Water-soluble Drugs Research Articles

Fenofibrate Nanosuspension: A Novel Strategy to Enhance its Bioavailability for the Management of Hyperlipidemia

Hyperlipidemia, a metabolic condition marked by elevated plasma levels of cholesterol or triglyceride-carrying lipoproteins, is a major contributor to atherosclerosis and cardiovascular diseases. Antihyperlipidemic drugs are classified according to their primary mechanism of action. Fenofibrate’s role in regulating cholesterol and managing insulin resistance-associated metabolic disorders makes it a preferred choice in combination therapies with statins for cardiovascular disease management. Nanoparticles have gained attention for enhancing the bioavailability of poorly water-soluble drugs by reducing particle size to the nanoscale (100-200 nm), which increases solubility, dissolution rate and adhesion to cell surfaces. Nanosuspensions improve drug solubility and bioavailability through methods like media milling, high-pressure homogenization and precipitation. Despite advancements, producing stable Fenofibrate nanoparticles below 100 nm at an industrial scale remains a challenge. Recent strategies include using sonication and freeze-drying to enhance bioavailability and solubility, achieving significant improvements in drug dissolution and therapeutic efficacy.

Preparation of Ibuprofen-Loaded Inhalable γCD-MOFs by Freeze-Drying Using the QbD Approach

Background/Objectives: Research on cyclodextrin-based metal-organic frameworks (CD-MOFs) is still in its infancy, but their potential for use in drug delivery—expressly in the lung—seems promising. We aimed to use the freeze-drying method to create a novel approach for preparing CD-MOFs. MOFs consisting of γ-cyclodextrin (γCD) and potassium cations (K+) were employed to encapsulate the poorly water-soluble model drug Ibuprofen (IBU) for the treatment of cystic fibrosis (CF). Methods: Using the LeanQbD® software (v2022), we designed the experiments based on the Quality by Design (QbD) concept. According to QbD, we identified the three most critical factors, which were the molar ratio of the IBU to the γCD, incubation time, and the percentage of the organic solvent. light-, scanning electron microscope (SEM) and laser diffraction were utilized to observe the morphology and particle size of the samples. In addition, the products were characterized by Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Results: Based on characterizations, we concluded that a γCD-MOF/IBU complex was also formed using the freeze-drying method. Using formulations with optimal aerodynamic properties, we achieved 38.10 ± 5.06 and 47.18 ± 4.18 Fine Particle Fraction% (FPF%) based on the Andersen Cascade Impactor measurement. With these formulations, we achieved a fast dissolution profile and increased IBU solubility. Conclusions: This research successfully demonstrates the innovative use of freeze-drying to produce γCD-MOFs for inhalable IBU delivery. The method enabled to modify the particle size, which was crucial for successful pulmonary intake, emphasizing the need for further investigation of these formulations as effective delivery systems.

The potential of supramolecular synthon to develop coamorphous systems with tailored physical stability: Mechanistic insights integrating kinetics and thermodynamics

Coamorphous drug delivery systems have received increasing interest owing to their potential to improve the solubility, dissolution and bioavailability of poorly water-soluble drugs. However, the crystallization risk is one of major limitations in their application. It has been widely recognized that the coformer plays a vital role in physical stability of coamorphous formulation. Unfortunately, the screen of optimal coformer still adopts a trial-and-error method, which is time-consuming and expensive. Herein, a supramolecular synthon approach based on the interaction between functional groups, was exploited to design coamorphous systems (CMs) consisting of lurasidone hydrochloride (LH) and three coformers, saccharin (SAC), L-tryptophan (TRP), and L-cysteine hydrochloride (CYS). X-ray powder diffraction suggested the order of physical stability of the coamorphous systems was ranked as LH-CYS CM > LH-TRP CM > LH-SAC CM. The charge-assisted hydrogen bond between LH and coformer was confirmed by infrared spectroscopy and solid-state 13C NMR. Moreover, structural, electronic, and molecular interaction information, especially hydrogen bonding interactions, were quantified by theoretical calculations, including miscibility calculations, molecular dynamics simulations and quantum chemical calculations. It was revealed that LH-CYS CM exhibited the best miscibility, strongest binding energy and strongest H-bond with partially covalent character, demonstrating the significant role of supramolecular synthon in stabilizing coamorphous formulations. Interestingly, LH-TRP CM, not LH-CYS CM, exhibited the lowest molecular mobility among three coamorphous systems, which was inconsistent with their physical stability. But from thermodynamic perspective, the order of configurational entropy and physical stability of coamorphous systems was completely consistent. We shed light on the comprehensive effects of molecular mobility and configurational entropy on physical stability of coamorphous systems. Importantly, the relationship between supramolecular synthon and kinetic/thermodynamic mechanisms was also discussed, and the positive correlation between configurational entropy and intermolecular interactions was proposed in this paper. Our findings demonstrated the great potential of supramolecular synthon in designing coamorphous systems with tailored physical stability, and further provided a deeper insight into the mechanisms of physical stability of coamorphous systems.

Melt-extruded formulations of fenofibrate with various grades of hydrogenated phospholipid exhibit promising in-vitro biopharmaceutical behavior

In the current study, it was demonstrated that three commercially available grades of hydrogenated phospholipids (HPL) differing in their content of phosphatidylcholine may be used as components for hot melt-extruded binary (HPL as sole excipient) or ternary (in combination with copovidone) solid dispersions of fenofibrate (FEN) at mass fractions between 0.5 and 20% (ternary) or 80% (binary). X-ray powder diffraction indicated complete conversion of crystalline fenofibrate into the amorphous state by hot melt extrusion for all ternary blends. In contrast, both the binary blends (HPL- and copovidone-based) contained minor remaining crystallites. Irrespectively, all solid dispersions induced during dissolution studies a supersaturated state of FEN, where the ternary ASDs showed enhanced and more complete release of FEN as compared to the binary blends and, even more pronounced, in comparison to the marketed micronized and nano-milled formulations. In terms of the cumulated amount permeated, there were marginal differences between the various formulations when combined dissolution/permeation was done using FeSSIF as donor medium; with FaSSIF as donor medium, the binary HPL-ASD containing the grade with the highest phosphatidylcholine fraction performed best in terms of permeation, even significantly better than the marketed nano-crystal formulation. Otherwise, no significant differences were seen between the various grades of HPL when FEN dissolution and permeation were analyzed for ternary solid dispersions. In conclusion, the in-vitro biopharmaceutical behaviour of hydrogenated phospholipid-containing blends manufactured by hot melt extrusion appears promising. They can be a viable formulation option for poorly water-soluble and lipophilic drug compounds like FEN.

A Comprehensive Review of Self-Nanoemulsifying Systems in the Delivery of Herbal Drugs.

Self-nanoemulsifying drug delivery systems (SNEDDS) are an isotropic mixture of oils, co-surfactants, and surfactants and can form fine O/W Nanoemulsions in aqueous media. These components are advantageous in terms of improved solubility and bioavailability. Limited permeability, solubility, and bioavailability remain a significant challenge in developing herbal drugs. This review explores the potential of self-nanoemulsifying drug delivery systems (SNEDDS) as a promising strategy to overcome this problem. The SNEDDS is considered a novel technique for the delivery of low water-soluble drugs. It can bypass the first-pass metabolism, resulting in steady and sustained drug levels in the systemic circulation. The present article provides a comprehensive overview of the SNEDDS formulation of herbal drugs. It includes their composition, characterization, in vitro and in vivo studies conducted in various disease conditions, and pharmacokinetic studies.

Acoustic resonance technology and quality by design approach facilitate the development of the robust tetrandrine nano-delivery system

The aim of this study was to develop a sufficiently robust tetrandrine (Tet) nano-delivery system using acoustic resonance (AR) technology and freeze-drying technology. This system can effectively improve the solubility and dissolution properties of Tet, along with high stability and scale-up adaptability. Firstly, 54 stabilizers were screened simultaneously in a high-throughput manner with the help of AR technology to fully explore the optimal prescription space of tetrandrine nanosuspension (Tet-NS). The Plackett-Burman design was used to screen for critical variables severely affecting the quality of Tet-NS. The Box-Behnken design was used to investigate and optimize critical variables to obtain optimal nanosuspensions. The optimal prescription was successfully scaled up by 100 times, which was the initial exploration of its commercial scale production. Solidification studies have shown that formulations with 2.44% fructose as the cryoprotectant have excellent redispersibility. Compared with pure Tet, Tet in Tet-NS showed a significant increase in solubility and dissolution rate in water. Fourier transform infrared (FT-IR) demonstrated that no significant interactions occurred between the drug and excipients in Tet-NS. Powder x-ray diffraction analysis (PXRD) indicated that some of the Tet transformed into amorphous state during the preparation process. In short-term stability study, Tet-NS successfully maintained its physical stability. In summary, under the guidance of the QbD concept, this study rapidly developed Tet-NS using acoustic resonance technology, which can effectively improve the solubility and dissolution properties of Tet. During the development of Tet-NS, AR technology has demonstrated high particle size reduction capability, the ability to process multiple sets of formulations in parallel, and excellent scale-up capability. Meanwhile, the method and concept of this study are not limited to Tet, but also applicable to other poorly water-soluble drugs.

Liquisolid Technique for Solubility Enhancement of Poorly Soluble Drug - A Brief Review.

Most of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, nonadherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery.

Exploring Deep Eutectic Solvents as Pharmaceutical Excipients: Enhancing the Solubility of Ibuprofen and Mefenamic Acid.

Objectives: The study explores the potential of various deep eutectic solvents (DESs) to serve as drug delivery systems and pharmaceutical excipients. The research focuses on two primary objectives: evaluating the ability of the selected DES systems to enhance the solubility of two poorly water-soluble model drugs (IBU and MFA), and evaluating their physicochemical properties, including density, viscosity, flow behavior, surface tension, thermal stability, and water dilution effects, to determine their suitability for pharmaceutical applications. Methods: A range of DES systems containing pharmaceutically acceptable constituents was explored, encompassing organic acid-based, sugar- and sugar alcohol-based, and hydrophobic systems, as well as menthol (MNT)-based DES systems with common pharmaceutical excipients. MNT-based DESs exhibited the most significant solubility enhancements. Results: IBU solubility reached 379.69 mg/g in MNT: PEG 400 (1:1) and 356.3 mg/g in MNT:oleic acid (1:1), while MFA solubility peaked at 17.07 mg/g in MNT:Miglyol 812®N (1:1). In contrast, solubility in hydrophilic DES systems was significantly lower, with choline chloride: glycerol (1:2) and arginine: glycolic acid (1:8) showing the best results. While demonstrating lower solubility compared to the MNT-based systems, sugar-based DESs exhibited increased tunability via water and glycerol addition both in terms of solubility and physicochemical properties, such as viscosity and surface tension. Conclusions: Our study introduces novel DES systems, expanding the repertoire of pharmaceutically acceptable DES formulations and opening new avenues for the rational design of tailored solvent systems to overcome solubility challenges and enhance drug delivery.

Leveraging solid solubility and miscibility of etoricoxib in Soluplus® towards manufacturing of 3D printed etoricoxib tablets by additive manufacturing

This research focuses on exploring the solid solubility and miscibility of Etoricoxib, a poorly water-soluble anti-inflammatory drug, within Soluplus®, a polymer used as a matrix for 3D-printed tablets. By utilizing hot-melt extrusion (HME), the drug was dispersed within Soluplus® to enhance its solubility. The extrudates were then employed in 3D printing to create customized solid oral dosage form. This study’s novelty lies in combining HME and 3D printing, aiming to improve drug incorporation, stability, and effectiveness in the final formulation. Comprehensive characterization techniques, including hot stage microscopy (HSM), scanning electron microscopy (SEM), micro-computed tomography (Micro-CT), florescence microscopy, optical microscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), solubility studies, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and aqueous solubility study were utilized to elucidate the physicochemical properties, thermal stability, and structural integrity for the extruded filaments (the printing ink), and 3D printed tablets made thereof. Furthermore, the in vitro drug release profile of the 3D printed tablet was systematically evaluated, revealing a controlled drug release pattern from the finished dosage form. The systematic investigation reported herein, starting from theoretical miscibility to the printing ink development through HME, detailed characterization of the extruded filaments, and further solid oral formulation development by additive manufacturing can be utilized as a platform technology or a pathway for the development of personalized medicine with drugs having similar physicochemical properties.

Characterization of Macrocyclic Peptide Drug Interactions with Bile Salts and Biorelevant Colloids via Single Amino Acid Mutations and 1H Nuclear Magnetic Resonance (NMR) Spectroscopy

There is growing interest in the oral delivery of poorly permeable peptide drugs; however, the effect of biorelevant colloids found in the aqueous gastrointestinal environment on peptide drug solution behavior has been largely understudied. In this work, we detail the molecular level interactions between octreotide, a water-soluble macrocyclic peptide drug, and biorelevant colloids, i.e. bile salt micelles and bile salt-phospholipid mixed micelles, via dialysis membrane flux experiments and proton nuclear magnetic resonance (1H NMR) spectroscopy. A modified alanine scan was employed to generate eight mutated octreotide analogs; the impact of individual amino acid mutations on peptide dialysis membrane flux rates in micellar (trihydroxy and dihydroxy) bile salt solutions as well as fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF) was evaluated and compared against the parent peptide, octreotide. We show that octreotide interacts more strongly with dihydroxy bile salt micelles than trihydroxy bile salt micelles in solution, and in FaSSIF/FeSSIF media, octreotide mainly interacts with the phospholipid component. These interactions are largely mediated by hydrophobic interactions of octreotide's aromatic residues as well as electrostatic interactions between octreotide's basic Lys residue and terminal amine.

Formulation and optimization of transferrin-modified genistein nanocrystals: In vitro anti-cancer assessment and pharmacokinetic evaluation

In this research work, nanocrystals (NC) of poorly water-soluble drug genistein (Gen) were formulated to improve its aqueous solubility and bioavailability. Genistein nanocrystals (Gen–NC) were prepared by wet ball milling. The formulation was optimized using Box Behnken Design Expert to evaluate the impact of stabilizer concentration, drug concentration and quantity of zirconium beads (milling media) on NC size, polydispersity and zeta potential. The NCs were surface-decorated with transferrin (Tf) to form Tf modified Gen-NCs (Tf-Gen-NC) for improving cancer cell selectivity and cytotoxicity. The NC formulations were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray power diffraction (XRD) and differential scanning calorimetry (DSC). The particle size distribution of the optimized formulation varied from 200 to 300 nm with poly dispersibility index (PDI) between 0.1 and 0.3. Tf-Gen-NC and Gen-NC released 96 % and 80 % of the drug content in 20 min at 37 °C, respectively, whereas only 18 % were released with the unprocessed drug. In vitro cytotoxicity was tested in pulmonary adenocarcinoma epithelial cells (A549) and fibroblast cell line (L929). The Tf-Gen-NC presented an enhanced anticancer effect. In vivo pharmacokinetic studies in mice after intraperitoneal administration showed that the Cmax of NC formulations were 2.5-fold higher compared to free Gen. The area under the curve from time of administration to 24 h was 2.5 to 3-fold higher when compared with unprocessed drug. This study shows the interest of Gen-NC in the development of new formulations for Gen as an anticancer drug.

Eutectic mixtures of nevirapine: Phase diagrams, solid-state characterization, and dissolution studies

Solid-state modifications can improve drug performance. Studies have shown that multicomponent crystals, such as cocrystals and eutectic compositions, have successfully improved the performance of certain drugs, including their solubility. Nevirapine (NEV) is an antiretroviral drug with low aqueous solubility, impacting its bioavailability. This work aimed to study different nevirapine/co-former solid eutectic systems, define their phase diagrams and evaluate their dissolution properties. Caffeine (CAF), Theobromine (TEOB), and Theophylline (THEO) were chosen as co-formers due to their functional groups that can interact with NEV. Aiming to determine both temperature and eutectic composition, phase and Tamman diagrams were obtained using the differential scanning calorimetry (DSC) analysis of the mixtures indifferent NEV-co-former compositions (%w/w). Powder X-ray diffraction (PXRD) and DSC were used to characterize the eutectic materials. To assess the influence of eutectic systems on dissolution properties, we determined the powder dissolution profiles and intrinsic dissolution rates of anhydrous NEV and eutectic systems NEV-CAF and NEV-THEO using different dissolution media (pH 1.2 and pH 6.8). The eutectic compositions were calculated through the phase diagrams, interpolating the curves obtained by linear regression. Thus, the eutectic composition of the NEV-CAF system was determined to be 36.55 % NEV and eutectic temperature at 201.1 °C, while in the NEV-THEO system, the eutectic was obtained in a composition of 71.04 % NEV and eutectic temperature at 217.8 °C. Tamman diagrams were generated using the enthalpy values obtained from the DSC curves, and eutectic compositions were calculated using linear regression. The analysis revealed a eutectic composition of 36.51 % of NEV for the NEV-CAF system, and a eutectic composition of 70.94 % of NEV for the NEV-THEO system. It was not possible to determine the eutectic mass fraction of NEV-TEOB. A comparison of dissolution profiles and intrinsic dissolution rates in different dissolution media showed a significant improvement in the NEV dissolution rate in both eutectic systems. In an acidic medium, NEV dissolved 16 times faster in the NEV-CAF sample and 4 times faster in the NEV-THEO sample compared to pure anhydrous NEV. In a neutral medium, the dissolution profile of NEV was even more favorable in the same eutectic systems, showing that the increase in dissolution is relevant in a wide range of pH. In addition, the intrinsic dissolution rate in the two eutectic systems was higher than that of anhydrous NEV in all employed dissolution mediums. These eutectic systems improve the dissolution rate compared to pure NEV, offering the potential for enhancing the dissolution of poorly water-soluble drugs in the future.

Correlation of surface properties with dissolution behavior of amorphous solid dispersion of Riluzole and its pharmacodynamic evaluation

Formulation of amorphous solid dispersion (ASD) of any poorly water-soluble drug is among the most promising techniques to increase the dissolution profile of drug and hence its bioavailability. Various literatures give evidences of the role of drug-polymer interactions in the ASD systems, very little information is available about the surface properties of the drug molecule and their ASDs which contributes to a higher dissolution profile. Current work focuses on exploring the surface behavior of a poorly water-soluble drug Riluzole (RLZ) and its ASDs prepared with two highly hydrophilic polymers, polyacrylic acid (PAA), and polyvinylpyrrolidone vinyl acetate (PVP VA). Initial characterization using X-ray diffraction (XRD) revealed about the weight fraction of drug required to prepare a single-phase homogenous system with both the polymers. The saturation solubility and the dissolution studies showed an increase in RLZ solubility as well as the dissolution profile due to the presence of polymers. The role of polymers in changing the surface properties in terms of wettability and polarity were explored using contact angle method and X-ray photon spectroscopy (XPS). Additionally, the neuroprotective efficacy and dose dependent hepatotoxicity were also evaluated in male wistar rats. These studies confirmed the increase in the surface polarity and hence the enhanced ability of ASD formulations to interact with water. The in vivo studies indicated that at the current recommended dose the efficacy as well as toxicity is increased for the ASD formulation. Hence, this formulation can be given at a lower dose to achieve same therapeutic effect with lower toxicity.

Mechanisms of dissolution and crystallization of amorphous glibenclamide

Amorphous solid dispersions enhance the dissolution and oral bioavailability of poorly water-soluble drugs. However, the link between polymer properties and formulation performance has not been fully clarified yet. We studied the effect of hydroxypropyl cellulose (HPC) polymers molecular weight (Mw) on the storage stability, dissolution kinetics and supersaturation stability of spray-dried amorphous glibenclamide (GLB) formulations. The solid-state stability of amorphous GLB during storage was significantly enhanced by both the 40 kDa (HPC-SSL) and 84 kDa (HPC-L) polymers, regardless of Mw differences. In contrast, HPC-SSL maintained significantly higher aqueous drug concentrations during dissolution, compared to HPC-L (its higher Mw analogue). Dedicated dissolution experiments, in situ optical microscopy and solid-state characterization revealed that aqueous drug concentrations were determined by the interplay between crystallization inhibition, drug ionization, wetting and solubilization effects: (1) HPC prevents surface nucleation, hence inhibiting crystallization, (2) intestinal colloids (bile salts and phospholipids) increase supersaturated drug concentrations via wetting and solubilization effects and (3) pH and drug ionization severely impact the degree of supersaturation. The better performance of the lower Mw HPC-SSL was due to its superior inhibition of surface crystallization. These insights into the molecular mechanisms of dissolution and crystallization of amorphous solids provide foundation for rational formulation development.

Magnetic lipid-poly(lactic-co-glycolic acid) nanoparticles conjugated with epidermal growth factor receptor antibody for dual-targeted delivery of CPT-11

To entrap sparingly water-soluble drugs like CPT-11 (irinotecan), the poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) is highly favored due to its low cytotoxicity and approval for clinical use. On the other hand, entrapping hydrophobic oleic acid-coated iron oxide magnetic nanoparticles (OMNP) in PLGA NP can provide a nanovehicle for magnetically targeted drug delivery. Our goal in this study is to develop a new dual-targeted magnetic lipid-polymer NP for the delivery of CPT-11. We first co-entrap OMNP and CPT-11 in self-assembled lipid-PLGA NP to prepare OLNP@CPT-11. The OLNP@CPT-11 surface was modified with an epidermal growth factor receptor (EGFR) antibody Cetuximab (CET), which can actively target the overexpressed EGFR on the U87 glioblastoma cell surface. The OLNP-CET@CPT-11 enables dual targeting through both external magnetic guidance and CET-mediated active targeting. The NP was characterized for physicochemical properties using various analytical techniques. In vitro study confirms ligand-receptor interaction results in enhanced endocytosis of OLNP-CET@CPT-11 by U87 cells, which offers increased cytotoxicity and elevated cell apoptosis rates. Furthermore, magnetic guidance of OLNP-CET@CPT-11 to U87 cells can induce cell death exclusively in the magnetically targeted zone. The dual-targeted strategy also provides the best therapeutic efficacy against subcutaneously implanted U87 tumors in nude mice with intravenously delivered OLNP-CET@CPT-11.

Comparing Low-Dose Carvedilol Continuous Manufacturing by Solid and Liquid Feeding in Self-Emulsifying Delivery Systems via Hot Melt EXtrusion (SEDEX)

Background/Objectives: This study compared two pilot scale continuous manufacturing methods of solid self-emulsifying drug delivery systems (SEDDSs) via hot melt extrusion (HME). Methods: A model poorly water-soluble drug carvedilol in low dose (0.5–1.0% w/w) was processed in HME either in a conventional powder form or pre-dissolved in the liquid SEDDS. Results: HME yielded a processable final product with up to 20% w/w SEDDS. Addition of carvedilol powder resulted in a non-homogeneous drug distribution in the extrudates, whereas a homogeneous drug distribution was observed in pre-dissolved carvedilol. SEDDSs were shown to have a plasticizing effect, reducing the HME process torque up to 50%. Compatibility between excipients and carvedilol in the studied ratios after HME was confirmed via DSC and WAXS, demonstrating their amorphous form. Solid SEDDSs with Kollidon® VA64 self-emulsified in aqueous medium within 15 min with mean droplet sizes 150–200 nm and were independent of the medium temperature, whereas reconstitution of Soluplus® took over 60 min and mean droplet size increased 2-fold from 70 nm to 150 nm after temperature increased from 25 °C to 37 °C, indicating emulsion phase inversion at cloud point. Conclusions: In conclusion, using Kollidon® VA64 and pre-dissolved carvedilol in SEDDS has shown to yield a stabile HME process with a homogenous carvedilol content in the extrudate.

Preparation and Characterization of Solid Dispersion of Sorafenib Tosylate for Enhancement of Bioavailability.

Solid dispersions have garnered significant attention as an effective strategy for enhancing the solubility and, consequently, the bioavailability of poorly water-soluble drugs. By forming solid dispersions of these drugs with water-soluble carriers, issues related to limited solubility have been mitigated, leading to improved dissolution rates. The core focus of solid dispersion technology revolves around the creation of two-component systems involving the drug and a polymer, where the successful dispersion and stabilization of the drug play pivotal roles in the formulation development process. As a result, this technology is widely acknowledged as a highly valuable approach for enhancing the dissolution properties of poorly water-soluble drugs. In recent years, a substantial body of knowledge has been amassed concerning solid dispersions. Nonetheless, their practical implementation in the commercial sphere remains somewhat limited. In the current investigation, we embarked on the preparation of a solid dispersion of sorafenib tosylate, with the primary objective of achieving the maximum release of the drug within the shortest possible timeframe. Our aim was to develop and optimize the solid dispersions of sorafenib tosylate in a manner that ensures the successful design and formulation of this system.

Investigation the binding and partition properties of azithromycin drug using drug-surfactant mixed micelles in the presence of trisodium citrate electrolyte

The significance of mixed micelle in pharmaceutical industries is improving the binding and solubility of poorly water-soluble drugs. This work highlighted the effect of organic counterion (NAC) for improving the micellization association of zwitterionic (CAPB) and cationic drug (DPC) by surface tension measurements. The Corrin–Harkins (CH) approach assessed the CAPB, DPC and CAPB-DPC counterion binding values for DPC in the aqueous and NAC media at 25 °C. The counterion binding B for CAPB-DPC from αDPC 1.0–0.0 was found 0.536, 0.3801, 0.368, 0.355, 0.310 and 0.272 in the presence of NAC which indicated that DPC improved the counterion binding in the mixed micellar system. The Gibb’s free energy of micellization (ΔGmic°) were increased and became more negative, suggesting that the CAPB–DPC interaction was controlled by electrostatic interaction. Furthermore, the application of mixed micelle was utilized to enhance the binding constant (LogKb) and partition coefficient (LogKx) of the poorly water-soluble drug (AZI) in aqueous and NAC media at 25 °C using a UV spectrophotometer. From UV spectra, The LogKb and LogKx of AZI were lower in single micellar systems and higher in mixed micellar systems of CAPB-DPC. The maximum LogKb values at αDPC 0.4 were found 3.091, 3.233, 3.417, and 3.368 and LogKx values were found 4.749, 4.919, 5.087 and 5.049 in the presence of 0.0, 0.5, 3.0 and 20 mmol L−1 of NAC. AZI molecules are found in the palisade layer of mixed micelle when the DPC mole fraction is less than αDPC 0.6, while more than αDPC 0.6 causes steric hindrance, increasing hydrophobicity in the system. Furthermore, surfactant-drug mixed micelles could serve as poorly drug-solubilizing agents, as well as a multidrug delivery system in pharmaceutical applications.

Novel Approaches and Emerging Trends in Hydrotropic Solubilization Technology

Hydrotropic solubilization technology enhances the solubility and bioavailability of poorly water-soluble drugs, a major challenge in pharmaceutical research. This review discusses hydrotropic agents’ structures, the solubilization process, and factors affecting drug solubility. It explores optimizing agent concentrations, the role of computer modeling and QSAR studies, and hydrotropes’ impact on overcoming biological barriers and improving pharmacokinetics and pharmacodynamics. The review highlights hydrotropic compounds’ potential in advancing pharmaceutical formulations and clinical applications.

Exploring Mixed Hydrotropy Concept in HPTLC Densitometric Estimation of Telmisartan.

Analysis of the poorly water-soluble drugs most frequently carried out by using organic solvents like methanol, ethanol, chloroform, acetonitrile, and hexane. Most of them have toxic effects on humans as well as the natural ecosystem. The volatile nature of organic solvents is a major source of inaccuracy. So, the current study provides the best approach to replace organic solvents as hydrotropic solubilization techniques and developed a green, eco-friendly method to estimate telmisartan by highperformance thin-layer chromatography (HPTLC). Using silica gel coated (60 F254) TLC plates, chromatographic separation was achieved with a mobile phase 30% Sodium Benzoate (SB): 20% sodium acetate (SA): 0.5% citric acid (CA) (6:3:0.5 v/v/v). The retention factor for telmisartan was 0.55. Concentrations were linear in between 500 to 900 µg/mL with a regression coefficient was 0.9930. This approach was successfully validated as per the International Conference on Harmonization and it exhibits satisfactory results for all parameters. The developed approach is capable of being used to conduct routine evaluations of telmisartan in bulk and marketed formulation.