Drug Research Articles

Development of a Rapid Analytical Method on UV Spectrophotometer for Analysis of Trace Level APIs Telmisartan in Cleaning Validation Sample

Since the 1990’s, cleaning validations have gained a lot of interest within pharmaceutical and bio-pharmaceutical companies. In 1988, the FDA experienced its first major incident with cross contamination traceable to inadequate cleaning and cleaning validation. The finished drug product, Cholestyramine Resin USP, was recalled due to contamination with low levels of intermediates and degradants from the production of agricultural pesticides. The cross-contamination was believed to have come from the use of drums in the production of the active pharmaceutical ingredient (API). These drums had previously been used to store solvents for the manufacture of agricultural pesticides at another plant. Extra pure methanol procured from Chempura Enterprises Indore of make Merck and Analytical Grade water procured from the SK Traders Indore M.P. Reference materials, Telmisartan from Axiom Analytical Services Indore M.P. HPLC grade methanol (MeOH), HPLC Grade Water were purchased from Chempura Enterprises Indore M.P.. All chemicals were used as received, without any further purification. In recent years, increased emphasis has been placed in pharmaceutical companies for implementing robust validated cleaning procedures. The cleaning procedure is one of the most important tasks to avoid contamination and cross- contamination of APIs in pharmaceutical products manufactured on the same equipment trains. The cleaning procedures must be supported byappropriate analytical methods and related sampling methodologies.

Analysis of Inventory Management System at Pharmacy of XYZ Hospital

This research examines inventory management at the XYZ Hospital Pharmacy Installation in Bandung, with a special focus on medicines and medical devices. The background to this research is the significant increase in health costs and the importance of effective supply chain management to reduce unnecessary costs. Based on monthly stock and daily sales data from October 2023 to February 2024, this research uses quantitative methods to calculate optimal inventory levels, including Economic Order Quantity (EOQ), safety stock, and reorder point (ROP). This research also applies ABC analysis and cycle counting to prioritize inventory control. The research results show that the proposed inventory policy, especially the continuous review strategy, has the potential for significant cost savings for the XYZ Hospital Pharmacy Installation. For pharmaceutical products, achieving a 99% service level can result in savings of IDR 302,697,429, which is 48.17% of the average inventory level. For medical devices, potential savings reach IDR 70,602,064, which is 48.77% of the average inventory level. The total potential savings for all products is IDR 373,299,493. These findings highlight that hospitals currently do not have effective controls in managing inventory of single-use medical devices. Implementing strong inventory policies and procedures is critical to improving cost efficiency and optimizing inventory levels within an organization.

Bioactives of the Freshwater Aquatic Plants, Nelumbo nucifera and Lemna minor, for Functional Foods, Cosmetics and Pharmaceutical Applications, with Antioxidant, Anti-Inflammatory and Antithrombotic Health Promoting Properties

Despite significant progress, certain inflammation related to chronic disorders, including cardiovascular diseases (CVD) and cancer, still present high mortality rates. Thus, further study is needed to address such pathologies more appropriately. Apart from classic therapeutics, natural bioactives with less toxic side effects have gained attention, including those with potential pharmaceutical properties derived from several plants. Within this article, the potential utilization of freshwater aquatic plants as sources of bioactives with antithrombotic, anti-inflammatory and antioxidant properties is outlined. Emphasis is given to a well-established aquatic plant with known but not fully clarified and overviewed bio-functional and pharmaceutical properties, the Chinese lotus (Nelumbo nucifera), as well as to a so far neglected aquatic plant, Lemna minor, which has not yet been thoroughly reviewed for such applications. The latent usually grows naturally in large numbers at the surface of stored water basins of retrieved water from the last stages of wastewater treatment facilities. The continuous growth of this aquatic plant in such conditions further suggests that it can be a sustainable source of natural bioactives, if appropriately valorized, with an economic benefit and in a friendly environmental approach. The abundant content of both freshwater aquatic plants in bioactive components with potent antioxidant, anti-inflammatory and antithrombotic activities is thoroughly outlined, while their applications as functional ingredients in several functional products (functional foods, cosmetics and pharmaceuticals) are also discussed. The outlined outcomes urge further study of both aquatic plants and especially of Lemna spp. to fully elucidate their potential as alternative sustainable sources of bioactive ingredients for functional foods, supplements, nutraceuticals, nutricosmetics, cosmeceuticals, cosmetics and pharmaceutical products with health-promoting properties against inflammation and thrombosis related manifestations and their associated chronic disorders.

Drug administration via feeding tubes-a procedure that carries risks: systematic identification of critical factors based on commonly administered drugs in a cohort of stroke patients.

Drug administration via feeding tubes is considered a process with many uncertainties. This review aimed to give a comprehensive overview of data available on feeding tube application and to carry out risk assessments for drug substances commonly administered to stroke patients. Drugs frequently administered via feeding tubes were identified through a retrospective analysis of discharge letters from a stroke unit. Physicochemical, pharmacokinetic, and stability properties of these drugs and data on drug-enteral nutrition interactions were systematically searched for in the European Pharmacopoeia, Hagers Handbook of Pharmaceutical Practice, Birchers clinical-pharmacological data compilation, and the Martindale Complete Drug Reference, as well as from databases including DrugBank, DrugDex, PubChem, Google Scholar, and PubMed. Of the drugs most commonly administered via feeding tubes in the present stroke patient cohort, bisoprolol, candesartan, and ramipril could be considered the least critical due to their overall favourable properties. Acetylsalicylic acid, amlodipine, hydrochlorothiazide, omeprazole and esomeprazole, simvastatin, and torasemide pose risks based on pH or light-dependent instability or proposed food effects. The most critical drugs to be administered via feeding tubes are considered to be furosemide, levodopa, and levothyroxine as they show relevant instabilities under administration conditions and substantial food effects; the latter two even possess a narrow therapeutic index. However, little information is available on drug-tube and drug-formula interactions. Feeding tube administration of medications turned out to be a highly complex process with several unmet risks. Therefore, investigations that systematically assess these risk factors using clinically relevant model systems are urgently needed.

Delphi method applicability in drug foresight

BackgroundThe aim of the current study was to assess the accuracy of expert predictions, which were derived using a Delphi panel foresight study between 2009 and 2011, on a variety of drug-related topics in Finland in 2020.MethodsThe material used to evaluate the accuracy of the predictions consists of published reports on statistics, survey results, official register data, wastewater analyses and official documents. Whenever possible, we used multiple information sources to ascertain possible changes related to the predictions.ResultsBetween 2009 and 2011, the majority – but not all – of the experts accurately predicted an increase in drug use. Indeed, more people experimented with or used drugs, and more drug residues were found in wastewater monitoring. The experts also correctly predicted an increase in population-level approval of drug use, but this development has been rather slow. Contrary to predictions, there was no marked increase in the use of new synthetic drugs. However, the misuse of buprenorphine increased during the 2010s. In the drug market, unit prices were surprisingly stable over the ten-year period. There were no changes in legislation related to the legal status of drugs, as was foreseen by the experts. However, enforcement moved in the direction foreseen by the experts: more lenient measures have been taken against users. Drug care system reforms favored a combination of mental health and addiction care units between 2009 and 2011, and 2020, as foreseen by the experts.ConclusionsIt seems to have been easier for the experts to foresee the continuation of existing trends, e.g., increasing use of drugs or widening approval of drugs, than to predict possible changes in the popularity of distinct groups of drugs such as new psychoactive substances (NPS). Even armed with the prediction that drug imports and wholesale would increasingly fall into the domain of organized crime, this undesirable development could not be stopped. Expert disagreement can also be seen as a valuable indication of uncertainty regarding the future. Foresight related to drug-related issues can produce relatively accurate and realistic views of the future at least up to ten years ahead.

Development and validation of stability-indicating assay method and identification of force degradation products of glucagon-like peptide-1 synthetic analog Exenatide using liquid chromatography coupled with Orbitrap mass spectrometer.

Exenatide is a synthetic glucagon-like peptide 1 analog, widely used in the management of type 2 diabetes mellitus. The stability of pharmaceutical products is significantly impacted by various environmental stress conditions. The present study reports the development of a validated reverse-phase high-performance liquid chromatography (RP-HPLC) stability-indicating method for the identification of force degradation products (DPs) of synthetic glucagon-like peptide-1 analog Exenatide using UHPLC-Orbitrap fusionTM mass spectrometer. Force degradation studies were performed by subjecting Exenatide to various stress conditions, such as hydrolytic, oxidative, photolytic and thermal to investigate the stability indicating ability of the method. Significant degradation was observed during acidic, oxidative, photolytic and thermal stress conditions. Exenatide and its major DPs identification and characterization were demonstrated by employing LC-HRMS and MS/MS method. In total, five major stress DPs were characterized, and their fragmentation pathway was proposed using MS/MS studies. Finally, the proposed RP-HPLC method was validated as per ICH guidance.

Automated multifactorial design of experiment and Bayesian optimisation algorithm approaches to method development for the green analysis by supercritical fluid chromatography of a pharmaceutical ingredient

During drug development, chromatography is frequently used for purity and stability testing of both drug substance and drug product. Reversed phase liquid chromatography (RPLC) is one of the most widely used methodologies due to its wide scope of application. In the later stages of drug development, the specified impurities and degradation products that define the critical quality attribute of the final API, also known as Key Predictive Sample Set (KPSS), are usually well defined and controlled. At this point, a method review enables selecting the most appropriate technique which should be the one providing optimal robustness (ICH-Q14[1]), with the support of Quality by Design (QbD) approaches. Supercritical Fluid Chromatography (SFC) is a preferred technique for its proven diversity in selectivity. The adoption of a technique which presents the most favourable environmental impact, such as, but not limited to, SFC, is also becoming increasingly important as laboratories strive to reduce carbon footprint. Re-developing a method requires high resource-demands in terms of staff, materials, and time. Any step of the process that can be automated can facilitate this approach, speeding up the delivery of the method whilst preserving robustness.In this article we describe how an SFC method was developed for the purity profiling of a late-stage oncology candidate, taking advantage of the superior selectivity of SFC towards structurally similar analytes, owed to the high orthogonality with R2 as low as 0.014 towards the KPSS. We describe two approaches to automate the method development. Firstly, a multifactorial design of experiments (DoE) and secondly, an optimization via a Bayesian algorithm, which was completed in one night, highlighting the potential and limitations, with an insight into the robustness. Both methods achieved baseline separation with varying levels of automation embedded into the process and a large reduction of the resource demands when compared to traditional optimisation methods. Finally, we describe the beneficial environmental impact that implementing SFC methods can yield, with a calculated green score reduced to a value between 17 and 30 % compared to RPLC, depending on the number of runs per sequence.

Access to Substituted 1,1-diarylalkanes by Friedel-Crafts Benzylations Mediated by FeCl3-based Deep Eutectic Solvents.

The development of new, more efficient Friedel-Crafts benzylation methodologies that provide access to 1,1-diarylalkanes is an important objective of interest for the production of pharmaceuticals and fine chemical products. In this regard, this study introduces a novel synthetic route to 1,1-diarylalkanes conducted in the Deep Eutectic Solvent (DES) 3FeCl3 · 6H2O/Gly, which serves as both a reaction medium and promoter. Under these conditions, Friedel-Crafts benzylations of various arenes bearing activating and deactivating ortho-/para-directing groups, can be performed using diverse benzylating reagents such as styrenes, alcohols, acetates, ethers, and chlorides. Importantly, highly electronically deactivated electrophiles, including those with CF3 and NO2 groups, are suitable substrates. This methodology provides a wide range of asymmetric 1,1-diarylalkanes (up to 132 examples) with generally good yields and high regioselectivities. The efficiency of this approach was demonstrated with the multigram-scale synthesis (10 mmol) of 1-phenyl-1-xylyl ethane (PXE), a liquid with great industrial applicability. Moreover, the Fe(III)-based DES could be reused for 20 consecutive cycles with no appreciable erosion of the yields.

Raman spectroscopy as an alternative rapid microbial bioburden test method for continuous, automated detection of contamination in biopharmaceutical drug substance manufacturing.

To investigate an in-line Raman method capable of detecting accidental microbial contamination in pharmaceutical vessels, such as bioreactors producing monoclonal antibodies via cell culture. The Raman method consists of a multivariate model built from Raman spectra collected in-line during reduced-scale bioreactor batches producing a monoclonal antibody, as well as a reduced-scale process with intentional spiking of representative compendial method microorganisms (n=4). The orthogonal partial least squares regression discriminant analysis model (OPLS-DA) Area Under the Curve (AUC), specificity and sensitivity were 0.96, 0.99 and 0.95, respectively. Furthermore, the model successfully detected contamination in an accidentally contaminated manufacturing-scale batch. In all cases, the time to detection (TTD) for Raman was superior compared to offline, traditional microbiological culturing. The Raman OPLS-DA method met acceptance criteria for equivalent decision making to be considered a viable alternative to the compendial method for in-process bioburden testing. The in-line method is automated, non-destructive, and provides a continuous assessment of bioburden compared to an offline compendial method, which is manual, results in loss of product, and in practice is only collected once daily and requires 3-5 days for enumeration.

Identification of infectious viruses for risk-based virus testing of CHO unprocessed bulk using next-generation sequencing.

It is important to increase manufacturing speed to make medicines more widely available. One bottleneck for CHO-based drug substance release is the in vitro viral (IVV) cell-based assay on unprocessed bulk. To increase process speed, we evaluate the suitability of replacing the IVV cell-based assay with next-generation sequencing (NGS). First, we outline how NGS is currently used in the pharmaceutical industry, and how it may apply to CHO virus testing. Second, we examine CHO virus contamination history. Since prior virus contaminants can replicate in the production bioreactor, we perform a literature search and classify 159 viruses as high, medium, low, or unknown risk based on their ability to infect CHO cells. Overall, the risk of virus contamination during the CHO manufacturing process is low. Only six viruses were reported to have contaminated CHO bioprocesses over the past several decades, and were primarily caused by fetal bovine serum or cell culture components. These virus contamination events can be mitigated through limitation and control of raw materials, combined with virus testing and virus clearance technologies. The list of CHO infectious viruses provides a starting framework for virus safety risk assessment and NGS development. Furthermore, ICH Q5A (R2) includes NGS as a molecular method for adventitious agent testing, paving a path forward for modernizing CHO virus testing.

Detecting univariate, bivariate, and overall effects of drug mixtures using Bayesian kernel machine regression

ABSTRACT Background: Innovative analytic approaches to drug studies are needed to understand better the co-use of opioids with non-opioids among people using illicit drugs. One approach is the Bayesian kernel machine regression (BKMR), widely applied in environmental epidemiology to study exposure mixtures but has received far less attention in substance use research. Objective: To describe the utility of the BKMR approach to study the effects of drug substance mixtures on health outcomes. Methods: We simulated data for 200 individuals. Using the Vale and Maurelli method, we simulated multivariate non-normal drug exposure data: xylazine (mean = 300 ng/mL, SD = 100 ng/mL), fentanyl (mean = 200 ng/mL, SD = 71 ng/mL), benzodiazepine (mean = 300 ng/mL, SD = 55 ng/mL), and nitazene (mean = 200 ng/mL, SD = 141 ng/mL) concentrations. We performed 10,000 MCMC sampling iterations with three Markov chains. Model diagnostics included trace plots, r-hat values, and effective sample sizes. We also provided visual relationships of the univariate and bivariate exposure-response and the overall mixture effect. Results: Higher levels of fentanyl and nitazene concentrations were associated with higher levels of the simulated health outcome, controlling for age. Trace plots, r-hat values, and effective sample size statistics demonstrated BKMR stability across multiple Markov chains. Conclusions: Our understanding of drug mixtures tends to be limited to studies of single-drug models. BKMR offers an innovative way to discern which substances pose a greater health risk than other substances and can be applied to assess univariate, bivariate, and cumulative drug effects on health outcomes.

Guyparkeria halophila: Novel cell platform for the efficient valorization of carbon dioxide and thiosulfate into ectoine

Utilizing carbon dioxide (CO2) for valuable chemical production is key to a circular economy. Current processes are costly due to limited microorganism use, low-value products, and the need for affordable energy. This study addresses these challenges by using industrial contaminants like thiosulfate (S2O32−) for CO2 conversion into ectoines. Ectoines, are important ingredients as pharmaceuticals and cosmetics. Here, six microbial genomes were identified as potential candidates to valorize CO2 and S2O32− into ectoine. After laboratory validation at 3 % NaCl, the fastest-growing strain, Guyparkeria halophila, was optimized at 6 %, 9 %, and 15 % NaCl, showing the highest specific ectoine contents (mgEct gbiomass−1) at 15 %. Batch bioreactors, combining optimal conditions, achieved maximum specific ectoine contents of 47 %. These results not only constitute the highest ectoine content so far reported by autotrophs and most of heterotrophs, but also the first proof of a novel valorization platform for CO2 and S2O32−, focused on pharmaceuticals production.

Catalytic Deoxygenative Transformation of Ketoacids/Esters for the Synthesis of Coumarin, Benzofuranone, and Dihydrobenzo[b]oxepin‐2(3H)‐one Derivatives.

We disclose herein a triflic acid and silane‐promoted reductive deoxygenative transformation of ketoacid/esters for the divergent synthesis of different‐sized lactones, which hold substantial significance in pharmaceutical and natural product chemistry. Owing to the simple reaction conditions and setup, this protocol features broad substrate generality, scalability, and good functional group tolerance, including late‐stage functionalization of pharmaceutical compounds and natural products. The control experiments and detailed NMR study provide insight into the reaction mechanism.

W single-atom mediated singlet oxygen formation on carbon nitride for powerful photocatalytic abatement of organic pollutants

Active single-atom W anchoring on graphitic carbon nitride (g-C3N4) with interplanar four-coordination with N was achieved via a microwave hydrothermal process followed by thermal polymerization. The optimal monoatomic W incorporated g-C3N4 (W-CN) catalyst exhibited a high photocatalytic activity toward a wide range of pharmaceutical and personal care products (PPCPs). The anchoring of W single atom narrowed the energy-band, negatively shifted the conduction band of g-C3N4, and promoted the charge transfer and photogenerated carrier separation. Moreover, W single-atom intercalation obviously favored the formation of singlet oxygen (1O2), as validated by the active species capture test and density functional theory (DFT) calculation, which played an important role in the photocatalytic degradation of PPCPs. The treatment of actual wastewater, toxicity assessment and hemp-pea-growth experiments further showed that the W-CN photocatalyst could effectively degrade the organic pollutants and reduce their poisonousness in the water environment. This work offers a facile route to obtain reactive g-C3N4 with single-metal active sites and some insights into its activity enhancement for the abatement of organic pollutant-containing wastewater.

Cocoa Butter: Evolution from Natural Food Ingredient to Pharmaceutical Excipient and Drug Delivery System.

For decades, cocoa butter has been extensively used in food industries, particularly in the production of chocolate confectioneries. The composition of fats within cocoa butter, such as stearic acid, palmitic acid, and oleic acid, determines its properties. Studies have indicated the existence of at least six polymorphic forms of cocoa butter, each possessing distinct characteristics and melting points. Recently, cocoa butter has garnered attention for its potential as a delivery system for pharmaceutical products. This review thoroughly explores cocoa butter, encompassing its production process, composition, properties, and polymorphism. It delves into its diverse applications across various industries including food, cosmetics, and pharmaceuticals. Additionally, the review investigates cocoa butter alternatives aiming to substitute cocoa butter and their roles in different drug delivery systems. The unique properties of cocoa butter have sparked interest in pharmaceutical industries, particularly since its introduction as a drug delivery system and excipient. This has prompted researchers and industry stakeholders to explore novel formulations and delivery methods, thereby expanding the range of options available to consumers in the pharmaceutical market.

New mathematical model from dynamic dissolution rate tests

In vitro dissolution experiments are becoming increasingly complex attempting to replicate in vivo behavior. The objective of these new methods is to explore the behavior of low-solubility drugs. This is more relevant for drugs classified in subclasses 2a, 2b and 2c of the BCS, considering their pH-dependent solubility and dissolution characteristics.A novel mathematical approach using a modified double Weibull equation is proposed to model the dissolution and precipitation kinetics observed in two-stage and transfer dissolution experiments (dumping test). This approach demonstrates a high level of accuracy in fitting experimental data for two drugs BCS class 2a and two BCS class 2b, providing valuable insights into their dissolution behavior under different conditions.The results highlight the versatility of the proposed model in capturing complex dissolution phenomena, including rapid dissolution, precipitation, and redissolution. The ease of implementation in Excel, using the Solver tool, makes it a practical and accessible tool for pharmaceutical researchers.Overall, the study contributes to the development of more effective in vitro dissolution testing methods, facilitating the formulation and optimization of pharmaceutical products and potentially aiding in the establishment of in vitro-in vivo correlations (IVIVC).

Explainable deep recurrent neural networks for the batch analysis of a pharmaceutical tableting process in the spirit of Pharma 4.0

Due to the continuously increasing Cost of Goods Sold, the pharmaceutical industry has faced several challenges, and the Right First-Time principle with data-driven decision-making has become more pressing to sustain competitiveness. Thus, in this work, three different types of artificial neural network (ANN) models were developed, compared, and interpreted by analyzing an open-access dataset from a real pharmaceutical tableting production process. First, the multilayer perceptron (MLP) model was used to describe the total waste based on 20 raw material properties and 25 statistical descriptors of the time series data collected throughout the tableting (e.g., tableting speed and compression force). Then using 10 process time series data in addition to the raw material properties, the cumulative waste, during manufacturing was also predicted by long short-term memory (LSTM) and bidirectional LSTM (biLSTM) recurrent neural networks (RNN). The LSTM network was used to forecast the waste production profile to allow preventive actions. The results showed that RNNs were able to predict the waste trajectory, the best model resulting in 1096 and 2174 tablets training and testing root mean squared errors, respectively. For a better understanding of the process, and the models and to help the decision-support systems and control strategies, interpretation methods were implemented for all ANNs, which increased the process understanding by identifying the most influential material attributes and process parameters. The presented methodology is applicable to various critical quality attributes in several fields of pharmaceutics and therefore is a useful tool for realizing the Pharma 4.0 concept.

Recent approaches of regulatory perspectives for the registration of drugs in southern states in India

Recent approaches in regulatory perspectives for the registration of drugs in Southern states of India have been characterized by a focus on enhancing efficiency, transparency, and safety in the drug approval process. This involves the adoption of stringent regulatory frameworks aligned with international standards to ensure the quality, efficacy, and safety of pharmaceutical products. One significant development is the implementation of electronic submission systems for the registration of drugs, streamlining the application process and reducing administrative burdens for regulators and pharmaceutical companies. Additionally, there has been an emphasis on strengthening post-marketing surveillance mechanisms to monitor the safety and efficacy of drugs once they are in the market, enabling prompt identification and mitigation of potential risks or adverse reactions. Collaborative efforts between regulatory authorities, industry stakeholders, and healthcare professionals have also been encouraged to facilitate knowledge exchange and capacity building in regulatory compliance and pharmacovigilance. Overall, these recent approaches reflect a concerted effort to uphold public health standards and ensure access to safe and effective medications for the population of Southern states in India.

In-situ wet milling for particle size control in continuous crystallization: Expanding the attainable region

Continuous mixed-suspension mixed-product removal crystallizer cascades are robust and proven options for continuous manufacturing. However, when applied to a late-stage drug substance the desired particle size could not be achieved due to rapid crystal growth and slow secondary nucleation kinetics. This necessitated a batch terminal milling operation to achieve particle size control (Johnson et al., 2021). To overcome this and to intensify the process, an in-situ high-shear wet mill was integrated into the continuous equipment train to achieve the target physical properties of the drug substance that met the quality and manufacturability criteria needed for the drug product. This article describes the workflow used to optimize the equipment set and operational parameters. Incorporation of a high-shear wet mill operated intermittently in the continuous drug substance process greatly expanded the attainable particle size region, improved product quality, reduced cycle time, and simplified process development and scale-up compared to the process of batch milling after continuous crystallization. Small scale batch milling experiments were used to characterize milling performance at lab and production scales and inform operational space. Several lab-scale continuous runs were then used to define the process operating space and validate the process parameters necessary to meet the particle specifications of the product. Scale-up of the equipment set for in-situ milling was also demonstrated. This approach was tested at lab-scale on representative material operating for 70 h while changing the particle size of the product in real time. This illustrated the potential of intermittent milling for model-free particle size control.

Evolutionary game model and simulation analysis of multi-stakeholder behaviour for promoting Braille labelling on pharmaceutical packaging in China’s legal framework

This study investigates the factors influencing the lack of Braille-embossed labels in Chinese pharmaceutical product packaging. To this end, this study constructs an evolutionary game model of multi-participant behaviour in drug production regulation and conducts simulation based on the perspective of stakeholders in order to study the evolutionary steady state of regulatory authorities, pharmaceutical companies, and visually impaired individuals and the influence of each parameter variable on the choice of strategic behaviour of the participants. The simulation results show that in the legal framework of China, administrative penalties, the production subsidy rate, and the Basic Medical Insurance (BMI) reimbursement rate are the main drivers of the system’s evolution towards a steady state. Reduced costs of drugs with Braille-embossed packaging is a prerequisite for the visually impaired to purchase such drugs, and the key for the whole system to converge to a stable state therefore lies in the BMI reimbursement rate for drugs with Braille-embossed packaging. This paper suggests that the Chinese government should improve the law enforcement mechanism for the regulation of the production of drugs with Braille-embossed packaging; increase the type and intensity of administrative penalties as well as production subsidies, tax incentives, and compliance incentives for pharmaceutical companies; and provide higher BMI reimbursement rates for the visually impaired. The results of the study provide valuable insights to improve accessibility to drugs and build a barrier-free environment for ensuring medication safety in China and other developing countries.