Pharmaceutics

Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.

Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil®, Ambisome®, DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes.

The focus of this review is to provide an overview of the chitosan based nanoparticles for various non-parenteral applications and also to put a spotlight on current research including sustained release and mucoadhesive chitosan dosage forms. Chitosan is a biodegradable, biocompatible polymer regarded as safe for human dietary use and approved for wound dressing applications. Chitosan has been used as a carrier in polymeric nanoparticles for drug delivery through various routes of administration. Chitosan has chemical functional groups that can be modified to achieve specific goals, making it a polymer with a tremendous range of potential applications. Nanoparticles (NP) prepared with chitosan and chitosan derivatives typically possess a positive surface charge and mucoadhesive properties such that can adhere to mucus membranes and release the drug payload in a sustained release manner. Chitosan-based NP have various applications in non-parenteral drug delivery for the treatment of cancer, gastrointestinal diseases, pulmonary diseases, drug delivery to the brain and ocular infections which will be exemplified in this review. Chitosan shows low toxicity both in vitro and some in vivo models. This review explores recent research on chitosan based NP for non-parenteral drug delivery, chitosan properties, modification, toxicity, pharmacokinetics and preclinical studies.

Skin wound healing shows an extraordinary cellular function mechanism, unique in nature and involving the interaction of several cells, growth factors and cytokines. Physiological wound healing restores tissue integrity, but in many cases the process is limited to wound repair. Ongoing studies aim to obtain more effective wound therapies with the intention of reducing inpatient costs, providing long-term relief and effective scar healing. The main goal of this comprehensive review is to focus on the progress in wound medication and how it has evolved over the years. The main complications related to the healing process and the clinical management of chronic wounds are described in the review. Moreover, advanced treatment strategies for skin regeneration and experimental techniques for cellular engineering and skin tissue engineering are addressed. Emerging skin regeneration techniques involving scaffolds activated with growth factors, bioactive molecules and genetically modified cells are exploited to overcome wound healing technology limitations and to implement personalized therapy design.

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that has gained great attention in the past years as a new therapy for cancer treatment. PDT uses photosensitizers that, after being excited by light at a specific wavelength, react with the molecular oxygen to create reactive oxygen species in the target tissue, resulting in cell death. Compared to conventional therapeutic modalities, PDT presents greater selectivity against tumor cells, due to the use of photosensitizers that are preferably localized in tumor lesions, and the precise light irradiation of these lesions. This paper presents a review of the principles, mechanisms, photosensitizers, and current applications of PDT. Moreover, the future path on the research of new photosensitizers with enhanced tumor selectivity, featuring the improvement of PDT effectiveness, has also been addressed. Finally, new applications of PDT have been covered.

The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.

Artificial intelligence (AI) has emerged as a powerful tool that harnesses anthropomorphic knowledge and provides expedited solutions to complex challenges. Remarkable advancements in AI technology and machine learning present a transformative opportunity in the drug discovery, formulation, and testing of pharmaceutical dosage forms. By utilizing AI algorithms that analyze extensive biological data, including genomics and proteomics, researchers can identify disease-associated targets and predict their interactions with potential drug candidates. This enables a more efficient and targeted approach to drug discovery, thereby increasing the likelihood of successful drug approvals. Furthermore, AI can contribute to reducing development costs by optimizing research and development processes. Machine learning algorithms assist in experimental design and can predict the pharmacokinetics and toxicity of drug candidates. This capability enables the prioritization and optimization of lead compounds, reducing the need for extensive and costly animal testing. Personalized medicine approaches can be facilitated through AI algorithms that analyze real-world patient data, leading to more effective treatment outcomes and improved patient adherence. This comprehensive review explores the wide-ranging applications of AI in drug discovery, drug delivery dosage form designs, process optimization, testing, and pharmacokinetics/pharmacodynamics (PK/PD) studies. This review provides an overview of various AI-based approaches utilized in pharmaceutical technology, highlighting their benefits and drawbacks. Nevertheless, the continued investment in and exploration of AI in the pharmaceutical industry offer exciting prospects for enhancing drug development processes and patient care.

Recent advancements in drug delivery technologies utilizing a variety of carriers have resulted in a path-breaking revolution in the approach towards diagnosis and therapy alike in the current times. Need for materials with high thermal, chemical and mechanical properties have led to the development of mesoporous silica nanoparticles (MSNs). These ordered porous materials have garnered immense attention as drug carriers owing to their distinctive features over the others. They can be synthesized using a relatively simple process, thus making it cost effective. Moreover, by controlling the parameters during the synthesis; the morphology, pore size and volume and particle size can be transformed accordingly. Over the last few years, a rapid increase in research on MSNs as drug carriers for the treatment of various diseases has been observed indicating its potential benefits in drug delivery. Their widespread application for the loading of small molecules as well as macromolecules such as proteins, siRNA and so forth, has made it a versatile carrier. In the recent times, researchers have sorted to several modifications in the framework of MSNs to explore its potential in drug resistant chemotherapy, antimicrobial therapy. In this review, we have discussed the synthesis of these multitalented nanoparticles and the factors influencing the size and morphology of this wonder carrier. The second part of this review emphasizes on the applications and the advances made in the MSNs to broaden the spectrum of its use especially in the field of biomedicine. We have also touched upon the lacunae in the thorough understanding of its interaction with a biological system which poses a major hurdle in the passage of this carrier to the clinical level. In the final part of this review, we have discussed some of the major patents filed in the field of MSNs for therapeutic purpose.

Routes of drug administration and the corresponding physicochemical characteristics of a given route play significant roles in therapeutic efficacy and short term/long term biological effects. Each delivery method has favorable aspects and limitations, each requiring a specific delivery vehicles design. Among various routes, oral delivery has been recognized as the most attractive method, mainly due to its potential for solid formulations with long shelf life, sustained delivery, ease of administration and intensified immune response. At the same time, a few challenges exist in oral delivery, which have been the main research focus in the field in the past few years. The present work concisely reviews different administration routes as well as the advantages and disadvantages of each method, highlighting why oral delivery is currently the most promising approach. Subsequently, the present work discusses the main obstacles for oral systems and explains the most recent solutions proposed to deal with each issue.

Natural polyphenols are valuable compounds possessing scavenging properties towards radical oxygen species, and complexing properties towards proteins. These abilities make polyphenols interesting for the treatment of various diseases like inflammation or cancer, but also for anti-ageing purposes in cosmetic formulations, or for nutraceutical applications. Unfortunately, these properties are also responsible for a lack in long-term stability, making these natural compounds very sensitive to light and heat. Moreover, polyphenols often present a poor biodisponibility mainly due to low water solubility. Lastly, many of these molecules possess a very astringent and bitter taste, which limits their use in food or in oral medications. To circumvent these drawbacks, delivery systems have been developed, and among them, encapsulation would appear to be a promising approach. Many encapsulation methods are described in the literature, among which some have been successfully applied to plant polyphenols. In this review, after a general presentation of the large chemical family of plant polyphenols and of their main chemical and biological properties, encapsulation processes applied to polyphenols are classified into physical, physico-chemical, chemical methods, and other connected stabilization methods. After a brief description of each encapsulation process, their applications to polyphenol encapsulation for pharmaceutical, food or cosmetological purposes are presented.

Background/Objectives: Better ocular delivery does not establish that a plant-derived bioactive functions as a material or adds a material-specific therapeutic benefit. Methods: A structured critical synthesis of seven databases mapped 327 eligible full-text records using parallel role, material-participation, bioactivity, comparison and interaction codes. Independent full-text reassessment and human adjudication were followed by sensitivity analysis in 313 report-family units. Results: External cargo accounted for 237 records (72.5%); delivery modulators, active/co-functional interfaces and structural/self-assembling participants accounted for 27 (8.3%), 29 (8.9%) and 34 (10.4%), respectively. Practical-formulation comparisons occurred in 234 records, whereas 35 included attribution-oriented comparisons. Three records reported model-based interaction analyses, with limitations that prevented unrestricted claims of ocular synergy. Family-sensitive analysis preserved the principal patterns. The synthesis distinguished released-drug exposure from retained-interface function and aligned dry-eye, infection and corneal-repair claims with their measured models, endpoints and controls. Conclusions: This corpus more often evaluates delivery performance than an isolated material-specific contribution. Added complexity should address a defined treatment limitation, demonstrate the claimed increment against a credible comparator and remain compatible with product use. The framework guides claim-matched experiments rather than ranking platforms or predicting clinical success.

Metallo-β-lactamase (MBL)-producing Enterobacterales represent a major antimicrobial-resistance threat because MBLs hydrolyse most clinically used β-lactams and are not inhibited by currently approved serine β-lactamase inhibitors. Aztreonam–avibactam (ATM-AVI; Emblaveo®) addresses this therapeutic gap by combining aztreonam, a monobactam that is stable to MBL-mediated hydrolysis, with avibactam, which inhibits many co-produced class A, class C, and selected class D serine β-lactamases. This narrative review synthesizes evidence on ATM-AVI pharmacology, microbiological activity, pharmacokinetics/pharmacodynamics, clinical efficacy, safety, resistance, and regulatory positioning. Large surveillance datasets show high in vitro activity against most MBL-producing Enterobacterales, including many co-producing β-lactamases from multiple Ambler classes. Population pharmacokinetic modelling supports a renal-function-adjusted fixed 3:1 dosing ratio and more reliable joint target attainment than separately administered ceftazidime–avibactam plus aztreonam. In the phase 3 REVISIT trial, clinical cure with ATM-AVI was comparable to meropenem in the overall population; however, few participants had confirmed MBL-positive infections. Direct clinical evidence therefore remains limited, supported by convergent microbiological, pharmacokinetic, and observational data. Regulatory indications differ substantially between the European Union and the United States. ATM-AVI is an important advance for selected MBL-producing and multi-class-co-producing Gram-negative infections, but its long-term value will depend on targeted use, reliable susceptibility testing, continued surveillance, and further trials in the intended target population.

Background/Objectives: Chlorogenic acid (CGA), a potent antioxidant polyphenol, scavenges reactive oxygen species (ROS) and ameliorates oxidative stress-induced dermal extracellular matrix deterioration. However, its high hydrophilicity causes poor stratum corneum partitioning, insufficient dermal retention and low bioavailability. This study aimed to develop a surfactant-optimized, palmitoyl pentapeptide-4 (PP-4)-functionalized ethosomal system to enhance dermal retention and skin-protective efficacy of CGA. Methods: Binary nonionic surfactants were employed to optimize ethosome performance, followed by noncovalent PP-4 bilayer functionalization. Vesicle physicochemical properties and molecular interactions were characterized. Ex vivo skin permeation, cellular uptake, cytoprotection, intracellular ROS scavenging, and extracellular matrix-related gene expression were evaluated. Results: Surfactant-optimized ethosomes (CGA-ES, ~146 nm, −2.0 mV) exhibited higher encapsulation efficiency (92 ± 2%) and superior transdermal permeation versus surfactant-free vesicles. Subsequent PP-4 insertion reduced particle size to ~137 nm, reversed charge to +6.7 mV, and retained favorable encapsulation (83 ± 2%), forming mixed unilamellar–multilamellar structures. FTIR revealed the formation of hydrogen-bonded networks at phospholipid interfaces, underpinning superior colloidal uniformity and stability. The modified vesicles achieved enhanced total skin deposition and 1.2-fold higher dermis targeting efficiency compared with CGA-ES, along with improved cellular internalization, superior cytoprotection, and 2.4-fold stronger ROS scavenging under oxidative stress. The system effectively suppressed oxidative stress-induced upregulation of matrix metalloproteinase-1 and -3 (MMP-1/MMP-3) and restored type I collagen expression. Blank PP-4-modified ethosomes verified intrinsic peptide bioactivity, demonstrating complementary protection between CGA and PP-4. Conclusions: Binary-surfactant optimization enhances ethosomal colloidal performance and skin permeation. PP-4-mediated bilayer remodeling further promotes intradermal deposition. This dual-functional nanoplatform achieves combined skin-protective effects of CGA and surface-bound PP-4, providing a formulation basis for further in vivo evaluation and a potential strategy for topical delivery of hydrophilic polyphenols.

Background/Objectives: Ya Pra Sa Kra Tung Pew Pai Nok is a traditional Thai medicinal formulation historically used for fever and inflammatory skin symptoms. This study characterized a lactose-containing vacuum-dried extract, evaluated its in vitro anti-inflammatory activity, and incorporated it into a topical spray formulation. Methods: The formulation comprised Brachypterum scandens (Roxb.) Miq., Tiliacora triandra (Colebr.) Diels., and Tamarindus indica L. in equal proportions. Genistein-7-O-[α-rhamnopyranosyl-(1→6)]-β-glucopyranoside (GTG) was selected as a chemical marker and quantified using a validated HPLC-DAD method. Results: The method showed good selectivity and linearity over 4–20 µg/mL, with intra- and inter-day precision RSD values of 4.04% and 3.43%, recoveries of 97.41–103.65%, and LOD and LOQ values of 0.15 and 0.49 µg/mL, respectively. CCK-8 analysis showed that both vacuum-dried extract preparations, with and without lactose, maintained RAW264.7 cell viability above 80% across all tested concentrations. At non-cytotoxic concentrations, the lactose-containing extract significantly reduced nitric oxide and prostaglandin E2 production in LPS-stimulated RAW264.7 macrophages, demonstrating in vitro anti-inflammatory activity of the extract. A topical spray containing 5% w/w dried extract was selected and exhibited an initial pH of 4.43. After 6 months of storage at 4, 30, and 40 °C, the remaining GTG contents were approximately 99.1%, 92.9%, and 87.6%, respectively, indicating temperature-dependent degradation. No microbial contamination was detected during storage. Human closed-patch testing in 30 healthy volunteers yielded an MCII of 0.05, indicating negligible irritation under the tested conditions. Conclusions: These findings support further development of Ya Pra Sa Kra Tung Pew Pai Nok as a standardized topical herbal formulation.

Objectives: Mycophenolate mofetil (MMF) is an immunosuppressant with complex pharmacokinetics (PK) used in pediatric transplant recipients. Therapeutic drug monitoring (TDM) of its active metabolite, mycophenolic acid (MPA), is recommended. Assessment of MPA exposure based on the area under the concentration–time curve (AUC) is challenging due to limited sampling strategies. This study aimed to characterize MPA PK across a broad pediatric age range and to examine MPA AUC0–12h estimated by MwPharm++, a clinical pharmacokinetic software tool used for model-informed therapeutic drug monitoring and individualized dosing. Methods: This retrospective single-center observational study collected steady state MPA levels at trough, 30 and 120 min. A population pharmacokinetic (popPK) approach (NONMEM) was used to characterize MPA PK. AUC0–12h was first estimated by MwPharm++ and then compared with AUC0–12h based on NONMEM post hoc estimates. Results: A total of 1368 MPA concentrations from 456 TDM occasions in 169 patients (infants: 0–≤ 2 years, n = 3; young children: > 2–≤ 5 years, n = 47; older children: > 5–≤12 years, n = 193; adolescents: > 12–≤ 17 years, n = 117; young adults: > 17–24 years, n = 96) were described by a two-compartment model with first-order absorption. After standard allometric scaling based on body weight, albumin and estimated glomerular filtration rate (but not age) significantly influenced apparent clearance (CL/F). Median CL/F was about 45.4% lower in young children compared with adolescents, while median AUC0–12h was similar across age groups from 2 to 24 years, taking into account that doses differed between patients, were initially based on BSA, and may have been adjusted according to previous TDM results or the clinical situation of the patient. AUC0–12h estimates were on average 8.59 mg·h/L higher with NONMEM than with MwPharm++. Conclusions: These findings suggest that allometric scaling captures body weight-related MPA PK changes across age groups in real-world data and support the use of simple pediatric popPK models for exposure assessment.

The construction of highly biomimetic in vitro tissue barrier models is essential for new drug development, as it enables accurate evaluation of the permeability efficiency, safety, and pharmacokinetic properties of drug candidates. Animal models have long been regarded as the standard criterion for assessing drug efficacy; however, they pose increasingly severe ethical concerns. Moreover, substantial interspecies differences in transmembrane transporter expression and metabolic pathways contribute to the low rate of successful clinical translation. Traditional 2D cell culture models lack a 3D matrix microenvironment and physiological mechanical signals similar to those in vivo. Consequently, epithelial or endothelial cells are prone to phenotypic alteration. They struggle to assemble structurally intact and functionally mature tight barriers. As a result, drug permeability and toxicity results often deviate markedly from in vivo physiological conditions. In contrast, electrospinning technology offers a promising approach for constructing biomimetic barriers. Electrospun nanofiber membranes closely resemble the fibrous network structure of the natural extracellular matrix and provide several distinct advantages, including precisely controllable pore sizes, large specific surface areas, and readily modifiable functional surfaces. Furthermore, the arrangement and physicochemical properties of the fibers can be precisely tailored to provide cells with inductive cues that mimic the in vivo physiological microenvironment. This review summarizes the design strategies of electrospun nanofiber membranes for the construction of key tissue barriers, including the lung, blood–brain barrier, intestine, kidney, and skin. In addition, it discusses recent advances in the application of these membranes for drug screening. Finally, universal design principles for cross-barrier construction are proposed. Overall, this review aims to support the development of more efficient and reliable in vitro drug-screening platforms.

Cutaneous melanoma is an aggressive malignancy for which conventional treatments are often limited by acquired resistance, systemic toxicity, and insufficient dermal penetration. To overcome these therapeutic limitations, green nanomedicine has emerged as a promising alternative, employing biological systems such as plant extracts to sustainably synthesize bioactive metal and metal oxide nanoparticles, including Silver nanoparticles (AgNPs), Gold nanoparticles (AuNPs), Zinc oxide nanoparticles (ZnONPs), Cerium oxide nanoparticles (CeO2NPs), and Copper nanoparticles (CuNPs). The phytochemical capping of these biogenic nanoplatforms enhances biocompatibility and enables multiple antineoplastic mechanisms, including targeted oxidative stress, metabolic disruption, and photothermal ablation. Translating these cellular-level effects into clinical efficacy requires overcoming significant physiological barriers, particularly the stratum corneum. As a result, research is increasingly focused on incorporating these bioactive metallic cores into advanced, stimuli-responsive delivery vehicles. Examples include polymeric scaffolds for enhanced payload retention and solid lipid nanoparticles for improved transdermal penetration. Although hierarchical bio-nanocomposites offer a promising approach to overcoming tumor resistance, successful clinical translation will require standardized large-scale synthesis and comprehensive in vivo evaluation to bridge the gap between preclinical studies and targeted precision therapy.

Background/Objectives: Voriconazole dosing in children is complicated by developmental and nonlinear pharmacokinetics, cytochrome P450 2C19 (CYP2C19) variation, variable oral bioavailability, inflammation, organ dysfunction, and drug interactions. We evaluated the characteristics, reporting completeness, and clinical applicability of pediatric and pediatric-inclusive voriconazole population pharmacokinetic (PopPK) models. Methods: PubMed, EMBASE, the Cochrane Library, Web of Science, and supplementary sources were searched from inception to 12 March 2026. Eligible studies developed a voriconazole PopPK model in patients aged 0–18 years or in a broader population with extractable or interpretable pediatric information. Reporting completeness was assessed using the 32-item Clinical Pharmacokinetic (ClinPK) checklist. Results: Eighteen studies published from 2004 to 2025 were included. Model-development cohorts contained 21–173 participants, and 15 studies reported 108–3336 concentrations. The median ClinPK reporting-completeness score was 82.6% (range, 74.2–90.0%). The included studies comprised one infant-specific, nine pediatric-only, six pediatric–young adult, and two mixed pediatric–adult models. Fifteen studies used parametric nonlinear mixed-effects methods and three used nonparametric methods; 15 selected two-compartment models and three selected one-compartment models. Body size was incorporated in 17 models and CYP2C19 phenotype was the most frequent retained covariate (10 models). Elimination structures, exposure targets, and dosing proposals were heterogeneous, and only one model underwent independent external validation. Conclusions: A population-matched model may support initial dosing, but early therapeutic drug monitoring and iterative Bayesian updating remain necessary. Current evidence does not support a universal pediatric model. Independent external validation and prospective implementation studies are required before routine clinical use.

Background/Objectives: Enhancing the bioavailability of active pharmaceutical ingredients (APIs) with low solubility –classified under the Biopharmaceutics Classification System (BCS) as class II and class IV –is a major challenge in pharmaceuticals development. Stabilizing APIs in amorphous form significantly increases their apparent solubility but results in complex dissolution profiles characterized by the “spring effect,” a temporal high concentration peak during dissolution. These dissolution profiles are very challenging to be quantitatively evaluated due to the lack of appropriate mathematical models compatible with a Quality-by-Design (QbD) approach. Methods: A kinetic model was developed by considering the mechanistic aspects of the process. The model postulates three stages of the dissolution: hydration and dissolution of the amorphous API within the carrier, diffusion of the dissolved API into the medium, and equilibrium-driven interactions between the dissolved API and its thermodynamically stable crystalline form. Results: This model provides insights into release acceleration, slow final dissolution, and the spring effect, and elucidates scenarios where complete dissolution cannot be achieved due to the absence of sink conditions. While microscopic molecular phenomena –such as liquid–liquid phase separation (LLPS) and polymeric crystallization inhibition –are extensively documented in the academic literature, their individual isolated parameters are inherently unobservable under routine pharmaceutical industrial and GMP testing conditions. To bridge this gap, the developed model establishes a robust, apparent kinetic framework that fits macroscopically observable dissolution profiles. Conclusions: This method provides a robust framework for interpreting drug release profiles and optimizing formulation development using a QbD approach, specifically supporting regulatory requirements and batch-to-batch consistency evaluations across similar polymer-matrix systems. The model enables the determination of kinetic parameters such as tmax and cmax, and explains their dependence on the actual pharmaceutical formulation.

Objectives: Crosslinking enhances solid dispersion (SD) stability but often restricts drug release, and this trade-off remains unresolved. In this study, crosslinked polyvinyl alcohol–suberic acid ester (CPSE) carriers with different crosslinking degrees were prepared to investigate the effects of crosslinking on the properties, dissolution and stability of andrographolide (AG)-SDs, aiming to identify crosslinking conditions that ensure both effective dissolution and improved stability. Methods: CPSE was prepared at 110 °C or 130 °C for 4, 8 or 12 h with uncrosslinked polyvinyl alcohol (PVA) as the control. AG-CPSE-SDs and AG-PVA-SD were compared in terms of AG relative crystallinity (RC), surface free energy, hygroscopicity, dissolution and stability. Stability was evaluated after 30-day storage at 40 ± 2 °C/75 ± 5% RH. Results: Compared with AG-PVA-SD, AG-CPSE-SDs showed higher RC but lower surface free energy and hygroscopicity. SDs with lower crosslinking degrees had dissolution profiles similar to AG-PVA-SD, whereas those with higher crosslinking degrees showed significantly reduced dissolution rates. After storage, the dense network in highly crosslinked SDs hindered water entry and diffusion and restricted AG migration and recrystallization, thereby conferring better hygroscopic stability, interaction stability, recrystallization stability and dissolution stability. Notably, the SD using CPSE crosslinked at 130 °C for 4 h as the carrier balanced effective dissolution and enhanced stability. Conclusions: By tuning the crosslinking degree, SD stability can be improved without sacrificing drug dissolution. Moderate rather than maximal crosslinking achieves the optimal balance, providing a practical strategy for designing crosslinked carriers for SDs.