Pharmaceutical Research[JOURNAL]
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200 papers
Trichomonas vaginalis Drug Targets and Their Role in Drug Discovery and Development.
Alves MSD, Sena-Lopes Â, Moron LD … +2 more , Fonseca BDR, Borsuk S
Pharm Res · 2026 May · PMID 42086875 · Full text
Trichomonas vaginalis is the causative agent of trichomoniasis, the most common and prevalent sexually transmitted infection (STI) globally, with about 156 million cases annually. Trichomoniasis is a critical public heal...
Trichomonas vaginalis is the causative agent of trichomoniasis, the most common and prevalent sexually transmitted infection (STI) globally, with about 156 million cases annually. Trichomoniasis is a critical public health problem, and it is aggravated due to its association with a higher risk of HIV-1 acquisition and transmission and complications such as preterm delivery and pelvic inflammatory disease. This STI is treated mainly through the 5-nitroimidazole class, specifically metronidazole and tinidazole. However, drug resistance, which can represent between 5 and 20% of clinical cases, and hypersensitivity reactions are a general concern. In this context, drug development for trichomoniasis is an ever-growing research field. Therefore, considering how important drug targets and the mechanism of action of compounds can be to drug discovery, there is a growing interest in better understanding how some molecules can be used as targets. This article offers an overview of T. vaginalis drug targets, their significance in metabolism, pathogenesis, or survival, and their contribution to drug development for trichomoniasis.
Development of a Water-soluble Form of Umifenovir Through the Synergistic Action of a Surfactant and a Hydrotropic Agent: A Multifactorial Study.
Volkova TV, Simonova OR, Perlovich GL
Pharm Res · 2026 May · PMID 42086874 · Publisher ↗
PURPOSE: The aim of this study was to develop a water-soluble form of umifenovir (UMF) through the synergistic action of the non-ionic surfactant Brij35 and choline bitartrate (ChB), and to investigate the solubility, ag...
PURPOSE: The aim of this study was to develop a water-soluble form of umifenovir (UMF) through the synergistic action of the non-ionic surfactant Brij35 and choline bitartrate (ChB), and to investigate the solubility, aggregation and diffusion. METHODS: UMF solubilization was assessed using the saturation shake-flask method. The hydrodynamic radii and aggregation behavior of Brij35 micelles were characterized by light scattering. UMF diffusion rate was investigated using a Franz diffusion cell and an artificial membrane. RESULT: Introduction of ChB into the UMF/Brij35 system reduced the degree of association with Brij35 micelles and the micelle/water partition coefficient, increased the solubilizing capacity, and modulated the aggregation behavior of Brij35 and permeability. The increase in total (micelle-associated and freely dissolved) drug solubility of UMF in buffer рН 7.4 in the system with the minimal Brij35 concentration (0.45%) was 18.4%, whereas upon addition of ChB (1.0%) - 35.2%. However, calculation of the molecularly dissolved fractions (f) of the compound showed that the increase in solubility of the freely dissolved drug in the system with ChB was only 10.6%. This finding is of fundamental importance because only the molecularly dissolved form of a drug can cross biological membranes. Optimization of membrane permeability in the UMF/Brij35 (0.45%)/ChB (1.0%) system was achieved by increasing the fraction of molecularly dissolved UMF molecules in the presence of ChB. CONCLUSION: This study highlights the advantage of simultaneously using low concentrations of Brij35 and ChB to achieve a synergistic action for maximal improvement in UMF solubility with a minimal reduction in permeability.
Thermally Stressed Solid-State Stability of Semaglutide: Understanding the Influence of Temperature on Protein Content, Secondary Structure, Phase Transition, and Chemical Degradation.
Akbar S, Malgave A, Joseph A … +2 more , Kumar A, Malayandi R
Pharm Res · 2026 May · PMID 42086873 · Publisher ↗
OBJECTIVE: Semaglutide (SMG), a clinically relevant peptide-based therapeutic whose physical and chemical stability are critical concerns during manufacturing and storage. Although the stability of SMG in solution has be...
OBJECTIVE: Semaglutide (SMG), a clinically relevant peptide-based therapeutic whose physical and chemical stability are critical concerns during manufacturing and storage. Although the stability of SMG in solution has been extensively studied, its solid-state behaviour remains unclear. This study aimed to systematically evaluate the impact of thermal stress on the solid-state physicochemical stability of SMG. METHODS: The solid-state stability of SMG was assessed using complementary analytical techniques, including Fourier transform-infrared (FT-IR) spectroscopy, circular dichroism (CD), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), reverse-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography-high-resolution mass spectrometry (LC-HRMS). RESULTS: FT-IR and CD analyses demonstrated that SMG retains its native α-helical conformation up to 60°C. However, the α-helical content decreased from 49.07% to 43.75% at 60°C and further to 0.2% at 80°C, indicating extensive conformational transitions at elevated temperatures that compromise receptor binding and in vivo performance. DSC and HSM confirmed that SMG remains amorphous under all tested conditions and revealed three major thermal events: residual water loss, enthalpy recovery associated with physical ageing, and thermal decomposition. The overlap of enthalpy recovery with the glass transition phase limited the determination of Tg by conventional DSC; however, modulated DSC enabled the separation of these events, establishing a Tg of 169°C. RP-HPLC and LC-HRMS analyses showed a temperature-dependent degradation and impurity formation. CONCLUSION: The solid-state stability study identified temperature as a critical factor influencing SMG stability and emphasises the importance of stringent process control in the development of SMG-based formulations.
Raman Imaging-based Analysis of Drug Powder Dissolution on Calu-3 Cell Monolayers as a Mechanistic Predictor of Nasal Absorption.
Furubayashi T, Tanaka A, Tatsuta R … +4 more , Fujiwara M, Izumi N, Kiyohara M, Moriyama K
Pharm Res · 2026 May · PMID 42086872 · Publisher ↗
BACKGROUND: Intranasal powder formulations offer advantages in terms of stability and portability; however, their absorption is critically dependent on dissolution within the limited fluid volume of the nasal cavity. Con...
BACKGROUND: Intranasal powder formulations offer advantages in terms of stability and portability; however, their absorption is critically dependent on dissolution within the limited fluid volume of the nasal cavity. Conventional dissolution tests, originally developed for oral medicines, fail to adequately capture dissolution dynamics under nasal conditions, making the prediction of bioavailability after intranasal powder administration (BAp) particularly challenging. METHODS: A Raman spectroscopy-based approach was established to directly monitor the time-dependent dissolution of drug particles in Calu-3 cell layers. Dissolution rate constants derived from particle size reduction were integrated with the nasal mean residence time (MRT) and bioavailability after intranasal solution administration (BAs) to define a predictive metric, the dissolution-MRT-BAs (DTB) parameter. RESULTS: Model drugs exhibited distinct dissolution profiles: rapid (antipyrine and atenolol), intermediate (acyclovir and levofloxacin), and limited (norfloxacin and griseofulvin). The DTB parameter was strongly correlated with BAp (R = 0.983, p < 0.001), and the enhancement of norfloxacin dissolution by lactose was also captured by this metric. CONCLUSION: The DTB parameter, which integrates dissolution kinetics, nasal residence time, and bioavailability, serves as a rational tool for predicting the absorption behavior of nasal powder formulations. This study highlights the potential of Raman spectroscopy as a quantitative method to support formulation design and establish in vitro-in vivo correlations in nasal drug delivery.
A Cell-Based Reporter Gene Assay for TNF-α Neutralization: Analytical Qualification and Application to Adalimumab and Its Biosimilars.
Ancajas CAF, Luo S, Zhang B
Pharm Res · 2026 May · PMID 42086871 · Publisher ↗
PURPOSE: To qualify a mechanism-of-action (MoA)-reflective reporter gene assay (RGA) for measuring the biological activity of adalimumab (Humira) and its biosimilars, supporting assessment of product quality, comparabili...
PURPOSE: To qualify a mechanism-of-action (MoA)-reflective reporter gene assay (RGA) for measuring the biological activity of adalimumab (Humira) and its biosimilars, supporting assessment of product quality, comparability, and functional consistency across the product lifecycle. METHODS: The assay evaluates TNF-α neutralization by monitoring inhibition of NF-κB signaling in a reporter system. Qualification focused on key performance attributes, including system suitability, working range, reproducibility, and intermediate precision, to confirm fitness for routine use. RESULTS: The RGA yielded MoA-relevant readouts of NF-κB pathway inhibition in the presence of adalimumab, demonstrating strong system suitability, a broad working range, high reproducibility, and consistent intermediate precision across repeated measures. These characteristics support reliable measurement of functional activity among adalimumab products and biosimilars. CONCLUSIONS: The qualified, MoA-reflective RGA provides a robust tool for lifecycle management of adalimumab products, enabling quality assessment, comparability exercises, and monitoring of functional consistency across indications in which adalimumab is broadly used (e.g., rheumatoid arthritis, Crohn's disease, psoriasis).
PK-PD Modeling Suggests Tumor Heterogeneity Limits Preclinical to Clinical Translation of Enzalutamide in Prostate Cancer.
Kim SJ, Bies R, Mager DE
Pharm Res · 2026 May · PMID 42086870 · Publisher ↗
PURPOSE: To assess the translational performance of preclinical models to anticipate enzalutamide clinical efficacy in prostate cancer using a cross-species physiologically-based pharmacokinetic (PBPK)-pharmacodynamic (P...
PURPOSE: To assess the translational performance of preclinical models to anticipate enzalutamide clinical efficacy in prostate cancer using a cross-species physiologically-based pharmacokinetic (PBPK)-pharmacodynamic (PD) model and published enzalutamide preclinical and clinical PK-PD data. METHODS: A mouse PBPK model was developed and linked to a tumor growth inhibition (TGI) model to describe tumor volume profiles in 5 cell line-derived and 3 patient-derived xenografts. Estimated preclinical PD model parameters were fixed to simulate clinical progression free survival (PFS) using a scaled-up human PBPK model and a calculated prostate cancer tumor growth rate. Tumor static concentrations (TSCs) were calculated and assessed relative to predicted steady-state concentrations from a standard dosing regimen. RESULTS: Estimated mouse model parameters were precise (CV% < 15% and 45% for most PK and PD parameters), and the estimated hepatic intrinsic clearance was comparable to conventional allometry (allometric exponent = 0.722). The 8 TSC values were near or below the simulated steady-state plasma drug concentration (18,000 ng/mL) achieved with a standard enzalutamide regimen (TSC range 203-20,740 ng/mL). The TGI model failed to predict clinical PFS unless a tumor heterogeneity model with sensitive and resistant tumor cell populations and individually calibrated growth rates were explicitly incorporated. CONCLUSIONS: The potential and the limitations of using preclinical PD parameters for clinical translation were assessed, and more biologically accurate TGI models are needed to enhance the use of translational modeling in oncology.
Cutaneous Bioavailability of Corticosteroids from Topical Formulations: a Retrospective Analysis of Data from In Vitro Permeation Testing (IVPT) and In Vivo Assessments.
Lehman PA, Franz TJ
Pharm Res · 2026 May · PMID 42084687 · Publisher ↗
BACKGROUND: The In Vitro Permeation Test (IVPT) is a valuable tool for the study of topical pharmacokinetics of dermatologic formulations. A 45 year retrospective analysis was performed on archived percutaneous absorptio...
BACKGROUND: The In Vitro Permeation Test (IVPT) is a valuable tool for the study of topical pharmacokinetics of dermatologic formulations. A 45 year retrospective analysis was performed on archived percutaneous absorption data from various corticosteroids found in the author's files. OBJECTIVE: The objective was to collate archived data on the relative bioavailability of topical corticosteroids from 15 steroids found in 62 formulations using the in vitro permeation test (IVPT) and the finite dose human cadaver skin model. Studies were conducted with and without occlusion, at different active ingredient concentrations and dose durations. Select steroids also had evaluations with vasoconstriction, and stratum corneum content by tape stripping. RESULTS: The percutaneous absorption of topical corticosteroids is highly dependent on formulation, but less so on steroid concentration within the formulation, and whether the applied dose is occluded or not occluded. In addition vasoconstriction does not necessarily correlate with steroid permeation. CONCLUSIONS: The IVPT method demonstrates that it can characterize the topical pharmacokinetics of topical corticosteroids. Overall, this retrospective analysis of data supports the value of the IVPT method for evaluating percutaneous absorption pharmacokinetics for topical therapeutic agents.
CFD Modeling of Airflow and Aerosol Transport in the Human Respiratory System: A Comprehensive Review.
Ciloglu D, Ucuncu H
Pharm Res · 2026 May · PMID 42082857 · Full text
BACKGROUND: Accurate modelling of airflow and aerosol/particle dynamics within the human respiratory system is essential for improving inhalation-based drug delivery strategies and for evaluating the health risks associa...
BACKGROUND: Accurate modelling of airflow and aerosol/particle dynamics within the human respiratory system is essential for improving inhalation-based drug delivery strategies and for evaluating the health risks associated with hazardous particulates. Owing to the complex geometry of the human airways, inter-individual anatomical variations, and variable breathing patterns, this process constitutes a highly complex multiphase flow problem. To address the constraints associated with in vivo and in vitro techniques, in silico approaches based on computational fluid dynamics (CFD) have been extensively utilized to examine respiratory airflow and aerosol dynamics at microscopic scales. OBJECTIVES: The aim of this study is to review recent CFD-based approaches for modeling airflow and aerosol behavior in the human respiratory system, summarize key modeling strategies and influential parameters, and identify future research directions. RESULTS: Recent studies indicate a transition of respiratory tract models toward more physiologically realistic and whole-lung representations. These studies demonstrate that coupling CFD with particle models enables reliable prediction of aerosol transport and deposition by accounting for the effects of geometric variations, breathing conditions, turbulence characteristics, and particle physical and chemical properties. CONCLUSION: CFD-based modeling, particularly when integrated with particle dynamics, provides a powerful and reliable framework for investigating airflow and aerosol behavior in the human respiratory system. Continued advancements toward realistic whole-lung models and improved representation of physiological and particle-related parameters are expected to further enhance predictive accuracy and support both clinical and environmental health applications.
Nano-DSF Technology as a Preliminary Decision-Making Tool for Long Term Stability Evaluation of Covid-19 Vaccine Antigens.
Misra R, Sharma S, Haer M … +3 more , Hu J, Kirkitadze M, Kowal P
Pharm Res · 2026 May · PMID 42026377 · Publisher ↗
PURPOSE: Nano differential scanning fluorimetry (nano-DSF) is a high-throughput screening technique that simultaneously assesses colloidal and conformational stabilities of protein antigens by monitoring their thermal un...
PURPOSE: Nano differential scanning fluorimetry (nano-DSF) is a high-throughput screening technique that simultaneously assesses colloidal and conformational stabilities of protein antigens by monitoring their thermal unfolding patterns and aggregation behaviors. It offers significant advantages over conventional approaches used for thermal stability assessment of proteins, such as Differential Scanning Calorimetry (DSC). METHODS: The present study evaluates the thermal unfolding and aggregation behavior of an in-house recombinant COVID-19 SARS-CoV-2 spike protein variant and its engineered prototype as vaccine antigens. We investigated their structural integrity and colloidal behavior under well-defined physical conditions such as pH transition, addition of excipients, and at different manufacturing stages. RESULTS: Changes in melting and aggregation temperatures (Tm and Tagg) were assessed as indicators of the structural integrity and colloidal stability of spike protein variants. CONCLUSION: We have shown how nano-DSF technology can be useful in developing a stable formulation which can minimize conformational changes and aggregation. Our study highlights the potential of nano-DSF for process optimization and as an advanced preliminary decision-making tool to be used before initiating long-term stability studies in biopharmaceutical R&D.
Microdermabrasion with Calcium Hydrogen Phosphate for Enhancing Skin Permeation of Lidocaine-tetracaine Eutectic Microemulsion Gel.
Chen Y, Yang Y, Su J … +10 more , Ji Y, Liu B, Chen Y, Peng Y, Cai X, Zhang H, Dong M, Wang Q, Sun C, Su Z
Pharm Res · 2026 May · PMID 42026376 · Publisher ↗
BACKGROUND: Transdermal drug delivery (TDD) offers a convenient administration for treating local or systemic diseases. However, the dense "brick-mortar" structure of the stratum corneum hinders the skin permeation of mo...
BACKGROUND: Transdermal drug delivery (TDD) offers a convenient administration for treating local or systemic diseases. However, the dense "brick-mortar" structure of the stratum corneum hinders the skin permeation of most of bioactive molecules, which highly constrained the application of TDD. METHODS: This study analyzed stratum corneum disruption and enhanced permeation by gently rubbing calcium hydrogen phosphate (Chp) particles of varying sizes on skin. Enhanced anesthetic efficacy of Chp-containing microemulsion gel (MG) loaded with lidocaine-tetracaine eutectic was evaluated in guinea pigs using a needle-prick model. RESULTS: Using Chp as dermabrasion particle could effectively disrupt the barrier of stratum corneum after applying gently rubbing on the skin, which resulted in increasing skin permeation of both FITC, FITC-Dextran4000 and MG loaded with lidocaine-tetracaine eutectic. The enhanced skin permeation depended not only on the increase of particle size and amount of Chp in the MG, but also on the increase of rubbing pressure and duration after being applied to the skin, finally shortening the onset time and improving the efficacy of local anesthetics. CONCLUSIONS: The incorporation of Chp into the topical formulation, followed by rubbing them on the skin with appropriate pressure and a certain duration, can significantly disrupt the stratum corneum, enhance drug permeation through the skin, and shorten the onset time of local anesthetics. This study provided a potential strategy for improving the skin permeation with well tolerance, which could be further used to expand the range of bioactive molecules for TDD.
Pharmaceutical Stability of Romiplostim: In-use Functional Study Using Microscale Thermophoresis New Strategy and Elisa.
Hermosilla J, Casares-Atienza S, Ruiz-Travé J … +4 more , Torrente-López A, Salmerón-García A, Cabeza J, Navas N
Pharm Res · 2026 May · PMID 42026375 · Full text
OBJECTIVE: Functional stability is crucial for therapeutic proteins at all stages of their lifecycle. Romiplostim (Nplate®) is world-wide used for treating immune thrombocytopenia purpura. Limited in-use stability data o...
OBJECTIVE: Functional stability is crucial for therapeutic proteins at all stages of their lifecycle. Romiplostim (Nplate®) is world-wide used for treating immune thrombocytopenia purpura. Limited in-use stability data on the proper romiplostim handling is publicly available. This study aimed to evaluate romiplostin in-use functional stability focusing on the interaction with its therapeutic target (TPO-R) and to improve the existing functional assessment strategies by developing a new one using microscale thermophoresis (MST). METHODS: Reconstituted romiplostim (Nplate®) samples were analysed. MST and ELISA functional methods were developed and optimized ad hoc to assess romiplostim functional stability. Far-UV-Circular-Dichroism and Intrinsic-Tryptophan-Fluorescence-Spectroscopy were used to ensure MST results by confirming the conformational stability of labelled TPO-R. In-use stability was assessed by subjecting romiplostim to conditions related to hospital handling, e.g. agitation and exposure to natural light; also, freezing and artificial light irradiation were checked as forced degraded condition. RESULTS: MST and ELISA were described and validated by their figures of merit. Regarding romiplostim functional stability, both approaches yielded similar stability profiles, but MST detected subtle functional declines that were not revealed by ELISA. Furthermore, MST revealed insights into romiplostim binding stoichiometry, suggesting 1:2 interaction at high concentrations. CONCLUSION: Regarding functionality, romiplostim was particularly sensitive to light exposure, with less sensitivity to agitation and freezing. These findings also demonstrate that MST serves as new orthogonal strategy to ELISA for assessing functionality, even providing additional data on binding dynamics and stoichiometry. This new MST strategy is applicable for any type of functional study of therapeutic proteins.
Mucolytic Core-Shell Particles to Boost Levofloxacin Penetration Through the Mucus Barrier in Cystic Fibrosis.
Ruggiero V, Mariano F, Larobina D … +5 more , D'Avino G, Trofa M, Tedesco C, Del Gaudio P, Russo P
Pharm Res · 2026 May · PMID 42026374 · Full text
PURPOSE: The purpose of this study was to investigate multi-fluid spray drying as a formulation strategy to engineer inhalable microparticles containing levofloxacin and mucolytic agents, and to evaluate how formulation...
PURPOSE: The purpose of this study was to investigate multi-fluid spray drying as a formulation strategy to engineer inhalable microparticles containing levofloxacin and mucolytic agents, and to evaluate how formulation and process parameters influence particle properties, aerosol performance, and drug release under mucus-relevant conditions. METHODS: Microparticles containing levofloxacin in combination with mucolytic agents were produced using a mini spray dryer equipped with a triple-fluid nozzle. Different compositions and particle architectures were obtained by varying formulation and excipient allocation. The resulting powders were characterized in terms of morphology, bulk, tapped and true density, aerodynamic performance, and in vitro drug release evaluated both in the absence and presence of a mucus layer. RESULTS: Ambroxol showed greater suitability for spray drying than N-acetylcysteine, resulting in markedly higher process yields (up to 74%). The incorporation of L-leucine as a functional excipient reduced particle agglomeration and improved powder handling and aerosolization, with fine particle fractions exceeding 38% for leucine containing formulations. Drug release experiments demonstrated that spray drying altered release behaviour under diffusion limiting conditions imposed by a mucus layer compared to dissolution under sink conditions. CONCLUSIONS: Overall, the results indicate that multi-fluid spray drying enables effective modulation of the physicochemical and aerodynamic properties of inhalable microparticles. This study provides mechanistic insight into how formulation composition and process design influence particle behaviour in mucus-relevant environments, supporting the use of this approach as a flexible platform for the development of inhalable formulations.
Recent Progress in Exosome-Derived Nanocarriers for Breast Cancer Therapy: Advances, Translational Barriers, and Scale-Up Considerations.
Youssef JR, Elgammal EM, Mahdy DM … +2 more , Ghazi NF, Bebawy G
Pharm Res · 2026 Apr · PMID 42014584 · Publisher ↗
Breast cancer remains the most prevalent malignancy among women worldwide and a major cause of cancer-related mortality. Despite remarkable progress in molecularly targeted and immune-based therapies, therapeutic resista...
Breast cancer remains the most prevalent malignancy among women worldwide and a major cause of cancer-related mortality. Despite remarkable progress in molecularly targeted and immune-based therapies, therapeutic resistance, dose-limiting systemic toxicity, and inefficient drug delivery continue to hinder clinical outcomes, particularly in aggressive subtypes such as triple-negative breast cancer. Exosomes, naturally secreted nanosized vesicles, have emerged as a transformative platform owing to their biocompatibility, intrinsic targeting capability, and ability to transport diverse therapeutic cargos across biological barriers. Recent advances in exosome biology, engineering, and isolation technologies have reignited interest in their clinical exploitation as drug delivery systems. However, translation into clinical oncology remains in its early stages. This review provides a comprehensive overview of exosome-based drug delivery systems specifically within the context of breast cancer therapy, critically evaluating their sources, isolation techniques, cargo loading strategies, targeting mechanisms, and formulation considerations. It also examines preclinical findings demonstrating enhanced therapeutic efficacy and reduced off-target toxicity, alongside the limited yet growing number of clinical trials investigating exosome therapeutics in solid tumours. Importantly, the review identifies major gaps, including lack of standardized manufacturing protocols, incomplete pharmacokinetic understanding, and unresolved safety concerns, that currently impede clinical translation. By bridging molecular insights with translational perspectives, this work underscores the untapped potential of exosomes as next-generation drug carriers in breast cancer. It highlights the urgent need for harmonized methodologies, scalable production systems, and regulatory frameworks to enable their safe and effective integration into future cancer therapeutics.
Bio-inspired White Tablet Coating Film Without Titanium Dioxide.
Tian Y, Song S, Shi Y … +5 more , Yuan L, Yan J, Wang D, Sha L, Yang L
Pharm Res · 2026 Apr · PMID 42010204 · Publisher ↗
BACKGROUND: Titanium dioxide (TiO) is widely used as a white additive in food and pharmaceuticals, but its safety has raised increasing concerns. Currently, calcium carbonate is commonly used as an alternative to TiO in...
BACKGROUND: Titanium dioxide (TiO) is widely used as a white additive in food and pharmaceuticals, but its safety has raised increasing concerns. Currently, calcium carbonate is commonly used as an alternative to TiO in white film coatings, although it provides inferior whiteness. With the development of the health industry, TiO-free and pigment-free white tablet coatings are becoming more desirable. METHODS: Inspired by white beetle scales, porous films were fabricated via phase separation between polyvinyl alcohol (PVA) and polyethylene glycol (PEG). The refractive index difference between polymer and air generated strong light scattering. Light-shielding effect of calcium carbonate of different morphologies was further investigated. RESULTS: Under the same type of calcium carbonate as the opacifier, porous PVA/PEG films showed CIELab whiteness all above 80 (up to 87), much higher than the dense films using lipid plasticizers. With the same porous structure, quasi-rhombohedral calcium carbonate increased whiteness by 8.2% compared with spindle aggregates. CONCLUSIONS: Porous structures dominated whiteness improvement. Bioinspired porous films via polymer-polymer phase separation represented a novel strategy for TiO-free white tablet coating, and could guide the screening of other phase-separating polymers to further improve the film whiteness and properties.
The Use of Digital Image Processing in the Modelling of a Roller Compaction Milling Operation.
Wilson D, Mesham A, Bölle FT
Pharm Res · 2026 Apr · PMID 42010203 · Publisher ↗
PURPOSE: Granulation by roller compaction is an important unit operation in the production of pharmaceutical oral solid dosages. This process involves producing a densified "ribbon" of compressed powder between two count...
PURPOSE: Granulation by roller compaction is an important unit operation in the production of pharmaceutical oral solid dosages. This process involves producing a densified "ribbon" of compressed powder between two counter rotating rolls that is then feed into a screening type mill and particulate matter of the order of 1-2 mm is produced. In roller compaction, rate of production is generally maximised by increasing the roll speed, thus increasing the rate of ribbon production. However, such increases in production could result in issues with ribbon milling, potentially causing the mill to become overwhelmed. Knowledge of important milling parameters such as mill residence time and steady state hold up value as a function of roll and mill speed would allow for this parameter to be scaled. Traditional experiments towards this objective are problematic. METHODS: Presented here is a digital image processing approach that allows the continual monitoring of the mass of powder within a roller compactor's mill utilising the equipment's observation window. This allowed for an assessment of steady state mass hold up and the mean residence time in the mill. In this study, mean residence times were calculated to be between 45 and 120 s. RESULTS: The approach allowed for the rapid accumulation of data sufficient to construct a, data driven model predicting both residence time and steady state hold up as a function of both roll speed and mill speed. CONCLUSION: It is the authors assertion that this kind of image processing approach, has great utility in pharmaceutical manufacturing.
The Role of Cyclodextrins in Modulating Stimuli-Responsiveness for Anticancer Drug Delivery.
Cesari A, Zhengming L, Bellina F
Pharm Res · 2026 May · PMID 41986603 · Publisher ↗
BACKGROUND: The precision delivery of active pharmaceutical ingredients remains a major challenge in modern pharmacology, where conventional therapies often lack selectivity and cause severe side effects. Stimuli-respons...
BACKGROUND: The precision delivery of active pharmaceutical ingredients remains a major challenge in modern pharmacology, where conventional therapies often lack selectivity and cause severe side effects. Stimuli-responsive drug delivery systems (SRDDS) represent a promising strategy to achieve controlled release in response to pathological microenvironments or external triggers. While various organic and inorganic carriers have been investigated, cyclodextrins (CDs) occupy a unique position due to their biocompatibility, safety record, and distinctive molecular architecture. Beyond their established role as solubilizing excipients, CDs can act as a fundamental component capable of driving responsiveness within drug delivery systems. OBJECTIVE: This review highlights cyclodextrin-based stimuli-responsive systems (SRCDS) in which CDs themselves mediate responsiveness, rather than serving as simple structural elements. SCOPE AND FOCUS: A comparative discussion of different responsive mechanisms is provided, offering insights into the design principles that may accelerate the clinical translation of CD-based SRDDS. A particular focus will be provided to chemical structure components exerting stimuli responsiveness. In addition, recent publications on SRCDS with pharmacological or biological experimental investigations and relevance are reviewed, with particular attention to applications in cancer therapy.
The Impact of Particle Properties on High Concentration Suspension Performance and Stability of Spray-Dried Monoclonal Antibodies.
Huang Y, Liu J, Qiu R … +3 more , Guo K, Devlin A, Raut A
Pharm Res · 2026 May · PMID 41981217 · Publisher ↗
OBJECTIVE: Subcutaneous (subQ) administration of biologic drug products is increasingly preferred to enable patient self-administration and reduce healthcare burden. However, the small dosing volume for subQ delivery nec...
OBJECTIVE: Subcutaneous (subQ) administration of biologic drug products is increasingly preferred to enable patient self-administration and reduce healthcare burden. However, the small dosing volume for subQ delivery necessitates high-concentration formulations, which often suffer from elevated viscosity and physical instability, creating challenges in manufacturing, injectability, and storage. Spray drying has emerged as a versatile particle engineering technique to produce solid biologic powders that can be redispersed into suspensions. While suspensions of spray-dried particles have shown promise in reducing viscosity compared to liquid solutions, the influence of biologic particle properties on suspension performance remains poorly understood. This study aimed to elucidate how particle size and surface characteristics affect viscosity and stability of high-concentration monoclonal antibody (mAb) suspensions. METHODS: Spray-dried mAb particles were prepared with varied sizes and leucine addition. Suspensions were evaluated for viscosity, injectability through 27G needles, sedimentation, physical, chemical and structural stability during storage at 5°C and 25°C for 3 months and at 40°C for 1 month. RESULTS: Larger particle size, less surface dimpling and leucine addition significantly reduced viscosity without compromising physical and chemical stability; no sedimentation was observed. All suspensions were injectable via 27G needles. No notable aggregation or fragmentation occurred under tested conditions. CONCLUSION: Particle size and surface properties modulate suspension viscosity but do not impact stability. Particle engineering through spray drying represents an effective approach to enable high-concentration biologic suspensions for subQ delivery.
The Versatile Role of GDF5 in Chondrogenic Progenitor Cell-mediated Cartilage Regeneration via a Hyaluronic Acid-fibrin IPN Hydrogel Platform.
He R, Ganesh V, Phruttiwanichakun P … +3 more , Martin JA, Seol D, Salem AK
Pharm Res · 2026 Apr · PMID 41981216 · Publisher ↗
OBJECTIVE: Focal damage to articular cartilage incurred during joint injuries frequently progresses to post-traumatic osteoarthritis (PTOA) due to the limited intrinsic repair capacity of cartilage. Chondrogenic progenit...
OBJECTIVE: Focal damage to articular cartilage incurred during joint injuries frequently progresses to post-traumatic osteoarthritis (PTOA) due to the limited intrinsic repair capacity of cartilage. Chondrogenic progenitor cells (CPCs) residing within the cartilage can contribute to repair if effectively recruited and activated. Early interventions that enhance CPC homing and their subsequent chondrogenesis offer a regenerative strategy to prevent PTOA progression, addressing the current lack of effective early clinical therapies. GDF5 stands out as a key protein involved in cartilage development, yet its potential to mobilize CPC-mediated regeneration remains underexplored. METHODS: We evaluated the effects of GDF5 on CPC migration, proliferation, chondrogenic differentiation, and anti-catabolic activity using in vitro CPC models. To assess CPC chemotaxis in a clinically relevant biomaterial context, GDF5 was incorporated into a hyaluronic acid/fibrin interpenetrating network (IPN) hydrogel and tested in an ex vivo cartilage defect model. RESULTS: GDF5 acted as a potent chemoattractant for CPCs, promoting their recruitment toward cartilage defects when delivered via a hyaluronic acid/fibrin IPN hydrogel in an ex vivo model. GDF5 also enhanced CPC proliferation, consistent with activation of a glycolysis-associated transcriptional program. In addition, GDF5 significantly upregulated chondrogenic markers, including SOX9, COL2a1, and ACAN, and elevated extracellular matrix components in CPCs, potentially through activation of the PI3K/AKT signaling pathway. Furthermore, GDF5 reduced expression of a key catabolic enzyme ADAMTS5, possibly through the WWP2/miR-140 axis. CONCLUSION: These findings highlight the versatile role of GDF5 on endogenous CPCs. When combined with a hydrogel platform, GDF5 may serve as an early therapeutic strategy to convert injured cartilage from a passive site of degeneration into one of active regeneration.
Correction: Chemoprevention of Colon Carcinogenesis by Oleanolic Acid and Its Analog in Male F344 Rats and Modulation of COX-2 and Apoptosis in Human Colon HT-29 Cancer Cells.
Janakiram NB, Indranie C, Malisetty SV … +3 more , Jagan P, Steele VE, Rao CV
Pharm Res · 2026 Apr · PMID 41957295 · Publisher ↗
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Effects of Airway Generation Depth on Particle Deposition Behaviour in the Main Respiratory Airways-A Computational Modelling Study.
Cai X, Chong D, Ong HX … +5 more , Inthavong K, Lee A, Dong J, Kourmatzis A, Cheng S
Pharm Res · 2026 Apr · PMID 41951865 · Publisher ↗
PURPOSE: Effective inhaled drug delivery depends on formulation, device, and a clear understanding of aerosol transport in the respiratory tract. This study explores how lower airway anatomical complexity affects airflow...
PURPOSE: Effective inhaled drug delivery depends on formulation, device, and a clear understanding of aerosol transport in the respiratory tract. This study explores how lower airway anatomical complexity affects airflow and particle deposition in the main respiratory airways. METHODS: Seven 3D bronchial models with varying airway generational depths were developed. Numerical simulations were conducted using the discrete phase model (DPM) to simulate aerosol transport and deposition under transient inspiratory flows at inhalation peak flow rates of 60 and 120 L/min. RESULTS: Our results showed that simplified models with three bronchial generations could underestimate the deposition efficiency in the main respiratory airways by up to 65.6% compared to the seven-generation lower airway model. Additionally, disparities in deposition outcomes and flow characteristics diminished with increasing lower airway complexity, with minimal changes in flow dynamics and deposition observed beyond the model with six bronchial generation. CONCLUSIONS: This study suggests that airway models incorporating at least up to the 6th generation of bronchial branching may be required to sufficiently capture the implications for inhalation therapy design and the development of reliable in silico testing frameworks. Notably, insufficient lower airway detail not only compromises lung deposition estimates but also affects airflow dynamics throughout the entire respiratory tract, including the upper airway. This study highlights the importance of retaining detailed geometry in the design of inhalation therapies and the development of in silico testing frameworks.
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