Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3020010

Authors: Agustín Videla Garrido Víctor Fernández Briceño Carolina Rodríguez Laboccetta Gladys B. Posse Alejandro D. Nusblat María L. Cuestas

Background: Histoplasmosis is a major opportunistic fungal infection in immunocompromised individuals, particularly people living with HIV in Latin America. Early diagnosis is essential to reduce morbidity and mortality, but commercial urinary Histoplasma antigen assays are not consistently accessible in many endemic settings. Methods: We developed a locally produced enzyme-linked immunosorbent assay (ELISA) to detect urinary Histoplasma antigen in urine and performed a preliminary clinical evaluation. The assay is based on a sandwich ELISA format using rabbit polyclonal antibodies raised against whole-killed yeast cells of Histoplasma capsulatum. Receiver operating characteristic (ROC) analysis was performed with urine samples from patients with progressive disseminated histoplasmosis (PDH) (n = 37) and healthy controls (n = 20). An exploratory disease-control panel (n = 11) was also tested to assess cross-reactivity. Preliminary analytical characterization included blank-based estimation of the limit of detection (LOD) and limit of quantification (LOQ). Results: Using a Youden-derived cutoff of OD492 = 0.243, the in-house ELISA showed a sensitivity of 73.0% (27/37; 95% CI: 55.9–86.2%) and a specificity of 100.0% (20/20; 95% CI: 83.2–100.0%) in the main ROC dataset, with an area under the curve of 0.856. In the exploratory disease-control panel, 2 of 11 specimens were reactive (one paracoccidioidomycosis and one cryptococcosis sample). Preliminary LOD and LOQ estimates were 4.46 ng/mL and 8.15 ng/mL, respectively. Conclusions: This locally developed ELISA represents a feasible and cost-effective alternative for urinary antigen detection of Histoplasma, with potential to improve access to early diagnosis in resource-limited settings. However, its current performance should be considered preliminary. Additional optimization and broader validation, including direct comparison with commercial assays, inter-assay precision, reagent stability, and larger multicenter control panels, are required before routine clinical implementation.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3020009

Authors: Sesha Rajeswari Talluri Brian Jeffrey Chan Bozena Michniak-Kohn

Personalized transdermal drug delivery systems (TDDS) represent a transformative approach in precision medicine by enabling patient-specific, non-invasive, and controlled therapeutic administration. Conventional transdermal patches are limited by fixed dosing, passive diffusion, and interindividual variability in skin permeability and metabolism, often leading to suboptimal therapeutic outcomes. Recent advances in materials science, nanotechnology, microneedle engineering, and digital health have enabled the development of next-generation personalized TDDS capable of programmable, adaptive, and feedback-controlled drug release. Smart wearable patches integrating biosensors, microfluidics, microneedles, and wireless connectivity allow real-time monitoring of physiological and biochemical parameters, enabling closed-loop drug delivery tailored to individual metabolic profiles. Nanocarriers such as lipid nanoparticles, polymeric nanoparticles, and stimuli-responsive hydrogels further enhance drug stability, penetration, and controlled release, while 3D-printing technologies facilitate patient-specific customization of patch geometry, drug loading, and release kinetics. Artificial intelligence (AI) and machine learning tools are increasingly being employed to predict drug permeation behavior, optimize enhancer combinations, and personalize dosing regimens based on pharmacogenomic and pharmacokinetic data. Despite these advances, regulatory complexity, manufacturing standardization, long-term biocompatibility, and cybersecurity considerations remain critical challenges for clinical translation. This review highlights recent innovations in personalized TDDS, discusses their clinical potential, and examines regulatory and technological barriers. Collectively, these emerging smart transdermal platforms offer a promising pathway toward adaptive, patient-centered therapeutics that can significantly improve treatment efficacy, safety, and compliance. Future research should focus on integrating multimodal biosensing, advanced biomaterials, scalable manufacturing strategies, and robust regulatory frameworks to enable clinically validated, fully autonomous transdermal systems that can dynamically adapt to real-time patient needs in diverse therapeutic settings.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3020008

Authors: Gregorio Juan Mc callum María Sol Rodriguez Christian Leandro Macoretta Ignacio Smith Federico Javier Wolman Alexandra Marisa Targovnik Adolfo Rafael de Roodt María Victoria Miranda Matías Fingermann

Background: Accidents caused by the Loxosceles laeta spider constitute a health problem in South America. Envenomation can lead to severe systemic manifestations, eventually compromising the patient’s life. Most regional health authorities consider antivenom administration the basis of effective treatment in the most serious cases. The availability of spider venom is the primary bottleneck for antivenom production. Herein, we present a novel biotechnological approach, based on the expression of recombinant versions of the most relevant toxin in loxoscelism, sphingomyelinase D (SphD), in insect larvae (Spodoptera frugiperda). Methods: We produced two versions of SphD: one conserving its biological activities (wtSphD) and a second alternative that was designed to be genetically detoxified (dSphD). Two horses were subjected to three consecutive hyperimmunization cycles with dSphD. The horses’ plasma was extracted at the end of each cycle and used to produce Active Pharmaceutical Ingredients (APIs) of antivenoms at a pilot scale. Results: Dermonecrotic activity of wtSphD was completely neutralized with the sera obtained from one horse and partially with that of the other. In contrast, the APIs derived in both cases completely neutralized wtSphD dermonecrotic activity. Direct hemolysis of human red blood cells by wtSphD was also neutralized by sera and APIs. Conclusions: These results show venom replacement or complementation potential by recombinant dSphD produced in this novel platform.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3020007

Authors: Jaimin R. Shah Abraham T. Phung Alexandra L. Krisiewicz Tao Dong William C. Trogler Eddie Y. Chung Han L. Lim Andrew C. Kummel

Viral vectors such as adenovirus (Ad) and lentivirus (LV) are central to gene therapy owing to their transduction efficiency and broad applicability; however, their clinical translation is often limited by immunogenicity, rapid clearance, and reduced bioavailability. Non-enveloped Ad vectors are highly susceptible to neutralization by pre-existing antibodies, while enveloped LVs remain vulnerable to immune surveillance and off-target clearance. In this study, a biomimetic encapsulation strategy using erythrocyte-derived membranes (EDMs) is reported to enhance viral immune resilience and functional gene delivery. Ad-GFP and LV-mCherry were successfully encapsulated within EDM using an extrusion-based assembly approach, resulting in uniform membrane-coated particles with physicochemical properties characteristic of erythrocyte membranes. EDM encapsulation significantly enhanced in vitro transduction efficiency of both viral platforms across multiple cancer cell lines without compromising viral activity. Notably, EDM-Ad-GFP demonstrated robust protection against neutralizing antibodies, achieving significantly higher transduction of HEK293 cells in the presence of diluted human serum compared to unencapsulated Ad. These findings indicate that EDM encapsulation can effectively shield viral vectors from immune recognition while improving cellular uptake and transduction performance. Collectively, this work establishes EDM encapsulation as a versatile and scalable platform to enhance the efficacy, durability, and translational potential of viral gene delivery systems.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3010006

Authors: Fernando Albericio

The pharmaceutical and biotechnology industries are experiencing rapid and multidimensional evolution, driven by advances in chemistry, biologics, data analytics, formulation, as well as regulatory and ethical frameworks [...]

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3010005

Authors: Borish Loushambam Venkateswaran Krishnaswami Munish Kumar Sivakumar Vijayaraghavalu

Insulin injection remains the best therapy for diabetes mellitus, but subcutaneous injection continues to pose challenges, including patient discomfort, poor compliance and fluctuating plasma glucose profiles. Recently, transdermal insulin delivery has emerged as a non-invasive strategy that bypasses gastrointestinal degradation and first-pass hepatic metabolism, thereby increasing insulin bioavailability and enhancing patient acceptance. Recent developments in nanomedicine have facilitated the development of transdermal patches with enhanced drug encapsulation, uptake and controlled release. Nanostructured lipid carriers, polymeric nanocomposites, liposomes and SLNs have demonstrated a five-fold enhancement of transdermal flux and an extended insulin effect in preclinical models. The addition of ionic liquids and polymeric nanogels leads to an additional increase in insulin aqueous solubility and permeation, resulting from the temporary regulation of stratum corneum lipid organization. Bright and stimuli-responsive patches with glucose oxidase or phenylboronic acid functional groups enable regulated insulin delivery in response to changes in blood glucose, demonstrating near-normoglycemia for up to 48 h in animal testing. Nanocomposite systems assisted by microneedles have also been advanced to the early clinical phase, offering enhanced reproducibility of their pharmacokinetics and a low risk of dermal irritation. Despite these encouraging results, several translational challenges remain, such as biocompatibility, repeatability in the production of nanocarriers, long-term stability of formulations and regulatory standardization. This review examines the physicochemical design principles, materials innovations and permeation mechanism of nanomedicine-engineered insulin patches, the current state of preclinical and clinical advancements, challenges in production and future perspectives in viable patient-focused transdermal insulin delivery.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3010004

Authors: Silvia L. Soto Espinoza Pamela A. Kikot M. Laura Carbajal Claudio C. Paolazzi Mariano Grasselli

Background: Fetuin (Ft) is the most abundant protein in fetal bovine serum (FBS) and is considered one of its essential components. This acidic glycoprotein plays a key role in cell adhesion and proliferation and is vital for maintaining in vitro cultures of animal and human cells, tissues, and organs. FBS is a natural source for Ft purification. However, the high demand for FBS as a standard reagent in cell culture severely limits its availability for use as a raw material for protein purification. Furthermore, the industrial production of FBS results in a significant amount of contaminated FBS. This contaminated fraction can thus be utilized for Ft recovery. Methods: In this work, we present a novel method for Ft recovery from FBS using a single chromatographic step based on anion exchange chromatography under acidic conditions. Results: Optimal adsorption conditions for Ft were studied using response surface methodology (RSM), which suggested a buffer pH of 4.2 and an FBS dilution of 40%. However, increasing the pH to 5 resulted in a 28% increase in Ft recovery, although with a slight reduction in Ft purity to 88%. A scale-up to half a liter of FBS was performed using a 400 mL column. A single-step elution with 0.3 M NaCl was employed, yielding an Ft recovery of 90% with a purity greater than 82%. Conclusions: The purified Ft demonstrated biological activity as a growth promoter in MDBK cell culture when utilized in a serum-free culture medium.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3010003

Authors: Nethra Viswaroopan Meheli Ghosh Jasim Khan Ritesh K. Srivastava Mohammad Athar Ajay K. Banga

Background/Objective: Effective topical delivery of 4-phenylbutyric acid (4-PBA) for arsenical vesicant-induced skin injury requires nanocarrier systems that maintain physicochemical and chemical stability during extended storage. This study systematically evaluated the six-month stability of five 4-PBA-loaded micro/nanoparticulate formulations—chitosan nanoparticles (N31, N35), emulsomes (E2), microsponges (MSs), and PLGA nanoparticles (P1)—to identify lead candidates suitable for field deployment and foam integration. Methods: Formulations were subjected to ICH-accelerated stability testing at 25 °C/60% RH and 40 °C/75% RH, with monthly evaluation of particle size, polydispersity index, zeta potential, drug content by HPLC, and chemical/thermal stability by FTIR and DSC. Results: N31 demonstrated superior colloidal stability, maintaining particle size within acceptable limits at both conditions despite progressive surface charge neutralization. E2 showed consistent drug content retention and preserved chemical integrity, though moderate vesicle fusion occurred. MS underwent complete physical degradation at 40 °C within the first month, while P1 exhibited hydrolytic degradation with substantial drug loss. N35 showed severe aggregation indicating colloidal instability. Conclusions: N31 and E2 emerged as lead candidates: N31 is recommended for field deployment where environmental control is limited, while E2 is suitable for controlled storage settings prioritizing drug loading capacity.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3010002

Authors: Afza Rizwan Karan Dubey Vishal Malhotra Seema Bhatnagar

There is a growing global demand for cost-effective alternatives to high-priced biologic therapies, which has significantly accelerated the development of biosimilars and positioned them as sustainable and affordable treatment options. Biosimilars include therapeutic products such as monoclonal antibodies, soluble receptors, growth factors, and hormones that demonstrate comparable efficacy, safety, and quality to their reference biologics. By providing lower-cost alternatives, biosimilars play a vital role in bridging the affordability gap and expanding patient access to essential, life-saving treatments, particularly in low- and middle-income countries. This review focuses on current Good Manufacturing Practices (cGMPs) in biosimilar development, highlighting critical processes such as cell line engineering, glycosylation optimization, and bioprocess refinement aimed at improving cell culture productivity and product yield while ensuring consistent safety, efficacy, and quality across production batches. Advances in biotechnology, especially in proteomics and advanced analytical characterization, have improved understanding of cellular mechanisms influencing product quality and strengthened comparability with reference biologics. These scientific innovations have enhanced regulatory and clinical confidence, supporting wider acceptance and use amongst patients. In addition, this review examines the evolving global regulatory landscape governing biosimilars and its role in reducing development timelines and costs. Together, scientific innovation, standardized manufacturing practices, and harmonized regulatory frameworks foster competition, accelerate market entry, and ultimately help bridge the gap between innovation and affordability, ensuring equitable and sustainable global access to advanced biologic therapies.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi3010001

Authors: Marcelo de Oliveira Elaine S. de Pádua Melo Diego Azevedo Zoccal Garcia Vanessa Torres Braga Marta Aratuza Pereira Ancel Valter Aragão do Nascimento

Dry eye disease is a common condition in which tear production or quality is insufficient to lubricate the eyes properly. Standard treatment usually involves lubricating eye drops. In this study, we assessed the human health risks, including both non-carcinogenic and carcinogenic effects, associated with long-term exposure to the chemical elements arsenic (As), cadmium (Cd), cobalt (Co), iron (Fe), nickel (Ni), lead (Pb), and zinc (Zn) in eye drops used in Brazil. The results indicated that the Co concentration (1.1048 mg/kg) in the eye drops sample 5 exceeded the limit established by the ICH Q3D (R2) guideline for parenteral products (0.5000 mg/kg). Additionally, As levels in eye drop samples 2, 8–10, 12, 13, and 16, as well as Cd levels in samples 2, 3, 8–10, and 12, exceeded the limits established by the Brazilian Pharmacopoeia for parenteral administration (0.0500–0.0532 mg/kg). The main health risk appears to come from oral exposure, as the drug can drain into the nasal cavity via the nasolacrimal duct and then be absorbed through the gastrointestinal tract. While none of the tested eye drops posed non-carcinogenic risks, carcinogenic risks from oral exposure to As and Cd were identified, with overall risk levels exceeding acceptable thresholds. These findings emphasize the need for strict regulation and continuous monitoring of these products to reduce health risks and prevent long-term damage.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2040019

Authors: Gopinath Rongala Druva Sarika Rongala Appalaswamy Naidu Rongala

Medicine is accelerating rapidly, offering the advantages of site-specific delivery, minimized side effects, and improved treatment outcomes. A diverse array of chronic diseases, such as cancer, diabetes, asthma, myocardial infarction, and Alzheimer’s disease, are often accompanied by severe adverse effects and limited specificity, necessitating concentrated attention on targeted therapies. Recent advancements in molecular profiling and understanding of target pathways have enabled the identification of specific biomarkers and gene targets. These advancements have led to the development of targeted therapies that focus on the specific molecular alterations responsible for disease progression. Such therapies offer a more personalized and effective approach to treatment. This review focuses on the benefits of targeted therapies compared to traditional therapeutics and provides an overview of currently available targeted therapies for chronic diseases. By highlighting these advancements, the review aims to illustrate the progress in disease treatment towards more personalized approaches. The goal is to underscore how targeted therapies have evolved and how they represent a significant shift towards personalized therapy.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2040018

Authors: Queli Cristina Fidelis Letícia Paula Benvindo Trajano Efraim Costa Pereira Tatielle Gomes Dias Thamyres Freitas Fernandes Adriana Gomes Nogueira Ferreira Ana Lucia Fernandes Pereira Marcelino Santos Neto Richard Pereira Dutra Francisco Eduardo Aragão Catunda-Junior

Lecythidaceae species are known worldwide for their ability to produce edible nuts of high nutritional value, such as Brazil nuts, and are also used in traditional medicine in countries across America, Asia, and Africa. The potential of these species has aroused interest in their chemical composition, nutritional properties, and biological activities, with emphasis on anti-inflammatory and antinociceptive actions. The objective of this review was to summarize data regarding the anti-inflammatory and antinociceptive activities of Lecythidaceae species, identify the most promising bioactive agents, and elucidate their potential mechanisms of action. This integrative review was conducted by comprehensively searching the main electronic databases for scientific articles, with no restriction on publication date, that were available in full. Based on this survey, thirty-four articles were identified, covering twelve Lecythidaceae species with anti-inflammatory and antinociceptive actions evaluated in in vitro and in vivo models and randomized clinical trials. Studies encompass extracts, fractions, nuts, and isolated compounds, among which the extracts and fractions of Barringtonia angusta Kurz, Couroupita guianensis Aubl., Lecythis pisonis Cambess., and Petersianthus macrocarpus (P. Beauv.) Liben demonstrated potent inhibition of inflammatory mediators through suppression of gene expression in vitro and in vivo, acting via blockade of the nuclear factor kappa-light-chain-enhancer of activated B cells (KN-κB) signaling pathway. This finding highlights a relevant molecular mechanism by which Lecythidaceae species may exert their anti-inflammatory potential and supports further studies focused on isolating active fractions and elucidating possible synergistic effects. Ethnopharmacological and chemical composition data are also presented and discussed within the scope of their biological applications, highlighting the therapeutic potential of Lecythidaceae species and identifying promising candidates for future development of novel anti-inflammatory phytopharmaceuticals.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2040017

Authors: Sushrut Marathe Samira Beyramysoltan Giulia Marchese Elaheh Ardalani Nathaniel Berendson Theodore Vu Gabriele Bano Sayantan Chattoraj

The design and development of a robust and consistent manufacturing process for monoclonal antibodies (mAbs), augmented by advanced process analytics capabilities, is a key current focus area in the pharmaceutical industry. In this work, we describe the development and operationalization of multivariate statistical process monitoring (MSPM), a data-driven modelling approach, to monitor biopharmaceutical manufacturing processes. This approach helps in understanding the correlations between the various variables and is used for the detection of the deviations and anomalies that may indicate abnormalities or changes in the process compared to the historical dataspace. Therefore, MSPM enables early fault detection with a scope for preventative intervention and corrective actions. In this work, we will additionally cover the value of in silico data in the development of MSPM models, principal component analysis (PCA), and batch modelling methods, as well as refining and validating the models in real time.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2040016

Authors: Jon Andrade del Olmo Alejandro Melero Ander Pino Nagore Martínez de Cestafe Oihane Gartziandia Miguel Ucelay López de Heredia Josune Torrecilla Laura Gómez Sandra Benito Cid José María Alonso Raúl Pérez González

Dry eye disease (DED) is a multifactorial ocular surface disorder that significantly affects vision and quality of life. While artificial tears are the standard first-line therapy, their effectiveness is limited by the complex pathophysiology of DED. This study evaluated DayDrop® Triple Action, a novel formulation combining hyaluronic acid (HA), ectoine, and carboxymethylcellulose (CMC), designed to enhance tear film stability and ocular surface protection. Physicochemical and rheological properties were assessed, including viscosity, pseudoplasticity, and viscoelastic behaviour under dynamic conditions, along with ectoine release over 24 h. An in vitro allergic conjunctivitis model using conjunctival fibroblasts exposed to a pro-allergic cytokine cocktail was employed to examine immunomodulatory effects. DayDrop® Triple Action demonstrated high viscosity with pronounced pseudoplasticity and stable viscoelasticity, supporting improved mucoadhesion. The formulation provided sustained ectoine release and exhibited a positive immunomodulatory effect, likely linked to ectoine’s preferential hydration mechanism, which stabilizes membranes and reduces inflammatory signalling. These findings suggest that DayDrop® Triple Action integrates viscoelastic optimization, osmoprotection, and targeted anti-inflammatory action, offering a promising non-pharmacological strategy for managing DED and allergic ocular surface disorders.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2030015

Authors: Jailson de Araújo Santos Ariel de Almeida Coelho

The growing threat of Antimicrobial Resistance (AMR) demands innovative drug discovery, yet conventional 2D cell cultures fail to accurately mimic in vivo conditions, leading to high failure rates in preclinical studies. This review addresses the critical need for more physiologically relevant platforms by exploring recent advancements in bioengineered 3D tissue models for studying bacterial pathogenesis and antimicrobial drug discovery. We conducted a systematic search of peer-reviewed articles from 2015 to 2025 across PubMed, Scopus, and Web of Science, focusing on studies that used 3D models to investigate host–pathogen interactions or antimicrobial screening. Data on model types, biomaterials, fabrication techniques, and key findings were systematically charted to provide a comprehensive overview. Our findings reveal that a diverse range of biomaterials, including biopolymers and synthetic polymers, combined with advanced techniques like 3D bioprinting, are effectively used to create sophisticated tissue scaffolds. While these 3D models demonstrate clear superiority in mimicking biofilm properties and complex host–pathogen dynamics, our analysis identified a significant research gap: very few studies directly integrate these advanced bioengineered 3D models for high-throughput antimicrobial drug discovery. In conclusion, this review highlights the urgent need to bridge this disparity through increased research, standardization, and scalability in this critical interdisciplinary field, with the ultimate goal of accelerating the development of new therapeutics to combat AMR.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2030014

Authors: Simay Ozsoysal Hamidreza Heidari Gulenay Guner Donald J. Clancy Ecevit Bilgili

Evaluating power consumption in stirred media mills over a wide range of process parameters is crucial for analyzing breakage kinetics and milling efficiency. Despite considerable research efforts, existing models predominantly rely on power-law approaches and fail to provide a holistic understanding of the relationship between process parameters and power consumption. The aim of this study is to introduce a new mathematical model that accurately captures this relationship, across all bead filling ratios (φ), using dimensionless numbers including power number (Ne) and Reynolds number (Re). First, we considered experimental data from literature and discriminated various models to correlate either Ne or Re separately for each φ (Class 1 models) or Ne to Re–φ simultaneously (Class 2 models). The best performing model (Model 2.6 with SSR = 36.71, RMSE = 0.591, R2 = 0.99) was subsequently applied to a new set of experimental data, confirming that this model is highly robust and reliable across various conditions. To the best of our knowledge, in stirred media mill research, this work is the first to show that a simple four-parameter nonlinear model provides a robust fit for Ne data across varying rotor Re (200 to 1 × 106) and bead filling ratios (0.35–0.90).

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2030013

Authors: Lembit Rägo Jacqueline Sawyer

Current estimates suggest that Africa contains about 14% of the world’s population and accounts for 20% of the global burden of disease. Yet, it accounts for a mere 3% of clinical trials globally. The time is ripe—even overdue—for determining how best to direct future health research efforts. In response, a call has been heard for a continent-wide Africa-centric research ethics framework to redirect health research in Africa, as well as address the health research ethics malpractices that have violated the rights, dignity and well-being of participating African communities. Nevertheless, we should remain aware of what already exists and what continues to be of value. Creating parallel frameworks risks fragmentation of research, increased costs in having to meet differing requirements and delayed access of patients to new treatments. Existing international consensus documents which have evolved and been fine-tuned over time, offer guidance for ensuring ethical instigation and management of health research. The Declaration of Helsinki enunciates clear principles for ensuring the ethical conduct of clinical research, while CIOMS’ 2016 International Ethical Guidelines for Health-related Research involving Humans offer guidance for implementing these principles. It is failure to apply existing ethical principles and guidance—and not any perceived inadequacy of those principles—that has resulted in sub-optimal protection of African research participants.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2030012

Authors: Gerrit Seifert Frank Erdnüß Wolfgang Kamin Irene Krämer

Background: Off-label nebulization of tranexamic acid (TXA) solution is common practice for the treatment of hemoptysis. However, data regarding nebulization protocols, resulting aerodynamic parameters of the generated aerosol, and corresponding biopharmaceutical parameters are missing. The aim of this in vitro study was to investigate the aerosol characteristics of nebulized sterile, aqueous TXA solution. Methods: TXA solution 100 mg/mL was nebulized for 2 min by a multi-dose vibrating mesh nebulizer using 15 L/min and 30 L/min air flow rates. The generated aerosol was analyzed by a Next Generation Cascade Impactor. For each air flow rate, the mean Fine Particle Dose (FPD), Fine Particle Fraction (FPF), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation (GSD) were quantified. Results: Nebulization at 15 L/min air flow rate resulted in a MMAD of 6.68 ± 0.23 µm and GSD of 2.02 ± 0.16. The FPD < 5 µm was 16.56 ± 0.45 mg, the FPF < 5 µm 28.91 ± 3.40%. Nebulization at 30 L/min air flow rate revealed a MMAD of 5.18 ± 0.12 µm and GSD of 2.14 ± 0.10. The FPD < 5 µm was 16.30 ± 1.38 mg, the FPF < 5 µm 35.43 ± 0.59%. Conclusions: Nebulization of TXA 100 mg/mL solution by a specified vibrating mesh nebulizer generated an aerosol particle distribution and deposition pattern suitable for the treatment of hemoptysis with bronchial origin.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2030011

Authors: David Melvin Braga Bharat S. Rawal

Developing a new drug costs approximately one to three billion dollars and takes around ten years; however, this process has only a ten percent success rate. To address this issue, new technologies that combine artificial intelligence (AI) and quantum computing can be leveraged in the pharmaceutical industry. The RSA cryptographic algorithm, developed by Rivest, Shamir, and Adleman in 1977, is one of the most widely used public-key encryption schemes in modern digital security. Its security foundation lies in the computational difficulty of factoring the product of two large prime numbers, a problem considered intractable for classical computers when the key size is sufficiently large (e.g., 2048 bits or more). A future application of using a detailed structural model of a protein is that digital drug design can be used to predict potential drug candidates, thereby reducing or eliminating the need for time-consuming laboratory and animal testing. Knowing the molecular structure of a possible candidate drug can provide insights into how drugs interact with targets at an atomic level, at significantly lower expenditures, and with maximum effectiveness. AI and quantum computers can rapidly screen out potential new drug candidates, determine the toxicity level of a known drug, and eliminate drugs with high toxicity at the beginning of the drug development phase, thereby avoiding expensive laboratory and animal testing. The Food and Drug Administration (FDA) and other regulatory bodies are increasingly supporting the use of in silico to in vitro/in vivo validation methods and assessments of drug safety and efficacy.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2030010

Authors: Daniil Ialama Polina Orlova Anna Skuredina Ivan Meshkov Aziz Muzafarov Irina Le-Deygen

The development of novel dosage forms of vitamin B12 is an urgent task for addressing vitamin deficiency in individuals with gastrointestinal diseases or those following stringent dietary limitations. The study illustrates the fundamental possibility of employing a non-toxic and biocompatible organosilicon hydrogel with significant sorption capacity for B12 delivery. Research indicated that 40 min of incubation suffices for optimal loading efficiency, influenced by both external diffusion and intradiffusion factors. The release of B12 in a medium that mimics the human gastrointestinal tract transpires almost entirely within a timeframe that aligns with physiological conditions. Consequently, organosilicon hydrogels serve as potential vehicles for the administration of vitamin B12.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2020009

Authors: Eric Freiermuth David Kohler Albert Hofstetter Juergen Thun Michael Juhnke

Tablet surface defects are typically controlled by visual inspection in the pharmaceutical industry. This is an insufficient response variable for knowledge-based formulation and process development, and it results in rather limited robustness of the control strategy. In this article, we present an analytical method for the quantitative characterization of visual tablet surface defects. The method involves analysis of the tablet surface by a digital microscope to obtain optical images and three-dimensional surface scans. Pre-processing procedures are applied for the simplification of the data to allow the detection of the imprint characters and tablet surface structures by a Faster R-CNN object detection model. Geometrical variables like perimeter and area were derived from the results of the object detection model and statistically analyzed for a selected number of tablets. The analysis allowed the development of product-specific acceptance criteria by a small reference dataset, and the quantitative evaluation of sticking, picking, chipping, and abrasion defects. The method showed high precision and sensitivity and demonstrated robust detection of visual tablet surface defects without false negative results. The image analysis was automated, and the developed algorithm can be operated by a simple routine on a standard computer in a few minutes. The method is suitable for industrial use and enables advancements in industrial formulation and process development while providing a novel opportunity for the quality control of visual tablet surface defects.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2020008

Authors: Anand Kyatanwar Bala Prabhakar

Poor drug entrapment, burst release, and variable drug release profiles are the most critical challenges associated with biodegradable-polymer-based microspheres. In this study, biodegradable-polymer-based microspheres were used to entrap an antiplatelet drug, eptifibatide, using a single-emulsion solvent evaporation method. Critical challenges associated with biodegradable-polymer-based microspheres were addressed by incorporating different additives in the drug or polymer phase. Additives such as hydroxy propyl beta cyclodextrins (HPβCD), carboxy methyl cellulose sodium (Na CMC), and trehalose were added to the drug phase to evaluate their impact on the entrapment and stability of eptifibatide. The effect of the addition of additives such as polyvinyl alcohol (PVA), polyethylene glycol-400 (PEG-400), and methoxy polyethylene glycol phospholipid dimyristoyl phosphatidylethanolamine (mPEG-2000-DMPE, Na) to the polymer phase on the release profile of eptifibatide was evaluated. The inclusion of HPβCD resulted in good drug entrapment and helped control the initial unwanted burst release. Including Na CMC increased eptifibatide entrapment from 75% to 95%. Trehalose helped prevent the degradation of eptifibatide during lyophilization, and including PVA and PEG-400 reduced the lag phase and led to a controlled-release profile. Thus, including additives in the formulation can effectively improve the drug load and address issues associated with biodegradable-polymer-based microspheres.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2020007

Authors: Zuhair A. Alqahtani Xiaomeng Yue Jeff J. Guo

Aims: To describe and analyze trends in the utilization, spending, and average per prescription price of disease-modifying antirheumatic drugs (DMARDs) in the US Medicaid population. Methods: Using the publicly available national outpatient Medicaid State Drug Utilization Data, a retrospective, descriptive trend analysis was conducted on DMARDs from 1991 to 2022. Annual prescription counts and reimbursement amounts were calculated for nonbiologic and biologic DMARDs. Average per prescription price and Market share competition were calculated and analyzed for DMARDs. Results: Medicaid utilization of nonbiologic peaked in 2021 with 884,000 while biologic DMARDs with 688,000 prescriptions. In 2022, biologic utilization took the lead and exceed nonbiologic with 1.5 million prescriptions. Over the last 32 years, biologics captured 94% of Medicaid expenditures toward DMARDs, of which, 56% was toward adalimumab alone. On the other hand, spending on conventional DMARDs accounted for 33% while 67% accounted toward Janus Kinase Inhibitors. Biologic DMARDs average prices increased from around $800 to around $6000. However, the average adalimumab price increased 12-fold from around $1200 in 2003 to over $15,000 in 2021. Medicaid spending toward adalimumab increased by 179%. Conclusions: The substantial increase of DMARDs utilization and expenditure contributed significant burden to Medicaid budget. Introducing biosimilars into the market in the past few years is eroding the market share for several established biologics. Further cost-containment policies may be necessary for costly DMARD pharmacotherapy.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2020006

Authors: Sudip Ghosh Munna Bhattacharya

This study investigates the comparative impact of fermentation versus conventional extraction methods on the bioactive potency of “FERMENZA”, a patented, affordable, natural fermented cider-based topical formulation. Through comprehensive in vitro analysis, the fermented extract demonstrated superior antioxidant efficacy, with an IC50 value of 0.77 ± 0.03 mg/mL, significantly outperforming solvent and steam-distilled extracts, which showed IC50 values of 2.49 ± 0.01 mg/mL and 4.11 ± 0.03 mg/mL, respectively. Notably, the nitric oxide scavenging activity of the fermented extracts was markedly higher than that of conventional extracts, with IC50 values ranging from 1.12 ± 0.03 to 2.29 ± 0.03 mg/mL. Fermentation also enhanced total phenolic content (TPC), with mixed fruit extracts (pomegranate-beetroot, banana-papaya) reaching TPC levels of 2.43 ± 0.03 mg gallic acid equivalent/g, surpassing individual and conventionally processed samples. The study employed a Quality by Design approach to optimize fermentation conditions, achieving peak yields of gallic acid and TPC at 35 °C and 72 h, which further validates the process affordability. Under these conditions, the fermented extracts from pomegranate and beetroot demonstrated exceptional antimicrobial properties against E. coli, S. aureus, P. aeruginosa, P. acne, and M. furfur, with minimum inhibitory concentration values ranging from 0.25 mg/mL to 0.60 mg/mL, superior to those observed in conventionally extracted samples from pomegranate and beetroot. These findings highlight the efficacy of fermentation in enhancing bioactive compound availability, positioning FERMENZA as a potent fermented formulation for probable skin and hair-related cosmeceutical applications.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2020005

Authors: Daniel R. Delgado Fleming Martinez María Ángeles Peña Abolghasem Jouyban William E. Acree

The main objective of this research was to correlate the equilibrium solubility of sodium sulfadiazine in several {ethanol (EtOH, 1) + water (2)} mixtures reported in mass/volume and mass/mass percentages at different temperatures. Aqueous solubility of sodium sulfadiazine decreases almost linearly with decreasing temperature, but it decreases non-linearly with the addition of EtOH to water. Logarithmic solubility was adequately correlated with a bivariate model involving temperature and mixture composition. These solubility results were also well correlated with the Jouyban–Acree-based models. Moreover, an adapted version of the Jouyban–Acree model was used to represent the density of the saturated solvent mixtures at different temperatures. Furthermore, the apparent specific volumes of this drug at saturation were also calculated from densities of saturated solutions and cosolvent mixtures free of drug as well as from the respective mixture compositions. These findings provide valuable insights into the solubility and volumetric behavior of sodium sulfadiazine, which could be useful for pharmaceutical formulation and process optimization.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2020004

Authors: Amita G. Dhadphale Kamini J. Donde

A selective inhibitor of cyclooxygenase-2 (COX-2), Celecoxib (CEB), known for its anti-inflammatory properties, can exhibit polymorphism, with Form III often emerging as an undesired crystalline impurity during the green manufacturing process of the preferred Form I. Controlling the Form III content in the drug product is crucial, as different crystalline forms can impact drug bioavailability and therapeutic efficacy. This study presents a method to quantify the weight percentage of Form III in the bulk of CEB Form I by employing powder X-ray diffraction (PXRD). Initially, pure Form I and III of CEB were characterized using DSC, FTIR, and PXRD, supporting the method’s development. Binary mixtures, with varying ratios of CEB polymorphs Form I and Form III, were prepared and analyzed using continuous scans over an angular (2θ) range of 2–40. The calibration curve was constructed using 2θ unique peaks for Form I and Form III, respectively. Linear regression analysis exhibited a strong linear relationship within the weight ratio range of 1–20%. The developed method was validated to assess recovery, precision, ruggedness, limits of detection, and quantitation. These findings indicate that the method exhibits repeatability, sensitivity, and accuracy. The newly developed and validated PXRD method is applicable for quality control of CEB Form I produced through the green melt crystallization process by detecting low levels of Form III polymorphic impurity. This research significantly contributes to ensuring the clinical efficacy and manufacturing quality of Celecoxib by providing a reliable method for controlling polymorphic impurities.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2010003

Authors: Lei Jiang Fan Fan Xuemei Wang Shaukat Ali Feng Zhou Jiantao Zhang

Lidocaine plays a significant role in postoperative analgesia by effectively reducing pain. However, due to its short half-life, it is challenging for lidocaine to achieve the desired duration of analgesia in clinical settings. Drug delivery systems can regulate the release rate over time, making them one of the most effective strategies for achieving sustained release. In this work, a multi-level drug delivery system was designed using hyaluronic acid-modified zeolitic imidazolate framework-8 (HA/ZIF-8) nanoparticles and injectable hydrogels composed of modified natural polymers. Lidocaine was incorporating into the modified ZIF-8 and uniformly dispersed within the hydrogel network. The dynamic light scattering (DLS) and Fourier transform infrared spectrometer (FTIR) results indicate the successful loading of lidocaine into ZIF-8, while the X-ray diffractometer (XRD) results confirm that the loading of lidocaine did not disrupt the crystal structure of ZIF-8. The coating of hyaluronic acid on ZIF-8 enhanced cell biocompatibility, with cell viability increasing by 89% at the same concentration. This multi-level drug delivery system can be injected through a 27-guage needle. In vitro release studies demonstrated a sustained release of lidocaine for more than 4 days and kinetic simulations aligned with the Bshakar model, indicating its potential for use in long-acting analgesic preparations.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2010002

Authors: Athanas A. Koynov Wei Lin Jameson R. Bothe Luke Schenck Bibek Parajuli Zhao Li Richard Ruzanski Natalie Hoffman Derek Frank Zachary VanAernum

Lyophilization, or freeze-drying, is the default technique for the manufacture of solid-state formulations of therapeutic proteins. This established method offers several advantages, including improved product stability by minimizing chemical degradation, reduced storage requirements through water removal, and elimination of cold chain dependence. However, the lyophilization process itself presents limitations. It is a lengthy, batch-based operation, potentially leading to product inconsistencies and high manufacturing costs. Additionally, some proteins are susceptible to structural alterations during the freezing step, impacting their biological activity. This paper presents an alternative approach based on the co-precipitation of protein and excipients using an organic solvent. We explore the impact of various processing parameters on the viability of the formulation. We also provide an extensive characterization of proteins reconstituted from precipitated formulations and compare protein stability in solution and in lyophilized and precipitated solid formulations under long-term, accelerated, and stressed storage conditions.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi2010001

Authors: Peter Roth Francis Wu Melisa Bilgili

It is with immeasurable sadness that we announce the untimely passing of Prof [...]

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi1010005

Authors: Simay Ozsoysal Ecevit Bilgili

Poor solubility of many drugs, with ensuing low bioavailability, is a big challenge in pharmaceutical development. Nanosuspensions have emerged as a platform approach for long-acting injectables and solid dosages that enhance drug bioavailability. Despite improvements in nanosuspension preparation methods, ensuring nanosuspension stability remains a critical issue. Conventionally, synthetic and semi-synthetic polymers and surfactants are used in nanosuspension formulations. However, no polymer or surfactant group is universally applicable to all drugs. This fact, as well as their toxicity and side effects, especially if used in excess, have sparked the interest of researchers in the search for novel, natural stabilizers. The objective of this paper is to provide a comprehensive analysis of non-traditional natural stabilizers reported in the literature published over the last decade. First, physical stability and stabilization mechanisms are briefly reviewed. Then, various classes of non-traditional natural stabilizers are introduced, with particular emphasis on their stabilization potential, safety, and pharmaceutical acceptability. Wherever data were available, their performance was compared with the traditional stabilizers. Furthermore, the benefits and limitations of using these stabilizers are examined, concluding with future prospects. This review is expected to serve as a valuable guide for researchers and formulators, offering insights into non-traditional natural stabilizers in drug nanosuspension formulations.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi1010004

Authors: Rukesh Machamasi Sung-Joo Hwang Linh Dinh

Celecoxib (CEL), a nonsteroidal anti-inflammation drug (NSAID), is categorized as a Class II drug (low solubility, high permeability) in the Biopharmaceutics Classification System (BCS). The aim of this study is to develop a novel formulation of CEL nanosuspensions in the form of dried powder for tableting or capsuling. In this study, CEL was formulated into nanosuspensions to improve its solubility. CEL nanosuspensions were prepared using the precipitation method followed by high-pressure homogenization. Drying of the nanosuspensions was performed by spray drying and freeze drying. We examined the impact of various formulation and processing parameters on the nanoparticles. The CEL nanoparticles were characterized by particle size analysis, differential scanning calorimetry (DSC), powder X-Ray diffraction (PXRD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and dissolution tests. The choice of solvent, stabilizer, and surfactant appeared to have significant impacts on the crystallization and particle size and, consequently, the solubility of the CEL nanoparticles. CEL chemical stability was maintained throughout both drying processes. Both spray-dried and freeze-dried CEL nanosuspensions showed rapid dissolution profiles compared to raw CEL due to the nanosized particle dispersion with the presence of a lag phase. The freeze-dried nanosuspension showed a slight delay in the first 20 min compared to the spray-dried nanosuspension, after which dissolution progressed with a lag phase that represents aggregation.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi1010003

Authors: Ecevit Bilgili

The pharmaceutical and biotechnology industry continues to be one of the most important industry sectors for various reasons [...]

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi1010002

Authors: Chih-Chin Hsu Chih-Tse Hung Ya-Hsuan Lin Hua-Jeng Tsai Po-Chih Hu Yi-Ping Lin Jyh-Chern Chen Shen-Fu Hsu Hsyue-Jen Hsieh

Background: The aqueous solubility of indomethacin, a poorly water-soluble anti-inflammatory drug, was enhanced by co-crystallization with co-formers. The co-crystals were characterized and compared by an X-ray diffraction (XRD) analysis, terahertz (THz) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy. Methods: Indomethacin co-crystals with either amides (saccharin, nicotine amide, and urea) or amino acids (lysine and histidine) as co-formers were prepared through the solvent evaporation method. The co-crystals were characterized by XRD, THz, and FT-IR analyses, followed by solubility tests to examine the solubility enhancement. Results: Both the XRD and THz analyses were capable of distinguishing co-crystals from physical mixtures; however, the THz spectra were relatively simpler and clearer than the XRD analysis. Furthermore, the solubility of indomethacin was successfully increased by two to three times that of pure indomethacin after co-crystallization with the above five co-formers. Conclusion: Five kinds of indomethacin co-crystals (with enhanced solubility) were successfully prepared and confirmed by the three spectroscopy techniques, XRD, THz, and FT-IR. The identification of co-crystals was achieved by a THz analysis, giving relatively simpler and clearer spectra with less noise. Hence, in addition to an XRD analysis, a THz analysis (a non-destructive, non-ionizing radiative, and relatively rapid measurement technique which is convenient and safe to use) is a good alternative method to characterize co-crystals.

Journal of Pharmaceutical and BioTech Industry doi: 10.3390/jpbi1010001

Authors: Ioana Craciun

Collaborations between academia and industry serve as a powerful catalyst for scientific progress, synergizing the strengths of both sectors [...]