Soluble Drugs Research Articles

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.

Nanosponges as a Drug Delivery System: Methods, Characteristics and Applications

Nanosponges, which are crosslinked polymer nanometers in sized used for drug transport, have a unique three-dimensional appearance. Their versatility lies in their ability to accommodate drugs of various sizes. The research approach, polymer type, and drug content determine the diversity of nanosponges. Nanosponges excel as delivery systems due to their capacity for controlled and targeted drug release. They offer the flexibility to regulate the duration of drug action and residence time. Their biodegradable composition ensures low toxicity and safe usage. Available voids, along with the size of the test molecule, play a crucial role in the efficiency of encapsulation. Nanosponges exhibit numerous applications such as cancer treatment, transportation of enzymes and biocatalysts, oxygen, modification of drug solubility, and immobilization of enzymes. This study emphasizes the preparation method, characterization, influencing factors, drug loading, recent advancements, and patents in the field of nanosponges.

Determination of mometasone furoate solubility, using deep eutectic systems, and topical formulation- experimental and computational studies

The low solubility of some drugs in aqueous medium, is currently a challenge for the pharmaceutical industry, affecting drug bioavailability and treatment efficacy, so there is the need to find new solutions for this challenge. In this work, the solubility of a glucocorticoid drug, mometasone furoate (MF), in different deep eutectic systems (DES) is studied. DES present the advantage of being sustainable solvents, which can be used directly in the final formulation, and establish a synergistic effect with the drug. The solubility of MF in different DES is increased, when compared to the solubility of this drug in an aqueous medium, particularly in DES composed by levulinic acid and terpenes such as menthol and thymol, where the solubility of MF was of 24.1 and 103.3 mgMF/gDES, respectively. Solubility was also assessed using the computational determination of the Hansen solubility parameters of MF in these DES, in particular the total solubility parameter (δT) and Relative Energy Difference (RED). The obtained results correlate well with the MF measured experimentally, showing that this computational tool can be further used to predict MF solubility in DES. Furthermore, oil-in-water emulsions containing DES with MF were developed, allowing more versatility compared to the drug in powdered form, and were prepared containing 1 and 5 % of DES with MF. This work highlights that DES can have an important role in drug solubilization and in the development of new formulation strategies for the pharmaceutical industries.

Plant-Derived Flavonoids as AMPK Activators: Unveiling Their Potential in Type 2 Diabetes Management through Mechanistic Insights, Docking Studies, and Pharmacokinetics

Type 2 diabetes mellitus (T2DM) remains a significant global health issue, marked by insulin resistance and disrupted glucose metabolism. AMP-activated protein kinase (AMPK) serves as a key regulator of cellular energy balance, playing a crucial role in enhancing insulin sensitivity, promoting glucose uptake, and reducing glucose production in the liver. Recently, there has been growing interest in plant-derived flavonoids as natural activators of AMPK, offering a promising complementary approach to conventional diabetes treatments. This review delves into ten flavonoids identified as AMPK activators, including baicalein, dihydromyricetin, bavachin, 7-O-MA, derrone, and alpinumisoflavone. Their activation mechanisms are explored, which include both direct binding to the AMPK complex and indirect pathways involving upstream signaling. Through molecular docking studies, the binding affinities and interaction profiles of these flavonoids with AMPK are assessed, revealing varying levels of activation potential. Notably, baicalein and dihydromyricetin showed strong binding to the α1 subunit of AMPK, indicating high potential for robust activation. Additionally, this review provides a thorough analysis of the pharmacokinetic properties and drug-likeness of these flavonoids using the SwissADME tool, focusing on aspects such as ADME (Absorption, Distribution, Metabolism, and Excretion). While the overall profiles of these compounds are promising, issues like solubility and possible drug–drug interactions are areas that need further refinement. In summary, plant-derived flavonoids emerge as a promising avenue for developing new natural therapies for T2DM. Moving forward, research should aim at optimizing these compounds for clinical application, elucidating their specific mechanisms of AMPK activation, and confirming their efficacy in T2DM treatment. This review highlights the potential of flavonoids as safer and more holistic alternatives or adjuncts to current diabetes therapies.

Development and Characterization of Olaparib-Loaded Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Pharmaceutical Applications.

This study aims to enhance the solubility of Olaparib, classified as biopharmaceutical classification system (BCS) class IV due to its low solubility and bioavailability using a solid self-nanoemulsifying drug delivery system (S-SNEDDS). For this purpose, SNEDDS formulations were created using Capmul MCM as the oil, Tween 80 as the surfactant, and PEG 400 as the co-surfactant. The SNEDDS formulation containing olaparib (OLS-352), selected as the optimal formulation, showed a mean droplet size of 87.0 ± 0.4 nm and drug content of 5.53 ± 0.09%. OLS-352 also demonstrated anticancer activity against commonly studied ovarian (SK-OV-3) and breast (MCF-7) cancer cell lines. Aerosil® 200 and polyvinylpyrrolidone (PVP) K30 were selected as solid carriers, and S-SNEDDS formulations were prepared using the spray drying method. The drug concentration in S-SNEDDS showed no significant changes (98.4 ± 0.30%, 25℃) with temperature fluctuations during the 4-week period, demonstrating improved storage stability compared to liquid SNEDDS (L-SNEDDS). Dissolution tests under simulated gastric and intestinal conditions revealed enhanced drug release profiles compared to those of the raw drug. Additionally, the S-SNEDDS formulation showed a fourfold greater absorption in the Caco-2 assay than the raw drug, suggesting that S-SNEDDS could improve the oral bioavailability of poorly soluble drugs like olaparib, thus enhancing therapeutic outcomes. Furthermore, this study holds significance in crafting a potent and cost-effective pharmaceutical formulation tailored for the oral delivery of poorly soluble drugs.

Nanocarrier-Based Delivery Approaches of Mangiferin: An Updated Review on Leveraging Biopharmaceutical Characteristics of the Bioactive.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.

Method Development for Analysis of Cyclodextrin Inclusion Complexes with HPLC

Cyclodextrin inclusion complexes have been widely used in the pharmaceutical industry to improve drug solubility and bioavailability. Analysis of these complexes using HPLC requires the development of appropriate and validated methods. To analyze and compare various HPLC methods used for the analysis of cyclodextrin inclusion complexes, and to identify challenges and trends in method development. A literature review was conducted of articles published in the last 10 years, focusing on HPLC methods for the analysis of cyclodextrin inclusion complexes. Parameters compared included column type, mobile phase composition, flow rate, and detection method. The majority of studies used C18 columns with varying lengths and particle sizes. The composition of the mobile phase varied, reflecting the diversity of properties of the complexes analyzed. The flow rate was generally 1.0 mL/min, with the exception of the HPLC/MS method. Detection methods included UV-Vis, PDA, fluorescence, and mass spectrometry. The main challenges included the dynamic equilibrium of the complexes and stability during analysis HPLC method development for the analysis of cyclodextrin inclusion complexes requires optimization of various parameters to overcome specific challenges. Future trends are towards the use of advanced technologies such as UHPLC and high-resolution mass detection.

Characterisation of colloidal structures and their solubilising potential for BCS class II drugs in fasted state simulated intestinal fluid

A suite of fasted state simulated intestinal fluid (SIF), based on variability observed in a range of fasted state human intestinal fluid (HIF) samples was used to study the solubility of eight poorly soluble drugs (three acidic drugs (naproxen, indomethacin and phenytoin), two basic drugs (carvedilol and tadalafil) and three neutral drugs (felodipine, fenofibrate, griseofulvin)). Particle size of the colloidal structures formed in these SIF in the presence and absence of drugs was measured using dynamic light scattering and nanoparticle tracking analysis.Results indicate that drug solubility tends to increase with increasing total amphiphile concentration (TAC) in SIF with acidic drugs proving to be more soluble than basic or neutral drug in the media evaluated. Dynamic light scattering showed that as the amphiphile concentration increased, the hydrodynamic diameters of the structures decreased. The scattering distribution confirmed the polydispersity of the simulated intestinal fluids compared to the monodisperse distribution observed for FaSSIF v1). There was a large difference in the size of the structures found based on the composition of the SIF, for example, the diameter of the structures measured in felodipine in the minimum TAC media was measured to be 170 ± 5 nm which decreased to 5.1 ± 0.2 nm in the maximum TAC media point. The size measured of the colloidal structures of felodipine in the FaSSIF v1 was 86 ± 1 nm. However, there was no simple correlation between solubility and colloidal size.Nanoparticle tracking analysis was used for the first time to characterise colloidal structures within SIF and the results were compared to those obtained by dynamic light scattering. The particle size measured by dynamic light scattering was generally greater in media with a lower concentration of amphiphiles and smaller in media of a higher concentration of amphiphiles, compared to that of the data yielded by nanoparticle tracking analysis.This work shows that the colloidal structures formed vary depending on the composition of SIF which affects the solubility. Work is ongoing to determine the relationship between colloidal structure and solubility.

Ascorbyl palmitate nanofiber-reinforced hydrogels for drug delivery in soft tissues

Nanofiber-based hydrogel delivery systems have recently shown great potential in biomedical applications, specifically due to their high surface-to-volume ratio of ultra-fine nanofibers and their ability to carry low solubility drugs. Herein, we introduce a visible light-triggered in situ-gelling drug vehicle (GAP Gel) composed of ascorbyl palmitate (AP) nanofibers and gelatin methacryloyl polymer. AP nanofibers form self-assembled structures through intermolecular interactions with a hydrophobic drug-loading core. We demonstrate that the hydrophilic periphery of AP nanofibers allows them to interact with other hydrophilic molecules via hydrogen bonds. The presence of AP nanofibers significantly enhances the viscoelasticity of GAP Gel in a concentration-dependent manner. Further, GAP Gel shows in vitro biocompatibility and sustained drug delivery efficacy when loaded with a hydrophobic antibiotic. Likewise, GAP Gel shows excellent in vivo biocompatibility when implanted in immunocompetent mice in various forms. Lastly, GAP Gels maintain cell viability when cultured in a 3D-environment over 7 days, establishing it as a promising and versatile hydrogel platform for the delivery of biotherapeutics.

Nanoemulgel: A Comprehensive Review of Formulation Strategies, Characterization, Patents and Applications

<p>Background: Delivering hydrophobic or poorly soluble drugs has become increasingly challenging, with issues like stability and bioavailability complicating the process. Among various strategies devised to address these problems, nanoemulgels have proven effective. Nanoemulgels combine a gel base and an emulsion at the nanoscale, making them excellent for drug delivery. The nanoemulsion component protects the active ingredient from degradative reactions like hydrolysis and enzymatic degradation. Meanwhile, the gel base enhances the emulsion's thermodynamic stability by increasing the viscosity of the aqueous phase and reducing surface and interfacial tension. </p><p> Objective: The primary objective of this review was to explore nanoemulgels as a drug delivery system in the pharmaceutical industry. It delves into the advantages and applications of nanoemulgels in various medical fields, compares them with conventional emulgel, and examines formulation strategies, preparation methods, patent trends, future prospects, and evaluation methods in detail. </p><p> Method: An exhaustive literature survey was conducted keeping in view the various aspects of nanoemulgel. Information from various resources, such as books, review articles, scientific reports, research articles, and patents, were searched, read, analyzed, and summarized. </p><p> Conclusion: This review article thoroughly examines nanoemulgels, discussing their formulation strategies, characterization techniques, and applications in various fields. It highlights their benefits, such as enhanced drug solubility, controlled release, improved stability, and targeted delivery. The article also covers patents related to nanoemulgel technology and explores its future prospects, emphasizing potential applications in pharmaceuticals, cosmetics, dermatology, and other industries.</p>

Apremilast Amorphous Solid Dispersions: Formulation Optimization using QbD and Comprehensive In vitro-In silico Assessment

Aim: The study aims to develop a 3rd generation amorphous solid dispersion (ASD) of Apremilast (APST) employing the Design of Experiment (DoE) methodology, followed by a thorough assessment including in silico pharmacokinetics. Background: APST, classified as a BCS-Class IV molecule due to its low solubility and permea-bility, exhibits highly variable oral bioavailability across different species. Objective: In this study, a 3rd generation ASD of APST was developed using the DoE approach. Methods: The miscibility of APST within polymers was assessed using solubility parameters and Flory Huggin equations. Phase solubility studies were conducted to identify the most suitable polymer-surfactant combination for maximizing drug solubility. The produced solid dispersions were characterized using FTIR, DSC, XRD, DVS, and SEM. Results: The combination of APST and Soluplus® in a 1:5 ratio resulted in the highest improve-ment in solubility and dissolution, with vitamin E TGPS being identified as the most efficient sur-factant. Stability studies were carried out, and findings revealed that the ASD remained stable un-der accelerated conditions for up to 3 months, suggesting its suitability for scaling up for industri-al applications. In silico predictions of the pharmacokinetics of APST following oral administra-tion of solid dispersion formulations were determined by PBBM using GastroPlus™. Conclusion: The simulation of oral absorption profiles for APST showed a significant improve-ment in both Cmax and AUC for the solid dispersion formulations compared to plain drugs. This study makes a significant contribution to the field of pharmaceutical science by addressing the formulation complexities inherent in poorly water-soluble compounds like APST.

Dual-continuous microneedle patch integrating transdermal delivery of pH-sensitive licorzinc MOFs and Zn2+ hydrogel sensors for treating alopecia areata

Licorzinc is a commonly used immunomodulator, but faces poor water solubility, high oral dose, and side effects of zinc accumulation by long-term administration. Herein, a new licorzincform was developed by adsorbing glycyrrhizic acid (GA) into zeolitic imidazolate framework-8 (GA@ZIF-8) with superior solubility and acid-responsive drug release properties. Then, a dual-continuous microneedle patch was developed for simultaneous transdermal delivery of GA@ZIF-8 and monitoring Zn2+ in local tissues, where dissolving microneedles as a drug delivery unit were fabricated from hyaluronic acid. In contrast, swollen hydrogel microneedles as a diagnostic unit were prepared from double cross-linking of N-acryloyl-glycinamide and α-methylacrylic acid and hybridized with Eu3+ and terpyridine (TPy). The microneedles for transdermal GA@ZIF-8 delivery were completely dissolved in 2 min, which improved the cyclophosphamide-induced hair follicle recession in mice by reducing CD8+NKG2D+ T cells infiltration, inhibiting Jak receptor activation, and decreasing IL-15 and IFN-γ. Additionally, as a sensor unit, the microneedles rapidly absorbed water swelled when stabbed into the skin, and fluoresced red when exposed to 365 nm light. Zn2+ in the inter tissue fluid competes with Eu3+ in the TPy-Eu3+ complex and coordinates with Tpy, which triggers a change in fluorescence. Notably, the detection Zn2+concentration range was 10–8 M–10–1 M, and it was not disturbed by metal ions including Na+, K+, Mg2+, and Ca2+, suggesting that it is competent to be applied as a real-time chemosensor of Zn2+. Collectively, this newly designed system with both therapeutic and diagnostic functions provides a new strategy for treating zinc-related diseases.

Insights into bismuthene and antimonene as cisplatin drug carriers: A theoretical comparative investigation

While effective targeted delivery is a challenge in nanomedicine for the delivery of anti-cancer drugs, this work focuses on the potential use of Bismuthene and antimonene nanosheets as nanocarriers for cisplatin anti-cancer using DFT methods. The results indicate that, compared to antimonene, bismuthene demonstrates significantly better physical stability, drug release rate, solubility, and biocompatibility, making it an excellent candidate for drug delivery systems. The parallel and perpendicular orientations of the anticancer drug were adsorbed on both nanosheets; the parallel configuration was the most energetically favored with an adsorption energy of −0.79 eV at the parallel site. A charge transfer from the drug to the bismuthene sheet is also revealed by the electronic charge analysis and DOS calculation, thus confirming efficient drug adsorption. Modeling a proton attack on the drug and the carrier surface near the adsorption sites was performed to model drug release, showing the stability and potential of bismuthene in this aspect of drug release mechanisms. Further, with an approach to studying its interactions with biomolecules, interactions of the drug molecule have been analyzed with amino acids, showing that drugs interact efficiently. Further assessments concerning work function, recovery time, electron localization function, and frontier molecular orbital analyses leave no doubt that bismuthene has beneficial features over antimonene. These thorough assessments present bismuthene as a more promising nanocarrier for the delivery of anti-cancer drugs and open a potential pathway to enhance the efficacy of strategies against cancer treatment.

Lipid-based nanoparticles: innovations in ocular drug delivery.

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

Multichannel 3D-printed bionanoparticles-loaded tablet (M3DPBT): designing, development, and in vitro functionality assessment

BackgroundThe intersubject variability which was related to the genetic makeup was the major cause of change in pharmacological and pharmacokinetic behavior of same dosage form in varied human being. 3D printing technology will help therapy evolve and eliminate the limitations of conventional technologies. Nebivolol's (NBL)-limited oral bioavailability is mainly due to its poor aqueous solubility. The research aims to combine advanced 3D printing technology and nanotechnology to design customized therapy and enhance the functionality of NBL using a statistical approach.Results and discussionThe results of the phase solubility indicated that NBL was a poorly aqueous soluble drug. Its solubility was increased by employing nanoparticle drug delivery, which is a promising solubility enhancement technique. The 32 full factorial design was employed to develop and optimize bionanoparticles (BNPs) by solvent evaporation technique using poly (lactic-co-glycolic acid 50:50) (PLGA 50:50) and poloxamer-407 as a surfactant. The BNPs were characterized by % encapsulation efficiency (% EE), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC), transmission electron microscope (TEM), zeta potential, polydispersity index (PDI), particle size, in vitro drug release, etc. The BNPs loaded of NBL were further incorporated into the multichannel 3D-controlled release tablets made by PVA filaments employing fused deposition modeling (FDM) technology optimized by central composite design (CCD). Multichannel 3D-printed bionanoparticles-loaded tablet (M3DPBT) was optimized using CCD. All designed M3DPBTs were evaluated for post-fabrication parameters. The optimized M3DPBT could release more than 85% NBL within 10 h.ConclusionsThe newly fabricated M3DPBT was found stable. The amount of PLGA 50:50 and Polaxomer was significant for developing BNPs. % infill and layer height were observed as critical for the designing M3DPBT. The combined novel 3D printing and nanotechnology technology will open a new direction for patient compliance and better therapeutic effects.Graphical abstractDesigning and developing of M3DPBT is substantially improve the patient compliance and therapeutic effectiveness of Nebivolol.

Mucoadhesive and drug release of cholic acid based thiomeric micelles and encapsulated silver and gold nanoparticles for anticancer studies

Among the various drug delivery system, mucoadhesive formulation is a promising approach to deliver drugs and vaccine through close contact with the absorption site and mucous membrane. Bile acids have received considerable interest in drug delivery (DD) applications owing to their advantages of biocompatibility, ability to act as both drug solubilizing and permeation-modifying agents. In this aspects, cholic acid (CA) based thiomeric micelles with improved mucoadhesive properties have been synthesized by functionalization of thiol groups and conjugation of PEG. The synthesized CA based thiomeric micelles (TCA-PEG) were characterized by 1HNMR, ATR-IR, GPC, Zeta potential and contact angle techniques. The critical micelle concentration (CMC) of TCA-PEG was measured by a fluorescence spectrometer using pyrene as a probe. The mucoadhesive properties of TCA-PEG polymeric micelles (PMs) were examined on the goat anterior tongue mucosa with an effectively higher adhesion of 40 % up to 3 h study period. Also, curcumin loaded TCA-PEG PMs showed only 13 % of the drug released up to the period of 3 h. The TCA-PEG PMs act as reducing and stabilizing agents for the preparation of gold and silver nanoparticle (Ag and Au NPs) and were characterized by UV–visible, DLS, Zeta potential, XPS, and HR-TEM techniques. The cytotoxicity and cellular apoptosis of TCA-PEG PMs encapsulated Ag and Au NPs were examined by MTT assay and AO/PI dual staining using MCF-7 breast cancer cells wherein AgNPs showed an effective cytotoxicity than AuNPs. The developed TCA-PEG PMs act as reservoir for soubilization of hydrophobic and hydrophilic drugs and ideal template for encapsulation of silver and gold nanoparticles for mucoadhesive DD system.

Dosage by design – 3D printing individualized cabozantinib tablets with immediate release

Production of patient-specific dosage forms is important to improve patient adherence and effectiveness while reducing the prevalence and severity of adverse effects. Due to its possibility of rapid prototyping 3D printing can be used to produce individual dosages while utilizing techniques such as hot melt extrusion to increase the bioavailability of poorly soluble drugs. In this work, Parteck MXP and Kollicoat IR were used as water-soluble polymer bases for formulation development for 3D printing of various dosages incorporating cabozantinib while enabling immediate release. The effect of tablet design and the excipients sorbitol, croscarmellose sodium, and sodium starch glycolate was investigated for this goal. A way to calculate the size of tablets for predetermined dosages is proposed to enable the printing of individual strengths from one formulation. Rheological data were collected to deepen the understanding of the role of melt viscosity in 3D printing and hot melt extrusion processes. The production of immediate-release cabozantinib tablets containing every therapeutically relevant dosage in a single unit produced by two-step 3D printing was realized.

Deep Eutectic Solvents Enhancing Drug Solubility and Its Delivery.

Deep eutectic solvents (DES) are environmentally friendly solvents with the potential to dissolve bioactive compounds without affecting their characteristics. DES has special qualities that can be customized to meet the unique characteristics of a biomolecule/active pharmaceutical ingredient (API) in accordance with various therapeutic needs, providing a reliable approach in opening the door for the creation of cutting-edge drug formulations by resolving solubility issues in pharmaceutics. This study outlines newly developing approaches to solve the problem of inefficient API extraction due to poor solubility. These emerging strategies also have the capacity to alter the chemical and physical stability of API, which triggers drug's shelf life and their possible health benefits. It is anticipated that the highlighted methods and processes will be developed to capitalize on the DES potential to improve drug solubility and delivery in the pharmaceutical sector.

Investigation of the Influence of Copovidone Properties and Hot-Melt Extrusion Process on Level of Impurities, In Vitro Release, and Stability of an Amorphous Solid Dispersion Product.

Hot-melt extrusion (HME) is a widely used method for creating amorphous solid dispersions (ASDs) of poorly soluble drug substances, where the drug is molecularly dispersed in a solid polymer matrix. This study examines the impact of three different copovidone excipients, their reactive impurity levels, HME barrel temperature, and the distribution of colloidal silicon dioxide (SiO2) on impurity levels, stability, and drug release of ASDs and their tablets. Initial peroxide levels were higher in Kollidon VA 64 (KVA64) and Plasdone S630 (PS630) compared to Plasdone S630 Ultra (PS630U), leading to greater oxidative degradation of the drug in fresh ASD tablets. However, stability testing (50 °C, closed container, 50 °C/30% RH, open conditions) showed lower oxidative degradation impurities in ASD tablets prepared at higher barrel temperatures, likely due to greater peroxide degradation. Plasdone S630 is suitable for ASDs with drugs prone to oxidative degradation, while standard purity grades may benefit drugs susceptible to free radical degradation, as they generate fewer free radicals post-HME. ASD tablets exhibited greater physical stability than milled extrudate samples, likely due to reduced exposure to stability conditions within the tablet matrix. Including SiO2 in the extrudate composition resulted in greater physical stability of the ASD system in the tablet; however, it negatively affected chemical stability, promoting greater oxidative degradation and hydroxylation of the drug substance. No impact of the distribution of SiO2 on drug release was observed. The study also confirmed the congruent release of copovidone, the drug substance, and Tween 80 using flow NMR coupled with in-line UV/vis. This research highlights the critical roles of peroxide levels and SiO2 in influencing the dissolution and physical and chemical stability of ASDs. The findings provide valuable insights for developing stable and effective pharmaceutical formulations, emphasizing the importance of controlling reactive impurities and excipient characteristics in ASD products prepared by using HME.

A Self-Skin Permeable Doxorubicin Loaded Nanogel Composite as a Transdermal Device for Breast Cancer Therapy.

Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The β-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The β-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. β-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of β-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. In vitro swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with in vivo pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.