Improved Drug Release Research Articles

Development of in vitro and in vivo evaluation of mucoadhesive in-situ gel for intranasal delivery of vinpocetine

Alzheimer’s disease (AD), which is marked by gradual neuronal decline and subsequent loss of cognitive functions and memory, poses significant treatment challenges. The present study involved the development, in vitro, and in vivo evaluation of a novel intranasal mucoadhesive in-situ gel of vinpocetine (VIN) with the aim to target the brain. An innovative gel formulation composed of poloxamer 407, HPMC E15 LV, and citric acid as a solubilizer was developed by 23 Factorial Design. The developed optimal formulation exhibited favorable rheological properties as it displayed ideal gelation time (31.6 ± 1.52 sec), optimum gelling temperature (32 ± 1.0 °C), enhanced mucoadhesive strength (6622 ± 2.64 dynes/cm2), prolonged adhesion (7.22 ± 0.57 hrs) compared with the baseline formulation (F18), and improved drug release in 12 hrs (39.59 ± 1.6%). In vivo, pharmacokinetics revealed a significant increase in Cmax (∼2-fold) and AUC0-t (∼2-fold) in the brain with the in-situ intranasal gel compared to the oral route. In the rat model of AD, in-situ intranasal gel demonstrated significantly greater efficacy (p < 0.001) than oral administration in alleviating AD symptoms as evidenced by behavioral and histological studies. Thus, VIN in-situ gel can be safe and noninvasive for nose-to-brain drug delivery.

Functionalized nanostructures and targeted delivery systems with a focus on plant-derived natural agents for COVID-19 therapy: A review and outlook

Abstract The COVID-19 pandemic strongly stimulated research on anti-SARS-CoV-2 virus treatments. The present study reviews a nanotechnology approach to this task, i.e., in other terms, a nanomedicine approach. Nanotechnology aims to create nanostructures or nanoparticles, also called nanoformulations, for targeted delivery of drugs, as well as improved drug release control. This approach is particularly promising to enhance the antiviral effect of natural pro-drugs. Here, we review several nanoformulations developed for the targeted delivery of medications against SARS-CoV-2. We draw special attention to repurposing strategies for known antiviral and natural therapies. Also, functionalized nanoparticles with specific targeting moieties and functional groups were discussed. The summary could motivate researchers to pursue more studies in this exciting area by seeking nanotechnology-based, cutting-edge, tailored delivery strategies for the SARS-CoV-2 virus.

Liquisolid Compacts: A Paradigm in Drug Delivery System

Liquisolid compacts (LSCs) are a fascinating drug delivery technology that offers numerous advantages, particularly for Biopharmaceutical Classification System (BCS) class 2 drugs. In essence, they convert liquid medications into free-flowing, compressible powder forms suitable for tablet production with improved drug release characteristics. Formulation of liquisolid compacts represents a valuable strategy for overcoming solubility challenges, ultimately contributing to the development of an effective and patient-friendly drug delivery system.

Light-Responsive Smart Nanoliposomes: Harnessing the Azobenzene Moiety for Controlled Drug Release under Near-Infrared Irradiation.

The azobenzene moiety is an intriguing structure that deforms under UV and visible light, indicating a high potential for biomedical applications. However, its reaction to UV radiation is problematic because of its high energy and low tissue penetration. Unlike previous research on azobenzene structures in photoresponsive materials, this study presents a novel method for imparting photostimulation-responsive properties to liposomes by incorporating the azobenzene moiety and extending the light wavelength with up-conversion nanoparticles. First, the azobenzene structure was incorporated into a phospholipid molecule to create Azo-PSG, which could spontaneously form vesicle assemblies in aqueous solutions and isomerizes within 1 h of light exposure. Furthermore, orthogonal up-conversion nanoparticles with a core-shell structure were created by sequentially growing lanthanide rare earths in the shell layer, which efficiently converts near-infrared light into ultraviolet (400 nm) and blue-green (540 nm) light. Combining these core-shell structured up-conversion nanomaterials with Azo-PSG molecules resulted in the creation of a near-infrared light-responsive smart nanoliposome system. Under near-infrared light irradiation, UCNPs emit UV and blue-green light, causing conformational changes in Azo-PSG molecules that allow drug release within 6 h. The reversible structural shift of Azo-PSG in response to light stimulation holds enormous promise for improving drug release techniques. This novel technique also expands the usage of UV-responsive compounds beyond their constraints of low penetration and high biotoxicity, allowing for rapid medication release under NIR light.

Targeted delivery of letrozole-loaded Mg-doped cobalt ferrite nanoparticles for breast cancer treatment

Breast cancer is the most common cancer in women globally. Letrozole is an aromatase inhibitor used as an anticancer drug. Conventional Letrozole therapies for breast cancer often cause adverse effects when administered orally or parenterally. Efforts have been made to develop an advanced drug delivery system for breast cancer treatment, aiming to improve drug release accuracy and therapeutic efficacy while minimizing side effects. This study focuses on magnesium-doped cobalt ferrite nanoparticles (Mg-doped CFNPs) as potential drug delivery carrier for breast cancer treatment. Mg-doped CFNPs with the chemical formula Co1-xMgxFe2O4 (where x = 0.0, 0.05, 0.10, 0.15, 0.20 and 0.25) were synthesized with different concentrations of 5 %, 10 %, 15 %, 20 %, and 25 % by the sol gel method with a fine size of 30–70 nm and their characteristics such as surface morphology, structural properties, chemical composition, and charge were investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and zeta potential analysis respectively. After synthesis, the Mg-doped CFNPs were coated with Poly ethylene glycol (PEG) and encapsulated with Letrozole, which exhibited <10 % hemolytic activity across all concentrations, as well as minimal cytotoxic effects on non-cancerous cells (HEK-293) but exhibited significant toxicity towards breast cancer cell lines (MCF-7, MDA-MB-231).The best results were obtained at a concentration of 25 % in both the hemolytic assay and the MTT assay, which indicated that increasing the amount of magnesium in cobalt decreased the toxicity and increased the drug release efficiency of nanoparticles.

The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations

One of the limitations with an amorphous solid dispersion (ASD) formulation strategy is low drug loading. Hydrophobic drugs have poor wettability and require a substantial amount of polymer to stabilize the amorphous drug and facilitate release. Using grazoprevir and hypromellose acetate succinate as model drug and polymer respectively, the interplay between particle surface composition, particle wettability, and release performance was investigated. A hierarchical particle approach was used where the surfaces of high drug loading ASDs generated by either solvent evaporation or co-precipitation were further modified with a secondary excipient (i.e., polymer or wetting agent). The surface-modified particles were characterized for drug release, wettability, morphology, and surface composition using two-stage dissolution studies, contact angle measurements, scanning electron microscopy, and X-ray photoelectron spectroscopy, respectively. Despite surface modification with hydrophilic polymers, hierarchical cPAD particles did not consistently exhibit good release performance. Contact angle measurements showed that the secondary excipient had a profound impact on particle wettability. Particles with good wettability showed improved drug release relative to particles that did not wet well, even with similar drug loadings. These observations underscore the intricate interplay between particle wettability and performance in amorphous dispersion formulations and illustrate a promising hierarchical particle approach to formulate high drug loading amorphous dispersions with improved dissolution performance.

An approach for pH-independent release of poorly soluble ionizable drugs using hot-melt extrusion

Hot melt extrudates with combinations of Soluplus® and Aqoat® AS-LF or Eudragit® E PO were investigated to improve drug release and to overcome the pH-dependent release of poorly water-soluble basic (itraconazole, ITZ) and acidic (mefenamic acid, MFA) drugs. The release of ITZ was improved in both 0.1 N HCl and PBS pH 6.8 by hot-melt extrusion with combinations of Soluplus®:Aqoat® AS-LF and can be adjusted by varying the ratio of the polymers. At the ratio Soluplus®:Aqoat® AS®LF 75:25, an almost pH-independent release was achieved without any drop in the drug concentration within 24 h. A pH-independent and extended release (over 24 h) was obtained from milled extrudates when formulated in erodible matrix tablets using 15 % Methocel® K15M as the carrier. The release of MFA from extrudates with Soluplus® was immediate only in PBS pH 6.8. From extrudates with cationic Eudragit® E PO the release of MFA was slow in 0.1 N HCl and PBS pH 6.8, due to poor drug solubility and insoluble Eudragit® EPO, respectively. However, in the medium with an intermediate pH of 5.5, both MFA and Eudragit® E PO are highly ionized, and the release was fast, complete, and stable within 24 h. These release behaviors could be to some degree applicable for immediate or enteric, but not for extended-release formulations.

Unleashing the Potential of β -cyclodextrin Inclusion Complexes in Bitter Taste Abatement: Development, Optimization and Evaluation of Taste Masked Anti-emetic Chewing Gum of Promethazine Hydrochloride.

Motion sickness also known as kinetosis is a condition in which there exists a disagreement between visually perceived movement and the vestibular system's sense of movement. Nausea, vomiting, dizziness, fatigue, and headache are the most common symptoms of motion sickness. This study mainly focuses on the taste masking of Promethazine Hydrochloride (PMZ) by inclusion complexation method, its formulation development in the chewing gum form by using directly compressible gum base HIG® and its quality and performance testing. Different molar ratios (1:1, 1:2, 1:3 and 1:4) of PMZ-cyclodextrin complexes were prepared by using β-Cyclodextrin(β-CD) as a taste masking agent. These complexes were evaluated for FTIR, DSC, % Entrapment Efficiency, % drug yield, and taste evaluation by E-Tongue. The optimized ratio was further evaluated by sophisticated analytical techniques such as Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD). A central composite design (CCD) (3 ^2) was utilized to examine the effects of independent variables (amount of gum-X1 and amount of plasticizer-X2) on dependent variables (%CDRY1 and hardness Y2). The prepared gums were evaluated for drug content, organoleptic properties, in-vitro dissolution testing by fabricated disintegration apparatus, texture analysis, etc. The optimization statistics showed that on decreasing the amount of gum, in- vitro drug release increases and hardness decreases. The optimized batch MCG-2 of Promethazine MCG showed 92.34 ± 0.92% of drug release, whereas for marketed formulation (Phenergan®-25mg) drug release value was 86.19 ± 1.88%. Results provided evidence that PMZ MCGs could be a better alternative to conventional tablet formulations with improved drug release, palatability and texture.

Nanoparticle-based targeted therapy through EGFR tyrosine kinase inhibitors and their recent advances in lung cancer therapy

The emergence and subsequent advancement of nanotechnology in recent years have greatly benefited the healthcare sector, particularly in the treatment of cancer. As per study, major fatalities are related to the lung cancer. For many years, oral tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor (EGFR) family of receptors have been used in the clinic to treat human malignancies, although they observed some very serious adverse effects in the treatment of lung cancer, especially in non-small cell lung cancer (NSCLC). Despite EGFR-TKIs’ exceptional qualities as small-molecule targeted medications, their applicability is nevertheless limited by their poor solubility, inconsistent oral bioavailability, high daily dose needs, high plasma albumin binding propensity, and initial/acquired drug resistance. Article’s purpose is to investigate EGFR-TKI’s effects on lung cancer and get around some of its drawbacks, nanotechnology will be an innovative strategy. An effective tool to increase the effectiveness of these pharmaceuticals is nanotechnology by methods other than oral. This article signifies that a range of nanomedicine delivery systems have been developed to effectively distribute EGFR-TKIs with improved drug release kinetics and tissue-targeting capacity. This review article intends to present information regarding lung cancer and EGFR relation, mechanism of recently approved EGFR-TKI’s targeted therapy, an updated landscape of EGFR-TKIs and their clinical status over lung cancer, advantages and disadvantages of nanotechnology, and new breakthroughs in nano-delivery which mentioned as a significantly better over traditional drug chemotherapy and delivery.

ZIF-8-mediated block copolymer micelles and its application in drug delivery

Block copolymer micelles have been widely used in drug delivery. Great efforts have been made to optimize the function of block copolymer micelles and further enhance their bioavailability. We propose a means of embedding ZIF-8 in block copolymer micelles to regulate its stability for improving the drug release kinetics. The block copolymer poly (2-(diisopropyl amino-ethyl methacrylate)-block-poly (vinylimidazole-co-poly (ethylene glycol) methyl methacrylate) (PDPA18-b-P(Vim18-co-P(EG)5MA21) (PDPV) bearing imidazole moiety was synthesized through reversible addition-cracking chain transfer (RAFT) polymerization. PDPV can self-assemble into micelles in aqueous solution and then be loaded with doxorubicin (DOX) to obtain DOX@PDPV, followed by Zn coordination to anchor ZIF-8 to the PVim moiety in DOX@PDPV to obtain the final drug delivery system DOX@PDPV@ZIF-8 hybrids. The DOX@PDPV@ZIF-8 hybrids can avoid the influence of the critical micelle concentration (CMC) on it, which was further prevent the premature leakage of DOX under physiological conditions. Furthermore, the pH-responsive properties of PDPA and ZIF-8 facilitated enabled the effective release of DOX in weakly acidic tumor environments. In vitro studies also confirmed that DOX@PDPV@ZIF-8 improved DOX accumulation in cells, leading to the inhibition of cancer cell growth. Therefore, the integrated design provided a promising strategy to regulate the stability of block copolymer micelles, improve drug release kinetics, and ultimately inhibit the growth of cancer cell.

Characterization of Prototype Gummy Formulations Provides Insight into Setting Quality Standards.

Gummy formulations are considered suitable alternatives to traditional oral dosage forms like tablets and capsules due to their merits that include chewability, softness/flexibility, improved drug release, administration without water, appealing organoleptic properties, better patient compliance, easy preparation and usefulness forpersonsof different ages (e.g. children). Though there is increasing interest in gummy formulations containing drugs, measurable parameters, and specification limits for evaluating their quality are scarce. Quality check forms an essential part of the pharmaceutical development process because drug products must be distributed as consistently stable, safe, and therapeutically effective entities. Consequently, some quality parameters that could contribute to the overall performance of typical gummy formulations were investigated employing sixbrands of non-medicinal gummies as specimens. Accordingly, key physicochemical and micromechanical characteristics namely adhesiveness (0.009 - 0.028mJ), adhesive force (0.009 - 0.055 N), chewiness (2.780 - 6.753 N), cohesiveness (0.910 - 0.990), hardness (2.984 - 7.453 N), springiness (0.960 - 1.000), and resilience (0.388 - 0.572), matrix firmness - compression load (2.653 - 6.753 N) and work done (3.288 - 6.829mJ), rupture (5.315 - 29.016 N), moisture content (< 5%), weight uniformity (< 2.5g; < 7.5% deviation), and intraoral dissolution pH (≥ 3.5 ≤ 6.8) were quantified to identify measures that may potentially function as specification limits and serve as prospective reference points for evaluating the quality of gummy formulations. Findings from this workcontribute to ongoing efforts to standardize the quality control strategies for gummy formulations, particularly those intended for oral drug delivery.

Combretastatin A4 phosphate encapsulated in hyaluronic acid nanoparticles is highly cytotoxic to oral squamous cell carcinoma.

To investigate the toxicity of combretastatin A4 phosphate (CA4P) hyaluronic acid (HA) gel nanoparticles (HA-CA4P-NPs) in OSCC (oral squamous cell carcinoma). Toxicity was investigated using fluorescence microscopy, MTT assay, flow cytometry, and OSCC xenograft mouse models. Compared with CA4P, HA-CA4P-NPs generated nearly 10 times more fluorescence in OSCC cells. Cytotoxicity assays showed that HACA4P-NPs were more toxic to SCC-4 cells but not to HNECs. Remarkable necrosis was induced in SCC-4 cells after exposure to HA-CA4P-NPs, and related proteins were upregulated. Furthermore, HA-CA4P-NPs significantly reduced the tumour size. HA-CA4P-NPs improved drug release and delivery, and increased cytotoxicity to cancer cells.

QbD Assisted Systematic Review for Optimizing the Selection of PVP as a Ternary Substance in Enhancing the Complexation Efficiency of Cyclodextrins: a Pilot Study.

Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (Ks) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a βCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and β-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.

Generality of Enhancing the Dissolution Rates of Free Acid Amorphous Solid Dispersions by the Incorporation of Sodium Hydroxide.

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated. When PVPVA was used as the polymer carrier for the drugs in this study, enhancements of dissolution rates from 7 to 78 times were observed by the incorporation of NaOH into the ASDs at a 1:1 molar ratio with respect to the drug. The drugs having lower amorphous solubilities showed greater enhancement ratios, providing a promising path to improve the drug release performance from their ASDs. Samples generated by rotary evaporation and spray drying demonstrated comparable dissolution rates and enhancements when NaOH was added, establishing a theoretical foundation to bridge the ASD dissolution performance for samples prepared by different solvent-removal processes. In the comparison of polymer carriers, when HPMCAS was applied in the selected system (indomethacin ASD), a dissolution rate enhancement of 2.7 times by the incorporated NaOH was observed, significantly lower than the enhancement of 53 times from the PVPVA-based ASD. This was attributed to the combination of a lower dissolution rate of HPMCAS and the competition for NaOH between IMC and HPMCAS. By studying the generality of enhancing ASD dissolution rates by the incorporation of counterions, this study provides valuable insights into further improving drug release from ASD formulations of poorly water-soluble drugs.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.

Exploring drug release performance of hollow‐structured CS/SA/POSS composite gel spheres employing hydrophilic polymerizable AS‐POSS as crosslinker

AbstractThis study prepares a series of hollow‐structured CS/SA/POSS composite gel spheres with a diameter of ~2.5 mm by using hydrophilic Janus‐type polyhedral oligomeric silsesquioxane (AS‐POSS) as a crosslinking agent in combination with sodium alginate and chitosan via electrostatic adsorption/free radical polymerization. As the content of POSS increases, the wall thickness of the gel spheres also increases from 20 to 30 μm, leading to a more compact and smooth wall structure in the polymerized CS/SA/POSS composite gel spheres. Additionally, the introduction and polymerization of POSS significantly enhance the stability, drug loading rate, and entrapment rate of the gel spheres, providing them with improved drug release capabilities. For hydrophilic drug doxorubicin, the loading rate and encapsulation rate reach 41.2% and 79.9%, respectively, while for the hydrophobic drug ibuprofen, they are 14.7% and 76.3%. Compared to some previously reported drug‐loaded gel materials, the gels prepared in this study demonstrate relatively higher drug loading performance. Thus, these hollow‐structured CS/SA/POSS composite gel spheres hold promise as innovative drug carriers in the biomedical field.

Design, fabrication, and evaluation of keratin and pectin incorporated supramolecular structured zero-oxidation state selenium nanogel blended 3D printed transdermal patch

This study investigates the synthesis of selenium nanoparticles (SeNPs), owing to the low cost and abundance of selenium. However, the toxicity of SeNP prompts the development of a selenium nanocomposite (SeNC) containing pectin, keratin, and ferulic acid to improve the bioactivity of Se[0]. Further, incorporating the SeNC in a suitable formulation for drug delivery as a transdermal patch was worth studying. Accordingly, various analytical techniques were used to characterize the SeNPs and the SeNC, confirming successful synthesis and encapsulation. The SeNC exhibited notable particle size of 448.2 ± 50.2 nm, high encapsulation efficiency (98.90 % ± 2.4 %), 28.1 ± 0.45 drug loading, and sustained drug release at pH 5.5. Zeta potential and XPS confirmed the zero-oxidation state. The supramolecular structure was evident from spectral analysis endorsing the semi-crystalline nature of the SeNC and SEM images showcasing flower-shaped structures. Further, the SeNC demonstrated sustained drug release (approx. 22 % at 48 h) and wound-healing potential in L929 fibroblast cells. Subsequently, the SeNC loaded into a gelling agent exhibited shear thinning properties and improved drug release by nearly 58 %. A 3D printed reservoir-type transdermal patch was developed utilizing the SeNC-loaded gel, surpassing commercially available patches in characteristics such as % moisture uptake, tensile strength, and hydrophobicity. The patch, evaluated through permeation studies and CAM assay, exhibited controlled drug release and angiogenic properties for enhanced wound healing. The study concludes that this patch can serve as a smart dressing with tailored functionality for different wound stages, offering a promising novel drug delivery system for wound healing.

Binary Mixtures of Meloxicam and L-Tartaric Acid for Oral Bioavailability Modulation of Pharmaceutical Dosage Forms.

Binary mixtures of active pharmaceutical ingredients (API) are researched to improve the oral bioavailability of pharmaceutical dosage forms. The purpose of this study was to obtain mixtures of meloxicam and L-tartaric acid because tartaric acid improves intestinal absorption and meloxicam is more soluble in a weakly basic environment. The mixtures in the 0-1 molar fraction range, obtained from solvent-assisted mechanosynthesis, were investigated by differential scanning calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, Fourier Transform Raman spectroscopy (FT-Raman), X-ray powder diffraction (XRD) and solubility tests. The physicochemical characteristics of the compounds obtained from DSC data reveal, for the first time, the formation of a co-crystal at meloxicam molar fraction of 0.5. FTIR spectroscopy data show the existence of hydrogen bonds between the co-crystal components meloxicam and L-tartaric acid. FT-Raman spectroscopy was used complementary with FT-IR spectroscopy to analyze the pure APIs and their mixtures, to emphasize the appearance/disappearance and the shifts of the position/intensity of vibrational bands, following the formation of hydrogen-bonded structures or van der Waals interactions, and to especially monitor the crystal lattice vibrations below 400 cm-1. The experimental results obtained by X-ray powder diffraction confirmed the formation of the co-crystal by the loss and, respectively, the apparition of peaks from the single components in the co-crystal diffractogram. The solubility tests showed that the co-crystal product has a lower aqueous solubility due to the acidic character of the other component, tartaric acid. However, when the solubility tests were performed in buffer solution of pH 7.4, the solubility of meloxicam from the co-crystal mixture was increased by 57% compared to that of pure meloxicam. In conclusion, the studied API mixtures may be considered potential biomaterials for improved drug release molecular solids.

Comprehensive Characterization and Comparative Assessment of Carvedilol Solid Dispersions: Insights into Enhanced Bioavailability and Stability Profiles

Carvedilol, a non-selective beta-adrenergic antagonist, poses a challenge in achieving optimal bioavailability due to its poor aqueous solubility. This study aimed to enhance the solubility and dissolution rate of carvedilol through the formulation and evaluation of solid dispersions. Various solid dispersion formulations were prepared using different carriers and methods, including solvent evaporation, fusion, and spray-drying techniques. The prepared formulations were systematically characterized using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM) to investigate drug-carrier interactions, solid-state changes, and morphological characteristics. Evaluation of the formulated solid dispersions involved in vitro dissolution studies, solubility enhancement assays, and stability assessments. Dissolution profiles revealed significantly improved drug release rates for the solid dispersion formulations compared to the pure drug. The solubility of carvedilol was notably enhanced in the solid dispersion systems, indicating improved drug dissolution behavior. Stability studies demonstrated the robustness of selected formulations against environmental factors over an extended period. Moreover, pharmacokinetic studies conducted in animal models showcased enhanced bioavailability of carvedilol from the optimized solid dispersion formulation compared to the conventional drug formulation. This comprehensive investigation provides valuable insights into the development of carvedilol solid dispersions, elucidating the influence of formulation variables on drug solubility, dissolution, stability, and ultimately, bioavailability enhancement. The findings underscore the potential of solid dispersion technology as a promising strategy to overcome the solubility challenges associated with carvedilol, paving the way for improved therapeutic efficacy and patient compliance.

Cathepsin B Processing Is Required for the In Vivo Efficacy of Albumin-Drug Conjugates.

Targeted drug delivery approaches that selectively and preferentially deliver therapeutic agents to specific tissues are of great interest for safer and more effective pharmaceutical treatments. We investigated whether cathepsin B cleavage of a valine-citrulline [VC(S)]-containing linker is required for the release of monomethyl auristatin E (MMAE) from albumin-drug conjugates. In this study, we used an engineered version of human serum albumin, Veltis High Binder II (HBII), which has enhanced binding to the neonatal Fc (fragment crystallizable) receptor (FcRn) to improve drug release upon binding and FcRn-mediated recycling. The linker-payload was conjugated to cysteine 34 of albumin using a carbonylacrylic (caa) reagent which produced homogeneous and plasma stable conjugates that retained FcRn binding. Two caa-linker-MMAE reagents were synthesized─one with a cleavable [VC(S)] linker and one with a noncleavable [VC(R)] linker─to question whether protease-mediated cleavage is needed for MMAE release. Our findings demonstrate that cathepsin B is required to achieve efficient and selective antitumor activity. The conjugates equipped with the cleavable [VC(S)] linker had potent antitumor activity in vivo facilitated by the release of free MMAE upon FcRn binding and internalization. In addition to the pronounced antitumor activity of the albumin conjugates in vivo, we also demonstrated their preferable tumor biodistribution and biocompatibility with no associated toxicity or side effects. These results suggest that the use of engineered albumins with high FcRn binding combined with protease cleavable linkers is an efficient strategy to target delivery of drugs to solid tumors.