Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner.

The aim of this study was to rapidly develop a sufficiently robust andrographolide nanosuspension (AG-NS) system using hummer acoustic resonance (HAR) technology. The system can effectively improve the dissolution properties of AG, while having high stability and scale-up adaptability. The formulation of AG-NS was optimized in a high-throughput manner using HAR technology and the preparation process was optimized stepwise. Optimal AG-NS with Z-Ave = 223.99 ± 3.16 nm, PDI=0.095 ± 0.007 and zeta potential = -33.20 ± 0.58 mV was successfully prepared with Polyvinylpyrrolidone K30 and Sodium dodecyl sulfate. The optimal prescription was successfully scaled up 100 and 150 times using HAR technology, which was the initial exploration of its commercial scale production. AG-NS was solidified using freeze drying and fluid bed technology, respectively. The optimal AG-NS and its solidified products were exhaustively characterized using various analytical techniques. The high energy input of HAR technology and drying process converted part of the drug into the amorphous state. The in-vitro drug dissolution studies demonstrated relatively higher drug dissolution for AG-NS and its solidified products compared to controls at both the dissolution media (pH 1.2 buffer and pH 6.8 buffer). AG-NS and its solidified products successfully maintained their physical stability in short-term stability and accelerated stability experiments, respectively.

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology.

Drug solubility and dissolution remain a significant challenge in pharmaceutical formulations. This study aimed to formulate and evaluate repanglinide (RPG) nanosuspension-based buccal fast-dissolving films (BDFs) for dissolution enhancement. RPG nanosuspension was prepared by the antisolvent-precipitation method using multiple hydrophilic polymers, including soluplus®, polyvinyl alcohol, polyvinyl pyrrolidine, poloxamers, and hydroxyl propyl methyl cellulose. The nanosuspension was then directly loaded into BDFs using the solvent casting technique. Twelve formulas were prepared with a particle size range of 81.6-1389 nm and PDI 0.002-1 for the different polymers. Nanosuspensions prepared with soluplus showed a favored mean particle size of 82.6 ± 3.2 nm. The particles were spherical and non-aggregating, as demonstrated by SEM imaging. FTIR showed no interaction between soluplus and RPG. Faster dissolution occurred for the nanosuspension in comparison with pure RPG (complete release vs 60% within 30 min). The nanosuspension was successfully incorporated into BDFs. The optimum film formula showed 28 s disintegration time, and 97.3% RPG released within 10 min. Ex-vivo permeation profiles revealed improved RPG nanosuspension permeation with the cumulative amount of RPG permeated is103.4% ± 10.1 and a flux of 0.00275 mg/cm2/min compared to 39.3% ± 9.57 and a flux of 0.001058 mg/cm2/min for pure RPG. RPG was successfully formulated into nanosuspension that boosted drug dissolution and permeation. The selection of the ultimate NP formula was driven by optimal particle size, distribution, and drug content. Soluplus NPs were shown to be the successful formulations, which were further incorporated into a buccal film. The film was evaluated for ex-vivo permeation, confirming successful RPG formulation with improved performance compared to pure drugs.

Many brain diseases pose serious challenges to human life. Alzheimer\'s Disease (AD) and Parkinson\'s Disease (PD) are common neurodegenerative diseases that seriously threaten human health. Glioma is a common malignant tumor. However, drugs cannot cross physiological and pathological barriers and most therapeutic drugs cannot enter the brain because of the presence of the Blood-brain Barrier (BBB) and Blood- -brain Tumor Barrier (BBTB). How to enable drugs to penetrate the BBB to enter the brain, reduce systemic toxicity, and penetrate BBTB to exert therapeutic effects has become a challenge. Nanosuspension can successfully formulate drugs that are difficult to dissolve in water and oil by using surfactants as stabilizers, which is suitable for the brain target delivery of class II and IV drugs in the Biopharmaceutical Classification System (BCS). In nanosuspension drug delivery systems, the physical properties of nanostructures have a great impact on the accumulation of drugs at the target site, such as the brain. Optimizing the physical parameters of the nanosuspension can improve the efficiency of brain drug delivery and disease treatment. Therefore, the key challenges, influencing factors, and future perspectives of nanosuspension in enhancing brain drug delivery are summarized and reviewed here. This article aims to provide a better understanding of nanosuspension formulation technology used for brain delivery and strategies used to overcome various physiological barriers.

The objective of the present study was to optimize the microwave-assisted synthesis of the acrylamide graft copolymer of Acacia nilotica gum (AM-co-ANG). Furthermore, graft copolymer was used for the formulation of a nanoparticulate system using a novel top to bottom solvent antisolvent technique for the delivery of melatonin. Grafting of ANG was optimized by using 32 factorial design, where concentrations of polymer and monomer (acrylamide) were used as independent variables and swelling index in acidic (0.1 N HCl) and basic (1 N NaOH) pH. Grafted polymers were further used to develop and optimize nanoparticulate system using concentration of the graft copolymer and concentration of drug as independent variables. The size of the nanoformulation and entrapment efficiency were selected as dependent variables. Difference in infrared spectrum and absorbance maxima in the ultraviolet region confirm that grafting has taken place. Porous structure and a higher contact angle confirmed hydrophobic nature of AM-co-ANG as compared with the native polymer. Acrylamide graft copolymers show more swelling in 1 N NaOH as compared with 0.1 N HCl. In vitro toxicity studies in hepatic (HepG2 cell line), brain (SHSY5Y cell line), and skin (HaCaT cell line) cells easily predict that synthesized polymer have no cytotoxicity. The entrapment efficiency ranged from 55.24 ± 1.35% to 73.21 ± 1.83%. A nonlinear correlation was observed between independent and dependent variables, as confirmed by multivariate analysis of variance, surface regression, and the correlation report. The prepared formulations were able to release drug up to 12 h. The regression coefficient easily predicted that most of the formulations followed Baker-Lonsdale drug release kinetics.

BACKGROUND: Nanosuspensions have emerged as a promising avenue in pharmaceutical innovation, particularly for enhancing the bioavailability of poorly soluble medications. This article explores the transformative potential of nanosuspensions, emphasizing the critical role of particle size reduction through nanonization techniques. With conventional approaches often falling short in addressing the bioavailability challenges of hydrophobic drugs, nanosuspensions offer multifaceted applications and distinctive advantages in drug delivery.
METHODS: The study delves into various nanosuspension preparation techniques, including high-pressure homogenization, media milling, emulsification-solvent evaporation, precipitation, and supercritical fluid processes. Each method brings unique advantages and limitations, contributing to the expanding repertoire of nanosuspension formulation methods. The article emphasizes the necessity for meticulous planning, evaluation, and ongoing research across different drugs to optimize their use effectively.
RESULTS: Nanosuspensions exhibit versatility in administration routes, spanning parenteral, peroral, ocular, and pulmonary pathways, making them applicable across diverse dosage forms. Current efforts are directed towards furthering their application in site-specific medication administration, indicating their potential in tailored therapeutic strategies. Nanosuspensions offer a promising solution for enhancing drug solubility and bioavailability, addressing the persistent challenge of poor solubility in pharmaceutical compounds.
CONCLUSIONS: The significance of careful formulation and stabilization using polymers and surfactants is underscored, ensuring the efficacy and safety of nanosuspensions. By discussing the benefits, drawbacks, and nuances of each preparation technique, the article aims to simplify future research endeavors in the field of nanosuspensions. Additionally, a comprehensive overview of nanosuspensions, including their preparation methods, benefits, characterization, patents, marketed products, and intended uses, sheds light on this evolving domain in pharmaceutical sciences.
CONCLUSIONS: Nanosuspensions represent a promising approach for overcoming bioavailability challenges associated with poorly soluble medications. The article highlights their transformative potential in pharmaceutical innovation, emphasizing the importance of continued research and optimization to harness their benefits effectively. Nanosuspensions offer a viable solution for enhancing drug solubility and bioavailability, with implications for improving therapeutic outcomes in various medical conditions.

Parkinson\'s disease (PD), affecting about ten million people globally, presents a significant health challenge. Rotigotine (RTG), a dopamine agonist, is currently administered as a transdermal patch (Neupro®) for PD treatment, but the daily application can be burdensome and cause skin irritation. This study introduces a combinatorial approach of dissolving microarray patch (MAP) and nanosuspension (NS) for the transdermal delivery of RTG, offering an alternative to Neupro®. The RTG-NS was formulated using a miniaturized media milling method, resulting in a nano-formulation with a mean particle size of 274.09 ± 7.43 nm, a PDI of 0.17 ± 0.04 and a zeta potential of -15.24 ± 2.86 mV. The in vitro dissolution study revealed an enhanced dissolution rate of the RTG-NS in comparison to the coarse RTG powder, under sink condition. The RTG-NS MAPs, containing a drug layer and a \'drug-free\' supporting baseplate, have a drug content of 3.06 ± 0.15 mg/0.5 cm2 and demonstrated greater amount of drug delivered per unit area (∼0.52 mg/0.5 cm2) than Neupro® (∼0.20 mg/1 cm2) in an ex vivo Franz cell study using full-thickness neonatal porcine skin. The in vivo pharmacokinetic studies demonstrated that RTG-NS MAPs, though smaller (2 cm2 for dissolving MAPs and 6 cm2 for Neupro®), delivered drug levels comparable to Neupro®, indicating higher efficiency per unit area. This could potentially avoid unnecessarily high plasma levels after the next dose at 24 h, highlighting the benefits of dissolving MAPs over conventional transdermal patches in PD treatment.

BACKGROUND: Desloratadine, a second-generation antihistaminic drug, is poorly watersoluble and requires amelioration of the dissolution rate to improve its pharmacokinetics properties.
METHODS: This study investigated the impact of polymer, surfactant types, and concentration on the particle size, zeta potential, and dissolution efficiency of nanosuspensions formulated through the solvent antisolvent precipitation method. To optimize the delivery of Desloratadine nanosuspension, we used Minitab software and a 4-factor, 2-level full factorial design. Physicochemical properties and drug release studies were conducted to evaluate the suggested nanosuspension formulations. The optimization goals included minimizing particle size and zeta potential while maximizing dissolution efficiencies.
RESULTS: The selected optimal nanosuspension demonstrated favourable values, including a particle size of 478.63 ± 15.67 nm, a zeta potential of -36.24 ± 3.21 mV, and dissolution efficiencies in double distilled water and buffer of 90.29 ± 3.75 % and 93.70 ± 3.67 %, respectively. The optimized formulation was subjected to additional analysis using X-ray powder diffraction (XPRD), scanning and transmission electron microscopy (SEM and TEM), and Fourier-transform infrared spectroscopy (FTIR).
CONCLUSIONS: The optimized nanosuspension formulation also underwent further studies under optimal lyophilization conditions, revealing the effectiveness of mannitol as a cryoprotectant at a concentration of 8%.

Vaginal drug delivery is often preferred over systemic delivery to reduce side effects and increase efficacy in treating diseases and conditions of the female reproductive tract (FRT). Current vaginal products have drawbacks, including spontaneous ejection of drug-eluting rings and unpleasant discharge from vaginal creams. Here, we describe the development and characterization of a hypotonic, gel-forming, Pluronic-based delivery system for vaginal drug administration. The rheological properties were characterized with and without common hydrogel polymers to demonstrate the versatility. Both qualitative and quantitative approaches were used to determine the Pluronic F127 concentration below the critical gel concentration (CGC) that was sufficient to achieve gelation when formulated to be hypotonic to the mouse vagina. The hypotonic, gel-forming formulation was found to form a thin, uniform gel layer along the vaginal epithelium in mice, in contrast to the rapidly forming conventional gelling formulation containing polymer above the CGC. When the hypotonic, gel-forming vehicle was formulated in combination with a progesterone nanosuspension (ProGel), equivalent efficacy was observed in the prevention of chemically-induced preterm birth (PTB) compared to commercial Crinone® vaginal cream. Further, ProGel showed marked benefits in reducing unpleasant discharge, reducing product-related toxicity, and improving compatibility with vaginal bacteria in vitro. A hypotonic, gel-forming delivery system may be a viable option for therapeutic delivery to the FRT.