Global Burden of Disease Study 2020 ranked acne vulgaris as the eighth most common skin condition, with a global estimated prevalence of 9.4%. The clinical presentation of acne vulgaris ranges from comedones to nodules and cysts. The main treatment options for acne are retinoids, antibiotics, and benzoyl peroxide (BPO). This study aimed to evaluate the reported efficacy and safety of the combination treatment with retinoid and benzoyl peroxide. Three databases (ScienceDirect, Google Scholar, and PubMed) were searched using keywords such as acne, adapalene/benzoyl peroxide, and randomized controlled trial, and specific search moods such as "Title and abstract" for PubMed and "Title, abstract, and keywords" for ScienceDirect. On Google Scholar, the "allintitle" option was utilized. The articles were searched for the years between 2003 and 2023. The eight trials selected for systematic review reported randomized controlled trials in 4,596 individuals with the first trials being conducted in February 2007 and the last one in May 2022. There were 52.8% females in the trials, and the trials reported a primary reduction of acne lesions (efficacy) from 27.5% to 70.2%.The occurrence of adverse effects was also variable (ranging from 2.7% to 57.9%), but these effects were mild and vanished with time. The results showed that the combination of adapalene and benzoyl peroxide is a safe and effective treatment.

Abstract 28: A major effect of aprocitentan on albuminuria in patients with resistant hypertension

Background and Objectives: Micro- and macroalbuminuria measured by urinary albumin-to-creatinine ratio (UACR) (30–300 mg/g and &gt;300 mg/g, respectively), and high normal UACR (10–30 mg/g) are associated with higher risk of mortality, CV disease and CKD progression in patients with hypertension, diabetes, decreased renal function, or even the general population and reduction can lower these risks. The endothelin ETA/ETB receptor antagonist aprocitentan reduced albuminuria in patients with confirmed resistant hypertension (RHT). In the PRECISION trial, in addition to standard background therapy including valsartan, aprocitentan 12.5 mg reduced UACR by 30% compared to placebo (LS Geom Mean [95 CL] 0.70 [0.61, 0.80], p&lt;0.0001) and 25 mg by 34% (0.66 [0.58,0.75], p&lt;0.0001) at the end of double-blind part 1 (4 weeks) in the overall population. In this analysis, we evaluated the effect of aprocitentan on UACR at both doses according to the baseline (BL) albuminuria (30–300 mg/g and &gt;300 mg/g). Methods: 730 patients with RHT on a standardized fixed-dose combination of amlodipine/ valsartan/hydrochlorothiazide were randomized to aprocitentan (12.5 mg or 25 mg) or placebo. Of these, 174 and 90 had BL microalbuminuria or macroalbuminuria, respectively. Changes from BL in UACR and office systolic blood pressure measured at trough (SBP, the primary endpoint in PRECISION) after 4 weeks of double-blind treatment. Results: In subjects with microalbuminuria, aprocitentan reduced UACR by 43% in the 12.5 mg group (0.57 [0.42, 0.78], p=0.0005) and by 45% in the 25 mg group (0.55 [0.40,0.77], p=0.0004) compared to placebo. In subjects with macroalbuminuria, aprocitentan reduced UACR by 48% with 12.5 mg (0.52 [0.37, 0.75], p=0.0006) and by 61% with 25 mg (0.39 [0.27,0.57], p&lt;0.0001) compared to placebo. In contrast, placebo did not have any noticeable effect on albuminuria in any group. The effect of aprocitentan in lowering blood pressure, measured at trough, was independent of the level of albuminuria at baseline. After 4 weeks, 53.3% and 60% of patients achieved a decrease of ≥10 mmHg from baseline with 12.5 mg aprocitentan, respectively in the microalbuminuria and macroalbuminuria groups, compared to 64% with aprocitentan 25 mg (both cohorts) and 48% and 29% in the placebo group. Conclusion: Aprocitentan produced a major decrease of albuminuria regardless of baseline level in patients with RHT. These findings suggest substantial clinical benefit of aprocitentan in CKD patients.

Sumatriptan-naproxen sodium in migraine: A review.

Varied responses to acute migraine medications have been observed, with over one-third (34.5%) of patients reporting insufficient headache relief. Sumatriptan-naproxen sodium, a single, fixed-dose combination tablet comprising sumatriptan 85 mg and naproxen sodium 500 mg, was developed with the rationale of targeting multiple putative mechanisms involved in the pathogenesis of migraine to optimise acute migraine care. A narrative review of clinical trials investigating sumatriptan-naproxen sodium for both adults and adolescents was performed in March 2024. Across a total of 14 clinical trials in nine publications, sumatriptan-naproxen sodium offered greater efficacy for 2-h pain freedom (14/14) and sustained pain-free response up to 24 h (13/14) compared with monotherapy and/or placebo for both adult and adolescent study participants with an acceptable and well-tolerated adverse effect profile. Clinical trial data also demonstrates the effectiveness of sumatriptan-naproxen sodium in participants with allodynia, probable migraine, menstrual-related migraine and those with poor responses to acute, non-specific, migraine medication. Multi-mechanistic therapeutic agents offer an opportunity to optimise acute medications by targeting multiple mediators involved in the pathogenesis of migraine. Sumatriptan-naproxen sodium resulted in greater initial and sustained pain freedom, compared with either sumatriptan, naproxen-sodium and/or placebo, for the treatment of single or multiple attacks of migraine across both adult and adolescent study populations.

Efficacy and safety of an oral complementary medicine combination in people with symptomatic knee osteoarthritis: Protocol for the double-blind, randomized, placebo-controlled ATLAS trial

ObjectiveTo investigate the efficacy and safety of an oral complementary medicine combination formulation relative to placebo, on changes in pain intensity from baseline to week 12, in people with knee osteoarthritis (OA). DesignA placebo-controlled, double-blind, two-arm, superiority, phase II, Randomized Controlled Trial (RCT) (ACTRN12623000380695). We will recruit 82 participants (∼41 per arm), aged ≥40 years, with a clinical diagnosis of symptomatic knee OA and radiographic change on x-ray (Kellgren-Lawrence Grade ≥2). Participants will be randomly allocated to receive either a complementary medicine formulation containing a daily dose of Boswellia serrata extract (Boswellin® Super, 250 ​mg/day), pine bark extract (Fenoprolic™ 70 Organic 100 ​mg/day), curcumin (500 ​mg/day), piperine (5 ​mg/day), and methylsulfonylmethane (MSM, 1500 ​mg/day), or placebo, for 12-weeks. The primary endpoint will be change from baseline in average knee pain intensity at 12-weeks (visual analogue scale). Secondary endpoints will include change in knee pain from baseline to 12-weeks in the Knee Injury and Osteoarthritis Outcome Score (KOOS), global assessment of disease activity, global rating of change, and health-related quality of life (AQoL-8D). Ethics and disseminationThis protocol has been approved by the University of Sydney Human Research Ethics Committee (#2021/877). Dissemination will occur through lay summaries, infographics, conference abstracts, oral presentations, theses, and scientific publications. ConclusionThis RCT will provide credible evidence about the efficacy and safety of this complementary medicine combination and inform updates to international clinical practice standards on the use of complementary medicines in the management of symptomatic knee OA.

Patient Profiling and Outcome Assessment of Vildagliptin and Dapagliflozin FDC in Persons with Type 2 Diabetes Mellitus

Introduction: Type 2 Diabetes Mellitus (T2D) is a condition characterized by rapid progression, and in certain instances, managing glucose levels may not be adequately achieved with a single pill. Vildagliptin and dapagliflozin in a Fixed-Dose Combination (FDC) complement each other’s actions, aiding in the control of glycemia. The primary goal of this retrospective investigation was to gain insight into the patient characteristics, safety profile, and efficacy of the FDC in reducing weight and glycated hemoglobin levels. Methods: Retrospective data from T2D patients who were prescribed the FDC and had two follow-up visits between May 1, 2022, and January 31, 2023, were enrolled in the study. Results: The average age of the study sample was 55.8 years, with nearly two-thirds being male (65.5%). At 6 months after FDC medication, glycated hemoglobin (HbA1c) significantly decreased by 1.2% (Baseline: 8.4%, Follow-up: 7.2%, p-value &lt;0.001), indicating improved glycemic control. An average weight decrease of 4.3 kg (Baseline: 76.9Kg, Follow-up: 72.5Kg, p-value &lt;0.001), was noted in patients receiving the FDC. Weight loss was higher in males (4.5 kg) than in females (4.0 kg). Safety analysis was carried out for all randomized patients and no major AEs were noted. No patients were withdrawn from the study due to safety concerns. No episode of hypoglycemia occurred during the study time. There were no statistical differences in the hepatic enzymes at the end of six months in the study groups. Conclusion: The Fixed Dose Combination of Vildagliptin and Dapagliflozin effectively enhances glycemic control by demonstrating a significant reduction in mean HbA1c levels after six months compared to baseline. However, further multicenter studies are necessary to substantiate these findings.

Rifaximin and Metronidazole Fixed Dose Combination: New Treatment Option in the Management of Diarrhea

Background: Endemic infectious diarrhea is a widespread problem around the world, caused by a combination of viruses, bacteria, and parasites. While commonly used fluoroquinolone antibiotics are effective for specific types of acute diarrhea, they carry potential side effects. Aim: To assess the effectiveness and tolerability of a fixed-dose combination of rifaximin and metronidazole as an alternative treatment approach for the management of acute diarrhea. Study Design: A multicentre, open-label, non-comparative and non-randomized trial was conducted in 370 patients suffering from acute diarrhea due to various factors. Methodology: Patients were given a tablet containing fixed-dose combination of 200 mg of rifaximin and 400 mg of metronidazole twice daily for 5 days. The primary outcomes evaluated were changes in the number of loose/watery stools, the presence of fever, nausea, vomiting, abdominal pain and gas/flatulence from baseline to day 5. A global assessment using a 3-point scale (Excellent/Good/Poor) was done by the investigators for efficacy and tolerability evaluation. Adverse drug reactions were monitored throughout the study period. Results: After 5-day therapy, the average number of watery stools per day decreased significantly from 7.853 ± 3.773 to 0.766 ± 0.949 (P &lt; .001). None of the patients experienced fever and vomiting, while few patients experienced nausea (0.31%), abdominal pain (0.31%), and gas/flatulence (0.93%) at the end of the study. According to the evaluation by the investigators, all patients reported good to excellent efficacy and tolerability. Conclusions: The combination therapy of rifaximin and metronidazole is clinically effective and safe to treat acute diarrhea caused by different factors and can serve as a new treatment option for managing acute diarrhea.

Clinical effectiveness of amlodipine/indapamide/perindopril fixed-dose combination in patients with metabolic disorders: results of post hoc analyzes of the TRICOLOR study

Aim. To describe antihypertensive effectiveness of triple fixed-dose combination of am lo dipine/indapamide/perindopril and assess predictors of its clinical effectiveness in pati ents depending on body mass index (BMI) and presence of type 2 diabetes (T2D).Material and methods. This observational prospective study TRICOLOR (NCT03722524) (n=1247) demonstrated high antihypertensive effectiveness and good tolerability of amlodipine/indapamide/perindopril fixed-dose combination. Subgroup analyzes based on BMI included data from 1144 patients. In a second subgroup analysis, 1128 patients were stratified according to concomitant T2D.Results. In patients with overweight/obesity and diabetes, good antihypertensive effectiveness of amlodipine/indapamide/perindopril was observed, comparable in blood pressure (BP) reduction with the comparison groups (patients with normal BMI and patients without diabetes). At the same time, patients with normal BMI, compared with patients with overweight and obesity, had significantly lower systolic BP (SBP) (after 4 and 12 weeks) and diastolic BP (DBP) (after 2 and 12 weeks). In the subgroups, depending on the diabetes status, there were no significant differences in the decrease in SBP and DBP levels at all follow-up points. By the 12th week, BP decrease in the group of patients with normal BMI was 32,9 (10,5)/15,3 (8,6) mm Hg, in the group with overweight — 33,2 (11,3)/14,2 (8,5) mm Hg, in the obesity group — 33,9 (12,3)/14,1 (8,8) mm Hg (p&gt;0,05 for intergroup comparison). Target BP &lt;140/90 mm Hg already after 2 weeks of therapy achieved a higher number of patients with a normal BMI compared to overweight group (50,8% vs 37,2%, p=0,009). By the 12th week, the vast majority of patients, regardless of BMI and diabetes status, achieved a target BP &lt;140/90 mm Hg, which demonstrates a good and rapid response to triple fixed-dose therapy.Conclusion. Thus, additional analyzes of the TRICOLOR study demonstrate the high antihypertensive effectiveness of amlodipine/indapamide/perindopril in hypertensive patients, regardless of the presence of diabetes, overweight or obesity.

Strategies to Address Statin Medication Intolerance Among Patients at Risk of Cardiovascular Disease Identified Through Electronic Health Records: A Literature Review and Pooled Analysis.

Statins are a group of medications that lower lipid and are used for primary and secondary prevention of cardiovascular diseases (CVD). Patients can either be partially (15%) or completely (5%) intolerant to statins. Symptoms of statin intolerance can include muscle aches (myalgia), weakness, cramps, myopathy, diabetes mellitus, and elevated creatine kinase levels. Decreasing statin intolerance also improves statin adherence, which in turn results in lower number of CVD events among patients. Studies on statin intolerance is often embedded within studies of statin adherence. However, relevant data can be obtained from digital health systems. This preliminary literature review looks at studies from the past 10 years to identify and determine the effectiveness of strategies to address statin intolerance. The NLA definition for statin intolerance was used in this review. The initial search results on EMBASE, PubMed, SCOPUS, and CINAHL showed 91 articles and applying the inclusion and exclusion criteria, four articles were used in this review and pooled analysis. The study patients were identified through electronic health records. The pooled analysis was done using the Metafor package in R, applying a random-effect model to estimate pooled effect size. The findings suggest that using fixed dose combination therapy and switching from a lipophilic statin to a hydrophilic statin, while correcting metabolic abnormalities, or initiating evolocumab alongside statin can address statin intolerance. The overall relative risk (RR) was 0.40 (95% CI, 0.09 to 1.70) with I2 90%, and the overall odds ratio (OR) was 0.11 (95% CI, 0.01 to 1.59) with I2 94%, suggesting that the interventions work well in addressing statin intolerance. Since statin intolerance is has a vast range of effects, further research works may be done on exploring the possibility of using digital health systems to identify and provide targeted interventions to patients.

Serratiopeptidase with diclofenac sodium for the management of post-operative pain and inflammation in a day care obstetric and gynaecological surgeries

Management of acute post-operative pain and swelling after the obstetric and gynaecological (OBG) surgeries is crucial part of patient care. Reduction or complete elimination of post-operative pain &amp; swelling, without excessive sedation is the most preferred treatment strategy helping patient’s recovery in terms of rapid mobilization and return to independence. Serratiopeptidase a proteolytic enzyme used for its anti-inflammatory properties. Diclofenac Sodium is commonly used to treat the pain and swelling. This study aimed to evaluate the effectiveness and tolerability of the fixed dose combination (FDC) of Serratiopeptidase (10 mg) with Diclofenac Sodium (50 mg) gastro-resistant tablets in day care OBG surgery. This was a single centre, retrospective, observational data collection in real-life scenario. Data of adult women who had undergone day care OBG surgery and received a FDC of Serratiopeptidase (10 mg) with Diclofenac Sodium (50 mg) gastro-resistant tablets TID for period of 24 hours was retrieved and analysed. VAS (Visual Analogue Scale) data on post-operative pain at rest and pain on movement as well as post-operative swelling were analyzed in conjunction with monitoring for adverse events. Among 61 patient’s data included in the study, 40 (65.57%) had undergone Minimally Invasive Vaginal Hysterectomy (MIVH), 4 (6.56%) had MIVH with Bilateral Salpingo-oophorectomy, and 17 (27.87%) had other OBG surgeries. The average VAS scores for pain at rest (VAS), pain on movement (VAS) and swelling were significantly reduced compared to baseline at all-time points (p&amp;#62;0.001). Clinical global impression of efficacy and safety for 95% physician’s and 93.3% patients was good to very good. FDC was found to be well tolerated without any serious adverse reaction. The results of this clinical study confirms the effectiveness and tolerability of FDC of Serratiopeptidase and Diclofenac sodium in day care OBG surgeries in the early post-operative period.

Design and Development of a Self-nanoemulsifying Drug Delivery System for Co-delivery of Curcumin and Naringin for Improved Wound Healing Activity in an Animal Model.

The present study endeavored to design and develop a self-nanoemulsifying drug delivery system to improve the solubility and dermatological absorption of curcumin and naringin. Curcumin and naringin-loaded self-nanoemulsifying drug delivery system formulations were developed using aqueous phase titration. Phase diagrams were used to pinpoint the self-nanoemulsifying drug delivery system zones. Tween 80 and Labrasol (surfactants), Transcutol (cosurfactant), and cinnamon oil were chosen from a large pool of surfactants, cosurfactants, and oils based on their solubility and greatest nano-emulsion region. Fourier transform infrared spectroscopy, zeta sizer, and atomic force microscopy were used to characterize the optimized formulations and test for dilution and thermodynamic stability. The optimized curcumin-naringin-self-nanoemulsifying drug delivery system demonstrated the following characteristics: polydispersity index (0.412 ± 0.03), % transmittance (97%), particle size (212.5 ± 05 nm), zeta potential (- 25.7 ± 1.80 mV) and having a smooth and spherical droplet shape, as shown by atomic force microscopy. The ability of their combined formulation to cure wounds was tested in comparison to pure curcumin suspension, empty self-nanoemulsifying drug delivery system, and standard fusidic acid. Upon topical administration, the optimized curcumin-naringin-self-nanoemulsifying drug delivery system demonstrated significant wound healing activity in comparison with a pure curcumin suspension, empty self-nanoemulsifying drug delivery system, and standard fusidic acid. Based upon this result, we assume that skin penetration was increased by using the optimized curcumin-naringin-self-nanoemulsifying drug delivery system with enhanced solubility.

Innovations in HIV Treatment and Care in Uganda: Evaluating the Impact of New Antiretroviral Therapies and Healthcare Models

Uganda has made significant strides in the fight against HIV/AIDS through the implementation of innovative treatment strategies and healthcare models. This review article examines recent advancements in antiretroviral therapy (ART) and novel healthcare models adopted in Uganda, evaluating their impact on patient outcomes and healthcare delivery. By analyzing the latest developments in ART, including new drug regimens and long-acting formulations, and exploring innovative healthcare models such as community-based care and task-shifting, this review aims to assess how these innovations contribute to improved HIV treatment and care in Uganda. This article evaluates these innovations’ impact on treatment outcomes and healthcare delivery, based on a comprehensive review of recent studies and programmatic reports. The findings highlight the effectiveness of these innovations in enhancing adherence, reducing transmission, and improving the overall quality of life for people living with HIV. Keywords: Antiretroviral Therapy (ART), Community-Based Care, Fixed-Dose Combinations (FDCs), Long-Acting Formulations, Task-Shifting

The concept of fixed-dose combination drugs in primary and secondary prevention of cardiovascular disease. Position paper of the Russian Society of Cardiology, the Russian Society for the Prevention of Noncommunicable Diseases, the Russian Scientific Medical Society of Internal Medicine, the Russian Association of Endocrinologists, the Association of Clinical Pharmacologists, the Eurasian Association of Internal Medicine, the Russian Association of Gerontologists

The paper describes the position of of the Russian Society of Cardiology, the Russian Society for the Prevention of Noncommunicable Diseases, the Russian Scientific Medical Society of Internal Medicine, the Russian Association of Endocrinologists, the Association of Clinical Pharmacologists, the Eurasian Association of Internal Medicine, the Russian Association of Gerontologists and Geriatricians on the most important and controversial issues of the use of fixed-dose combination drugs in the primary and secondary prevention of cardiovascular disease.

Simultaneous spectrophotometric and chromatographic determination of Ketorolac and Dexamethasone: Overall assessment regarding environmental Impact, Practicality, and functionality principles

Determination of a drug combination that contains a minor component that is also a poorly UV absorbing analyte represents greet challenges in drug analysis. A fixed-dose ophthalmic combination of ketorolac tromethamine (KET) and dexamethasone sodium phosphate (DEX) (in the ratio of 5:1) is used to relieve post-surgical inflammation and seasonal allergic conjunctivitis due to their analgesic and anti-inflammatory activity. Five spectrophotometric methods and a reversed phase chromatographic separation method were developed and validated for simultaneous determination of both drugs in lab-prepared eye drops. Direct spectrophotometric determination of KET (the major, highly UV absorbing analyte) was achieved from the zero-order UV absorption spectra at 323 nm while DEX (which is the minor, poorly UV absorbing analyte) was quantified after applying several spectrophotometric methods. Either fundamental zero-order spectra or ratio spectra were used, and measurements were done at either single or dual wavelengths. The developed methods were: isosbestic point method, absorption factor method, dual wavelength method, ratio difference UV spectrophotometric method, and simultaneous equation method. The developed spectrophotometric methods determine KET in the linearity range of 2.0–12.0 μg/mL and DEX in the range of 5.0 – 35.0 μg/mL. For accurate spectrophotometric determination of DEX in the ratio of the dosage form, multiple standard addition method was applied. HPLC technique was also applied for separation and quantification of both drugs. Chromatographic separation was attained by using Hypersil ODS-C18 (150 x 4.6 mm, 5 μm) column. The mobile phase was composed of 50 % methanol: 50 % phosphate buffer (pH 2.5). The column compartment was maintained at 25 °C. Flow rate was adjusted at 1.2 mL/min and detection was performed by DAD at 254 nm. The linearity of HPLC method was 5.0–100.0 μg/mL, and 5.0–50.0 μg/mL for KET and DEX, respectively. Simultaneous determination of both drugs was applied to lab-prepared eye drops that contain also benzalkonium chloride as inactive ingredient. The developed methods determined the cited drugs with good and acceptable % recovery. The results of the developed methods and a reported HPLC method were compared using one-way ANOVA test, F-test and student’s t-test at confidence level 95 %, and they show no significant statistical difference. Assessment of greenness of the developed methods in comparison with reported HPLC method was performed using different tools, including analytical eco-scale, GAPI and AGREE. HPLC-EAT was also performed to ensure greenness of developed HPLC method. Moreover, assessment of practicality, applicability, and functionality of developed and reported methods was evaluated by BAGI metric tool and WAC calculator, respectively. The developed methods allow simple, rapid, and accurate analysis of quality control samples that contain KET and DEX.

Green micellar UPLC and complementary eco-friendly spectroscopic techniques for simultaneous analysis of anti-COVID drugs: a comprehensive evaluation of greenness, blueness, and whiteness

The development of sustainable analytical methodologies that minimize hazards, waste generation, and energy consumption has become crucial. This study introduces pioneering green‒blue-white approaches for the simultaneous quantification of montelukast sodium (MLK) and fexofenadine hydrochloride (FEX) in combination formulations. The first approach employs an ultra-performance liquid chromatographic method (UPLC) with a green micellar mobile phase of 0.02 M sodium dodecyl sulfate and 10% 1-pentanol (65:35%). The method demonstrated excellent resolution, peak symmetry, and a short analysis time, with retention times of 3.53 min for MLK and 1.67 min for FEX. The MLK and FEX linearities were 1–260 and 1.2–312 μg/mL, respectively. The second approach involves complementary built-in spectroscopic techniques (second derivative, third derivative, and ratio difference methods) using water as a solvent, providing a green, simple, low-cost alternative in laboratories where expensive chromatographic devices may not be readily available. The MLK and FEX linearities were 3–50 and 3–60 μg/mL, respectively. All methods were comprehensively validated and showed satisfactory results. The proposed methods demonstrated excellent linearity (r2 ≥ 0.9990), accuracy (recovery 98.5–101.5%), and precision (RSD ≤ 2%) across wide concentration ranges. A multifaceted evaluation was conducted to assess the environmental sustainability, real-world applicability, and economic viability of the proposed methods in comparison with previously reported techniques. This comprehensive assessment leveraged several state-of-the-art tools, including NEMI, ComplexGAPI, AGREE, ESA, BAGI, and RGB12. The suggested approaches exhibited favorable quadrant profiles in the NEMI and ComplexGAPI assessments, coupled with higher AGREE scores (0.90, 0.86) than reported (0.62, 0.74, 0.75, 0.69, 0.74, 0.74, and 0.75), in addition to higher ESA score (88, 92) than reported (75, 84, 85, 79, 82, 82, and 83), collectively affirming their environmentally friendly credentials. Moreover, we embraced the innovative notions of 'blueness' and 'whiteness' assessment by harnessing the recently formulated BAGI and RGB12 algorithms. The higher BAGI score (90, 82.5) than reported (72.5, 70, 70, 67.5, 67.5, 67.5, and 72.5), confirmed the excellent real-world applicability of the proposed methods, while the notable RGB12 indices (89.8, 88.1) than reported (67.8, 72.8, 71.5, 67.1, 73.7, 70.3, and 73.2), validated their cost-effectiveness and overall sustainability, contributing to an eco-friendly future for quality control processes.

Quantitative analysis of mixed lipid nanostructures in rat skin by HPLC-MS

Abstract Liquid chromatography-mass spectrometry (LC-MS) is a very sensitive technique for determining small concentrations of drugs in fixed dose combinations or even those deposited in skin layers. Therefore, an LC-MS method was applied for determining the drugs under investigation, namely, clioquinol (CLIO), tolnaftate (TOL), and betamethasone (BETA) in Quadriderm® cream and mixed lipid nanostructures (MLNs) prepared in laboratory in the presence of potential interferents, and was applied as a dermato-kinetic study in rat’s skin. The separation was achieved within 4.5 min by using C18 column as a stationary phase and the mobile phase used were 20% phase A composed of 0.1% formic acid (v/v) and 80% phase B composed of 0.1% formic acid in acetonitrile (v/v), coupled with triple quadrupole mass spectrometer. MLNs were prepared and characterized to be compared with the conventional commercially available Quadriderm® cream. The proposed method was accurate and precise with a linearity range of 0.2–20.0 µg·mL−1 for BETA, and 0.5–400.0 µg·mL−1 for CLIO and TOL and a better bioavailability of the new formulation was obtained ensuring the capability of the nanoparticles to accumulate the drugs within the skin layers. In conclusion, the LC-MS method was accurate and precise for the determination of the three drugs under investigation in cream dosage form and skin tissues.