Drug Research Articles

Effect of alternative dosing strategies of pembrolizumab and nivolumab on health-care emissions in the Netherlands: a carbon footprint analysis

Hospitals contribute substantially to greenhouse gas emissions and face a moral obligation to prioritise emission reduction. Drugs constitute an important component of the greenhouse gas emissions of hospitals. Alternative dosing strategies (ADS) have been implemented to improve the cost-effectiveness of pembrolizumab and nivolumab. However, the impact of these ADS on greenhouse gas emissions remains unknown. Therefore, we aimed to analyse the effect of ADS implementation on the carbon emissions of treatment with pembrolizumab and nivolumab. We used a process-based lifecycle assessment to quantify the environmental impact of pembrolizumab and nivolumab, focused on equivalent carbon dioxide emissions (CO2e). Lifecycle inventory and impact data from Erasmus University Medical Center (Rotterdam, Netherlands) were used to calculate the CO2e for pembrolizumab and nivolumab, their dosing intervals, and the impact of ADS on CO2e. The functional unit of the study was the administration of a single dose of pembrolizumab or nivolumab. In 2022, the annual carbon emissions related to pembrolizumab and nivolumab treatment in the Erasmus University Medical Center were 445 tons of CO2e, averaging 94 kg of CO2e per dose. Pharmaceutical production was the main driver of treatment-related carbon emissions (mean 92·9% of total emissions). Applying ADS resulted in 21-26% and 9-11% CO2e reductions for pembrolizumab and nivolumab, respectively. This study shows the environmental impact of pembrolizumab and nivolumab treatment and calls for further implementation of ADS for pembrolizumab, nivolumab, and other anti-PD-(L)1 monoclonal antibodies, and more sustainable pharmaceutical production processes. Our findings create environmental awareness and contribute to the promotion and understanding of health-care practices with lower carbon emissions. None.

In vitro hepatic 3D cell models and their application in genetic toxicology: a systematic review

The rapid development of new chemicals and consumer products has raised concerns about their potential genotoxic effects on human health, including DNA damage leading to serious diseases. For such new chemicals and pharmaceutical products, international regulations require genotoxicity data, initially obtained through in vitro tests, followed by in vivo experiments, if needed. Traditionally, laboratory animals have been used for this purpose, however, they are costly, ethically problematic, and often unreliable due to species differences. Therefore, innovative more accurate in vitro testing approaches are rapidly being developed to replace, refine and reduce (3R) the use of animals for experimental purposes and to improve the relevance for humans in toxicology studies. One of such innovative approaches are in vitro three-dimensional (3D) cell models, which are already being highlighted as superior alternatives to the two-dimensional (2D) cell cultures that are traditionally used as in vitro models for the safety testing of chemicals and pharmaceuticals. 3D cell models provide physiologically relevant information and more predictive data for in vivo conditions. In the review article, we provide a comprehensive overview of 3D hepatic cell models, including HepG2, HepG2/C3A, HepaRG, human primary hepatocytes, and iPSC-derived hepatocytes, and their application in the field of genotoxicology. Through a detailed literature analysis, we identified 31 studies conducted between 2007 and April 2024 that used a variety of standard methods, such as the comet assay, the micronucleus assay, and the γH2AX assay, as well as new methodological approaches, including toxicogenomics, to assess the cytotoxic and genotoxic activity of chemicals, nanoparticles and natural toxins. Based on our search, we can conclude that the use of in vitro 3D cell models for genotoxicity testing has been increasing over the years and that 3D cell models have an even greater potential for future implementation and further refinement in genetic toxicology and risk assessment.

Development and validation of an LC-MS/MS method for highly concentrated tacrolimus and cyclosporine samples prepared from pharmaceutical products to assess drug loss from feeding tubes

IntroductionTacrolimus and cyclosporine are common immunosuppressants utilized post-organ transplantation to manage allograft rejection. Both have narrow therapeutic indices and are frequently measured to support dose adjustments. Although nasogastric tubes are commonly used to provide nutritional support and serve as a route for immunosuppressant administration, they were never validated for such purposes. ObjectiveTo develop and validate a liquid chromatography – tandem mass spectrometry (LC-MS/MS) method for highly concentrated tacrolimus and cyclosporine samples prepared from pharmaceutical products to support the validation of feeding tube administration of these immunosuppressants. MethodsThe method involved stepwise dilutions with dimethyl sulfoxide before analysis using online sample preparation and LC-MS/MS. It was validated in a CLIA-certified clinical laboratory that measures immunosuppressants by LC-MS/MS and is designed to support clinical studies evaluating drug loss from feeding tubes. ResultsThe method was linear between 6.8 µg/mL and 75 µg/mL for tacrolimus, and between 0.9 mg/mL and 10 mg/mL for cyclosporine, with r2 > 0.99 and total precision <5 % at all QC levels. The method demonstrated good recovery using certified cyclosporine reference material, European pharmacopeia reference standard tacrolimus, and prepared pharmaceutical products. Minimal matrix effects were observed. ConclusionAn analytical method was developed and validated for in vitro studies with simulated administration of tacrolimus or cyclosporine to assess loss during drug administration using feeding tubes.

The withdrawal time of enrofloxacin, sulfachloropyrazine sodium, and doxycycline as well as the in vitro binding interaction with melanin in black-feathered silky fowl

The problem of veterinary drug residues in black-feathered silky fowl (BFS) has garnered significant attention. This study investigated the residue elimination patterns and causes of enrofloxacin (ENR), sulfachloropyrazine sodium (SPZ), and doxycycline (DOX) in BFS using ultra-high performance liquid chromatography mass spectrometry (UPLC-MS), along with the drug adsorption and melanin binding tests. The findings indicated that ENR and SPZ were metabolized slowly, DOX was metabolized faster in BFS, with optimum withdrawal time was 87.8, 37.26, and 24.7 days, respectively. The adsorption capacity of skin + fat to drugs and the binding capacity of melanin to the three drugs in BFS were in the order of ENR > SPZ > DOX, confirming that melanin's binding ability influences the drug residues in BFS. This study is highly significant for addressing the issue of veterinary drug residues in BFS.

Electronic structure of biochar modified through self-doping with boron, nitrogen and sulfur atoms for rapid and efficient adsorption of COVID-19 drug residues

Self-doping of biochar with various heteroatoms can significantly modify its electronic structure and surface properties, thereby enhancing its adsorption capacity. Allium mongolicum Regel (AM) was a desert herb known for hyperaccumulating boron and possessing a cavity structure. AMAC-3 derived from the pyrolysis of AM, exhibited a high specific surface area (2754 cm2g−1), a larger pore volume (2.513 cm3g−1), an appropriate degree of graphitization (IG/ID = 0.99), and a certain content of heteroatoms (boron, nitrogen and sulfur). AMAC-3 achieved equilibrium adsorption of 20 mg L−1COVID-19 drugs residues within 5–8 min, with equilibrium adsorption capacity ranging from 158 to 195mg g−1 and the drug removal rate between 79 % and 98 %. Furthermore, AMAC-3 maintained high adsorption efficiency in the presence of coexisting anions and spiked real water samples. The shorter adsorption equilibrium time and higher removal rate of AMAC-3 were attributed to the rapid mass transfer in the 3D pores, as well as the rapid binding of more electrons. Boron was the preferred binding site for heteroatom sites due to its electron deficient nature. This study offered insights into the utilization of self-doped heteroatoms for modulating the electronic structure of adsorbent, thereby reducing adsorption equilibrium time and enhancing removal efficiency.

Effects of gamma and electron-beam irradiations on the stability of free radicals, bioactive compounds and microbial characteristics of turmeric powder

Turmeric is a functional ingredient commonly used in food, pharmaceutical, and cosmetic products due to its health benefits and bioactivity, including anti-inflammatory, antioxidant, and anticancer benefits. Irradiation is a common technique used to decontaminate microorganisms and extend the shelf life of spices. However, there are scientific debates over the use of irradiation in food products. This study aimed to assess the effects of ionizing radiation, including gamma rays and electron beams, on bioactive compounds and microbial characteristics of turmeric powder. Technically, high-performance liquid chromatography with UV-Vis detection was used to assess bioactive compounds. Another aim of the present study was to determine free radicals in irradiated and non-irradiated samples within one month of storage using electron paramagnetic resonance (EPR). Results showed that gamma and electron-beam irradiations could decrease microbial contamination of turmeric by approximately 5 and 6 log cfu/g, respectively. Contents of bioactive compounds increased in irradiated samples and curcumin contents in gamma and electron-beam irradiated samples were 232–248 and 215–266 mg/g dry weight (dw), respectively. Furthermore, the study detected that free radicals increased in all irradiated samples immediately after irradiation but decreased over time. Decrease in EPR signals was faster in gamma-irradiated samples during storage. Numbers of free radicals induced by gamma and electron-beam irradiations were 6.59–4.70, 2.69–1.60, 1.61–1.34, and 0.99–1.05 on days 0, 7, 14, and 21, respectively. After 21 days of storage, the numbers of free radicals in all non-irradiated and irradiated samples were similar. Therefore, free radicals induced by irradiations were degraded during storage and eliminated after 21 days.

3D Printed Personalized Colon-targeted Tablets: A Novel Approach in Ulcerative Colitis Management.

Ulcerative colitis (UC) and Crohn's disease (CD) are two types of idiopathic inflammatory bowel disease (IBD) that are increasing in frequency and incidence worldwide, particularly in highly industrialized countries. Conventional tablets struggle to effectively deliver anti-inflammatory drugs since the inflammation is localized in different areas of the colon in each patient. The goal of 3D printing technology in pharmaceutics is to create personalized drug delivery systems (DDS) that are tailored to each individual's specific needs. This review provides an overview of existing 3D printing processes, with a focus on extrusion-based technologies, which have received the most attention. Personalized pharmaceutical products offer numerous benefits to patients worldwide, and 3D printing technology is becoming more affordable every day. Custom manufacturing of 3D printed tablets provides innovative ideas for developing a tailored colon DDS. In the future, 3D printing could be used to manufacture personalized tablets for UC patients based on the location of inflammation in the colon, resulting in improved therapeutic outcomes and a better quality of life.

Automated tablet defect detection and the prediction of disintegration time and crushing strength with deep learning based on tablet surface images

This paper presents novel measurement methods, where deep learning was used to detect tableting defects and determine the crushing strength and disintegration time of tablets on images captured by machine vision. Five different classes of defects were used and the accuracy of the real-time defect recognition performed with the deep learning algorithm YOLOv5 was 99.2%. The system can already match the production capability of tablet presses, with still further room left for improvement. The YOLOv5 algorithm was also used to determine the disintegration time and crushing strength of tablets produced at different compression force settings based on their surface texture. With these accurate, low-cost methods, the 100% screening of the produced tablets could be carried out, resulting in the improvement of quality control and effectiveness of pharmaceutical production.

Understanding the effect of plasticizers in film coat materials on the physical stability of amorphous solid dispersions

Amorphous solid dispersions (ASDs) have been extensively utilized to improve the bioavailability of drugs that have low aqueous solubility. The influence of different excipients on the conversion of amorphous drugs into their crystalline forms in ASDs has been extensively researched. However, there is limited knowledge examining the impact of film coating materials on the physical stability of oral tablet formulations containing ASDs. In this study, we demonstrate that plasticizers present in film coats can have a detrimental impact on the physical stability of ASDs. We systematically compared two frequently used plasticizers in film coats: triacetin and polyethylene glycol 3350 (PEG 3350). To gain mechanistic insights into the detrimental effects of plasticizers on the physical stability of ASDs, plasticizer leaching studies and physical stability studies of solvent-evaporated and spray-dried intermediates (SDI) using two BCS class II drugs were conducted. Triacetin was found to leach into the tablet core within one week when stressed at 40°C/75% RH, whereas no leaching was observed for PEG 3350, as discerned from spectroscopic studies. We also found that triacetin-containing ASDs exhibited greater amorphous to crystalline form conversion of the drug compared to PEG 3350-containing ASDs after stability testing. Moreover, the incorporation of triacetin into polymers was found to cause a significant depression of glass transition temperature and upon equilibration with moisture, a drop below room temperature. Overall, these observations underscore the importance of carefully selecting plasticizers to be present in film coatings when developing ASD pharmaceutical products.

New Drug Delivery Systems for Stable Oral Absorption: Theory, Strategies, and Applications.

The oral dosage route still remains the most common and preferred route for drug administration due to convenient handling, high patient compliance, and cost-effectiveness. However, the oral absorption of drugs can be a complex process depending upon: (i) physicochemical properties of the drug (e.g., pKa, lipophilicity, solubility), (ii) pharmaceutical factors (e.g., dosage form), and (iii) physiological factors (e.g., gastrointestinal pH values, gastric emptying rate, gastric and intestinal pH, metabolism). Oral administration of drugs sometimes leads to poor and/or variable oral bioavailability, possible leading to unstable clinical outcomes. To offer stable and improved pharmacokinetic behavior of drugs, a number of formulation approaches have been developed with a focus on enhancement of the solubility, dissolution rate, and oral bioavailability of drugs. To provide new formulation platforms for better and safe medication, it is considered essential to understand the physicochemical, biochemical, metabolic, and biological barriers which limit overall drug bioavailability in more detail. The review article considers several crucial factors affecting oral absorption of drug substances. This article also describes the recent progress in formulation approaches to achieve stable and improved biopharmaceutical properties of orally-taken drugs.

An Experimental and Modeling Approach to Study Tangential Flow Filtration Performance for mRNA Drug Substance Purification.

Following the recent COVID-19 pandemic, mRNA manufacturing processes are being actively developed and optimized to produce the next generation of mRNA vaccines and therapeutics. Herein, the performance of the tangential flow filtration (TFF) was evaluated for high-recovery, and high-purity separation of mRNA from unreacted nucleoside triphosphates (NTPs) from the in vitro transcription (IVT) reaction mixture.For the first time, the fouling modelwas successfully validated with TFF experimentaldata to describe the adsorption of mRNA on filtration membrane. The fouling model enables monitoring of the mRNA purification processes, designing an appropriate strategy for filter clean-up, replacing the column at the right time and reducing the process cost. Recovery greater than 70% mRNA without degradation was obtained by implementing a capacity load of ∼19g/m2, <2.5psi transmembrane pressure (TMP) and feed flux of 300 LMH.This approach also enables the purification of multiple mRNA drug substance sequences for the treatment of a wide range of different diseases.

Recent Advances in Cyclodextrin-Based Nanoscale Drug Delivery Systems.

Cyclodextrins (CDs) belong to a class of cyclic oligosaccharides characterized by their toroidal shape consisting of glucose units linked via α-1,4-glycosidic bonds. This distinctive toroidal shape exhibits a dual nature, comprising a hydrophobic interior and a hydrophilic exterior, making CDs highly versatile in various pharmaceutical products. They serve multiple roles: they act as solubilizers, stabilizers, controlled release promoters, enhancers of drug bioavailability, and effective means of masking undesirable tastes and odors. Taking advantage of these inherent benefits, CDs have been integrated into numerous nanoscale drug delivery systems. The resulting nanomaterials exploit the exceptional properties of CDs, including their ability to solubilize hydrophobic drugs for substantial drug loading, engage in supramolecular complexation for engineered nanomaterials, increase bioavailability for improved therapeutic efficacy, stabilize labile drugs, and exhibit biocompatibility and versatility. This paper compiles recent studies on CD functional nanoscale drug delivery platforms. First, we described the physicochemical and toxicological aspects of CDs, CD/drug inclusion complexation, and their impact on improving drug bioavailability. We then summarized applications for CD-functional nano delivery systems based on polymeric, hybrid, lipid-based nanoparticles, and CD-based nanofibers. Particular interest was in the targeted applications and the function of the CD molecules used. In most applications, CD molecules were used for drug solubilization and loading, while in some studies, CD molecules were employed for supramolecular complexation to construct nanoscale drug delivery systems. Finally, the review concludes with a thoughtful consideration of the current challenges and outlook.

Neurotoxicity and Cardiovascular Toxicity of Zinc Oxide Nanoparticles to Oryzias melastigma.

Zinc oxide nanoparticles (ZnO NPs) are widely used in manufacturing cosmetic and pharmaceutical products. Although previous studies have reported their toxic effects on fish, the underlying mechanisms behind their toxic effects are yet to be identified. This study evaluated the impact of ZnO NPs on marine medaka's survival, heart rates (Oryzias melastigma), and the expression of genes linked to neurotoxicity and cardiovascular toxicity. Marine medaka samples were exposed to ZnO NPs at varying concentrations: 0.01, 0.1, 1, and 10 mg/L. Survival rates and heart rates were monitored on the 12th day postfertilization. Gene expression related to neurotoxicity (α-tubulin, elavl3, gap43, gfap) and cardiovascular toxicity (cdh2, atp2a1, cacna1da, crhr1, ahrra, arnt2) was assessed by performing real-time polymerase chain reaction. The survival rate of marine medaka samples was not significantly impacted by exposure to up to 1 mg/L of ZnO NPs; however, exposure to 10 mg/L of ZnO NPs resulted in a 60% reduction in survival rate. The heart rate of the samples did not significantly change across all concentrations. High ZnO NP concentrations (10 mg/L) significantly suppressed the expression of neurotoxic and cardiotoxic genes, including elavl3 and gfap. ZnO NPs exhibited dose-dependent toxic effects on the marine medaka samples by affecting the expression of genes related to neurological and cardiovascular functions. These findings underscore the potential risks of ZnO NPs to aquatic organisms. The distinct toxic actions of ZnO NPs and dissolved ions complicate the interpretation of results, as this study did not measure ion release, a critical factor in understanding NP toxicity. Moreover, ZnO NPs may cause oxidative stress and disrupt cellular pathways. Furthermore, without distinguishing between NP and ion effects, it is challenging to determine the exact cause of toxicity. These findings highlight the need for future studies to measure dissolved ions and particles separately to clarify their contributions to toxicity, where the mechanisms of action are still debated.

A Review on Genotoxic Impurities in Pharmaceutical Dosage Forms and Strategies for Identification

Abstract: Genotoxic pollutants can be broadly defined as pollutants that, regardless of the mechanism, cause significant changes in genetic material. People all over the world suffer from various health problems due to genotoxic pollutants. Recent recommendations from drug regulatory agencies in Europe and the United States (USA) require the monitoring of genotoxic and potentially genotoxic contamination in drug formulations at the ppm level. Therefore, this review evaluates several regulatory agency guidelines for monitoring genotoxic contamination, impurity levels, and toxicity in pharmaceutical products. The review also discusses analytical considerations for measuring genotoxic pollutants at trace levels and concludes with several examples of measuring several important classes of genotoxic pollutants. We will also explain our results. The article provides detailed information on genotoxicity studies of waste solutions, metal wastes, and isolated pollutants.

Effect of ethanol extract from Enterolobium cyclocarpum fruit on Leghorn chickens exposed to Eimeria.

There are concerns about residues of drugs in meat that are used to prevent coccidiosis in chickens. Natural compounds are an alternative to drugs. Two studies investigated the effect of an extract of Enterolobium cyclocarpum fruits (EEC) in the feed of male Leghorn chickens exposed to Eimeria spp. In the first experiment, the administration of EEC after infection with Eimeria spp. was investigated over 16 days. One thousand chickens were randomly housed in 20 pens of 1 m2 each. The pens were randomly assigned to each treatment. Five treatments were administered, containing 150, 300 and 450mg/kg of EEC in the feed, the fourth treatment (C) contained 0.5g/kg of a commercial anticoccidial, and the fifth treatment provided no treatment (WA). The second experiment lasted 18 days. Administration of the EEC began five days before the chickens were infected with Eimeria spp. Four hundred and eighty chickens were randomly allocated to 24 pens of 1 m2. The pens were randomly assigned to each treatment. In the second experiment, the same five treatments were tested and one additional treatment containing 300mg EEC plus 1g of polyethylene glycol (PEG)/kg of feed (E300PEG). In the experiment one chickens in the EEC treatments had lower faecal oocyst excretion (OE) on day 14 post infection with Eimeria spp., than chickens in the WA treatment (P < 0.05). A reduction in live weight gain (LWG) was observed in the EEC treatments (P < 0.05). In the second experiment, the excretion of oocysts in chickens from the EEC and E300PEG treatments on day 13 post-infection with Eimeria spp. was the same as in the C treatment and lower than in the WA treatment (P < 0.05). LWG was lower in the EEC treatments than in the C treatment (P < 0.05). However, the Chickens in the E300PEG and C treatments had similar LWG (P > 0.05) suggesting that PEG inhibits the negative effect of EEC tannins on LWG. In conclusion, the addition of EEC to chicken feed reduced both OE and LWG. Treatment with EEC and PEG (E300PEG) reduced the excretion of oocysts without negative effects on LWG.

Quantitative estimation and validation of Alectinib hydrochloride drug substance using quantitative nuclear magnetic resonance spectroscopy

Nuclear magnetic resonance spectroscopy has been recently used for quantitative estimation of drug substance which has numerous merits in pharmaceutical applications when compared to traditional methods of chromatography. Present study focuses on method development and validation of quantitative proton nuclear magnetic spectroscopy method for estimation of alectinib hydrochloride drug substance. This method involves use of internal standard in presence of alectinib hydrochloride. For quantitation, 1H NMR signals at 8.4 ppm and 6.7 ppm corresponding to analyte proton of alectinib and ethyl 4-(dimethyl amino) benzoate internal standard respectively were used. Moreover, this method was validated as per ICH guidelines for accuracy, precision, linearity, limit of detection, limit of quantitation, range and robustness. Assay estimation by Q-NMR is facile and time-efficient which does not require reference standard of analyte and yet accurate and precise alternative as compared to estimation by other chromatographic techniques.

Nanomaterial Texture-Based Machine Learning of Ciprofloxacin Adsorption on Nanoporous Carbon.

Drug substances in water bodies and groundwater have become a significant threat to the surrounding environment. This study focuses on the ability of the nanoporous carbon materials to remove ciprofloxacin from aqueous solutions under specific experimental conditions and on the development of the mathematical model that would allow describing the molecular interactions of the adsorption process and calculating the adsorption capacity of the material. Thus, based on the adsorption measurements of the 87 carbon materials, it was found that, depending on the porosity and pore size distribution, adsorption capacity values varied between 55 and 495 mg g-1. For a more detailed analysis of the effects of different carbon textures and pores characteristics, a Quantitative nano-Structure-Property Relationship (QnSPR) was developed to describe and predict the ability of a nanoporous carbon material to remove ciprofloxacin from aqueous solutions. The adsorption capacity of potential nanoporous carbon-based adsorbents for the removal of ciprofloxacin was shown to be sufficiently accurately described by a three-parameter multi-linear QnSPR equation (R2 = 0.70). This description was achieved only with parameters describing the texture of the carbon material such as specific surface area (Sdft) and pore size fractions of 1.1-1.2 nm (VN21.1-1.2) and 3.3-3.4 nm (VN23.3-3.4) for pores.

Role of Nanomaterials in Degradation of Cosmetics and Pharmaceutical Wastewater: A Review

Biodiversity progress impacts the quality and availability of renewable natural resources. Ecological concerns about air and water pollution have been raised on communal and commercial levels. The continuous release and accumulation of cosmetics and pharmaceutical items in the environment pose significant threats to both ecosystems and human health. The presence of these emerging pollutants from pharmaceutical and cosmetic products has been reported in wastewater streams coming from industrial as well as wastewater treatment plants. This need has driven the development of technologies like advanced oxidation processes such as ozonation, Fenton’s oxidation, photocatalysis, etc. for conventional wastewater treatments. Among these, the photocatalytic processes are presently being efficient since they not only utilize UV light but also visible light. This article mainly focuses on the review of preparation and comparative activity of photocatalysts on cosmetic as well as pharmaceutical wastes degradation. Photocatalysts, in their different forms like nanoparticles, nanorods and nanocomposites, hold great promise due to their stability, non-toxicity and reusability.

A sales force effectiveness framework for enhancing healthcare access through pharmaceutical sales and training programs

This paper introduces a conceptual framework aimed at enhancing sales force effectiveness within the pharmaceutical industry, specifically focusing on improving healthcare access through optimized sales training programs and customer relationship management (CRM) systems. The proposed framework recognizes the critical role that pharmaceutical sales teams play in facilitating healthcare delivery, particularly during public health crises. It emphasizes the integration of effective training strategies and advanced CRM tools to enhance engagement with healthcare professionals, thereby improving product distribution and patient outcomes. The framework comprises three essential components Sales Force Training Enhancement, which focuses on developing targeted training programs that equip sales representatives with the necessary skills and knowledge to effectively communicate the value of pharmaceutical products to healthcare providers. This includes understanding clinical data, addressing healthcare providers’ concerns, and fostering a consultative selling approach. Secondly, CRM System Implementation, which underscores the significance of adopting robust CRM systems that streamline interactions between sales teams and healthcare professionals. By leveraging data analytics and customer insights, pharmaceutical companies can tailor their approach to meet the specific needs of healthcare providers, thereby enhancing relationship-building and communication. Thirdly, engagement and Outcome Measurement, which highlights the importance of measuring engagement levels and patient outcomes resulting from effective sales strategies. This component advocates for the use of key performance indicators (KPIs) to assess the impact of training and CRM initiatives on product distribution and healthcare access. The framework ultimately aims to foster a more collaborative environment between pharmaceutical sales teams and healthcare professionals, ensuring that patients receive timely access to essential medications and services. By focusing on the strategic integration of training and CRM systems, this framework presents a comprehensive approach to improving sales force effectiveness in the pharmaceutical sector. Future research and practical applications of this framework can further explore its implications for enhancing healthcare access, particularly in times of public health challenges.

ОПЫТ ПРИМЕНЕНИЯ ФУНКЦИИ ЖЕЛАТЕЛЬНОСТИ ХАРРИНГТОНА ПРИ ВЫБОРЕ ОПТИМАЛЬНОГО СОСТАВА ПЛЁНОК И ГЕЛЯ С НАФТОХИНОНОВЫМ КОМПЛЕКСОМ

When a new pharmaceutical product development comes to the stage of selecting the optimal combination of components, researchers often need a comprehensive assessment method for experimental samples. The difficulty is caused by overall complexity of choosing the correct qualitative and quantitative parameters expressed in different units of measurement and establishing priorities between the criteria for the combined assessment. In this case membership functions can help, for example the generalized Harrington desirability function, which allows to combine individual indicators that differ in value and dimension. The article provides examples of the practical application of the generalized Harrington desirability function in assessing several parameters of experimental samples of films and gel developed by us with a naphthoquinone complex of Lithospermum erythrorhizon in order to determine the best composition of these forms. The chosen method made it possible to calculate the generalized desirability for each experimental sample, taking into account all the studied criteria and to determine the most successful experimental samples for further work.