Development Of Pharmaceutical Products Research Articles

A Bayesian Approach to Kinetic Modeling of Accelerated Stability Studies and Shelf Life Determination.

Kinetic modeling of accelerated stability data serves an important purpose in the development of pharmaceutical products, providing support for shelf life claims and expediting the path to clinical implementation. In this context, a Bayesian kinetic modeling framework is considered, accommodating different types of nonlinear kinetics with temperature and humidity dependent rates of degradation and accounting for the humidity conditions within the packaging to predict the shelf life. In comparison to kinetic modeling based on nonlinear least-squares regression, the Bayesian approach allows for interpretable posterior inference, flexible error modeling and the opportunity to include prior information based on historical data or expert knowledge. While both frameworks perform comparably for high-quality data from well-designed studies, the Bayesian approach provides additional robustness when the data are sparse or of limited quality. This is illustrated by modeling accelerated stability data from two solid dosage forms and is further examined by means of artificial data subsets and simulated data.

Soft Gelatine Capsules- Critical Quality Attributes of Chosen Excipients and Capsules Parameters Following the Quality by Design Concept

Soft gel capsules are a common form of medicine and food supplements. Quality, productivity and manufacturing time is crucial for producers during their development and industrial operations. To ensure the best quality of the product, it is necessary to know all critical process steps and parameters. The use of QbD elements is to ensure the quality of the drug product throughout its "life cycle". Quality by design (QbD) and its elements are described by the International Council of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and in their guideline - chapter ICH Q8 (Pharmaceutical Development). One of the first steps in pharmaceutical product development is to prepare Quality Target Product Profile (QTPP) and analyse Critical Material Attributes (CMAs) and Critical Quality Attributes (CQAs) of excipients, active pharmaceutical ingredient (API) and final product. During this research, we investigated the CQAs of the excipients used in vitamin D3 soft gelatin capsules containing high doses of cholecalciferol, from 10 000 to 200 000 IU per capsule. We considered the viscosity of the gelatin mass, the effect of the addition of dye on the viscosity, and the impact of the colour of the gelatin mass on the active substance content in the final capsules. It was also investigated oily carriers (medium chain triglycerides and safflower oil) and antioxidants (alpha-tocopherol acetate vs butylhydroxytoluene), and their effect on API concentration in the capsule.

Development of a target quality profile for capsules containing a dry extract of salvia sclarea l. grown in tajikistan

Aim. To work out the concept of scientific research on the pharmaceutical development of capsules based on the substance of a dry extract of Salvia sclarea L. (clary sage) grown in Tajikistan by developing a target drug quality profile.
 Materials and methods. During the research, methods of a systematic approach, scientific analysis, comparison, analogy, and generalization of information on the pharmaceutical development of herbal medicines were used. Tabular and schematic tools for visual presentation of the data obtained were also applied.
 Results. The pharmacological studies of a dry extract of Salvia sclarea L. grown in Tajikistan using the “elevated plus maze” test indicate the prospects of its use as an active substance of a moderate anxiolytic action in the dose of 300 mg/kg. The results obtained served as the basis for developing a target quality profile for capsules containing a dry extract as the first stage of the pharmaceutical development, implementing the programmable quality concept “Quality by Design”. When developing the target quality profile for capsules, a set of complementary provisions, recommendations, and methods of the State Pharmacopoeia of Ukraine and the Eurasian Economic Union concerning the issues of technological, chemical, and microbiological requirements for the development of pharmaceutical products was analyzed.
 Conclusions. Thus, the development of a target quality profile for capsules containing a dry extract of Salvia sclarea L. will make it possible to rationally use material resources and implement the programmable quality concept.

Development and Acceptability of Cookie Product Made from Marang (Artocarpus Odoratissimus) Seed Flour

Marang, known for its distinctive flavor and texture, is a tropical fruit hailing from Southeast Asia, featuring sweet, custard-like flesh and a fragrant scent. This study aimed to create Marang seed (Artocarpus odoratissimus) flour and cookies, establishing the optimal ingredient ratios to deliver a delightful flavor. Employing both quantitative and qualitative approaches, this research enlisted consumer respondents and food professionals to assess sensory qualities using the DOST’s 9-point hedonic scale. Statistical analysis, including mean and standard deviation, was employed to evaluate cookie acceptability based on qualitative criteria encompassing appearance, aroma, taste, and texture. Phyto-chemical analysis revealed the presence of alkaloids, naturally occurring substances with potential pharmacological effects, in Marang extract. Quaternary bases and amin e oxides, organic compounds featuring positively charged nitrogen atoms, were identified, alongside steroids with diverse biological functions. The grading system denoted the relative concentration of alkaloids. While 2-deoxysugars were detected, unsaturated steroids were absent. Flavonoids, known for their antioxidant properties, and saponins, foaming agents with potential health benefits, were also present. Tannins, recognized for their astringency, appeared with different colors indicating condensed and hydrolyzable tannins. Marang seed flour exhibited a chemical composition with 18.2% oil content, 16% moisture content, 10.7% crude protein content, and notable levels of manganese and copper at 31.8 ppm and 7.5 ppm, respectively, along with 161 ppm of phosphorus. The overall acceptability of the developed cookie was moderately liked, with a grand mean rating of 7.76. Taste held the greatest influence on overall acceptability, followed by texture, appearance, and aroma. This study recommends further investigation into the pharmacological effects and potential health benefits of Marang extract components, potentially leading to pharmaceutical or functional product development. Utilizing Marang seed flour in various food products can leverage its nutritional value and meet potential commercial demand. Improving and standardizing the Marang cookie recipe for uniform quality and flavor is advisable. The development of packaging and branding to highlight the unique qualities and health benefits of Marang cookies can cater to health-conscious consumers.

Product contamination during mechanochemical synthesis of praziquantel co-crystal, polymeric dispersion and cyclodextrin complex

This paper aims to evaluate the product contamination by elemental impurities during the mechanochemical synthesis of praziquantel (PZQ) co-crystal, polymeric dispersion and cyclodextrin complex by grinding. To assess that, PZQ was co-ground with malic acid (MA), Poloxamer F-127 (F-127) and hydroxypropyl-β-cyclodextrin (HPβCD) in high-energy vibrational mills using stainless steel and agate grinding tools, applying different processing time (30 and 90 min). Differential scanning calorimetry and X-ray powder diffraction confirmed the formation of the targeted products, regardless of applied processing time and grinding tool type. After digestion of the solid powder products, the levels of selected elemental impurities were analysed by inductively coupled plasma mass spectrometry (ICP-MS). The analysis revealed that the content of Mg, Ca, and V are below the limit of quantification in all samples analysed. The contents of P and Na are not related to the type of ball mill and reaction time, but to the starting materials themselves, considering that Na is found in HPβCD and MA, while P was found in F-127. The detected Si impurities in the co-ground products can be related to the use of the agate balls and jars, while the presence of Cr and Fe can be related to the use of the stainless steel grinding tools. The risk assessment showed that the oral administration of the prepared co-ground products in quantities corresponding to regular PZQ oral doses resulted in only insignificant exposure to Cr. Finally, the use of agate grinding tools should be preferred, as administration of such products results in lower Cr exposure. The presented elemental impurities did not lead to any significant drug degradation as PZQ content at the end of the six-month testing period was still in the range of 95–105 % of the initial content. Regardless, ICP-MS analysis of the elemental impurities should be considered in regular quality control procedures in the development and production of novel pharmaceutical products prepared by grinding.

BIOAVAILABILITY AND POLYMORPHIC STABILITY CHALLENGES AFFECTING DRUG PRODUCT’S POTENTIAL: A CRITICAL EVALUATION AND PERTINENT SOLUTION

Clinical failure remains an ongoing challenge in pharmaceutical drug product development. Solubility and permeability therefore play a very critical role in achieving desired bioavailability and pharmacological response, which in turns affects clinical safety and efficacy significantly. The situation becomes more critical when the drug candidate exhibits polymorphism and undergoes polymorphic transformation due to its meta-stable nature. This review article outlines the available technologies, pertinent regulations, the concepts involved in the enhancement of bioavailability and polymorphic stability to overcome the clinical failures. Various available technologies for bioavailability enhancement such as salification, micronization, complexation, microemulsification, nano emulsification, cocrystal formation, and amorphous solid dispersion with their advantage and disadvantage in formulating a stable drug product containing a polymorphic and meta-stable drug substance. Thermodynamic and kinetic aspects of polymorphic transformation are discussed to understand different excipient and process-induced transformation during manufacturing and shelf life of the drug product. Selecting the right instrument from the analytical toolbox is equally important to understand the diverse nature of polymorphic transformation. This review provides state-of-the-art information available on advanced analytical tools along with their capabilities, advantages, and disadvantage with respect to physical/structural analysis of polymorphs and polymorphic transformation.

Exotic fruits patents trends: An overview based on technological prospection with a focus on Amazonian

The Amazon rainforest encompasses one of the largest biodiversities of the world and is home to a wide variety of food and therapeutic plants. Due to the diversity of components, the fruits of the Amazon biome possess essential physicochemical, nutritional, and pharmacological properties, strengthening the idea that fruit consumption may provide benefits to human health. Thus, the objective of this study was to investigate the current scenario of the use of Amazonian fruits on the development of food, pharmaceutical, nutraceutical, or cosmetic products through the study of filed patents. A prospecting strategy conducted focusing on patents was used to investigate the application of the following fruits: Euterpe oleracea, Oenocarpus bacaba, Caryocar brasiliense, Garcinia gardneriana, Nephelium lappaceum, and Astrocaryum vulgare. A total of 264 patent documents were found. In 2016, a peak of 33 applications was reached, followed by a peak in 2019 with 32 applications. The study is distributed in three main application areas: cosmetics, pharmaceuticals, and food. The Asian continent was the region with the world leadership in this theme, followed by Brazil. Thus, technological prospection studies can foster investments in translational research to elucidate the effects and properties of Amazonian fruits, which can generate sustainable development of new products with industrial potential.

Characterization and Reverse Engineering of Pharmaceuticals: Role of Thermoanalytical Techniques

During pharmaceutical or biopharmaceutical drug product development, one of the most important steps to be followed is characterization and reverse engineering of the drug product. Out of so many characterization tools and orthogonal reverse engineering techniques, thermoanalytical methods are the most useful techniques. Different thermoanalytical techniques are used to identify, quantify and understand the interaction between different polymorphic forms of drug substances and excipients. These techniques are also used to monitor the physical form (amorphous or crystalline) of the drug substance in drug product throughout its manufacturing processes and helps in identifying, omitting or modifying the steps or processes responsible for change in physical or polymorphic form of the drug substance in the finished drug product. Thermoanalytical techniques are not only useful for characterization of small molecules but also extensively applied in analysis of biological samples and nano-formulations. In current scenario, pharmaceutical development specifically during generic drug development the most useful step is the reverse engineering. When reverse engineering of drug product is concerned, thermoanalytical techniques are the best tools to be used to prove the similarity of physico-chemical properties or same state of matter or arrangement of matter between test and reference products. However, in earlier days these techniques were not used as frequently as the other techniques like spectroscopy and chromatography. Various reasons for limited use of thermoanalytical techniques were unavailability of software or compatible hardware, manual sampling process and a tedious process of manual calculation which consumes lots of time. Now a day, due to advancement of technology, automation, use of robotics, and better understanding, and the thermal analysis not only become a powerful tool but also increase the throughput. The present review focuses on some of the most commonly used Thermoanalytical techniques e.g. Differential Scanning Calorimeter (DSC), Thermogravimetric Analysis (TGA), Solution Calorimeter (SC), Thermo Mechanical Analysis (TMA) and Isothermal Titration Calorimeter (ITC) for characterization and reverse engineering of different dosage forms like solid oral dosage forms, injectable formulation, inhalation formulation, ophthalmic formulation, and biosimilar formulation products such as peptides and proteins using specific case studies.

Visualisation of drug distribution in skin using correlative optical spectroscopy and mass spectrometry imaging

A correlative methodology for label-free chemical imaging of soft tissue has been developed, combining non-linear optical spectroscopies and mass spectrometry to achieve sub-micron spatial resolution and critically improved drug detection sensitivity. The approach was applied to visualise the kinetics of drug reservoir formation within human skin following in vitro topical treatment with a commercial diclofenac gel. Non-destructive optical spectroscopic techniques, namely stimulated Raman scattering, second harmonic generation and two photon fluorescence microscopies, were used to provide chemical and structural contrast. The same tissue sections were subsequently analysed by secondary ion mass spectrometry, which offered higher sensitivity for diclofenac detection throughout the epidermis and dermis. A method was developed to combine the optical and mass spectrometric datasets using image registration techniques. The label-free, high-resolution visualisation of tissue structure coupled with sensitive chemical detection offers a powerful method for drug biodistribution studies in the skin that impact directly on topical pharmaceutical product development.

Cost of illness in inclusion body myositis: results from a cross-sectional study in Germany

BackgroundInclusion body myositis (IBM) is the most frequent type of myositis in elder patients with a slow chronic progression and refractory to treatment. Previous cost of illness (COI) studies in IBM used claims data to estimate direct costs in the US. No evidence exists globally on both direct and indirect costs in IBM from a societal perspective. We conducted a survey in patients registered in the German IBM patient registry. Self-developed items were used to assess the utilized healthcare resources and estimate the cost. The German Self-Administered Comorbidity Questionnaire (SCQ-D), the sIBM Physical Functioning Assessment (sIFA) and patient-reported measures for satisfaction and improvements in healthcare were applied for an explorative analysis.ResultsIn total, 82 patients completed the survey. We estimated the mean total annual per capita COI of US$102,682 (95% CI US$82,763–US$123,090) in 2021. 92.7% of the total COI were direct costs. Medical costs were similar to nonmedical costs, with substantial costs for pharmacotherapy and informal care. Depending on the prevalence estimate, the total national COI per year were US$42.7 million–US$213.7 million. Significant differences in total COI were identified for the degree of disability, marital and employment status (p < 0.05).ConclusionsWe identified remarkable and heterogenous cost in IBM. As informal care costs represented the most relevant cost driver, caregiver burden is a major factor in the patient journey. For the first time, comprehensive economic potentials were identified as a basis to improve the actual care situations and prioritizing future activities for research, pharmaceutical and digital product development as well as health politics.

SUSIE: Pharmaceutical CMC ontology-based information extraction for drug development using machine learning

Automatically extracting information from unstructured text in pharmaceutical documents is important for drug discovery and development. This information can be integrated with structured datasets to ultimately accelerate pharmaceutical product development. To this end, we report an end-to-end information extraction framework based on a custom-built pharmaceutical drug development ontology, a weak supervision framework, contextualization algorithms, and a fine-tuned BioBERT model (adaptation of BERT or Bidirectional Encoder Representations from Transformers for biomedical text). The proposed framework, SUSIE (Schema-based Unsupervised Semantic Information Extraction), was trained on ICH (International Conference on Harmonization) documents to identify important entities and relations from unstructured text and auto-generate knowledge graphs representing crucial information in a structured format. On the entity identification task, the framework achieves a test accuracy and F1-score of 96% and 88%, respectively, on out-of-sample documents. A major contribution of this work is to build an automated, unsupervised information extraction framework around a domain-specific, custom-built pharmaceutical drug development ontology without the need for manual curation of training datasets for specific tasks. The efficacy of the approach was tested on out-of-sample documents including an internal Eli Lilly technical document.

Unique structural characteristics and biological activities of heparan sulfate isolated from the mantle of the scallop Chlamys farreri

Marine animals are a huge resource of various glycosaminoglycans (GAGs) with specific structures and functions. A large number of byproducts, such as low-edible mantle, are produced during the processing of Chlamys farreri, which is one of the most cultured scallops in China. In this study, a major GAG component was isolated from the mantle of C. farreri, and its structural characteristics and biological activities were determined in detail. Preliminary analysis by agarose electrophoresis combined with specific enzymatic degradation evaluations showed that this component was heparan sulfate and was named CMHS. Further analysis by HPLC and NMR revealed that CMHS has an average molecular weight of 35.9 kDa and contains a high proportion (80%) of 6-O-sulfated N-acetyl-D-glucosamine/N-sulfated-D-glucosamine (6-O-sulfated GlcNAc/GlcNS) residues and rare 3-O-sulfated β-D-glucuronic acid residues. Bioactivity analysis showed that CMHS has much lower anticoagulant activity than heparin and it can interact with various growth factors with high affinity. Moreover, CMHS binds strongly to the morphogen Wnt 3a to inhibit glypican-3-stimulated Wnt 3a signaling. Thus, the identification of CMHS with unique structural and bioactive features will provide a promising candidate for the development of GAG-type pharmaceutical products and promote the high-value utilization of C. farreri mantle.

COVID-19 and Global Distributive Justice

COVID-19 has had a detrimental effect on the world economy. Serious inequality in terms of vaccination has been found between developed countries and developing countries. This article analyzes the development, production, and allocation of vaccines and other essential pharmaceutical products during the COVID-19 pandemic, particularly from the viewpoint of global distributive justice. Analysis of this issue is expected to provide important lessons in preparing for future pandemics. This article analyzes how the world system could be strengthened and suggests ways to reform the World Trade Organization system regarding the special and differential treatment afforded to developing countries.

Sensitization Assessment of Extractables and Leachables in Pharmaceuticals: ELSIE Database Analysis.

Quality by design is the foundation of the risk management framework for extractables and leachables (E&Ls) recommended by the Extractables and Leachables Safety Information Exchange (ELSIE). Following these principles during the selection of materials for pharmaceutical product development minimizes the presence of highly toxic substances and decreases the health risk of potential leachables in the drug product. Therefore, in the context of the broad arena of chemicals, it is important to distinguish E&Ls as a subset of chemicals and evaluate this relevant chemical space to derive appropriate analytical and safety thresholds. When considering the health hazards posed by E&Ls, one area presenting a challenge is understanding the sensitization potential and whether it poses a risk to patients. A dataset of E&Ls compiled by ELSIE (n = 466) was analyzed to determine the prevalence and potency of skin sensitizers in this chemical subset and explore a scientifically justified approach to the sensitization assessment of potential leachables in parenteral drug products. Approximately half of the compounds (56%, 259/466) had sensitization data recorded in the ELSIE database and of these, 20% (52/259) are potential skin sensitizers. Only 3% (8/259) of the E&L dataset with sensitization data were considered potent (strong or extreme) sensitizers following in silico analysis and expert review, illustrating that potent sensitizers are not routinely observed as leachables in pharmaceutical products. Our analysis highlights that in silico potency prediction and expert review are key tools during the sensitization assessment process for E&Ls. The results confirm where material selection is anticipated to mitigate the risk of presence of strong and/or extreme sensitizers (e.g., extractable testing via ISO 10993-10), and that implementing thresholds per ICH M7 and/or Masuda-Herrera et al. provides a reasonably conservative approach for establishing the analytical testing and safety thresholds.

A Guide to Best Practice in Sensory Analysis of Pharmaceutical Formulations.

It is well established that treatment regime compliance is linked to the acceptability of a pharmaceutical formulation, and hence also to therapeutic outcomes. To that end, acceptability must be assessed during the development of all pharmaceutical products and especially for those intended for paediatric patients. Although acceptability is a multifaceted concept, poor sensory characteristics often contribute to poor patient acceptability. In particular, poor taste is often cited as a major reason for many patients, especially children, to refuse to take their medicine. It is thus important to understand and, as far as possible, optimise the sensory characteristics and, in particular, the taste/flavour/mouthfeel of the formulation throughout the development of the product. Sensory analysis has been widely practiced, providing objective data concerning the sensory aspects of food and cosmetic products. In this paper, we present proposals concerning how the well-established principles of sensory analysis can best be applied to pharmaceutical product development, allowing objective, scientifically valid, sensory data to be obtained safely. We briefly discuss methodologies that may be helpful in reducing the number of samples that may need to be assessed by human volunteers. However, it is only possible to be sure whether or not the sensory characteristics of a pharmaceutical product are non-aversive to potential users by undertaking sensory assessments in human volunteers. Testing is also required during formulation assessment and to ensure that the sensory characteristics remain acceptable throughout the product shelf life. We provide a risk assessment procedure to aid developers to define where studies are low risk, the results of a survey of European regulators on their views concerning such studies, and detailed guidance concerning the types of sensory studies that can be undertaken at each phase of product development, along with guidance about the practicalities of performing such sensory studies. We hope that this guidance will also lead to the development of internationally agreed standards between industry and regulators concerning how these aspects should be measured and assessed throughout the development process and when writing and evaluating regulatory submissions. Finally, we hope that the guidance herein will help formulators as they seek to develop better medicines for all patients and, in particular, paediatric patients.

Organoid-on-a-chip: Current challenges, trends, and future scope toward medicine.

In vitro organoid models, typically defined as 3D multicellular aggregates, have been extensively used as a promising tool in drug screening, disease progression research, and precision medicine. Combined with advanced microfluidics technique, organoid-on-a-chip can flexibly replicate in vivo organs within the biomimetic physiological microenvironment by accurately regulating different parameters, such as fluid conditions and concentration gradients of biochemical factors. Since engineered organ reconstruction has opened a new paradigm in biomedicine, innovative approaches are increasingly required in micro-nano fabrication, tissue construction, and development of pharmaceutical products. In this Perspective review, the advantages and characteristics of organoid-on-a-chip are first introduced. Challenges in current organoid culture, extracellular matrix building, and device manufacturing techniques are subsequently demonstrated, followed by potential alternative approaches, respectively. The future directions and emerging application scenarios of organoid-on-a-chip are finally prospected to further satisfy the clinical demands.

Determination of Heavy Metal Content: Arsenic, Cadmium, Mercury, and Lead in Cyano-Phycocyanin Isolated from the Cyanobacterial Biomass.

Cyano-phycocyanin (C-PC) is a light-absorbing biliprotein found in cyanobacteria, commonly known as blue-green algae. Due to its antioxidative, anti-inflammatory, and anticancer properties, this protein is a promising substance in medicine and pharmaceuticals. However, cyanobacteria tend to bind heavy metals from the environment, making it necessary to ensure the safety of C-PC for the development of pharmaceutical products, with C-PC isolated from naturally collected cyanobacterial biomass. This study aimed to determine the content of the most toxic heavy metals, arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in C-PC isolated from different cyanobacterial biomasses collected in the Kaunas Lagoon during 2019-2022, and compare them with the content of heavy metals in C-PC isolated from cultivated Spirulina platensis (S. platensis). Cyanobacteria of Aphanizomenon flos-aquae (A. flos-aquae) dominated the biomass collected in 2019, while the genus Microcystis dominated the biomasses collected in the years 2020 and 2022. Heavy metals were determined using inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS analysis revealed higher levels of the most investigated heavy metals (Pb, Cd, and As) in C-PC isolated from the biomass with the dominant Microcystis spp. compared to C-PC isolated from the biomass with the predominant A. flos-aquae. Meanwhile, C-PC isolated from cultivated S. platensis exhibited lower concentrations of As and Pb than C-PC isolated from naturally collected cyanobacterial biomass.

Intriguing of pharmaceutical product development processes with the help of artificial intelligence and deep/machine learning or artificial neural network

Intriguing of pharmaceutical product development processes with the help of artificial intelligence and deep/machine learning or artificial neural network

Sulfated Polysaccharides from Seaweeds: A Promising Strategy for Combatting Viral Diseases-A Review.

The limited availability of treatments for many infectious diseases highlights the need for new treatments, particularly for viral infections. Natural compounds from seaweed are attracting increasing attention for the treatment of various viral diseases, and thousands of novel compounds have been isolated for the development of pharmaceutical products. Seaweed is a rich source of natural bioactive compounds, including polysaccharides. The discovery of algal polysaccharides with antiviral activity has significantly increased in the past few decades. Furthermore, unique polysaccharides isolated from seaweeds, such as carrageenan, alginates, fucoidans, galactans, laminarians, and ulvans, have been shown to act against viral infections. The antiviral mechanisms of these agents are based on their inhibition of DNA or RNA synthesis, viral entry, and viral replication. In this article, we review and provide an inclusive description of the antiviral activities of algal polysaccharides. Additionally, we discuss the challenges and opportunities for developing polysaccharide-based antiviral therapies, including issues related to drug delivery and formulation. Finally, this review highlights the need for further research for fully understanding the potential of seaweed polysaccharides as a source of antiviral agents and for developing effective treatments for viral diseases.

Enhancing Antioxidant Properties of Prunus spinosa Fruit Extracts via Extraction Optimization

Prunus spinosa fruit, commonly known as blackthorn or sloe, possesses a wide range of health-promoting properties, including antioxidant and antibacterial activities. In this study, we investigated the effects of various extraction parameters, such as temperature, time, and solvent composition, on the extraction of bioactive compounds from P. spinosa fruit. Response surface methodology was employed to optimize these parameters and evaluate their impact on the antioxidant properties of the extracts. Furthermore, techniques such as ultrasound (US) and pulsed electric field (PEF) were applied, both individually and in combination, to explore their potential effects on the extraction process. The optimal extraction technique proved to be the combination of PEF and US, followed by stirring. The most suitable solvent was 75% ethanol, whereas the optimum extraction time and temperature were 30 min and 80 °C, respectively. Our findings revealed that under the optimum extraction parameters, a significant improvement in the extraction efficiency of bioactive compounds from P. spinosa fruit was achieved. More specifically, the optimal conditions, according to partial least squares (PLS) analysis, were a combination of all three extraction modes (PEF‒US‒ST), the shorter extraction time of the present study (30 min), and the corresponding higher temperature (80 °C). As expected, the presence of ethanol was considered necessary, even in an amount of 25%. The total polyphenol content was found to be 30.74 mg gallic acid equivalent (GAE)/g, the total flavonoids content 3.23 mg rutin equivalents (RtE)/g and the total anthocyanins 125.2 μg cyanidin-3-O-glucoside equivalents (CyE)/g. HPLC-DAD analysis showed that neochlorogenic acid was the polyphenol with the highest concentration (4.13 mg GAE/g) in P. spinosa fruit. The antioxidant activity of the optimized, according to PLS analysis, extract was evaluated and found to be 146.09 μmol ascorbic acid equivalent (AAE)/g determined by ferric reducing antioxidant power (FRAP) assay, and by the radical scavenging activity (DPPH) assay was 18.56 μmol AAE/g. Additionally, the ascorbic acid was determined to be 119.4 mg/100 g. Overall, this study contributes valuable insights into the extraction optimization process and the potential applications of P. spinosa fruit in the development of functional foods and pharmaceutical products.