Pharmaceutical Regulation Research Articles

Developing Ultra-High Concentration Formulations of Human Immune Globulins for Subcutaneous Injectables.

This work describes the first development of high-concentration suspension formulations of human immune globulin. Colloidal-level dispersions of immune globulin were achieved by suspending a spray dried solid powder of protein in a protein solution made saturated by the addition of pharmaceutical excipients. The spray drying process was used to generate ∼90% of particles below 20μ. The monomer and aggregates content of immunoglobulin were found to be 93% and 0.3%, respectively. The injection forces for the colloidal suspensions were characterized using a dynamic compression test. The concentrations of 300, 380, and 400 mg/mL formulations were injected at 3.8 N, 10 N, and 16.5 N of maximum injection forces, respectively, when a 24-gauge needle was used. The viscosity of a 300 mg/mL suspension was 128 cP. The viscosity of a 380 mg/mL suspension was 284 cP, and the viscosity was higher for the 400 mg/mL formulation; however, injectability was not an issue, which remains rare for non-Newtonian, shear-thickening systems. It is acknowledged that the 400 mg/mL suspension formulation remained relatively challenging as compared to other suspensions for injection because of its very high viscosity, and significant force was required to inject it. We show that where ultra-high-concentration immune globulin is being developed within reasonable constraints of pharmaceutical regulation, with an injectability parameter, formulations might make their way to the clinic when viscosity could say otherwise. However, further work should be conducted to assess chemical stability (using methods such as mass spectrometry) along with forced degradation studies prior any clinical use.

Ethical Considerations in Pharmaceutical Gift-Giving Practices: A Case Study of Bangladesh

The Bangladeshi healthcare system grapples with the entrenched practice of pharmaceutical companies showering medical representatives (MRs) with gifts to influence healthcare professionals (HCPs). Despite legal frameworks like the Drug Act (1940), which, until 2023, served as the core of Bangladesh's pharmaceutical sector regulation framework, was repealed by the Drugs and Cosmetics Act, 2023 and Drug Rules (1946) prohibiting the exchange of gifts and incentives to HCPs, a 2022 survey by Transparency International Bangladesh (TIB) revealed that 77% of physicians acknowledge receiving gifts from pharmaceutical companies. This article explores the reasons behind this phenomenon, including fierce industry competition, manipulation of prescribing habits, and financial allure for HCPs. Further, the article examines the multifaceted impact of gift-giving on patient care, healthcare expenditure, and public trust in the medical profession. It delves into the ethical considerations surrounding conflicts of interest, transparency, and accountability in the pharmaceutical-HCP nexus. Additionally, it analyzes the evolving role of regulatory bodies like the Directorate General of Drug Administration (DGDA) in enforcing regulations governing gift-giving practices. Through a critical examination of recent case studies and relevant literature, this article sheds light on the complex dynamics at play and proposes evidence-based recommendations for fostering transparency, integrity, and ethical conduct within the Bangladeshi pharmaceutical industry and healthcare sector. By drawing comparisons with international regulatory frameworks and ethical standards, the article aims to provide a comprehensive understanding of the challenges and potential solutions to curb unethical practices in Bangladesh.

The Political Sociology of NICE: Investigating Pharmaceutical Cost-Effectiveness Regulation in the UK.

The National Institute for Health and Care Excellence (NICE) was established a quarter of a century ago in 1999 to regulate the cost-effectiveness of pharmaceuticals (and other health technologies) for the NHS. Drawing on medical sociology theories of corporate bias, neoliberalism, pluralism/polycentricity and regulatory capture, the purpose of this article is to examine the applicability of those theories to NICE as a key regulatory agency in the UK health system. Based on approximately 7years of documentary research, interviews with expert informants and observations of NICE-related meetings, this paper focuses particularly on NICE's relationship with the interests of the pharmaceutical industry compared with other stakeholder interests at the meso-organisational level. Consideration of the interaction between the UK Government and the pharmaceutical industry in relation to NICE is presented together with the analysis of revolving doors and conflicts of interest of NICE experts/advisors. The nature of policy changes over time (e.g. accelerated assessment pathways and industry fees for regulatory appraisals) and how they relate to the relevant stakeholder interests is also investigated. It is concluded that NICE is largely characterised by neoliberal corporate bias, though some elements of its organisation are also consistent with theories of capture, pluralism and polycentricity.

Ensuring Quality Medicine: A Comprehensive Overview of EMA and DGDA's History, Structure, and Functions.

The study highlights the origins of drug regulation, tracing back to the early 19th century in the United States with the establishment of the Food and Drug Administration (FDA), and discusses the evolution and significance of drug regulatory bodies worldwide. The EMA and DGDA are scrutinized for their efforts in maintaining high standards for drug approval, monitoring clinical trials, and managing post-marketing surveillance to prevent adverse drug reactions (ADRs). The EMA’s role in coordinating with EU member states on pharmacovigilance and the DGDA’s initiatives in Bangladesh, including the implementation of a nationwide drug database and pharmacovigilance system, are explored in detail. The article concludes by emphasizing the essential role of these regulatory bodies in safeguarding public health through stringent regulation and continuous monitoring of pharmaceuticals, thereby ensuring that only safe and effective medicines are available to consumers . It also provides an in-depth analysis of the roles, structures, and historical contexts of the European Medicines Agency (EMA) and the Directorate General of Drug Administration (DGDA). It outlines how these regulatory bodies ensure the safety, efficacy, and quality of medicinal products. The EMA, serving the European Union, and the DGDA, operating in Bangladesh, play critical roles in drug approval processes, pharmacovigilance, and maintaining public health standards. By setting rigorous guidelines and monitoring compliance, these agencies help safeguard the health of millions, ensuring that only safe and effective medications are available in the market. The paper underscores the importance of these regulatory bodies in promoting public health and supporting the pharmaceutical industry's development and innovation.

An exploratory study of the mandate and functions of national pharmaceutical services units: global trends and the cases of Côte d'Ivoire, Kenya, and Nepal.

National pharmaceutical services units (NPSUs) - organisational units within the central government usually responsible for pharmaceutical services and management - have an increasingly narrow mandate. Anecdotal evidence points to an increasing focus, almost exclusively, on logistics management, while pharmaceutical care and policy oversight have become fragmented. This study examined NPSUs' current functions and mandates, and proposed what should be the critical functions and roles of these units going forward. Using case studies of Côte d'Ivoire, Kenya and Nepal, the study relied on a literature review and in-depth interviews. We triangulated and synthesised the findings to identify NPSUs by level in the health ministry's hierarchy and reporting line, mandate, and function. We identified medicine regulation, procurement and supply chain management, selection and rational use of medicines, and pharmacy practice regulation as four broad sets of functions that NPSUs commonly have as their mandate. A clear position in the Ministry of Health's hierarchical structure, the legal or administrative framework that mandates an NPSU's functions, and national pharmaceutical policies and regulations to guide the pharmaceutical sector are three critical factors for effective functioning. It is essential to have a legislative framework that at a minimum identifies one NPSU as responsible for pharmaceutical policy and governance, serving as the steward for the pharmaceutical system. This role encompasses pharmaceutical system coordination and administrative functions, formulating and implementing policies for organising, managing, financing, regulating, monitoring, and evaluating the pharmaceutical system. As such, we recommend that NPSUs should at a minimum have four broad sets of functions: pharmaceutical policy and governance, medicine regulation, pharmacy practice regulation and procurement and supply chain management. The study substantiates the need for a pharmaceutical policy and governance unit that stewards the pharmaceutical system and is empowered to monitor and evaluate system performance and coordinate efforts for system strengthening.

Methimazole-Related Substances: Structural Characterization and In Silico Toxicity Assessment

The continuous tightening of pharmaceutical regulations forces drug manufacturers to unambiguously characterize the substances related to the active pharmaceutical ingredients (API). Here, we report the synthesis, complete spectroscopic, chromatographic, thermal and computational characterization, as well as in silico prediction of bacterial mutagenicity for two previously reported but never fully characterized impurities of methimazole. Additionally, their structures were analyzed by single-crystal X-ray diffraction. 1-Methyl-(2-methylthio)-1H-imidazole also known as methimazole impurity C, was obtained mainly in the form of the iodide salt (C5H9IN2S) crystallizing in monoclinic space group P21/c. The disulfide (2,2′-disulphanylbis(1-methyl-1H-imidazole)), C8H10N4S2) was obtained in yellow form crystallizing in the monoclinic C2/c space group.

Leveraging regulatory pharmacist expertise to develop a framework for drug repurposing in underserved areas of the USA

The United States continues to grapple with healthcare access disparities, particularly in underserved regions. Regulatory pharmacists, with their unique expertise in pharmaceutical laws, drug development, and safety regulations, can play a vital role in drug repurposing efforts. This paper proposes a framework for utilising regulatory pharmacist expertise to develop drug repurposing strategies to meet unmet medical needs in underserved areas. We explore the regulatory hurdles, the necessity for collaborative efforts between healthcare professionals, and the potential for drug repurposing to improve healthcare outcomes in rural and socioeconomically disadvantaged communities.

Using the German National Medication Plan for Clinical Studies in Practice-Based Research Networks.

The German National Medication Plan (GNMP) can be a valuable and interoperable data source for clinical studies, due to its digital specification and mandatory provisioning for chronically ill patients. Digital transfer of a patients current GNMP from the Patient Data Management System (PDMS) into electronic case report forms would avoid error prone manual data capturing. It is also essential for studies in practice-based research networks (PBRN), where data capturing must have as little impact as possible on everyday practice. The following issues are currently preventing seamless digital integration: There is no standardized interoperable export of the GNMP from PDMS. In the current form, pharmaceutical catalogs are needed to decode the contained pharmaceutical registration numbers. As accessibility to the pharmaceutical catalogs is restricted, there is no generic access to the actual information needed for study data evaluation. In order to conduct studies, feasible workarounds for these issues had to be implemented in the standard operating procedures, tools and participating GP practices. To overcome the GNMP's current lack of digital interoperability, the proposed solution combines semi-automated data export from PDMS at the GP practice and manual database search at the study center with a semi-automated processing pipeline to balance workload between GP practices, study management and evaluation.

Multiple criteria qualitative value-based pricing framework “MARIE” for new drugs

Multiple criteria qualitative value-based pricing framework “MARIE” for new drugs

The role of Blockchain technology in ensuring pharmaceutical supply chain integrity and traceability

This review paper explores blockchain technology's transformative role in enhancing pharmaceutical supply chains' integrity and traceability. As the pharmaceutical industry grapples with challenges such as counterfeiting, fraud, and data discrepancies, blockchain emerges as a promising solution, offering a decentralized and immutable ledger that enhances transparency and security. Blockchain addresses critical issues that compromise patient safety and public health by enabling real-time monitoring and providing a single source of truth for all stakeholders. The paper highlights key findings on the benefits of blockchain, including improved traceability, automation through smart contracts, and enhanced collaboration among stakeholders. Additionally, it presents recommendations for pharmaceutical companies, regulators, and technology developers to facilitate the adoption and implementation of blockchain solutions in the pharmaceutical sector. Ultimately, this review underscores the potential of blockchain to revolutionize pharmaceutical supply chains, ensuring the delivery of safe and legitimate medications to consumers. Keywords: Blockchain Technology, Pharmaceutical Supply Chain, Traceability, Counterfeiting, Smart Contracts, Public Health.

Stakeholder-led proactive risk assessment of medication safety in the pharmaceutical supply chain

Abstract Introduction In 2022/23, 1.08 billion medications were dispensed to patients using NHS England, at a cost of £19.04 billion1 . However, Elliot et al (2019)2 estimate every year there are 237 million medication errors at some point of the medication process, with a high associated cost. Increasingly, media is reporting medication shortages of critical medicines3 that can contribute to errors of omission. Medication errors suggests system, tasks and processes should be explored to understand if they have been poorly designed. This paper is a pre-Brexit study that examines the pharmaceutical supply chain with stakeholders. Aim To explore risk to medication safety in the pharmaceutical supply chain using qualitative interviews of stakeholders across the supply chain and proactive risk assessment method SHERPA (Systematic Human Error Reduction and Prediction Approach). Method 1. Qualitative interviews with process models System process models were developed (by literature, field observations and interviewees) and employed to elicit stakeholder perceptions about risk to medication safety in 31 qualitative interviews. Participants included pharmacists, wholesalers, pharmaceutical industry representatives, regulators and policymakers. Ethical approval was granted by Cambridge LREC to include healthcare professionals and 6 patients. Interviews were audio-recorded, transcribed and thematically analysed using N-Vivo. 2. Focus group for SHERPA Six stakeholders participated in the SHERPA focus group4 , including pharmacists and representatives from pharmaceutical manufacturing and wholesale industries. Interview participants were invited and those that agreed, attended. The SHERPA template was completed by the group. The session was audio-recorded, transcribed and thematically analysed using N-Vivo. Results The system models led to a greater understanding of the current system ‘as-is’ and created an overview of the supply chain. SHERPA is a validated method and provided the rigour to risk assess the supply chain process and identify sources of risk. However, the error mode terminology required adjustment to healthcare. Across all supply routes, the main source of risk was failure to supply medicines that caused errors of omission and the risk of counterfeit medicines. Failure to supply resulted from shortages that take place from trading activities that result in stockpiling or exporting of medicines. A lack of robust regulation and parallel imports increased the risk of counterfeit medicines. Stakeholders highlighted deficiencies in the supply chain and poor performance of stakeholders, as medication safety concerns. In order of frequency, the deficiencies include fragmented supply chain; complacency by stakeholders; poor communication and integration across supply chain; and end-user often regarded as the pharmacist, rather than the patient. Discussion and conclusion From the findings, strategies emerged as possible solutions. These included communication of shortages in each component of supply chain; robust counterfeit strategies; use of technology (automation/digital tools); and re-design tasks and processes in dispensaries and wards. Staff training, education, and revalidation of stakeholders is vital. Key limitations in this study include biases that can occur from recruitment strategy and small sample size. The SHERPA method posed terminology problems. In conclusion, this multi-method approach reveals risk and possible solutions to improve safety and reduce cost in the NHS. It is clear this study needs to be repeated to understand the impact of Brexit and current reconfiguration of NHS.

Relationship Between Working Length of Pharmacy Personnel, Working Length of Doctors and Treatment Length of Patients with the Availability of Medicine in the Era of National Health Insurance (JKN) in the Hospital Grandmed Lubuk Pakam in 2024

Background: Quality public health services must have sufficient quantities and varieties of medicines when needed. The availability of these medicines can be ensured through good pharmaceutical standards and regulations. Optimal availability of medicines is the availability of medicines that can meet patient needs. One important step in medication management is the purchase of medicines. If the purchase of medicines is not managed carefully and responsibly, for example buying more medicines than needed, it will result in wasteful budget, increased purchasing and storage costs, and medicines or goods cannot be distributed. or expired.Objectives: To find out what factors influence the availability of drugs in the health insurance era (JKN) at the Grandmed Lubuk Pakam Hospital in 2024.Research method: This type of research is quantitative and is descriptive quantitative with a cross-sectional time approach. Results: There is a relationship between the length of service of pharmacists. The length of service of doctors and the length of treatment of patients with the availability of drugs in the era of JKN at the Grandmed Hospital in Lubuk Pakam in 2024. Conclusion: The availability of medicine for the community is one of the government's commitments in implementing public health services. The efforts made by the government are certainly aimed at maintaining public health.

Strengthening regulation for medical products in Tanzania: An assessment of regulatory capacity development, 1978-2020.

Improving medicines regulation can lead to better population health, but how this process works in low- and middle-income countries remains underexplored. Tanzania's pharmaceutical sector is often cited as a successful example of a well-functioning regulatory system in a developing country, attributed to the work of the Tanzania Food and Drugs Authority (TFDA), now the Tanzania Medicines and Medical Devices Authority (TMDA). This raises the question: how was this regulatory capacity developed, and what lessons can other countries learn from Tanzania's experience? This paper analyzes changes in Tanzania's pharmaceutical regulation over three periods of significant sectoral reform. A desk review was conducted of Tanzania's policies, laws, regulations, guidelines, procedures, and institutional reports. The study reveals that Tanzania's regulatory capacity improved significantly through targeted reforms that addressed challenges in key regulatory areas. The three key periods examined are: 1) The separation of medicines regulation from food safety (1978-2003), 2) The expansion of regulatory domains and the establishment of a semi-autonomous regulatory agency (2003-2011), and 3) The expanded role of the Pharmacy Council to include premises regulation (2011-2020). The development of a well-functioning regulatory system in Tanzania resulted from advancements in four key areas: 1) The evolution of a legal regulatory framework, 2) Strong stakeholder engagement, 3) Continuous capacity building, and 4) Effective organizational leadership. Tanzania's regulatory system has evolved from being relatively ineffective to leading regional harmonization efforts in East Africa. This progress was not linear, requiring sustained effort, collaboration, and support from key development partners such as the Global Fund, WHO, and UNDP. Future efforts to enhance regulatory effectiveness should focus on creating adaptive systems that respond to changing needs, rather than solely prescriptive functions.

Implementation of a Clinical Decision Support System for Antimicrobial Prescribing in Sub-Saharan Africa: Multisectoral Qualitative Study.

Suboptimal use of antimicrobials is a driver of antimicrobial resistance in West Africa. Clinical decision support systems (CDSSs) can facilitate access to updated and reliable recommendations. This study aimed to assess contextual factors that could facilitate the implementation of a CDSS for antimicrobial prescribing in West Africa and Central Africa and to identify tailored implementation strategies. This qualitative study was conducted through 21 semistructured individual interviews via videoconference with health care professionals between September and December 2020. Participants were recruited using purposive sampling in a transnational capacity-building network for hospital preparedness in West Africa. The interview guide included multiple constructs derived from the Consolidated Framework for Implementation Research. Interviews were transcribed, and data were analyzed using thematic analysis. The panel of participants included health practitioners (12/21, 57%), health actors trained in engineering (2/21, 10%), project managers (3/21, 14%), antimicrobial resistance research experts (2/21, 10%), a clinical microbiologist (1/21, 5%), and an anthropologist (1/21, 5%). Contextual factors influencing the implementation of eHealth tools existed at the individual, health care system, and national levels. At the individual level, the main challenge was to design a user-centered CDSS adapted to the prescriber's clinical routine and structural constraints. Most of the participants stated that the CDSS should not only target physicians in academic hospitals who can use their network to disseminate the tool but also general practitioners, primary care nurses, midwives, and other health care workers who are the main prescribers of antimicrobials in rural areas of West Africa. The heterogeneity in antimicrobial prescribing training among prescribers was a significant challenge to the use of a common CDSS. At the country level, weak pharmaceutical regulations, the lack of official guidelines for antimicrobial prescribing, limited access to clinical microbiology laboratories, self-medication, and disparity in health care coverage lead to inappropriate antimicrobial use and could limit the implementation and diffusion of CDSS for antimicrobial prescribing. Participants emphasized the importance of building a solid eHealth ecosystem in their countries by establishing academic partnerships, developing physician networks, and involving diverse stakeholders to address challenges. Additional implementation strategies included conducting a local needs assessment, identifying early adopters, promoting network weaving, using implementation advisers, and creating a learning collaborative. Participants noted that a CDSS for antimicrobial prescribing could be a powerful tool for the development and dissemination of official guidelines for infectious diseases in West Africa. These results suggest that a CDSS for antimicrobial prescribing adapted for nonspecialized prescribers could have a role in improving clinical decisions. They also confirm the relevance of adopting a cross-disciplinary approach with participants from different backgrounds to assess contextual factors, including social, political, and economic determinants.

Blockchain-enabled traceability systems for supply chain quality management: empirical insights from pharmaceutical manufacturers

PurposeThe emergence of blockchain technology has the potential to bring about transformative changes in various industries, with supply chain management being a prominent domain of application. This study investigates the strategic performance benefits of using blockchain-enabled traceability systems for improving supply chain quality management.Design/methodology/approachThe present study employed structural equation modelling to analyse data obtained from 200 practitioners working in Indian pharmaceutical companies.FindingsThe results reflect that blockchain-enabled traceability systems have a positive impact on multi-tier quality governance (MQG); supply chain process alignment and coordination (SPAC) and quality centric collaboration (QCC); all of which are the facets of supply chain quality management. Furthermore, when examining the impact of blockchain-enabled traceability systems on firm quality performance and economic performance, the mediation role of SPAC and QCC was confirmed, whereas the mediation role of MQG could not be established.Practical implicationsThe study’s empirical insights offer practical guidance for pharmaceutical manufacturers, regulators and other industry participants seeking to harness the potential of blockchain technology for creating resilient and transparent supply chains that uphold product quality and safety standards.Originality/valueThese findings underscore the significance of blockchain-enabled traceability systems in revolutionizing supply chain quality management practices to achieve superior strategic performance in the pharmaceutical sector.

Prescribers' perspectives: The impact of the controlled substance scheduling system on providing optimal patient care

Prescribers' perspectives: The impact of the controlled substance scheduling system on providing optimal patient care

A Review on Pharmaceutical Regulatory Authority of India, USA, UK, Australia

Medicines play an important role in saving lives, maintaining health, preventing disease, curbing epidemics and promoting national economic development. This is why people, governments, the pharmaceutical industry and research institutes pay for drugs. However, to do this, the drugs must be safe, effective and of high quality. This means that the development, production, import, export and distribution of drugs are regulated to ensure that they meet prescribed standards. To effectively regulate medicines, the government has established strong National Regulatory Authorities (NRAs) to ensure that medicines are effectively regulated to protect and promote public health. Pharmaceutical regulations around the world play an important role in ensuring the safety, quality and efficacy of medicines. Medicines regulatory agencies are responsible for enforcing regulations and issuing guidelines for the development, licensing, registration, manufacture, labelling, storage, marketing, distribution, pricing of drugs, drug importation and post marketing studies. While seeking international markets, the pharmaceutical industry must comply with the pharmaceutical regulations of other countries with different regulatory requirements. A single regulatory approach for marketing authorization (MA) applications for medicines in different countries is difficult. Therefore, the Common Technical Document (CTD) was developed to provide a common format for the electronic submission of drug registration applications.

Achieving synchrony: bridging the gap between pharmaceutical companies and regulators on safety labeling updates

Achieving synchrony: bridging the gap between pharmaceutical companies and regulators on safety labeling updates

Nonclinical Profile of PF-06952229 (MDV6058), a Novel TGFβRI/Activin Like Kinase 5 Inhibitor Supports Clinical Evaluation in Cancer.

The development of transforming growth factor βreceptor inhibitors (TGFβRi) as new medicines has been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. PF-06952229 inhibited clinically translatable phospho-SMAD2 biomarker (≥60%) in human and cynomolgus monkey peripheral blood mononuclear cells, as well as in mouse and rat splenocytes. Using an optimized, intermittent dosing schedule (7-day on/7-day off/cycle; 5 cycles), PF-06952229 demonstrated efficacy in a 63-day syngeneic MC38 colon carcinoma mouse model. In the pivotal repeat-dose toxicity studies (rat and cynomolgus monkey), PF-06952229 on an intermittent dosing schedule (5-day on/5-day off cycle; 5 cycles, 28 doses) showed no cardiac-related adverse findings. However, new toxicity findings related to PF-06952229 included reversible hepatocellular (hepatocyte necrosis with corresponding clinically monitorable transaminase increases) and lung (hemorrhage with mixed cell inflammation) findings at ≥ targeted projected clinical efficacious exposures. Furthermore, partially reversible cartilage hypertrophy (trachea and femur in rat; femur in monkey) and partially to fully reversible, clinically monitorable decreases in serum phosphorus and urinary phosphate at ≥ projected clinically efficacious exposures were observed. Given the integral role of TGFβ in endochondral bone formation, cartilage findings in toxicity studies have been observed with other TGFβRi classes of compounds. The favorable cumulative profile of PF-06952229 in biochemical, pharmacodynamic, pharmacokinetic, and nonclinical studies allowed for its evaluation in cancer patients using the intermittent dosing schedule (7-day on/7-day off) and careful protocol-defined monitoring. SIGNIFICANCE STATEMENT: Only a few TGFβRi have progressed for clinical evaluation due to adverse cardiac findings in pivotal nonclinical toxicity studies. The potential translations of such findings in patients are of major concern. Using a carefully optimized intermittent dosing schedule, PF-06952229 has demonstrated impressive pharmacological efficacy in the syngeneic MC38 colon carcinoma mouse model. Additionally, a nonclinical toxicology package without cardiovascular liabilities and generally monitorable toxicity profile has been completed. The compound presents an acceptable International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use S9-compliant profile for the intended-to-treat cancer patients.

Development and Validation of a Simple UV-HPLC Method to Quantify the Memantine Drug Used in Alzheimer's Treatment.

Memantine, a non-competitive NMDA receptor antagonist, is used to treat Alzheimer's disease. Therefore, loading memantine in nanoparticles (NPs) could be an essential tool to improve the treatment effectiveness while reducing drug toxicity. Even though some approaches have been described to quantify memantine, none reported optimized methods using high-performance liquid chromatography resorting to ultraviolet detection (UV-HPLC) to determine encapsulation in NPs. The present research developed a HPLC method using pre-column derivatization for quantitatively analyzing memantine hydrochloride in NPs. Memantine was derivatized using 9-fluorenylmethyl chloroformate (FMOC). The developed method was fully validated regarding suitability, specificity, linearity, sensitivity, precision, accuracy, and robustness according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The retention time of memantine was 11.393 ± 0.003 min, with a mean recovery of 92.9 ± 3.7%. The new chromatographic method was validated and found to respond linearly over 5-140 μg/mL, with a high coefficient of determination. Intraday precision lay between 3.6% and 4.6%, and interday precision between 4.2% and 9.3%. The stability of memantine was also tested at 4 °C and -20 °C, and no signs of decay were found for up to 6 months. The new method was properly validated and proved simple, sensitive, specific, accurate, and precise for determining memantine encapsulation efficiency in lipid NPs. Greenness was evaluated, presenting a final score of 0.45. In the future, this methodology could also be applied to quantify memantine in different nanoformulations.