Int J Pharm [JOURNAL]
Sun
200 papers
Sprayable macrophage-targeting apoptotic-body-inspired nanotherapeutics for the prevention of postoperative peritoneal adhesions.
Huang Q, Zhang G, Li Y … +4 more , Lin M, Su Z, Zeng R, Liu J
Int J Pharm · 2026 Jun · PMID 42289211 · Publisher ↗
Postoperative peritoneal adhesion is a common complication of abdominal and pelvic surgeries, often leading to chronic pain, bowel obstruction, and increased reoperation rates. Despite clinical efforts, effective prevent...
Postoperative peritoneal adhesion is a common complication of abdominal and pelvic surgeries, often leading to chronic pain, bowel obstruction, and increased reoperation rates. Despite clinical efforts, effective preventive strategies remain limited. In this study, we develope a sprayable, biomimetic nanotherapeutic system - designated Apo-Q - composed of phosphatidylserine (PS)-exposing liposomes encapsulating quercetin (Que@PSLs), inspired by the biological features of apoptotic bodies and prepared by a thin-film hydration-extrusion method. The obtained Apo-Q with the particle size about 140 nm and PS-functionalized surface can be selectively recognized and internalized by macrophages, thereby promoting targeted modulation of the postoperative inflammatory microenvironment. In a mouse model of peritoneal adhesion, Apo-Q promotes macrophage polarization from the pro-inflammatory M1 phenotype to the reparative M2 phenotype, suppresses inflammatory response, and also prevents pathological accumulation of GATA6 macrophages at injury sites, significantly reducing adhesion formation and severity. These findings demonstrate that Apo-Q exerts potent anti-inflammatory and anti-fibrotic effects probably via a similar mechanism to macrophage efferocytosis, offering a minimally invasive and translationally promising strategy for preventing postoperative peritoneal adhesions.
3D-printed long-acting implants for risperidone delivery using VAT photopolymerisation: a potential alternative for schizophrenia treatment.
Picco CJ, Utomo E, Magill ER … +9 more , Anjani QK, Adhami M, Lu Y, Byrne NM, Ammar AA, Coulter JA, Donnelly RF, Domínguez-Robles J, Larrañeta E
Int J Pharm · 2026 Jun · PMID 42289210 · Publisher ↗
Chronic conditions are increasingly prevalent worldwide, with the oral route being the most common for drug administration. However, limitations such as low bioavailability and patient nonadherence can result in complica...
Chronic conditions are increasingly prevalent worldwide, with the oral route being the most common for drug administration. However, limitations such as low bioavailability and patient nonadherence can result in complications that affect the patient's quality of life and increase healthcare costs. In schizophrenia, up to 75% of patients discontinue treatment within 18 months, raising risks of relapse, hospitalization and suicide. Therefore, sustained drug delivery systems offer a promising alternative. To this end, different long-acting subcutaneous implants, loaded with risperidone (RIS) were prepared through the variation of polymers and drug loading, by VAT photopolymerisation 3D-printing technique. The obtained implants were comprehensively characterized in terms of morphology, swelling and release profile. Among these, two polyethylene glycol diacrylate (PEGDA 700)-based implants, one incorporating polylactic acid-polyurethane (PLA-PUA) (R2L2P76) and the other without (R2P78), showed promising in vitro release characteristics (up to 300 and 100 days, respectively) and therefore were selected as lead formulations for further investigation. R2P78 and R2L2P76 lead implants were further characterised using different techniques such as thermal analysis and infrared spectroscopy. Finally, their cytotoxicity was tested in 3 T3 murine fibroblasts showing biocompatibility and insignificant effect on cell viability. This study demonstrates the feasibility of preparing versatile subcutaneous implants via VAT photopolymerisation 3D-printing, that can be customised to patients' needs at the point of care, as a promising alternative for the sustained delivery of RIS. Such long-acting implants have the potential for increasing patient compliance and improving therapeutic efficiency for schizophrenia treatment.
Multi-functional purine nucleoside-modified chitosan polymer micelles for improving the oral absorption of doxorubicin based on nucleoside transporter mediation.
Wei Y, Chen Y, Zhang H … +7 more , Li Q, He H, Liang X, Lin S, Chen H, Wu W, Zhang W
Int J Pharm · 2026 Jul · PMID 42289209 · Publisher ↗
A kind of purine nucleoside-chitosan-silybin (PN-CS-SB) polymeric micelles were developed for enhancing the oral absorption of doxorubicin (DOX) by intestinal nucleoside transporter mediation, the inhibition of P-glycopr...
A kind of purine nucleoside-chitosan-silybin (PN-CS-SB) polymeric micelles were developed for enhancing the oral absorption of doxorubicin (DOX) by intestinal nucleoside transporter mediation, the inhibition of P-glycoprotein (P-gp) efflux and CYP3A4 metabolism. The four types of PN, including adenosine, deoxyadenosine, guanosine and deoxyguanosine, respectively, and silybin, were conjugated to chitosan via the linker succinic acid. The synthesized PN-CS-SB were identified by H NMR and FT-IR, and the doxorubicin (DOX)-loaded micelles were prepared by ultrasonication. The micelles demonstrated a series of the excellent properties, including the high drug loading capacity of above 8.2%, the regular spherical shapes with the small particle sizes of below 150 nm, and the low critical micelle concentration of below 5.82 × 10⁻⁶ g/mL. The oral bioavailability of the DOX-loaded micelles against DOX solution achieved to as high as 453.28%. The rapid and tremendous absorption of micelles was visually demonstrated by in vivo imaging. The micelle absorption mechanism was proved to be nucleoside transporter-mediation as well as the dual inhibition of P-gp and CYP3A4 by the cellular uptake, enzyme inhibition and immunofluorescence location test. The cellular endocytosis and transportation pathway of micelles across intestinal epithelial cells involved nucleoside transporter target, caveolin mediation or macropinocytosis with energy consumption.
Study on transdermal delivery system of sulforaphane chitosan nanoparticles based on methacryloylated chitosan microneedles: application in the treatment of irritant contact dermatitis.
Wang T, Han Y, Chen J … +5 more , Zhou G, Cai L, Li T, Guo X, Han J
Int J Pharm · 2026 Jul · PMID 42289208 · Publisher ↗
Treatment of irritant contact dermatitis (ICD) is limited by the stratum corneum barrier, which hinders drug delivery and bioavailability. Sulforaphane (SFN) offers anti-inflammatory potential but suffers from poor stabi...
Treatment of irritant contact dermatitis (ICD) is limited by the stratum corneum barrier, which hinders drug delivery and bioavailability. Sulforaphane (SFN) offers anti-inflammatory potential but suffers from poor stability and a short half-life. To address this, we developed a chitosan methacrylate (CSMA) hydrogel microneedle (MN) patch loaded with SFN-chitosan nanoparticles (SFN-CSNPs) for enhanced transdermal delivery.Network pharmacology identified 33 potential ICD-related targets of SFN, including SRC, EGFR, and JAK2, implicating pathways such as AGE-RAGE and Relaxin signaling. SFN-CSNPs were optimized via a Box-Behnken design, yielding nanoparticles with a size of 180-220 nm, PDI < 0.3, a Zeta potential of ∼ 24 mV, and a high encapsulation efficiency (91.94 ± 1.22%). These were incorporated into CSMA MNs using micromolding. The MN arrays exhibited robust mechanical strength (1.53 N/needle), enabling effective stratum corneum penetration. In vitro, the system achieved sustained release (183.6 ± 2.1 µg/cm over 60 h) and 11-fold higher skin retention than the SFN solution. It also demonstrated excellent stability, retaining > 85% drug content after 30 days at 4 °C. In an ICD mouse model, SFN-CSNPs@CSMA MNs significantly reduced erythema, edema, and epidermal thickening (45.37 ± 2.86 µm), approaching normal levels (20.03 ± 3.20 µm), and outperformed both SFN-CSNPs solution and dexamethasone ointment. This nano-MN platform effectively overcomes skin barriers, enhances drug stability, and enables localized, sustained release, offering a promising strategy for delivering unstable natural compounds such as SFN to treat inflammatory skin diseases.
Chondroitin sulfate-functionalized ultradeformable liposomes for dual effect in rheumatoid arthritis: systematic QbD development and in vivo characterization.
Gujarathi NA, Girase R, Sukhia A … +4 more , Aher AA, Patil TS, Agrawal YO, Nikitha Kota SS
Int J Pharm · 2026 Jul · PMID 42288317 · Publisher ↗
Chondroitin sulfate-functionalized ultra-deformable liposomes (CS-ACE-UDFLs) were developed for dual action, enhanced skin penetration and CD44-receptor-mediated precise delivery of drug. Optimization of critical paramet...
Chondroitin sulfate-functionalized ultra-deformable liposomes (CS-ACE-UDFLs) were developed for dual action, enhanced skin penetration and CD44-receptor-mediated precise delivery of drug. Optimization of critical parameters such as lipid concentration, sonication time, and edge activator concentration executed by Box-Behnken design. DLS particle size analyzer revealed nano-vesicle size (229.6 ± 7.95 nm), stable negative zeta potential (-41.30 ± 1.80 mV), high entrapment efficiency (73.53 ± 1.27%), and a low polydispersity index (0.253 ± 0.014) for CS-ACE-UDFLs. The encapsulation of aceclofenac confirmed through differential scanning calorimetry and X-ray diffraction studies. Surface characterization of CS-ACE-UDFLs with TEM analysis revealed a spherical morphology with a distinct chondroitin sulfate coating on the vesicle surface. In vitro release kinetics depicted the Korsmeyer-Peppas model, implying a complex release pattern, resulting from coupling of diffusion processes and matrix relaxation mechanisms. Enhanced drug release reported for CS-ACE-UDFLs (56.04% in 4 h, 91.80% in 8 h) post-incorporation edge activator compared to conventional liposomes (35.54% in 4 h, 68.51% in 8 h). The physicochemical parameters of CS-ACE-UDFLs were maintained during preliminary stability studies at 5°C. Confocal microscopy studies demonstrated a higher fluorescence intensity of functionalized ultradeformable liposomes hydrogel. Compared to ACE solution and ACE-UDFLs, CS-ACE-UDFLs showed superior anti-inflammatory activity in LPS-activated RAW 264.7 cells, characterized by enhanced cellular uptake and significantly lower levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). In vivo studies on the CFA-induced arthritis rat model exhibited a significant reduction in paw volume and arthritis score (P < 0.0001) after treatment with the CS-ACE-UDFLs hydrogel system, indicating its potential in rheumatoid arthritis therapy.
Drug delivery based on circadian rhythm: mechanisms, applications, and prospects.
Wang B, Zhou Y, Wang H … +4 more , Ran C, Shen Y, Li S, Liu J
Int J Pharm · 2026 Jun · PMID 42288316 · Publisher ↗
Biological circadian rhythm is a ubiquitous phenomenon in living organisms that regulates numerous physiological and biochemical processes. In the field of drug delivery, it exerts profound impacts on the pharmacokinetic...
Biological circadian rhythm is a ubiquitous phenomenon in living organisms that regulates numerous physiological and biochemical processes. In the field of drug delivery, it exerts profound impacts on the pharmacokinetics and pharmacodynamics of drugs, as well as the efficiency and therapeutic outcomes of drug delivery. Accordingly, optimizing drug delivery strategies based on human circadian rhythms to achieve optimal therapeutic efficacy has emerged as a highly popular research direction. Compared with conventional drug delivery systems (DDS), circadian rhythm-adapted DDS can precisely control the release time and dosage of drugs to align with the intrinsic rhythms of hormone secretion, gene expression and disease progression in the body, thereby enhancing therapeutic efficacy, reducing toxic and side effects, and improving patients' medication compliance under certain circumstances. Such DDS are mainly classified into two categories: circadian rhythm-compliant and circadian rhythm-modulating drug delivery systems. The former adopts controlled or sustained drug release to match drug administration with the optimal time window for drug absorption in organisms so as to boost therapeutic effects, while the latter employs chemical ligands targeting the circadian rhythm system to interfere with circadian rhythm expression, facilitating drug delivery and pharmacological action. To date, circadian rhythm-based DDS have been extensively investigated and applied in the treatment of metabolic diseases, cardiovascular diseases, cancers and many other disorders. This review elaborates on the significant influences of biological circadian rhythms on drug delivery and their implications for the optimization of drug delivery systems, summarizes drugs capable of modulating circadian rhythms, and discusses the key challenges that need to be addressed to further broaden the application of circadian rhythms in the field of drug delivery.
Corrigendum to "Lipid monolayer composition and production efficiency in DSPC/PEG40St microbubbles for ultrasound applications" [Int. J. Pharm. 685 (2025) 126254].
Kilic S, Ayaz IU, Ozdemir E
Int J Pharm · 2026 Jul · PMID 42288111 · Publisher ↗
Abstract loading — click title to view on PubMed.
A hybrid modelling framework for the description of friction forces in autoinjector devices.
Friso A, Palmer M, Galvanin F
Int J Pharm · 2026 Jun · PMID 42285383 · Publisher ↗
Autoinjectors (AJs) are medical devices enabling precise subcutaneous self-administration of medicines. An important challenge in modelling these devices is accurately predicting injection time, which significantly impac...
Autoinjectors (AJs) are medical devices enabling precise subcutaneous self-administration of medicines. An important challenge in modelling these devices is accurately predicting injection time, which significantly impacts device usability, drug delivery and patient experience. Existing literature models for injection time are based on the balance of forces acting on the stopper. These typically include a driving force, resistance due to the flow of liquid through the needle, and friction between the stopper and syringe wall. In some cases, incomplete mechanistic understanding can lead to an oversimplified treatment of friction resulting in poor predictions of delivery time. This study presents a hybrid modelling approach that integrates physics-based and data-driven components including Artificial Neural Networks and Gaussian Processes. By integrating mechanistic modelling with surrogate models, the proposed approach overcomes key limitations of existing models and provides an accurate dynamic representation of the friction forces involved in the injection process. The hybrid models developed demonstrate enhanced descriptive capabilities for friction forces acting between the plunger and the syringe inner walls, offering a more comprehensive understanding of the complex physical phenomena involved in the AJ.
Isoquercitrin-loaded adipose-derived stem cell exosomes synchronize immunomodulation and neurovascular remodeling to accelerate spinal cord regeneration.
Xia W, Liu S, Gao T … +4 more , Xue F, Guo Q, Lou Z, He Y
Int J Pharm · 2026 Jun · PMID 42285382 · Publisher ↗
Spinal cord injury (SCI) involves complex and interconnected pathological processes, including microglia-driven inflammation, vascular disruption, and impaired neuronal metabolic homeostasis, which collectively limit fun...
Spinal cord injury (SCI) involves complex and interconnected pathological processes, including microglia-driven inflammation, vascular disruption, and impaired neuronal metabolic homeostasis, which collectively limit functional recovery. Here, we developed an isoquercitrin-loaded adipose-derived stem cell exosomes formulation (IQC@ADSCs-EXOs) as a natural nanocarrier delivery platform to coordinately modulate key cellular components within the lesion niche. IQC@ADSCs-EXOs exhibited typical vesicular morphology with nanoscale size distribution and a negative surface potential, and were efficiently internalized by microglia, endothelial cells (ECs), and neurons. Functionally, IQC@ADSCs-EXOs attenuated myelin debris-induced lipid droplet accumulation, lipid peroxidation, and intracellular ROS in BV2 cells, accompanied by a shift toward an anti-inflammatory phenotype. Meanwhile, IQC@ADSCs-EXOs promoted endothelial proliferation, migration, and tube formation, and enhanced mitochondrial activity with increased neurite outgrowth in PC12 cells. In a mouse contusive SCI model, local administration of IQC@ADSCs-EXOs was associated with improved vascular rebuilding, reduced neuroinflammation, enhanced axonal regeneration, and better locomotor and electrophysiological outcomes compared with controls. Collectively, these findings support IQC@ADSCs-EXOs as a nanotherapeutic platform with multicellular targeting capacity and translational potential for SCI repair.
A dual-microneedle system for integrated continuous glucose monitoring and feedback insulin delivery.
Zhao K, Niu Y, Cao X … +2 more , Ma T, You X
Int J Pharm · 2026 Jun · PMID 42285381 · Publisher ↗
Effective precision diabetes management requires seamless integration of continuous glucose monitoring and therapeutic intervention. In this study, we present a novel dual-microneedle regulatory system, which combines a...
Effective precision diabetes management requires seamless integration of continuous glucose monitoring and therapeutic intervention. In this study, we present a novel dual-microneedle regulatory system, which combines a biosensing microneedle for real-time interstitial glucose monitoring and a therapeutic microneedle for precise transdermal insulin delivery. The biosensing microneedle utilizes glucose oxidase-functionalized electrodes for continuous glucose sensing (demonstrating a broad linear range of 1-34 mM ), while the therapeutic microneedle employs electroosmotic flow to regulate insulin infusion through hollow channels under a constant 5 V voltage. This integrated system was demonstrated to provide accurate glycemic control in diabetic Wistar rat models (achieving a 55 % blood glucose reduction within 144 min and demonstrating high clinical accuracy with 88 % of points in Zone A of the Clarke Error Grid), successfully merging continuous glucose monitoring with on-demand insulin delivery. The proposed system demonstrates a solid proof-of-concept for physically segregated closed-loop regulation, paving the way for the development of miniaturized, wearable artificial pancreas platforms for more effective diabetes management.
Determination of compartment properties of press-coated tablets by non-destructive terahertz technology.
Leung CK, Brauns H, Ward-Berry JN … +2 more , Finke JH, Zeitler JA
Int J Pharm · 2026 Jun · PMID 42285380 · Publisher ↗
Compared to conventional film coating, press-coated tablets (PCTs) excel in their suitability for heat- and moisture-sensitive drugs and in their ability to produce thicker functional coats with higher drug loading. Prev...
Compared to conventional film coating, press-coated tablets (PCTs) excel in their suitability for heat- and moisture-sensitive drugs and in their ability to produce thicker functional coats with higher drug loading. Previous work has demonstrated the importance of porosity to the mechanical properties of PCTs, but determining the porosities of the press coating separately from the tablet cores in the finished tablets remains challenging. Terahertz time-domain spectroscopy (THz-TDS) overcomes this challenge and non-destructively interrogates the PCT's compartment properties, including porosity, mass, height and thickness. The THz-TDS results align with reported literature values, are more physically consistent, and more closely reflect PCT compartments than the conventional method, which is affected by elastic recovery and material loss during physical separation of compartments. The robust THz-TDS approach is demonstrated with a range of PCT geometries, and its sensitivity to defective PCTs is confirmed. Its non-destructiveness permits the systematic determination of the material, process, and structural properties of each PCT, enabling more comprehensive analysis. With a thorough mechanical understanding of PCTs enabled by THz-TDS, predictive models can be developed to support Quality by Design (QbD) or Quality by Digital Design (QbDD) of PCTs.
Predictive population balance modeling of pharmaceutical tablet disintegration and dissolution behavior.
Yang MH, Rossi F, Zhang X … +2 more , Reklaitis GV, Nagy ZK
Int J Pharm · 2026 Jun · PMID 42276264 · Publisher ↗
Predicting tablet disintegration and dissolution remains challenging due to the complex and nonlinear interplay of critical material attributes (CMAs) and physicochemical properties. This study introduces a population ba...
Predicting tablet disintegration and dissolution remains challenging due to the complex and nonlinear interplay of critical material attributes (CMAs) and physicochemical properties. This study introduces a population balance model (PBM) framework to simulate the disintegration and dissolution of tablets produced via granulation and direct compression while reducing the required experimental dataset. The framework captures the influence of CMAs, including crystal size distribution (CSD), granule size distribution (GSD), tablet and granule porosity, manufacturing routes, and active pharmaceutical ingredient (API) solubility. For granule-based tablets, an integrated system of three PBMs characterizes the number density evolution of (i) granules bound within the tablet, (ii) granules released into the solvent, and (iii) crystals. Two breakage kernels describing tablet break-up and granule fragmentation incorporate tablet porosity, granule size and porosity, and swelling-driven diffusion effects. Dissolution of crystals and granule surface erosion are modeled using a modified Noyes-Whitney equation. Experimentally determined GSD and CSD are used as initial conditions and model inputs. This framework can also be simplified into two PBMs to simulate dissolution behavior of direct compression tablets. Model accurately reproduced the dissolution behavior of acetaminophen, indomethacin, and lomustine tablets prepared via dry granulation and direct compression, with similarity factor f values above 50 between predicted and experimental profiles. The semi-mechanistic nature of the framework provides mechanistic insight into dissolution behavior while reducing the need for extensive dissolution data, which may facilitate and accelerate tablet formulation development.
Formulation of amorphous solid dispersion of clofazimine, an extremely water-insoluble basic drug, via hot-melt extrusion by applying acid-base supersolubilization principle.
Kathawala MH, Kandagatla HP, Avdeef A … +3 more , Kuentz M, Verbić TŽ, Serajuddin ATM
Int J Pharm · 2026 Jul · PMID 42276263 · Publisher ↗
Clofazimine (CFZ) is an anti-leprosy and anti-tuberculosis drug listed on the World Health Organization's (WHO) Model List of Essential Medicines, but it is extremely water-insoluble and has major dissolution and bioavai...
Clofazimine (CFZ) is an anti-leprosy and anti-tuberculosis drug listed on the World Health Organization's (WHO) Model List of Essential Medicines, but it is extremely water-insoluble and has major dissolution and bioavailability issues, and presumably for these reasons, its only commercially available formulation, Lamprene®, was withdrawn from the US market by its manufacturer. The present investigation was undertaken to develop amorphous solid dispersions (ASDs) of CFZ using hot-melt extrusion (HME) to increase its dissolution rate. The process was, however, challenging because CFZ has a high melting point of 224 ℃, requiring high processing temperatures, at which the drug and the polymer used could degrade. Moreover, dissolution of CFZ from ASDs was low and incomplete. These issues were resolved by interacting the basic CFZ with glutaric acid (GA) using the acid-base supersolubilization (ABS) principle, enabling HME at 120 ℃ and achieving high drug dissolution. The final ASDs consisted of a mixture of CFZ (10% w/w), GA (11% w/w), poloxamer 407 (10% w/w), and either Kollidon® VA64 or HPMCAS-LG (69% w/w). The dissolution of 5-mg and 50-mg doses of the formulations with both polymers was studied in 250 mL of fed-state intestinal fluid (FeSSIF-V2, pH 5.8) over 2 h. While only 30-40% of the 50-mg dose dissolved under these conditions, the 5-mg dose dissolved completely (100%). It is postulated that the bioavailability of CFZ would be much higher from new ASDs, thereby reducing the dose.
Platelet-rich plasma-loaded hydrogels: diffusivity and release of individual proteins in multicomponent complex environments.
Stealey S, Rathinam M, Rai MF … +2 more , Brophy RH, Zustiak SP
Int J Pharm · 2026 Jun · PMID 42276262 · Publisher ↗
Platelet-rich plasma (PRP) treatments have demonstrated clinical benefit for osteoarthritis (OA), although reported outcomes remain inconsistent. Hydrogel-based delivery devices can enhance therapeutic efficacy by prolon...
Platelet-rich plasma (PRP) treatments have demonstrated clinical benefit for osteoarthritis (OA), although reported outcomes remain inconsistent. Hydrogel-based delivery devices can enhance therapeutic efficacy by prolonging local protein exposure, but effective design depends on characterizing PRP diffusion and the complex protein-protein and protein-matrix interactions that govern release kinetics. Conventional bulk release studies provide limited mechanistic insight into protein transport within complex, physiologically relevant microenvironments, where macromolecular crowding, protein-protein interactions, hydrogel confinement, and patient-specific synovial fluid composition collectively affect release kinetics. To capture this complexity, we used fluorescence correlation spectroscopy (FCS) to directly quantify diffusion coefficients of four representative PRP proteins with varying size and properties across a series of complex environments that represent PRP, the delivery device, and the intended host microenvironment. Diffusivity decreased with increasing protein size, solution viscosity, crowding density, micro-clot formation, and confinement from the hydrogel. Diffusion coefficients obtained via FCS correlated strongly (R = 0.84) with effective diffusivities calculated from bulk release experiments and enabled mathematical modeling of protein release kinetics using Fickian diffusion models from both slab hydrogels and microspheres of varying diameter. Together, this study demonstrated a framework for the utility of FCS in characterizing hindered diffusion within complex, multicomponent biological systems, thereby guiding the rational design of hydrogel-based PRP delivery platforms.
Choline chloride-DESs as green solvents for drug solubilization and formulation.
Jabeen S, Naseem Z, Siddique W … +3 more , Cheng Y, Liu N, Li H
Int J Pharm · 2026 Jul · PMID 42269796 · Publisher ↗
Drug solubility is a critical consideration in the development of drugs, as poor solubility can reduce efficacy by lowering bioavailability and making it more difficult for the body to absorb the drug. In view of various...
Drug solubility is a critical consideration in the development of drugs, as poor solubility can reduce efficacy by lowering bioavailability and making it more difficult for the body to absorb the drug. In view of various advantages, deep eutectic solvents (DESs) have gained cumulative attention in pharmaceutics as drug excipients and for the solubility enhancement of drugs. Choline chloride (ChCl)-based DESs are prepared via the combination of ChCl as a hydrogen bond acceptor (HBA) with hydrogen bond donors (HBD) such as urea, glycerol, lactic acid, etc., and consider as green choice as compared to traditional organic solvents. These solvents offer various advantages over conventional solvents, including favorable polarity, low toxicity, low volatility, thermal and photostability, biodegradability, and biocompatibility. The latest improvements in utilizing ChCl-based DESs involve the manufacturing of diverse drugs, including anticancer, antibiotic, and anti-inflammatory agents. The potential of these green solvents as drug excipients and for solubility enhancement in generating sustainable drug formulations has been discussed here. Overall, this review revealed the potential use of ChCl-based DESs as a green and sustainable alternative to traditional solvents in drug formulation, potentially contributing to the development of safe and effective drug formulations.
Evaporative coupled with antisolvent crystallization for additive manufacturing of personalized solid dosage forms.
Mbodji A, Gomez AA, Silva GB … +9 more , Vlaar CP, Duconge J, Monbaliu JM, Cersonsky RK, Yu L, Zhang GG, Coquerel G, Romañach RJ, Stelzer T
Int J Pharm · 2026 Jul · PMID 42269795 · Publisher ↗
Flexible solid dosage manufacturing platforms that enable customizing doses for personalized medicine, are recognized as the future standard in pharmaceutical therapy. This study uses a solution-based additive manufactur...
Flexible solid dosage manufacturing platforms that enable customizing doses for personalized medicine, are recognized as the future standard in pharmaceutical therapy. This study uses a solution-based additive manufacturing approach for the solid dosage formulation of individualized doses, precisely controlled in increments as little as 0.2 mg. The drug substance warfarin sodium isopropanol (WS-IPA) has relevant personalized formulation needs and was used as the highly potent model compound. A solution (drug substance, solvent, antisolvent, polymer) is dispensed into a capsule carrier (pullulan) based on a model-informed precision dosing algorithm to manufacture crystalline solid dispersion (CrySoD). Upon a controlled evaporative antisolvent-solvent crystallization (heptane/IPA), WS-IPA crystallizes inside the polymer matrix (polyethylene glycol, PEG). By controlling the critical process parameters (temperature, drug substance - PEG concentration, antisolvent composition) of the coupled crystallization and formulation process, the commercial crystalline solid form of WS-IPA can be obtained. The CrySoD capsules (commercial and individualized doses) met key performance metrics (e.g., dissolution profile) of commercially formulated WS-IPA tablets (Coumadin®) following United States Pharmacopeia (USP) protocols. The workflow and insights provide a generalizable proof-of-concept for a model-informed solid dosage formulation platform enabled by process intensification. This study might be used as a rationale for further investigations, including other personalized medicine relevant drug substances, regulatory science, and technoeconomic analysis.
Near-infrared light-triggered, self-amplifying targeted drug-delivery platform achieves precision treatment of retinoblastoma.
Cai S, Zhao J, Liu H … +10 more , Zhao J, Zhao M, Xiang R, Cheng M, Wu T, Su Y, Zhao J, Yin T, Ji M, Zhang Y
Int J Pharm · 2026 Jun · PMID 42269794 · Publisher ↗
The management of advanced retinoblastoma (RB), the most common pediatric intraocular cancer, is severely limited by the toxic side effects of conventional chemotherapy and the surgical radicality of enucleation. To addr...
The management of advanced retinoblastoma (RB), the most common pediatric intraocular cancer, is severely limited by the toxic side effects of conventional chemotherapy and the surgical radicality of enucleation. To address this, we engineered a tumor-specific, Reactive Oxygen Species (ROS)-responsive nano-co-delivery system that synergizes chemotherapy and Photodynamic Therapy (PDT) for precise and potent RB treatment. We designed a dimeric cabazitaxel (CTX) prodrug linked via a thioketal (TK) bridge, which is co-assembled with the photosensitizer chlorin e6 (Ce6) into stable nanoparticles. These nanoparticles are further functionalized with a cRGD peptide on their surface for active targeting of integrin αvβ3, which is overexpressed in RB. Upon accumulation at the tumor site and exposure to near-infrared (NIR) light, Ce6 generates a burst of cytotoxic ROS, initiating PDT-mediated cell death. Crucially, this exogenous ROS surge acts as a molecular trigger to cleave the TK linkers, on-demand releasing active CTX monomers directly within the tumor microenvironment. This ROS-triggered drug release creates a powerful positive feedback loop, amplifying the therapeutic effect. In vitro, the cRGD-decorated nanoparticles demonstrated superior cellular uptake and potent cytotoxicity against Y79 RB cells upon irradiation. In an orthotopic xenograft RB mouse model, the targeted nano-platform showed enhanced tumor accumulation, deep tissue penetration, and complete tumor ablation after NIR irradiation, with no observable systemic toxicity. This self-amplifying strategy represents a paradigm shift in targeted RB therapy, offering a highly precise and effective alternative to current standard-of-care treatments.
Solvent-free engineering of a co-amorphous efavirenz-ritonavir system by hot-melt extrusion: Solid-state stabilisation and improved bioavailability.
Ghatole S, Taladhi K, Kumari M … +4 more , Pulimamidi SS, Borkar RM, Roy S, Kaity S
Int J Pharm · 2026 Jul · PMID 42269793 · Publisher ↗
Combination antiretroviral therapy remains the most successful approach for effective HIV management, as the simultaneous targeting of multiple stages of the viral replication cycle improves therapeutic efficacy and limi...
Combination antiretroviral therapy remains the most successful approach for effective HIV management, as the simultaneous targeting of multiple stages of the viral replication cycle improves therapeutic efficacy and limits the emergence of drug resistance. Efavirenz (EFV) and ritonavir (RTV) form a mechanistically complementary drug pair; however, both exhibit poor aqueous solubility, leading to dissolution-limited oral absorption. In this work, a dose- and mechanism-informed co-amorphous formulation strategy was developed using hot-melt extrusion (HME) to improve the biopharmaceutical performance of EFV and RTV. Three EFV:RTV molar ratios were designed to preserve EFV-dominant dosing while sufficient RTV content to facilitate intermolecular stabilisation and amorphous phase formation. Molecular docking served as a pre-formulation screening tool and revealed favourable drug-drug compatibility. Among the investigated compositions, the 1:0.5 (EFV:RTV) system (CM3) achieved complete amorphisation, whereas other ratios retained residual crystallinity. Solid-state characterisation using PXRD, DSC, TGA, FT-IR, and H NMR confirmed the formation of a single-phase amorphous system with enhanced thermal stability, while SEM demonstrated pronounced morphological changes, supporting the HME-induced transformation. CM3 exhibited substantially improved solubility and accelerated dissolution, alongside short-term physical and chemical stability. In rat in-vivo pharmacokinetic study, the co-amorphous system produced 8.7-fold higher C and 10.1-fold greater systemic exposure (AUC) for EFV compared with the pure drug suspension, indicating improved absorption and bioavailability. RTV exhibited sustained plasma exposure, enhanced overall systemic availability, and modulated absorption behaviour from the CM3 system. The improved pharmacokinetic performance was attributed to the amorphous conversion, improved molecular dispersion, and dissolution enhancement achieved through HME processing.
A data-driven process control strategy aligned with quality by design using a local linear modelling method and fault detection & diagnosis for twin-screw granulation.
Sivanathan K, Mhaskar P, Thompson MR
Int J Pharm · 2026 Jul · PMID 42269792 · Publisher ↗
The commercial implementation of continuous granulation requires an intelligent control framework compliant with Quality by Design (QbD) principles. To satisfy regulatory requirements this 'control system' cannot simply...
The commercial implementation of continuous granulation requires an intelligent control framework compliant with Quality by Design (QbD) principles. To satisfy regulatory requirements this 'control system' cannot simply vary multiple operational variables simultaneously to regain quality attributes but should recognize the source of a disturbance and make the appropriate correction. A Fault Detection and Diagnosis (FDD) method is proposed as a novel element for such a framework, automating identification of the root cause within a non-linear design space. The disclosed method is considered a first step to realizing a QbD control system by presently assuming only one disturbance can occur at a time to highlight the value of this new approach, not producing a ready-to-use product. The design space for twin-screw granulation was modelled using linear Partial Least Squares (PLS) with data collected using the Prediction Reliability Enhancing Parameter (PREP) method, which navigates non-linear data, producing a more comprehensive dataset. Particle size distribution (PSD) was the primary output used for assessing the granulation process. To address the inherently complex design space, local models were dynamically generated around the operation/disturbance point to reduce the error of fit for the FDD algorithm. Fault detection involved the verification of a disturbance and perturbation of a verified input whereas the fault diagnosis phase employed an optimization framework comparing observed and predicted PSDs associated with the deviations. This design helps overcome the interdependent behavior of process inputs and enables systematic isolation of the correct root cause. The algorithm is evaluated in this study by three case studies.
Microfluidic-active loading integration enables rapid two-step manufacturing of antibiotic-loaded liposomes with intravesicular drug nanocrystallization.
Natsaridis E, Gkartziou F, Mouzoura P … +3 more , Karatolios N, Stuart M, Antimisiaris SG
Int J Pharm · 2026 Jul · PMID 42269791 · Publisher ↗
Liposome manufacturing remains a critical challenge in the translation of nanomedicines due to multi-step preparation procedures and limited process integration. Microfluidic manufacturing enables controlled liposome for...
Liposome manufacturing remains a critical challenge in the translation of nanomedicines due to multi-step preparation procedures and limited process integration. Microfluidic manufacturing enables controlled liposome formation, whereas remote ion-gradient loading provides highly efficient drug encapsulation; however, these processes are typically performed separately. Here, we present a two-step microfluidic-active loading (MF-AL) strategy that integrates Staggered Herringbone Micromixer (SHM) microfluidics with ammonium-sulfate-driven remote loading for rapid production of antibiotic-loaded liposomes. Empty liposomes were first generated in ammonium sulfate using a SHM, followed by a second microfluidic cycle enabling active drug loading without intermediate processing steps. Using moxifloxacin (MOX) as a model amphiphilic antibiotic, liposomes with diameters between 83-117 nm were obtained, having high drug loading efficiencies (D/L ≈ 0.50 mol/mol for most lipid compositions). Importantly, the MF-AL method achieves drug loading and physicochemical properties (size distribution, morphology, crystallinity, and release kinetics) comparable to classical remote loading while eliminating intermediate processing steps, thereby simplifying liposome manufacturing. Cryo-EM revealed granular electron-dense domains within highly loaded vesicles, which, together with the presence of characteristic XRD diffraction peaks, strongly suggests the formation of intravesicular drug nanocrystals produced during ion-gradient-driven loading. Furthermore, MF-AL liposomes showed antimicrobial activity against Staphylococcus epidermidis (planktonic and biofilm models) superior to free drug and comparable to conventionally prepared formulations proving that in addition to structural, also the functional characteristics of MOX-liposomes were preserved. The MF-AL method was further validated using doxorubicin, demonstrating its applicability to other amphiphilic therapeutics. Overall, the MF-AL approach represents a simple, rapid, and scalable strategy for liposome manufacturing, enabling efficient drug loading while preserving the structural and functional characteristics of remotely loaded nanomedicines.
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