The Cost-Effectiveness of Computer-Assisted Compared with Conventional Total Knee Arthroplasty: A Payer's Perspective.

BACKGROUND: Recent evidence showing that computer-assisted total knee arthroplasty (TKA) is associated with better outcomes compared with conventional TKA for patients with end-stage knee osteoarthritis has not been included in economic evaluations of computer-assisted TKA, which are needed to support coverage decisions. This study evaluated the cost-effectiveness of computer-assisted TKA from a payer's perspective, incorporating recent evidence. METHODS: We compared computer-assisted TKA with conventional TKA with regard to costs (in 2022 U.S. dollars) and quality-adjusted life-years (QALYs) using Markov models for elderly patients (≥65 years of age) and patients who were not elderly (55 to 64 years of age). Costs and QALYs were estimated in the lifetime for elderly patients and in the short term for patients who were not elderly, under a bundled payment program and a Fee-for-Service program. Transition probabilities, costs, and QALYs were retrieved from the literature, a national knee arthroplasty registry, and the National Center for Health Statistics. Threshold and probabilistic sensitivity analyses were conducted to examine the robustness of key estimates used in the base-case analysis. Using projected estimates of TKA utilization, the total cost savings of performing computer-assisted TKA rather than conventional TKA were estimated. RESULTS: Compared with conventional TKA, computer-assisted TKA was associated with higher QALYs and lower costs for both elderly patients and patients who were not elderly, regardless of payment programs, making computer-assisted TKA a favorable treatment option. Widespread adoption of computer-assisted TKA in all U.S. patients would result in an estimated total cost saving of $1 billion for payers. CONCLUSIONS: Compared with conventional TKA, computer-assisted TKA reduces costs to payers while providing favorable outcomes. Payers may consider providing additional payment incentives to providers for performing computer-assisted TKA, to achieve outcome improvement and cost control by facilitating widespread adoption of computer-assisted TKA. LEVEL OF EVIDENCE: Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence.

A Comprehensive Review on Unveiling the Journey of Digoxin: Past, Present, and Future Perspectives.

Digoxin, a cardiac glycoside derived from the foxglove plant (Digitalis spp.), has been utilized for centuries in managing various cardiac conditions due to its ability to increase myocardial contractility and regulate heart rate. This comprehensive review explores the historical context, pharmacological properties, clinical applications, efficacy, safety profile, challenges, and future perspectives of digoxin. Tracing its journey from traditional medicine to modern cardiovascular therapeutics, we delve into its mechanism of action, therapeutic indications, and clinical guidelines. While digoxin remains a cornerstone therapy for heart failure and atrial fibrillation, its narrow therapeutic index and individual variability in response pose challenges in clinical practice. Nevertheless, ongoing research efforts aim to elucidate its role in emerging therapeutic areas and technological advancements in drug delivery. Despite the advent of newer pharmacological agents, digoxin's enduring relevance lies in its established efficacy, affordability, and global accessibility. This review underscores the symbiotic relationship between tradition and progress in cardiovascular medicine, highlighting the timeless pursuit of medical innovation to optimize patient care.

Expanding the access to kidney transplantation: Strategies for kidney transplant programs.

Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such partnerships. Providing early culturally congruent and patient-centered education as well as maximizing the use of local resources to facilitate the transplant work up should be prioritized. Every opportunity to facilitate pre-emptive kidney transplantation and living donation must be taken. Promoting the use of telemedicine and kidney paired donation as standards of care can positively impact the work up completion and maximize the chances of a living donor kidney transplant.

Illuminating Progress: A Comprehensive Review of the Evolution of Phototherapy for Neonatal Hyperbilirubinemia.

This comprehensive review thoroughly examines the historical evolution, physiological foundations, and contemporary advancements in the application of phototherapy for neonatal hyperbilirubinemia. Neonatal hyperbilirubinemia, a common condition resulting from the immature hepatic processes in newborns, poses potential risks, including neurotoxicity, if left untreated. The review traces the historical progression from early recognition of neonatal jaundice to the development of various phototherapy modalities, showcasing the dynamic landscape of neonatal care. Emphasizing the physiological intricacies of bilirubin metabolism in neonates, the study underscores the vulnerability of newborns to hyperbilirubinemia due to delayed hepatic maturation. Phototherapy is a cornerstone in managing hyperbilirubinemia, demonstrating consistent efficacy in reducing unconjugated bilirubin levels. The implications for clinical practice are significant, offering healthcare professionals insights into tailoring treatment strategies based on individual neonatal characteristics and the severity of jaundice. Integrating advanced monitoring and control systems enhances the precision and safety of phototherapy. Recommendations for future research emphasize the need to investigate long-term outcomes, explore adjunctive therapies, and address resource limitations to ensure global access to effective neonatal care. Overall, this review contributes to the ongoing refinement of neonatal care practices, offering a comprehensive understanding of neonatal hyperbilirubinemia and its evolving treatment landscape.

Navigating Pediatric Capnography: A Comprehensive Review of Scope and Limitations.

This review comprehensively explores pediatric capnography, a vital tool in contemporary respiratory monitoring. The overview encompasses the foundational principles of capnography, elucidating its real-time measurement of carbon dioxide (CO2) in respiratory gases. The review emphasizes its paramount role in pediatric care and underscores capnography's significance in detecting respiratory abnormalities and guiding timely interventions. The distinctions between mainstream and sidestream capnography, the key to understanding their applications, are meticulously outlined. Addressing the importance of ongoing research and education, the review advocates for a dynamic approach to refine guidelines and optimize capnography utilization in pediatric settings. The conclusion reflects on the scope and limitations of pediatric capnography, acknowledging its transformative impact while advocating for a judicious recognition of constraints. As we navigate the future of pediatric respiratory care, the synergy of research, education, and clinical application emerges as the cornerstone for advancing pediatric capnography to new horizons.

Exploring the Microbial Landscape of Neonatal Skin Flora: A Comprehensive Review.

This comprehensive review explores the intricate landscape of the neonatal skin microbiome, shedding light on its dynamic composition, developmental nuances, and influential factors. The neonatal period represents a critical window during which microbial colonization significantly impacts local skin health and the foundational development of the immune system. Factors such as mode of delivery and gestational age underscore the vulnerability of neonates to disruptions in microbial establishment. Key findings emphasize the broader systemic implications of the neonatal skin microbiome, extending beyond immediate health outcomes to influence susceptibility to infections, allergies, and immune-related disorders. This review advocates for a paradigm shift in neonatal care, proposing strategies to preserve and promote a healthy skin microbiome for long-term health benefits. The implications of this research extend to public health, where interventions targeting the neonatal skin microbiome could potentially mitigate diseases originating in early life. As we navigate the intersection of research and practical applications, bridging the gap between knowledge and implementation becomes imperative for translating these findings into evidence-based practices and improving neonatal well-being on a broader scale.

A Rare Pediatric Neurological Case: Dyke-Davidoff-Masson Syndrome Unprecedented at 10 Months.

This case report presents a rare occurrence of Dyke-Davidoff-Masson Syndrome (DDMS) in a 10-month-old male child, highlighting the atypical presentation of this neurological disorder in early infancy. The child initially presented with irritability, loss of appetite, and right-sided weakness following episodes of fever. A comprehensive medical history revealed the sudden onset of generalized tonic-clonic seizures, prompting further investigation. Diagnostic imaging, including CT and MRI, confirmed features consistent with DDMS, including cerebral hemiatrophy, ventricular enlargement, and calvarial thickening. Notably, the child's seizures were successfully managed with antiepileptic medication, leading to stabilized vital signs. This case emphasizes the importance of considering rare neurological disorders in pediatric patients with unusual presentations and underscores the challenges in diagnosing and managing DDMS in infancy. Further research is warranted to elucidate the underlying mechanisms, contributing factors, and optimal management strategies for DDMS in this age group.

A Rare Case of a Subgaleal Hematoma With Global Developmental Delay, Scurvy, and Congenital Toxoplasmosis, Rubella, Cytomegalovirus, Herpes Simplex, and HIV (TORCH) Infection.

This case report details the complex presentation of a six-year-old female child with global developmental delay (GDD), scurvy, congenital toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and HIV (TORCH) infection and a subgaleal hematoma. The patient's medical history included delayed developmental milestones, bilateral congenital cataract, and a previous generalized tonic-clonic seizure. Thorough investigations revealed cerebral atrophy, bilateral ventricular dilatation, and periosteal thinning consistent with scurvy. The interdisciplinary approach involving neurology, ophthalmology, and orthopedics resolved the subgaleal hematoma. This case underscores the intricate interplay of neurological, nutritional, and infectious factors in pediatric conditions and highlights the importance of a collaborative, multidisciplinary approach for accurate diagnosis and effective management.

Complement-mediated thrombotic microangiopathy treated with anticomplement protein 5 therapy, a retrospective study.

BACKGROUND: Complement-mediated thrombotic microangiopathy (CM-TMA), also called atypical hemolytic uremic syndrome (aHUS), is a difficult-to-diagnose rare disease that carries severe morbidity and mortality. Anti-C5 monoclonal antibodies (aC5-mab) are standard treatments, but large studies and long-term data are scarce. Here, we report our single institution experience to augment the knowledge of CM-TMA treated with aC5-mab therapy. METHODS: We aimed to assess the short and long-term effects of aC5-mab in patients diagnosed with CM-TMA treated outside of a clinical trial. This was a retrospective study. We included all patients diagnosed with CM-TMA and treated with aC5-mab at our institution. There were no exclusion criteria. Endpoints included complete TMA response (CR) defined as normalization of hematological parameters and ≥25% improvement in serum creatinine (Cr) from baseline in patients with renal disease, relapse defined as losing the previously achieved CR, morbidity, adverse events, and survival. RESULTS: We found 28 patients with CM-TMA treated with aC5-mab. The median age was 50 years. Baseline laboratories: platelet counts 93 × 109 /L, hemoglobin 8.6 g/dL, lactate dehydrogenase 1326 U/L, serum Cr 4.7 mg/dL, and estimated glomerular filtration rate 19 mL/min. One individual was on renal replacement therapy (RRT) and 10 initiated RRT within 5 days of the first dose of aC5-mab. Genetic variants associated with CM-TMA included mutations in C3, CFB, CFH, CFHR1/3, CFI, and MCP. The mean duration of hospitalization was 24 days. The median time to initiation of aC5-mab was 10 days. Sixteen subjects received RRT. At the time of hospital discharge, 27 were alive, 14 remained on RRT, and 4 had a CR. At 6 months, 23 patients were alive, 18 continued aC5-mab, 8 remained on RRT, and 9 had a CR. At the last follow-up visit past 6 months, 20 were alive, 14 continued aC5-mab, 5 remained on RRT, 12 had a CR, and 1 was lost to follow-up. CONCLUSIONS: Our study provides real-world experience and insight into the long-term outcomes of CM-TMA treated with aC5-mab. Our findings validate that CM-TMA is an aggressive disease with significant morbidity and mortality, and confirm that aC5-mab is a relatively effective therapy for CM-TMA. Our study adds practical, real-world experience to the literature, but future research remains imperative.

Long-Term Survival in Patients Treated by Cytoreductive Surgery with or Without HIPEC for Peritoneal Surface Malignancies-A report from the Indian HIPEC Registry.

A previous report from the Indian HIPEC registry showed acceptable early survival and morbidity in patients undergoing cytoreductive surgery (CRS) + / - hyperthermic intraperitoneal chemotherapy (HIPEC). The goal of this retrospective study was to evaluate the long-term outcomes in these patients. Three hundred seventy-four patients treated from December 2010 to December 2016 and enrolled in the Indian HIPEC registry were included. All patients had completed 5 years from the date of surgery. The 1-, 3-, 5- and 7-year progression-free (PFS) and overall survival (OS) and factors affecting these were evaluated. The histology was epithelial ovarian cancer in 209 (46.5%), pseudomyxoma peritonei (PMP) in 65 (17.3%) and colorectal cancer in 46 (12.9%) patients. The peritoneal cancer index (PCI) was ≥ 15 in 160 (42.8%). A completeness of cytoreduction (CC) score of 0/1 resection was obtained in 83% (CC-0-65%; CC-1-18%). HIPEC was performed in 59.2%. At a median, follow-up of 77 months (6-120 months), 243 (64.9%) patients developed recurrence, and 236 (63%) died of any cause; 138 (36.9%) were lost to follow-up. The median OS was 56 months (95% CI 53.42-61.07), and the median PFS was 28 months (95% CI 37.5-44.4). The 1-, 3-, 5- and 7-year OS was 97.6%, 63%, 37.7% and 24% respectively. The 1-, 3-, 5- and 7-year PFS was 84.8%, 36.5%, 27.3% and 22% respectively. The use of HIPEC (p = 0.03) and PMP of appendiceal origin (p = 0.01) was independent predictors of a longer OS. CRS + / - /HIPEC may achieve long-term survival in patients with PM from different primary sites in the Indian scenario. More prospective studies are needed to confirm these findings and identify factors influencing long-term survival. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01727-7.

A Descriptive Analysis of Patients Undergoing Cytoreductive Surgery for the First Peritoneal Recurrence from Adult Granulosa Cell Tumours: Focus on Disease Distribution, Morphology of Peritoneal Disease and the Role of HIPEC - a Retrospective Study by INDEPSO.

The aim of the present study was to report the clinical outcome and factors affecting survival in patients with first recurrence of AGC treated with cytoreductive surgery with or without HIPEC. The second aim was to study the disease distribution in the peritoneal cavity according to the peritoneal carcinomatosis index (PCI) and the morphology of peritoneal deposits. In this retrospective multicentric study, all patients of adult granulosa cell tumor with peritoneal recurrence were treated with CRS with or without HIPEC. Relevant clinical and demographic data were captured. Multivariable logistic regression was performed to evaluate the factors affecting recurrence after CRS ± HIPEC. Factors affecting survival and second recurrences were evaluated in addition to studying the disease distribution at first recurrence. In the period from January 2013 to December 2021, 30 consecutive patients of recurrent adult type granulosa cell tumor of the ovary undergoing CRS ± HIPEC were included in this study. The median follow-up duration was 55 months [12-96 months]. The median rPFS and rOS were both not reached. HIPEC (p = 0.015) was the only factor independently associated with a longer rPFS. CRS with or without HIPEC can be performed with an acceptable morbidity in patients with the first recurrence from adult granulosa cell tumours. The role of HIPEC, patterns of peritoneal spread and impact of other prognostic factors on the treatment outcome all need further evaluation in larger series of patients.

Cytoreductive Surgery With or Without HIPEC in the Management of Peritoneal Dissemination from Rare Histological Subtypes of Ovarian Cancer - a Retrospective Study by INDEPSO.

The aim of this study was to evaluate the potential role of optimal cytoreductive surgery with or without HIPEC in the management of peritoneal dissemination from rare histological subtypes of ovarian cancer and to report the prognostic factors affecting survival. In this retrospective multicentric study, all patients with diagnosis of locally advanced ca ovary with histology other than high-grade serous carcinoma and those having undergone cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy for the same were included. Factors affecting survival were evaluated in addition to studying the clinicopathological features. In the period from January 2013 to December 2021, 101 consecutive patients of ovarian cancer with rare histology underwent cytoreductive surgery with or without HIPEC. The median OS was not reached (NR), and the median PFS was 60 months. On evaluation of factors affecting overall survival (OS) and progression-free survival (PFS), PCI > 15 was associated with not only a decreased PFS (p = 0.019) but also a decreased OS (P = 0.019) on univariate and multivariate analysis. With respect to histology, the best OS and PFS were seen with granulosa cell tumor, mucinous tumors for which median OS and median PFS were NR respectively. Cytoreductive surgery can be performed with an acceptable morbidity in patients with peritoneal dissemination from ovarian tumors of rare histology. The role of HIPEC and impact of other prognostic factors on the treatment and survival outcome need further evaluation in larger series of patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01640-5.

Antimalarial Drug Resistance Profiling of Plasmodium falciparum Infections in India Using Next-Generation Sequencing.

Background: Tracking the emergence and spread of antimalarial drug resistance has become critical to sustaining progress towards the control and eventual elimination of malaria in South Asia, especially India. Methods: An amplicon sequencing protocol was used for high-throughput molecular surveillance of antimalarial drug resistance in a total of 158 isolates at three sites in India: Chennai, Nadiad and Rourkela. Five genes of the Plasmodium falciparum implicated in antimalarial resistance were investigated here; Pfcrt for chloroquine resistance, Pfdhfr for pyrimethamine resistance, Pfdhps for sulfadoxine resistance, Pfk13 for artemisinin resistance and Pfmdr1 for resistance to multiple antimalarials. Results: Mutations in the propeller domain of PfK13 were observed in two samples only, however these mutations are not validated for artemisinin resistance. A high proportion of parasites from the P. falciparum dominant site Rourkela showed wild-type Pfcrt and Pfdhfr haplotypes, while mutant Pfcrt and Pfdhfr haplotypes were fixed at the P. vivax dominant sites Chennai and Nadiad. The wild-type PfDHPS haplotype was predominant across all study sites. Finally, we observed the largest proportion of suspected multi-clonal infections at Rourkela, which has the highest transmission of P. falciparum among our study sites. Conclusion: This is the first simultaneous high-throughput next generation sequencing of five complete P. falciparum genes from infected patients in India.

Can we lower the platelet threshold of ≥ 50 × 109/L for performing a lumbar puncture safely in patients with hematological malignancies?

Lumbar punctures (LP) are routinely used to administer intrathecal chemotherapy for children and adults with hematologic malignancies. The current guidelines suggest a platelet threshold of ≥ 50 × 109/L prior to LP for intrathecal chemotherapy (ITC). This can be challenging in patients with hematological malignancies who are thrombocytopenic. We conducted a retrospective chart review of 900 LPs for ITC and compared adverse events in patients with a platelet count of ≥ 50 × 109/L and < 50 × 109/L. Cohort 1 included 682 LPs (75.8%) with a pre-procedure platelet count ≥ 50 × 109/L, and cohort 2 included 218 LPs (24.2%) with a pre-procedure platelet count < 50 × 109/L. Cohort 2 was further subdivided into pre-procedure platelet counts of 41 × 109/L-49 × 109/L (n = 43), 31 × 109/L-40 × 109/L (n = 77), 21 × 109/L-30 × 109/L (n = 84), and 11 × 109/L-20 × 109/L (n = 14). Among 900 LP procedures, a pre-procedure platelet count < 50 × 109/L did not demonstrate a higher rate of post-procedure adverse events (6.5% vs 6.8%, p = 0.8237). When cohort 2 was further stratified, the cohort with a pre-procedure platelet count of 21 × 109/L-30 × 109/L had the highest percentage of complications from LP (9.5%) and the highest rates of traumatic taps with observed LP RBC count > 200 (35.7%, p = 0.0015). The rate of red blood cells (RBC) in the CSF was significantly higher in the group with platelets < 50 × 109/L with observed LP RBC count ≥ 200 (31.2% vs 20.5%, p = 0.0016), ≥ 500 (27.1% vs 14.6%, p < 0.0001), and ≥ 1000 (23% vs 11.6%, p < 0.0001). No instances of epidural hematomas were seen. We found no significant difference in bleeding complications between patients undergoing LPs for ITC with a platelet count above or below 50 × 109/L.

Simultaneous Estimation of Telmisartan, Chlorthalidone, Amlodipine Besylate and Atorvastatin by RP-HPLC Method for Synchronous Assay of Multiple FDC Products Using Analytical FMCEA-Based AQbD Approach.

Numerous reversed-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) techniques have been published for the estimation of fixed-dose combinations (FDCs) of telmisartan (TEL). No published literature has been reported to date which described the synchronous estimation of FDCs of TEL using a single chromatography condition. Hence, the RP-HPLC method has been developed and validated for synchronous analysis of FDCs of TEL using an enhanced analytical quality by design (AQbD) approach to save time, cost and solvent for analysis. The implementation of AQbD was initiated with the identification of failure modes (FMs) using the Ishikawa diagram, and their critical effect analysis was carried out by risk priority number ranking and filtering method. The identified critical FMs were optimized by design of experiments-based response surface modeling using the Box-Behnken design. The method operable design region was navigated and control strategy was framed to mitigate the risk of critical FM. The RP-HPLC method was developed using Shim-Pack octadecyl silane C18 column and acetonitrile: 1.0%v/v triethylamine (pH 6.5 adjusted using perchloric acid; 42:58, %v/v). The developed method was found to be validated as per the International Council For Harmonization Q2 (R1) guideline. The method was applied for the synchronous assay of seven different FDCs of TEL and assay results were found in good compliance with the respective labeled claim.

Outcomes of de novo belatacept-based immunosuppression regimen and avoidance of calcineurin inhibitors in recipients of kidney allografts at higher risk for underutilization.

To describe an experience using a protocol using de novo belatacept (DNB) based maintenance immunosuppression in the setting of lymphocyte depletion. A retrospective, observational study was performed on 37 kidney transplant recipients treated with the DNB protocol, which was defined as belatacept initiated within 7 days after a kidney transplant with steroids and mycophenolate with anti-thymocyte globulin (ATG) induction without concomitant calcineurin inhibitors (CNIs). Patients who received a deceased donor kidney meeting one or more of the following criteria: anticipated cold ischemia time (CIT) greater than 24 h, donation after cardiac death, donor acute kidney injury, and a Kidney Donor Profile Index (KDPI) >85% during the study period were included. Patient survival at 1 year was 97.3% and graft survival was 94.6%. Delayed graft function (DGF) occurred in 40.54% of the patients. Two patients experienced a Banff 1B acute cellular rejection. BK viremia was detected in 32.4% of patients. The mean estimated glomerular filtration rate (eGFR) calculated with the use of modification of diet in renal disease (MDRD) equation at 1 year in the study group was 54.7 ml/min/1.73 m2 . We believe that utilization of the DNB protocol, which allows early CNI avoidance, may decrease organ discard rates.

Feasibility and Safety of Taxane-PIPAC in Patients with Peritoneal Malignancies-a Retrospective Bi-institutional Study.

Taxanes have a favorable pharmacokinetic profile for intraperitoneal application. We report our initial experience with taxane-PIPAC (pressurized intraperitoneal chemotherapy) for unresectable peritoneal metastases from different primary sites in terms of safety, feasibility, response rate, and conversion to resectability. In this retrospective study, PIPAC was performed alone or in combination with systemic chemotherapy. Paclitaxel was used as a single agent, whereas docetaxel was used in combination with cisplatin-adriamycin or oxaliplatin-adriamycin. From December 2019 to December 2021, 47 patients underwent 82 PIPAC procedures (1 PIPAC in 55.3%, 2 in 29.7%, 3 in 14.8%). The most common primary sites were ovarian cancer (31.9%), gastric cancer (23.4%), and colorectal cancer (21.2%). Docetaxel-cisplatin-adriamycin was used in 33 (70.2%) patients, docetaxel-oxaliplatin-adriamycin in 12 (25.5%), and paclitaxel alone in 2 (4.2%) patients. Grade 1-2 complications were observed in 24 (51%) and grade 3-4 complications in 6 (12.7%) patients (8.5% of 82 PIPACs). 16/47 (34.0%) patients had a clinical response to PIPAC. The mean PCI was 25.9 ± 9.2 for the first PIPACs and 22.4 ± 9 for the subsequent PIPACs with an average reduction of 3.6 points [change in PCI ranged from - 14 to + 8]. The PRGS was 1/2 in 4/47 (8.5%) patients (19.0% patients with > 1 PIPAC). A reduction in ascites was observed in 35.4% presenting with ascites. Nine (19.1%) patients had conversion to operability leading to a subsequent cytoreductive surgery in 8 (17%) patients. PIPAC with docetaxel is feasible and safe. The role of PIPAC with both docetaxel and paclitaxel either alone or in combination with other drugs should be investigated in prospective studies.

DoE-Based Analytical Quality Risk Management for Enhanced AQbD Approach to Economical and Eco-Friendly RP-HPLC Method for Synchronous Estimation of Multiple FDC Products of Antihypertensive Drugs.

According to the literature review, numerous chromatographic methods have been published for estimation of fixed-dose combination products of telmisartan but no reverse-phase high-pressure liquid chromatographic (RP-HPLC) method has been published yet for synchronous estimation of fixed-dose combination (FDC) products of telmisartan to save time, cost and solvent for analysis. Hence, an economical and eco-friendly RP-HPLC method has been developed for synchronous estimation of multiple FDC products of antihypertensive drugs using the quality risk management (QRM) and DoE-based enhanced analytical quality by design approach. The analytical-QRM was started with the identification of potential method risk parameters followed by their risk assessment by risk priority number ranking and filtering. The identified critical method parameters were optimized using the DoE-based central composite design. The method operable design range was navigated and the control strategy was framed for control and mitigation of risk throughout the life-cycle of the developed method. The method was developed using Shimpack Octadecyl silane (ODS) C18 column and acetonitrile-1.0%v/v triethylamine in water (pH 6.0; 45 + 55, %v/v). The developed method was validated as per the International Council for Harmonization Q2 (R1) guideline. The developed method was applied for the analysis of seven different antihypertensive dosage forms. The developed RP-HPLC method can be used as an eco-friendly, robust and economical alternative analytical tool to several published methods for estimation of FDC products of antihypertensive drugs in the pharmaceutical industry.

DoE-Based Analytical-FMCEA for Enhanced AQbD Approach to MEER-RP-HPLC Method for Synchronous Estimation of 15 Anti-Hypertensive Pharmaceutical Dosage Forms.

BACKGROUND: In the recent scenario of green chemistry, the usage of organic solvents should be minimized in the development of analytical methods for the safety of the environment and analysts. OBJECTIVE: An RP-HPLC method has been developed as an economical and eco-friendly alternative to published RP-HPLC methods for the analysis of fixed-dose combinations (FDCs) of anti-hypertensive drugs, for saving time, resources, costs, and organic solvent. METHODS: The method has been developed through the implementation of an enhanced analytical quality by design (AQbD) approach using a design of experiment (DoE)-based analytical failure mode critical effect analysis (AFMCEA). The AFMCEA was performed by identifying potential analytical failure modes and assessing their risk using risk priority number ranking and filtering. The DoE-based AFMCEA was implemented for response surface analysis and mitigation of high-risk analytical failure modes by Box-Behnken design (BBD). The method operable design ranges and control strategy were set for lifecycle management of the developed method. RESULTS: The RP-HPLC method was developed using a Shimpack octadecyl silane (ODS) C18 column and acetonitrile-water (pH 6.2; 42:58 %, v/v). The method was validated as per ICH Q2 (R1) guidelines. The method was applied for the synchronous assay of 15 FDCs of anti-hypertensive drugs. CONCLUSION: The developed method has fulfilled the requirements of numerous published RP-HPLC and HPTLC methods. Hence, this method is a multipurpose chromatography method for synchronous estimation of FDC products of anti-hypertensive drugs. This method can be used as a multipurpose (M), economical (E), eco-friendly (E), and rapid (R), MEER-RP-HPLC for quality control of multiple FDCs of anti-hypertensive drugs in the pharmaceutical industry. HIGHLIGHTS: Development of a MEER-RP-HPLC method for synchronous estimation of 15 pharmaceutical dosage forms of anti-hypertensive drugs. Implementation of an enhanced AQbD approach using a DoE-based AFMCEA to develop the method which was applied to the assay of 15 anti-hypertensive dosage forms.