Soluble Drugs Research Articles

The stability and bioavailability of xanthohumol loaded by sophorolipid‐based microemulsions in functional beer

AbstractXanthohumol (XN) exhibits numerous physiological activities, yet its instability and proneness to degradation limit its use. Microemulsions, noted for effective drug solubilization and delivery, have been employed to enhance XN's stability and bioavailability in functional beers, using sophorolipids (SL) and Tween 80 (T80) as surfactants. Our development of T80‐ME and T80‐SL‐ME stabilized XN, as confirmed by reduced degradation in high‐performance liquid chromatography analysis and kinetic modeling. We established in vitro release and in vivo pharmacokinetic models, demonstrating improved outcomes with XN‐enriched beer. Our study also assessed total phenols, flavonoids, and antiaging effects in the beer. The formulation minimally affected beer's physicochemical properties, including pH, turbidity, and bitterness. Notably, XN's bioavailability in beer improved 1.79‐ to 7.33‐fold, underscoring microemulsion technology's role in enhancing XN absorption and metabolism. We analyzed the sensory flavor impact of SL biosurfactants in beer, finding them acceptable to consumers. This study highlights microemulsions' potential in elevating functional beer's nutritive value and applications.

Recent Advances in the Synthesis of Sulfonamides Intermediates

AbstractSulfonamides are one of the most important synthons in drug synthesis, which can increase the water solubility of drugs and regulate their metabolism in vivo. According to statistics, nearly 30% of sulfur-containing drugs on the market contain sulfonamide groups, including omeprazole, hydrochlorothiazide, and other best-selling drugs. Synthesis of sulfonamide is therefore a very important part of new drug development and active pharmaceutical ingredient manufacturing. In this review, we will focus on the recent 5-year advances in the field of synthetic research and structural modification of sulfonamide-containing drugs and their intermediates. The synthesis strategies, including S−N construction, C−N cross-coupling, N−H functionalization, and C−H sulfonamidation, are discussed, hoping to provide new ideas for the researchers to prepare sulfonamides in a green and efficient way.

Quantitative Analysis of Physical Stability Mechanisms of Amorphous Solid Dispersions by Molecular Dynamic Simulation.

Amorphous solid dispersions (ASDs) represent a promising strategy for enhancing the solubility of poorly soluble drugs. However, the mechanisms underlying the physical stability of ASDs remain insufficiently understood. This study aims to investigate these mechanisms and propose quantitative thresholds to predict the maximum stable drug loading using molecular dynamics simulations. Poly(vinylpyrrolidone) (PVP) and poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA64) are selected as polymeric carriers, while naproxen and acetaminophen serve as model drugs, resulting in the formulation of 18 distinct ASDs across four types for comparison with experimental results. Our findings indicate that the molecular mobility of active pharmaceutical ingredients (APIs) is the primary determinant of solid dispersion stability. High polymer concentrations limit drug molecular mobility through spatial structural constraints and ASD viscosity. As drug loading increases, the polymer concentration reaches a critical threshold (C*), beyond which drug-rich regions form, leading to potential aggregation, rearrangement, and recrystallization of drug molecules into more energetically stable forms. Notably, both the interaction energy and diffusion coefficient show sharp fluctuations at the maximum stable drug loading, which can serve as predictive indicators for ASD stability. Additionally, a search strategy is used to identify potential pre-crystalline sites. By integrating kinetic, thermodynamic, and pre-crystalline analyses through molecular dynamics simulations, this study provides a foundation for more accurate predictions of ASD stability, significantly aiding future formulation development.

Formulating abiraterone acetate-HPMCAS-based amorphous solid dispersions: insights into in vitro and biorelevant dissolution assessments and pharmacokinetic evaluations.

Abiraterone acetate (ABTA) is used as a primary treatment for metastatic castration-resistant prostate cancer. Its low aqueous solubility results in inadequate dissolution and poor oral bioavailability (<10%), necessitating the consumption of large doses of ABTA (1000 mg per day) for desired efficacy. The aim of this study is to enhance the solubility, dissolution, and bioavailability of ABTA through amorphous solid dispersions (SDs). ABTA-SD was prepared via a solvent granulation method with different grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS 716 and 912). The theoretical solubility parameter between ABTA and HPMCAS was below 7 MPa1/2, indicating miscibility between the drug and the polymer according to the Hansen solubility parameter. HPMCAS showed a remarkable recrystallization inhibition of up to 180 min compared to the free drug (10 min), maintaining the soluble drug in supersaturation state and exhibiting the "spring and parachute" phenomenon. ABTA-SD exhibited a higher solubility (1.16-fold to 52-fold) in different media than free ABTA. The results of DSC, PXRD, ATR-FTIR, and FE-SEM indicated that the crystallinity of ABTA was completely transformed to an amorphous form and maintained in the SD formulation. In vitro and bio-relevant dissolution behavior of ABTA was studied in various dissolution media, indicating the higher dissolution of ABTA-SD than that of free ABTA. The pharmacokinetic study conducted in Wistar rats revealed that C max and AUC0-t of the optimized ABTA-SD formulation were significantly enhanced by 1.92-fold and 2.87-fold, respectively, compared to those of free ABTA.

Effects of Different Weak Small Organic Acids on Clofazimine Solubility in Aqueous Media

Background/Objectives: Clofazimine (CFZ) is a Biopharmaceutics Classification System (BCS) II drug introduced in the US market in 1986 for the treatment of leprosy. However, CFZ was later withdrawn from the market due to its extremely low aqueous solubility and low absorption. In the literature, the intrinsic solubility of CFZ has been estimated to be &lt;0.01 μg/mL, and solubilities of its different salt forms in simulated gastric and intestinal fluids are &lt;10 µg/mL. These are extremely low solubilities for the dissolution of a drug administered orally at 100–200 mg doses. Methods: In the present investigation, seven weak organic acids (adipic, citric, glutaric, maleic, malic, succinic, and tartaric) were tested by determining the aqueous solubility of CFZ as the function of acid concentration to investigate whether any of the acids would lead to the supersolubilization of CFZ. Results: There were only minimal increases in solubilities when concentrations of acids in water were increased up to 2.4 M. The solubilities, however, increased to 0.32, 1.23, and 10.68 mg/mL, respectively, in 5 M solutions of tartaric, malic, and glutaric acids after equilibration for 24 h at 25 °C. Crystalline solids were formed after the equilibration of CFZ with all acids. Apparently, salts or cocrystals were formed with all acids, except for glutaric acid, as their melting endotherms in DSC scans were in the range of 207.6 to 248.5 °C, which were close to that of CFZ itself (224.8 °C). In contrast, the adduct formed with glutaric acid melted at the low temperature of 77 °C, and no other peak was observed at a higher temperature, indicating that the material converted to an amorphous state. Conclusions: The increase in CFZ solubility to &gt;10 mg/mL in the presence of 5 M glutaric acid could be called supersolubilization when compared to the intrinsic solubility of the basic drug. Such an increase in CFZ solubility and the conversion of the glutarate adduct to an amorphous state are being exploited to develop rapidly dissolving dosage forms.

High-Speed Imaging-Based Particle Attribute Analysis of Spray-Dried Amorphous Solid Dispersions Using a Convolution Neural Network.

Spray drying is a well-established method for preparing amorphous solid dispersion (ASD) formulations to improve the oral bioavailability of poorly soluble drugs. In addition to the characterization of the amorphous phase, particle attributes of spray-dried intermediates (SDIs), including particle size, morphology, and microstructure, need to be carefully studied and controlled for optimizing drug product performance. Although recent developments in microscopy technology have enabled the analysis of morphological attributes for individual SDI particles, a high-throughput method is highly desirable. In this work, a fingerprinting method exploiting high-speed dynamic imaging, laser diffraction (LD), and a convolutional neural network (CNN) was developed to characterize and quantify size and morphological distributions of particles in batches of spray-dried ASDs. This imaging technology enables the generation of hundreds of thousands of single-particle images in a few minutes that are analyzed by both unsupervised and supervised CNN models. The unsupervised data mining analysis demonstrated that a batch of SDI is a mixture of diverse particle subpopulations with varying sizes and morphological attributes. Motivated by this observation, we developed a CNN model that enabled rapid computation of the volumetric composition of the distinct particle subpopulations in a SDI batch, thus generating a morphological fingerprint. We implemented this high-speed imaging-based particle attribute analysis method to investigate SDIs containing hypromellose acetate succinate as a model system. The CNN fingerprint results enabled quantification of the changes in the morphological distribution of SDI batches prepared with variations in the spray drying process parameters, and the results were in line with the LD and electron microscopy data. Our experiments and analysis demonstrate the robustness and throughput of this fingerprinting approach for quantifying particle size and morphological distributions of individual SDI batches, which can help guide spray drying process development and thereby enable the development of a drug product with more robust process and optimized performance.

High-dose modified-release formulation of a poorly soluble drug via twin-screw melt coating and granulation

High-dose modified-release formulation of a poorly soluble drug via twin-screw melt coating and granulation

Nanostructured lipid carriers as a strategy to enhance oral levosulpiride delivery: An in vitro and ex vivo assessment.

Oral absorption is limited for many small-molecule drugs due to their poor aqueous solubility as well as, for some, poor membrane permeation. One such is levosulpiride (LSP), used to treat psychotic and other conditions. The present study aims to explore the effect of nanostructured lipid carriers (NLCs) for the delivery of LSP. The permeation of LSP in vitro and ex vivo as well as effects on the epithelium and mucosa was monitored. In vitro and ex vivo permeation studies exhibited an 8-fold and 1.6-fold increase in the Papp of LSP respectively, as compared to unformulated LSP applied as a suspension. Transepithelial electrical resistance (TEER) measured in real-time by impedance spectroscopy decreased during exposure yet recovered upon removal of the NLCs. Together with the increased passage of the paracellular markers [14C]-mannitol and FD4 applied together with blank NLCs, but not the transcellular marker [3H]-metoprolol, this indicates permeation of LSP via the paracellular pathway. The reversible effect on integrity was associated with altered cell morphology confirmed by occludin and f-actin localization with insignificant effect on metabolic activity. These results suggest that the NLCs and/or components thereof can mediate improved absorption of drugs by increasing the permeability of the intestinal epithelial membrane, further facilitated by increased drug solubilization.

Different mesoporous carbon carriers for the improvement of solubility and physical stability of poorly soluble drugs

Different mesoporous carbon carriers for the improvement of solubility and physical stability of poorly soluble drugs

Lipid-Based Niclosamide Delivery: Comparative Efficacy, Bioavailability, and Potential as a Cancer Drug

Niclosamide, an FDA-approved anti-parasitic drug, has demonstrated significant potential as a repurposed anti-cancer agent due to its ability to interfere with multiple oncogenic pathways. However, its clinical application has been hindered by poor solubility and bioavailability. Lipid-based nanocarrier systems such as liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoemulsions (LNE), along with lipid prodrugs, have successfully been employed by researchers to overcome these limitations and improve niclosamide’s pharmacokinetic profile. Lipids are the core organic compounds which serve as the foundation of these advanced drug delivery methods and in turn play a critical role in enhancing niclosamide’s therapeutic efficacy through improving drug solubility and bioavailability. Lipid-based nanoparticles encapsulate niclosamide, protect it from degradation, facilitate drug delivery and release, and may facilitate targeted delivery in the future. While niclosamide holds significant potential as an anticancer agent due to its multi-pathway inhibitory effects, the challenges associated with its poor bioavailability and rapid clearance underscore the need for innovative delivery methods and chemical modifications to unlock its full therapeutic potential. This review aims to present the latest instances of lipid-based delivery of niclosamide and to compile successful strategies which may be employed when aiming to develop effective anticancer therapies.

Improved topical delivery of curcumin by hydrogels formed by composite carriers integrated with cyclodextrin metal-organic frameworks and cyclodextrin nanosponges

Curcumin (CUR) is highly promising for topical therapeutic applications, but water-insolubility is one of the major challenges plaguing its drugability, while conventional lipid nanocarriers are limited by low drug-carrying capacity, many additives, and complex processes. In the current work, we constructed a composite carrier integrated with cyclodextrin metal-organic framework (γ-CD-MOF) and cyclodextrin nanosponge (β-CDNS), in which the γ-CD-MOF had 13.9 % drug loading and 267.1-fold increase in solubility in water for CUR, and the β-CDNS showed bioadhesion and further increasing drug solubility. The composite carrier (γ-CD-MOF@β-CDNS) significantly improved the in vitro release and transdermal permeation of CUR, and its limited water absorption properties and excellent bioadhesion create an advantage in the local administration of the drug for treating diseases with high exudate, which prevents the affected area from deteriorating the condition by counter-absorption of water from the formulation. Thus, this composite carrier contributes a new option to address the local delivery of insoluble drugs and offers a promising strategy for the clinical application of CUR.

Engineering sodium alginate microparticles with different crystallinities for niclosamide repositioning and solubilization to improve solubility and oral bioavailability in rats

Niclosamide is a commonly used anthelmintic; however, its poor aqueous solubility limits its oral bioavailability. Enhancing its solubility and oral bioavailability is crucial for its repositioning as an anticancer agent. Here, we aimed to develop new sodium alginate–poloxamer microparticles with different crystallinities to increase drug solubility and oral bioavailability. Sodium alginate and poloxamer were used as the polymer and surfactant, respectively, to prepare niclosamide-loaded microparticles via spray drying. The optimized amorphous and crystalline microparticles were prepared with niclosamide/sodium alginate/poloxamer weight ratios of 1:2.5:3 and 1:1.125:0.375, respectively. Their solubilities, dissolution rates, physicochemical properties, and oral bioavailabilities were compared with those of drug powder in rats. Physicochemical characterization of the developed particles revealed changed structure from crystalline to amorphous, with no irregular crystalline characteristics but decreased particle size. Compared to the pure drug powder, crystalline microparticles retained their crystalline nature with no significant changes in particle size. Both microparticles showed significantly higher aqueous solubilities, dissolution rates, and oral bioavailabilities than niclosamide powder in rats. Amorphous microparticles showed higher solubility (approximately 1775-fold) and oral bioavailability (approximately 5.6-fold) than niclosamide powder due to the crystalline-to-amorphous change and decreased particle size. The developed amorphous microparticles can be used to improve niclosamide solubility and oral bioavailability.

Computational intelligence analysis on drug solubility using thermodynamics and interaction mechanism via models comparison and validation

This study investigates the application of various regression models for predicting drug solubility in polymer and API-polymer interactions in complex datasets. Four models—Gaussian Process Regression (GPR), Support Vector Regression (SVR), Bayesian Ridge Regression (BRR), and Kernel Ridge Regression (KRR)—are evaluated. Preprocessing the dataset using the Z-score approach helped to detect outliers, further improving the accuracy and dependability of the analysis. Also, Fireworks Algorithm (FWA) is employed for hyper-parameter tuning in this work. The GPR model demonstrated superior performance, achieving the lowest MSE and MAE for both drug solubility and gamma predictions, with R2 scores of 0.9980 and 0.9950 for training and test data, respectively. The results of this study show the robustness of GPR in generating reliable and precise forecasts, thus providing a strong method for intricate regression tasks in pharmaceutical and other scientific fields. In addition, the Fireworks Algorithm (FWA) is presented as an optimization method, demonstrating its potential in improving the model’s predictive abilities by effectively exploring and exploiting the search space. The results emphasize the significance of choosing suitable regression models and optimization techniques to attain dependable and superior predictive analytics.

Breaking barriers: enhancing solubility and dissolution of efonidipine using co-amorphous formulations.

The study aims to enhance the solubility and dissolution characteristics of efonidipine hydrochloride ethanolate (EFD), an antihypertensive drug, through the co-amorphous approach. Hypertension is a prevalent chronic condition characterized by consistently elevated blood pressure. Efonidipine, a BCS class II drug, has high permeability but low solubility, limiting its therapeutic effectiveness. Amorphization, which disrupts the crystal lattice of crystalline medications, can significantly enhance drug solubility and dissolution rates. Co-amorphous systems of EFD were prepared using solvent evaporation, ball milling, and liquid-assisted grinding methods. The drug and co-former were used in a different ratio, a stoichiometric proportion known for forming stable amorphous phases. The in vitro dissolution of the co-amorphous form was evaluated and compared with the pure crystalline form of EFD. The co-amorphous system of EFD with benzoic acid demonstrated significantly higher dissolution rates in vitro compared to the pure drug. PXRD analysis confirmed the transformation from a crystalline to an amorphous state, indicated by the disappearance of sharp peaks characteristic of the crystalline form. The resultant co-amorphous system exhibited dissolution properties. The co-amorphous approach effectively improved the solubility and dissolution of efonidipine hydrochloride ethanolate. Benzoic acid, as a co-former, facilitated the formation of a stable amorphous phase, thereby enhancing the drug's dissolution rate. The developed a co-amorphous system of EFD with benzoic acid, significantly enhancing its dissolution characteristics. PXRD analysis confirmed the amorphous nature and improved stability of the co-amorphous form, indicating its potential for better therapeutic efficacy in hypertension management.

Cyclodextrin-Nanosponge-Loaded Cyclo-Oxygenase-2 Inhibitor-Based Topical Gel for Treatment of Psoriatic Arthritis: Formulation Design, Development, and In vitro Evaluations

Background: Psoriatic arthritis (PsA), a chronic inflammatory disease, mainly affects the joints, with approximately 30% of psoriasis patients eventually developing PsA. Characterized by both innate and adaptive immune responses, PsA poses significant challenges for effective treatment. Recent advances in drug delivery systems have sparked interest in developing novel formulations to improve therapeutic outcomes. The current research focuses on the development and evaluation of a nanosponge-loaded, cyclo-oxygenase-2 (COX-2) inhibitor-based topical gel for the treatment of PsA. Methods: Nanosponges (NSs) were prepared by using beta-cyclodextrin as a polymer and dimethyl carbonate (DMC) as a crosslinker by melting, and gels were prepared by employing carbopol and badam gum as polymers. Results: Solubility studies confirmed that the prepared nanosponges were highly soluble. FT-IR studies confirmed the formation of hydrogen bonds between lumiracoxib and beta-cyclodextrin. SEM confirmed that the prepared formulations were roughly spherical and porous in nature. The average particle size was 190.5 ± 0.02 nm, with a zeta potential of −18.9 mv. XRD studies showed that the crystallinity of lumiracoxib decreased after encapsulation, which helped to increase its solubility. The optimized nanosponges (NS2) were incorporated in an optimized gel (FG10) to formulate a nanosponge-loaded topical gel. The optimized gel formulation exhibited a homogeneous consistency, with a pH of 6.8 and a viscosity of 1.15 PaS, indicating its suitability for topical application and stability. The in vitro diffusion studies for the topical gel showed drug release of 82.32% in 24 h. The optimized formulation demonstrated significant antipsoriatic activity, as confirmed through cytotoxicity studies conducted on HaCaT cells. Conclusions: On the basis of the findings, it can be concluded that the prepared nanosponge-loaded topical gel formulation presents a promising solution for the effective management of PsA, offering enhanced drug solubility, sustained release, and improved therapeutic potential.

Dissolution Thermodynamics of the Solubility of Sulfamethazine in (Acetonitrile + 1-Propanol) Mixtures

Background: Solubility is one of the most important parameters in the research and development processes of the pharmaceutical industry. In this context, cosolubility is one of the most used strategies to improve the solubility of poorly soluble drugs, besides allowing to identify some factors involved in the dissolution process. The aim of this research is to evaluate the solubility of sulfamethazine in acetotinitrile + 1-propanol cosolvent mixtures at 9 temperatures (278.15, 283.15, 288.15, 293.15, 298.15, 303.15, 308.15, 313.15, and 318.15 K); a drug used in human and veterinary therapy and two solvents of great chemical–pharmaceutical interest. Methods: The determination was carried out by the shaking flask method and the drug was quantified by UV/Vis spectrophotometry. Results: The solubility of sulfamethazine increases from pure 1-propanol (solvent in which it reaches its lowest solubility at 278.15 K) to pure acetonitrile (solvent in which it reaches its maximum solubility at 318.15 K), behaving in a logarithmic-linear fashion. Conclusions: The increase in solubility is related to the acid/base character of the cosolvent mixtures and not to the solubility parameter of the mixtures. The dissolution process is endothermic and favored by the solution entropy, and also shows a strong entropic compensation.

Recent development of nanotechnology-based approaches for gynecologic cancer therapy.

Gynecological cancer is a life-threatening malignancy among women. Traditional therapies, including chemotherapy, often face challenges in terms of chemotherapeutic drug solubility and resistance, specificity, tumor site targeting, and toxicity to healthy tissues, leading to shortened efficacy and unfavorable patient outcomes and survival rates in patients with gynecologic malignancies. Recently, nanotechnology-based therapeutic methods such as targeted drug delivery and phototherapies have emerged as an appropriate alternative to overcome issues associated with traditional therapeutic methods. Specifically, nanomaterials and nanomaterial-based methods enhance the delivery of therapeutic/targeting agents to tumor sites and cellular uptakes and improve the tumor-suppressing effect. This review aims to provide an overview and future perspective on the potential impact of nanotechnology-based therapeutic methods for effective therapies for gynecologic cancer.

Synthesis, characterization and irritant effects of nonivamide irritant riot control agent based on ionic liquids.

Active Pharmaceutical Ingredients-Ionic liquids (API-ILs) can increase drug solubility and bioavailability of solid drugs without changing the structure of drug molecules. In the present work, nonivamide (pelargonic acid vanillylamide, PAVA) was used as the active drug and choline (Ch) and citric acid (CA) were selected as the ions to prepare PAVA-based ionic liquid ([Ch][PAVA] and [PAVA]3 [CA]), respectively. The characterization and physical properties of [Ch][PAVA] and [PAVA]3 [CA], such as FT-IR spectra, 1H NMR spectra, thermal stability and hydrophilicity, were investigated. And the irritant effects of the PAVA-based ionic liquids were measured by the animal irritation experiment. [Ch][PAVA] has higher decomposition temperatures, better hydrophilicity and comparable irritant effects. The results show that the PAVA-based ILs synthesized in this study may potentially serve as a promising novel riot control agent.

Impact of components of biorelevant media on solubilization of methotrexate and sulfasalazine by Pluronic F127

Pluronics are micelle-based solubilizers, improving the therapeutic potential of orally administrated drugs. In this connection, solubilizing action of Pluronics is being intensively studied in standard buffers simulating gastrointestinal fluids and consisting of inorganic components. However, human gastrointestinal fluids have more complicate composition due to the presence of organic compounds such as enzymes, mucus, and bile, which are able to form supramolecular aggregates and influence the solubilizing effect of Pluronics. Therefore, the use of specially designed biorelevant media is a promising approach to assessing the effectiveness of solubilizing activity of Pluronics in vitro.Based on this, we studied the solubilization of poorly soluble methotrexate and sulfasalazine, which are used in the treatment of autoimmune and oncological diseases, by Pluronic F127 in Fasted State Simulated Gastric Fluid and Fasted State Simulated Intestinal Fluid. Taurocholic acid and lecithin being the main components of these biorelevant media form micelles and thereby enhance the solubility of drugs that are insoluble or sparingly soluble in water. The affinity of drugs under consideration to the micelles of different nature, which are present in the dissolution medium, is examined in this work. The possible competing interactions of drug-micelle and drug-unimer are discussed in terms of the ionization state of drug molecules and the nature of surfactants.

Effect of Process Parameters on Nano-Microparticle Formation During Supercritical Antisolvent Process Using Mixed Solvent: Application for Enhanced Dissolution and Oral Bioavailability of Telmisartan Through Particle-Size Control Based on Experimental Design

Background/Objectives: This study investigates the impact of supercritical antisolvent (SAS) process parameters on the particle formation of telmisartan, a poorly water-soluble drug. Methods: A fractional factorial design was employed to examine the influence of the SAS process parameters, including solvent ratio, drug solution concentration, temperature, pressure, injection rate of drug solution, and CO₂ flow rate, on particle formation. Solid-state characterizations of the SAS process particles using XRD and FT-IR confirmed their amorphous nature. The effect of particle size on the kinetic solubility, dissolution, and oral bioavailability of telmisartan was also assessed. Results: Using a mixture of dichloromethane and methanol, telmisartan amorphous nano-microparticles with sizes between 200 and 2000 nm were produced. The key parameters, particularly drug solution concentration and temperature, significantly affected the particle size. Interestingly, the ratio of the solvent mixture also had a significant effect on the particle morphology. Further experiments were performed to determine the conditions for preparing telmisartan amorphous nano-microparticles with various sizes by controlling the solvent mixture ratio and the concentration of the drug solution. It was revealed that a reduction in the amorphous particle size enhanced both the kinetic solubility and dissolution rates, leading to a significantly increased in vivo oral bioavailability in rats compared to unprocessed telmisartan. Conclusions: These findings suggest that SAS processing, utilizing adjustments of process parameters, offers an effective strategy for enhancing the bioavailability of poorly soluble drugs by generating amorphous spherical nano-microparticles with optimized particle size.