Search Results (523)

Active molecules derived from traditional Chinese medicine (TCM) represent a valuable source of lead compounds for modern drug discovery, demonstrating considerable potential in the prevention and treatment of chronic diseases, cancer therapy, and immune modulation. Nevertheless, their clinical translation is often impeded by intrinsic limitations such as poor aqueous solubility, low bioavailability, inadequate chemical stability, and significant gastrointestinal irritation. Cyclodextrins (CDs) and their derivatives, characterized by a hydrophobic internal cavity, are capable of forming inclusion complexes with TCM and their derived active constituents, thereby improving their physicochemical and pharmacokinetic profiles. Over the past five years, substantial progress has been made in this domain. CD-based inclusion strategies have been shown to markedly enhance the solubility and dissolution rate of poorly water-soluble TCM compounds, including flavonoids, alkaloids, and terpenoids. Moreover, this approach contributes to improved drug stability, effective taste masking, and the achievement of modified release profiles, such as sustained or targeted delivery, ultimately leading to enhanced therapeutic efficacy and reduced adverse effects. The development of novel CD derivatives and smart delivery systems has further broadened their application potential. This review summarizes recent advances in the CD-based encapsulation of TCM active molecules, highlighting key formulation strategies that address persistent challenges in the modernization of TCM. It also provides a foundation for future research and development in natural product-based therapeutics. Full article

Background/Objectives: Shikonin (SKN) is a potential anti-psoriatic agent, yet its clinical application is hindered by poor water solubility and low stratum corneum permeability. This study aimed to develop a reactive oxygen species (ROS)-responsive hydrogel microneedle system encapsulating SKN-loaded polymeric micelles (SKN-M@MN) to enhance transdermal delivery and evaluate its therapeutic effects in psoriasis. Methods: Shikonin-loaded micelles (SKN-M) were optimised using a thin-film hydration method. SKN-M@MN was fabricated via a two-step casting method using phenylboronic acid-modified hyaluronic acid (HA-PBA) and polyvinylpyrrolidone K90 as the tip matrix. Skin penetration, ROS-responsive release, and anti-psoriatic efficacy were assessed in an imiquimod (IMQ)-induced mouse model. Mechanistic studies included RNA-seq, qPCR, and Western blotting. Results: SKN-M achieved an encapsulation efficiency of 93.45 ± 0.24%, a particle size of 62.49 ± 0.92 nm, and a zeta potential of −36.78 ± 1.12 mV. SKN-M@MN showed 100% skin penetration, sustained drug release, and accelerated degradation under high ROS conditions. In psoriatic mice, SKN-M@MN significantly alleviated skin lesions, reduced epidermal hyperplasia (Ki67), and downregulated IL-17A and TNF-α levels both locally and systemically. Mechanistically, it inhibited the PI3K/AKT and NF-κB signalling pathways. Conclusions: The SKN-M@MN microneedle platform integrates physical skin penetration, ROS-responsive drug release, and pathway inhibition, offering an effective strategy for transdermal delivery of poorly soluble drugs in psoriasis therapy. Full article

Background/Objectives: Corneal neovascularization (CNV) is a leading cause of vision loss, but current treatments are limited by poor ocular drug penetration and rapid tear clearance. Luteolin (LUT) is a poorly water-soluble natural anti-angiogenic agent. To address this limitation, we develop an ion- and pH-responsive in situ gel system (LUT-NLC-ISG) by incorporating LUT-loaded nanostructured lipid carriers (LUT-NLC) into a gellan gum/Carbopol matrix, aiming to enhance ocular bioavailability and therapeutic efficacy against CNV. Methods: LUT-NLC-ISG was optimized using a central composite design-response surface methodology (CCD-RSM) and characterized by physicochemical properties (particle size, viscosity, gelation behavior). Ocular pharmacokinetics and biodistribution were evaluated in rabbits after a single topical administration. Biocompatibility was assessed via Hen’s egg test–chorioallantoic membrane assay (HET-CAM), Draize tests, and cytotoxicity studies. Therapeutic efficacy and mechanism were investigated in a murine model of alkali burn-induced CNV. Results: The optimized LUT-NLC-ISG had a particle size of 25.27 ± 0.23 nm and exhibited a 45-fold viscosity increase upon simulated tear fluid (STF) exposure. In rabbits, LUT-NLC-ISG significantly increased the bioavailability of LUT in ocular tissues compared with LUT-NLC alone, with 2.57-, 1.83-, and 10.59-fold higher area under the concentration–time curve (AUC) in the cornea, conjunctiva, and tears, respectively and exhibited excellent ocular biocompatibility. In the CNV mouse model, 0.1% (w/v) LUT-NLC-ISG effectively inhibited corneal neovascularization, comparable to 0.025% dexamethasone, and downregulated VEGF-A and MMP-9 expression. Conclusions: LUT-NLC-ISG synergistically combines NLC technology and dual-sensitive in situ gelation to significantly improve LUT ocular bioavailability, offering a promising non-invasive candidate for CNV management. Full article

Background: Pulmonary drug delivery represents a promising approach for the potential localised treatment of respiratory of non-small-cell lung cancer (NSCLC). However, the efficient delivery of poorly water-soluble drugs remains challenging due to limited solubility and inadequate aerodynamic performance. This study aimed to develop and characterise inhalable dry powder formulations of zinc diethyldithiocarbamate (Zn(DDC)₂) complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) for potential pulmonary administration. Methods: Formulations were prepared by freeze-drying and spray-drying, with leucine incorporated at 0%, 5%, and 10% w/w. Formulations were prepared via freeze-drying and spray-drying with leucine incorporation (0%, 5% and 10% w/w) to evaluate their physicochemical properties, flowability and aerodynamic performance. Results: Spray-dried formulations exhibited significantly lower densities (as low as 1.03 ± 0.71 g/cm³), enhanced flowability, improved aerosolisation and higher fine particle fraction (FPF) values (up to 40.12 ± 0.60%) compared to freeze-dried powders (20.03 ± 2.79%). The incorporation of leucine further reduced powder density down to 0.72 ± 0.34 g/cm³ and increased surface corrugation as shown in SEM images, improving aerosolisation performance, with FPF values up to 76.77 ± 1.18%. Next Generation Impactor (NGI) analysis confirmed that leucine-containing formulations exhibited a greater proportion of particles within the respirable aerodynamic diameter range (1–5 μm), suggesting suitability for deep lung deposition. Conclusions: These results demonstrate that spray-dried Zn(DDC)₂–cyclodextrin powders, particularly those modified with 10% leucine, offer excellent potential for pulmonary delivery in NSCLC therapy. Further in vivo studies are warranted to evaluate therapeutic efficacy and safety. Full article

Background: The therapeutic potential of many natural products, including curcumin (CUR), betulinic acid (BA), and oleanolic acid (OA), is limited by poor oral exposure caused by low aqueous solubility, metabolic instability, and/or first-pass metabolism. Lipid–drug conjugate (LDC) strategies that mimic endogenous dietary lipid processing may provide a useful approach for improving oral absorption and lymphatic transport. Methods: A 1,3-diolein-based lipidic promoiety (IN-4) was synthesized and conjugated to curcumin, betulinic acid, and oleanolic acid to generate three representative LDCs: CUR-PRO, BA-PRO, and OA-PRO. Their oral pharmacokinetic behavior was evaluated in rats. For CUR-PRO, matched-vehicle comparisons across three oral vehicles were performed, together with mesenteric lymph duct cannulation and in vitro stability/conversion studies in simulated gastrointestinal media, rat liver microsomes, and rat plasma. Results: All three prodrugs were successfully synthesized and showed improved systemic exposure to the corresponding parent-drug-related analytes under the tested conditions. For CUR-PRO, dose-normalized AUC_0-last of released curcumin was markedly higher than direct curcumin administration across all three vehicles (increases of 15.0-, 70.9-, and 54.3-fold), and intact CUR-PRO was also detected in plasma. Mesenteric lymph sampling showed that CUR-PRO dosing, but not free-curcumin dosing, generated detectable curcumin-related signals under the present analytical conditions. In vitro, no free curcumin was detected during CUR-PRO incubation in enzyme-free simulated gastrointestinal media; CUR-PRO underwent rapid depletion in pancreatic-lipase-supplemented medium, showed greater microsomal stability than curcumin, and displayed plasma conversion that was markedly accelerated by exogenous LPL. BA-PRO and OA-PRO also increased systemic exposure of their released parent drugs, with 16.0- and 38.4-fold dose-normalized AUC_0-last increases, respectively. Conclusions: These findings provide proof-of-concept evidence that 1,3-diolein-based lipidation can improve the oral exposure of selected poorly water-soluble natural products. The lymphatic transport data provide qualitative evidence supporting lymphatic access of CUR-PRO, although the quantitative contribution of this pathway to the overall exposure increase remains to be established. Full article

Background/Objectives: Diclofenac (DCF) and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation management; however, their clinical significance is limited by poor aqueous solubility, short biological half-life, and dose-dependent gastrointestinal, renal, and cardiovascular adverse effects. Nanocarrier-based delivery systems have been extensively explored because they can enhance the apparent solubility of poorly water-soluble NSAIDs, provide controlled and sustained drug release, prolong systemic circulation, and improve drug localization at the site of action. By reducing peak plasma concentrations and off-target exposure, these systems may decrease dose-dependent gastrointestinal and systemic adverse effects while maintaining therapeutic efficacy. Most studies focus on optimizing formulation composition, while the manufacturing process is often treated as a secondary parameter. The research critically evaluates conventional and emerging fabrication methods for NSAID nanocarriers, using DCF as the principal reference compound, with emphasis on their impact on physicochemical characteristics, reproducibility, scalability, and translational potential. Methods: A structured literature search was performed in PubMed/MEDLINE, Scopus, and Web of Science (2015–2026, with emphasis on 2022–2026) for DCF and NSAID-loaded submicron delivery systems reporting quantitative formulation data and clearly defined fabrication methods, resulting in a narrative review of approximately 375–395 eligible studies, comprising 75 DCF-specific studies and approximately 300–320 studies involving other NSAIDs that were included as representative surrogate systems when DCF-specific evidence was unavailable for particular fabrication approaches. The review followed Scale for the Assessment of Narrative Review Articles (SANRA) recommendations. Studies were analyzed using a standardized seven-parameter framework including encapsulation efficiency, release profile, particle size control, polydispersity, scalability, reproducibility, and process complexity. Results: Batch-based techniques, such as thin-film hydration for chitosan-coated liposomal systems, consistently provide high encapsulation efficiency, sustained drug release, and good biocompatibility. However, these methods are often associated with batch-to-batch variability, operator dependence, and limited scalability. In contrast, continuous manufacturing approaches, including microfluidic mixing, nanostructured lipid carriers, and Quality-by-Design (QbD)–guided processes, demonstrate improved control over particle size distribution and polydispersity, enhanced reproducibility, and better scalability potential. Conclusions: Manufacturing methodology is an important determinant of DCF and NSAID nanocarrier performance alongside formulation composition. Continuous manufacturing approaches offer promising improvements in reproducibility, process control, and scalability, but current evidence remains uneven across different nanocarrier classes. Further standardized comparative studies are needed to support their broader translation into clinical applications. Full article

Coccidiosis is one of the most economically important parasitic diseases in poultry, causing intestinal damage, impaired nutrient utilization, and substantial production losses. The extensive use of anticoccidial drugs has raised concerns regarding drug resistance, chemical residues in poultry products, and the environmental burden associated with veterinary drug use, highlighting the need for complementary control strategies. This study evaluated the anticoccidial efficacy of phytogenic formulations containing Curcuma longa and Piper longum extracts prepared using a solid-dispersion technique designed to enhance the dissolution characteristics of poorly water-soluble phytogenic compounds. The in vitro activity of the formulations was evaluated against mixed Eimeria spp. field-isolated oocysts using scanning electron microscopy (SEM) to examine ultrastructural alterations, whereas in vivo efficacy was investigated in broiler chickens experimentally challenged with Eimeria tenella. Cecal lesion scores, oocyst shedding, and growth performance were evaluated as indicators of infection severity and treatment response. SEM observations revealed marked structural damage to mixed Eimeria spp. oocysts following exposure to the phytogenic formulations. In the animal trial, all phytogenic treatment groups exhibited lower cecal lesion scores and reduced oocyst shedding than the infected control group. Among the phytogenic formulations evaluated, the combination containing 6 g/kg P. longum (T3) tended to produce the lowest numerical lesion score and oocyst shedding, although differences among phytogenic treatments were limited. Although some treatment groups also exhibited numerically favorable growth performance under challenge conditions, these observations should be interpreted cautiously because the study was designed primarily as a preliminary evaluation of anticoccidial efficacy, and feed intake and feed conversion ratio were assessed without independent pen-level replication. The observed biological responses may be associated, in part, with the improved dissolution characteristics afforded by the solid-dispersion formulation; however, this proposed mechanism was not directly investigated in the present study. In conclusion, solid-dispersion formulations containing C. longa and P. longum extracts demonstrated promising anticoccidial activity against experimental E. tenella infection and support further investigation as promising phytogenic candidates for complementary coccidiosis control strategies in broiler chickens. Full article

Resveratrol (RSV) is a poorly water-soluble polyphenolic compound with various potential health benefits, but its pharmaceutical application is limited by low aqueous solubility and poor oral bioavailability. Additive manufacturing (AM), particularly fused deposition modeling (FDM) 3D printing, offers a flexible approach for fabricating oral dosage forms with customized geometry and internal architecture. In this study, hot-melt extrusion (HME) combined with fused deposition modeling (FDM) 3D printing was used to prepare RSV-loaded tablets with different infill patterns. Hydroxypropyl methylcellulose acetate succinate and hydroxypropyl cellulose were selected as polymeric carriers to prepare RSV-loaded filaments suitable for FDM printing. The effects of infill pattern on the solid-state characteristics, dimensional accuracy, mechanical properties, floating behavior, and in vitro drug release of the printed tablets were systematically investigated. Differential scanning calorimetry, powder X-ray diffraction, and polarized light microscopy indicated that RSV was mainly converted into an amorphous or molecularly dispersed state after HME and FDM processing. All designed tablets were successfully printed and showed acceptable shape fidelity, while different infill patterns resulted in variations in tablet weight, mechanical strength, floating duration, and release behavior. In vitro dissolution studies showed that the RSV release profiles were dependent on the internal infill architecture. Tablets with more complex infill patterns generally exhibited slower drug release, which may be related to differences in internal pore structure, medium penetration pathways, matrix hydration, and diffusion distance. Release kinetic analysis further suggested that RSV release from the printed tablets involved a combination of diffusion and polymer relaxation processes. These results demonstrate that infill pattern is an important structural parameter for modulating the mechanical performance and drug release behavior of FDM 3D-printed RSV tablets. This study provides useful guidance for the design of 3D-printed oral dosage forms with tunable release characteristics. Full article

Background/Objectives: Paclitaxel is a chemotherapy drug used to treat various tumours, but its use is often limited by an acute and chronic pain syndrome that is poorly managed. Naringin and its aglycone, naringenin, exhibit antioxidant, antitumour, anti-inflammatory, and antinociceptive effects, making them potential alternative treatments. However, their low water solubility limits their oral bioavailability in humans. Micronisation in a supercritical medium reduces particle size and enhances the dissolution of compounds, offering a possible solution. In this study, we investigated whether micronising naringin and naringenin via supercritical technology could improve their dissolution and oral efficacy against paclitaxel-induced pain syndrome. Methods: Micronisation was performed using supercritical CO₂. Molecular docking was used to analyse the binding of naringin and naringenin to TRPV1, a key target for pain relief. Swiss mice were used in capsaicin (TRPV1 agonist)-induced nociception and paclitaxel-caused acute and chronic pain models. We assessed mechanical, cold, and heat sensitivity, potential adverse effects, and TRPV1 mRNA expression. Results: Micronisation improved the apparent dissolution profile of molecules. Docking results showed that naringin and naringenin bind to TRPV1. Both micronised compounds reduced capsaicin-induced nociception without affecting locomotion or body temperature. Micronised naringin and naringenin alleviated mechanical and cold allodynia, as well as thermal hyperalgesia in both acute and chronic paclitaxel-induced pain, outperforming their conventional forms. They also downregulated TRPV1 mRNA expression in the mice’s sciatic nerve. Conclusions: Taken together, these results show that supercritical micronisation improved the apparent dissolution and oral antinociceptive efficacy of naringin and naringenin, emphasising their potential as promising alternatives for managing paclitaxel-induced pain, with TRPV1 being a probable contributor to the observed antinociceptive effects. Full article

The rational design of mixed micellar systems has emerged as a cornerstone of modern nanomedicine, offering unprecedented control over the solubility and bioavailability of challenging therapeutic agents. This review provides a comprehensive analysis of the physicochemical principles governing the assembly of amphiphilic drugs and surfactants into synergistic nanostructures. By articulating the transition from traditional guest/host solubilization to “drug-as-component” models, we highlight the critical role of molecular interactions in achieving therapeutic precision. It further outlines the experimental methodologies used to investigate these systems and elucidates how they enhance the solubility, stability, and bioavailability of poorly water-soluble drugs. Special emphasis is placed on the practical applications of synergy in reducing systemic toxicity and optimizing drug release kinetics, providing a roadmap for the development of next-generation nano-pharmaceuticals. The functionality of these systems is significantly influenced by the molecular interactions among their constituents; thus, quantitative analysis of these interactions might enhance the formulation of more effective pharmaceuticals. This review outlines the key physicochemical principles of mixed micelle formation, including thermodynamics and synergistic interactions of amphiphiles, while emphasizing their relevance in current research and practical pharmaceutical applications. Various experimental methods, such as surface tension measurement, conductometric and calorimetric tests, and spectroscopic techniques, are compared in terms of their conditions of application and performance in understanding micelle formation and micelle structure. We clearly point out that the interpretation and evaluation of the properties of colloidal systems containing drug molecules solubilized by mixed micelles and an amphiphilic drug incorporated into micelles must be discussed and evaluated separately. Understanding the limitations and characteristics of the physical/chemical principles applied is essential for the rational design of mixed micelle carriers tailored to specific therapeutic needs. Full article

Background: Polymeric drug-eluting films are promising platforms for local antibacterial delivery, but their release profiles depend strongly on the permeability and morphology of the barrier layer. Here, the previously proposed concept of additively manufactured PLACE (Printed Layered Adjustable Cargo Encapsulation) coatings was extended from "single orifice"-defined release toward porosity-assisted barrier control. Two conventional water-soluble porogens, polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), were compared with poly(2-ethyl-2-oxazoline) (PEOx), a hydrophilic polymer proposed as an alternative to PEG in biomedical formulations, but whose use as a leachable porogen has received little attention. Methods: Each porogen was introduced into the upper PLGA barrier of multilayer PLACE films. The resulting films were characterized for film formation, post-hydration morphology by SEM, release of methylene blue and vancomycin, and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Results/Conclusions: PEG was poorly compatible with PLGA and mainly produced surface-localized defects rather than a barrier with controlled permeability suitable for prolonged delivery. PVP K17 provided sustained release at 10 wt.%, whereas 20 wt.% PVP caused burst-dominated release and stronger morphological disruption. PEOx formed developed porosity at lower loading and produced release regimes ranging from several days to approximately two weeks. Vancomycin-loaded films containing 5 wt.% PEOx enabled near-complete release over two weeks while preserving film integrity and showed pronounced early anti-MRSA activity. These results identify porogen selection as a key formulation step and support PEOx as a useful porogen for early high-output antibacterial PLACE coatings. Full article

Poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) copolymer micelles have emerged as promising drug delivery systems for enhancing the solubility and bioavailability of poorly water-soluble benzimidazole drugs. In this study, we prepared and characterized PEG-b-PCL micelles to encapsulate poorly water-soluble anthelmintics such as albendazole (ABZ) and fenbendazole (FBZ), with a focus on comparing their encapsulation behaviour, release profiles, and biological activity in cancer therapy. Drug-loaded micelles were analysed using dynamic light scattering (DLS), which revealed uniform nanosized micelles with a narrow polydispersity index (PDI). The morphology and size of both empty and drug-loaded micelles were examined using transmission electron microscopy (TEM), confirming that the micelles were spherical and consistent in size. Both drugs were efficiently encapsulated within the micellar core, demonstrating a high loading capacity. The release profiles of PEG-b-PCL micelles containing albendazole (ABZ) and fenbendazole (FBZ) at pH 7.4 were also evaluated. FBZ exhibited slower release kinetics compared to ABZ, likely due to its higher lipophilicity and stronger interactions with the hydrophobic PCL core, resulting in enhanced retention within the micelles. In contrast, ABZ had faster release kinetics. Finally, the in vitro MTT assays performed on the highly invasive triple-negative breast cancer (TNBC) cell line revealed the potential of these micelles as effective drug delivery systems. Full article

The cornea and conjunctiva are particularly susceptible to injury and adverse effects, either induced by topically applied drugs or excipients used in ophthalmic formulations. Surfactants and cosurfactants are important for producing topical eye formulations of poorly water-soluble drugs, yet they have not been always used in concentrations that are nontoxic and non-irritating to the ocular surface. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. The ocular irritation of Tween 80, Cremophor EL, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) was examined using the HET-CAM (conjunctival) and BCOP (corneal) eye assays. The toxic effect of the four excipients after 24 h on HLE-B3 cell growth was investigated and found to be dose-dependent. The highest tolerable concentrations of Tween 80 and Cremophor EL were 0.25% (w/w), whereas PEG 400 and PG were non-toxic at 5% (w/w). Tween 80 and Cremophor EL at 0.25% (w/w) and PEG 400 and PG at 5% (w/w) were all devoid of conjunctival and corneal irritation. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. Interestingly, there is strong agreement between the results obtained using the HET-CAM and BCOP assays, where both have been successfully used to evaluate the potential for ocular irritation caused by the aforementioned excipients. Full article

Achieving precise control over anticancer drug release remains one of the key challenges in modern pharmaceutical development, as it directly determines therapeutic efficacy, systemic toxicity, and patient outcomes. This review critically evaluates recent advances in three major formulation strategies: polymeric solid dispersions, cyclodextrin-based inclusion complexes, and metal–organic frameworks (MOFs), with a particular focus on their capacity to tailor anticancer drug release. Over the past decade, polymeric solid dispersions and cyclodextrin-based carriers have played a central role in improving the dissolution and bioavailability of poorly water-soluble anticancer agents, while also enabling modified release profiles through rational formulation design. Increasing structural complexity, including ternary systems and supramolecular assemblies, reflects a shift toward more controllable delivery platforms. In recent years, MOFs have emerged as highly adaptable porous materials capable of supporting controlled and stimuli-responsive release. The integration of imaging agents, magnetic components, and photothermal functionalities has further enabled the design of multifunctional and theranostic platforms. Taken together, these technologies reflect a shift from conventional solubility enhancement toward structurally engineered systems designed to achieve predictable and controlled drug release. Continued advances in material design and formulation strategies are expected to further refine release kinetics and support the development of next-generation anticancer therapies aligned with the growing demand for precision medicine. Full article

The low water solubility of numerous drug candidates and phytochemicals continues to pose a significant challenge in pharmaceutical development, greatly limiting their bioavailability and therapeutic performance. This review presents a detailed overview of formulation strategies aimed at improving the solubility and dissolution of poorly aqueous-soluble compounds. The biopharmaceutics classification system and the relevance of in vitro–in vivo correlation, as well as key challenges in formulation development, are briefed. Solid-state and particle engineering approaches, including micronization, supercritical fluid technology, electrospinning, and cryogenic techniques, are discussed. Extensive critical examination of amorphous solid dispersions and their preparation methods, as well as crystallization inhibition strategies, is covered. Cocrystallization is highlighted as a promising approach, with emphasis on design principles and preparation methods. Various solubilization techniques, such as pH modification, cosolvency, hydrotropy, micellar solubilization, and cyclodextrin-based complexation, including advanced hybrid systems, are also explored. Emerging solvent platforms, such as deep eutectic systems and lipid-based and nanotechnology-driven approaches, are reviewed for their role in improving solubility and drug delivery. Additionally, enabling technologies such as liquisolid systems and hydrophilic polymers are addressed. Despite notable progress, limitations such as scalability, reproducibility, regulatory constraints, and long-term safety persist. Overall, this review provides integrated insights into formulation design approaches to enhance the solubility and therapeutic efficacy of poorly soluble drugs. Full article