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- Foam-Based Drug Delivery Systems for Skin Disorders: A Comprehensive
Review-
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Abstract: Foam-based drug delivery systems signify a significant innovation in dermatology, facilitating improved drug penetration and administration via a gas-liquid dispersion matrix. These formulations have shown considerable promise in the medical, cosmetic, and pharmaceutical fields. Recent improvements in topical foams have resulted in their extensive utilization in dermatological therapies, with a growing emphasis on categorization techniques grounded in formulation composition and the creation of novel methodologies for assessing essential physicochemical factors. Foam formulations comprising calcipotriol and betamethasone demonstrate 30% enhanced therapeutic effectiveness in the treatment of psoriasis compared to traditional topical therapies. The low-density, aerated structure of foams promotes improved skin covering and hydration, which is especially advantageous for disorders like eczema. Moreover, novel advances such as propellant-free foams and the incorporation of nanotechnology have broadened the use of foam-based delivery methods in targeted drug administration and customized medicine. Ongoing research into new biomaterials and refined formulation procedures seeks to overcome these constraints, ensuring that foam-based systems emerge as a breakthrough method in dermatological care. These systems promise to enhance clinical results and overall patient quality of life by increasing medication bioavailability, patient adherence, and therapeutic effectiveness. Graphical Abstract
PubDate: 2025-04-04
- Correction: Gene Therapy: Towards a New Era of Medicine
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PubDate: 2025-04-03
- QbD-Based Development of Fluocinolone Nanocomposite Transdermal Gel:
Optimization, Characterization, and Enhanced Anti-hyperpigmentation
Efficacy Assessment-
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Abstract: The current study presents a comprehensive pharmaceutical engineering approach to developing an advanced transdermal drug delivery system for addressing skin hyperpigmentation through innovative nanocomposite gel formulation. Utilizing a systematic Quality-by-Design (QbD) methodology with Box-Behnken design, we developed a novel fluocinolone-loaded chitosan-graphene oxide nanocomposite (FCGN1) aimed at optimizing pharmaceutical performance and therapeutic efficacy. The nanocomposite formulation demonstrated critical pharmaceutical quality attributes: a precisely controlled nanoscale particle size of 144.78 ± 0.15 nm, stable zeta potential of -17.93 ± 3.75 mV, and high drug entrapment efficiency of 81.3 ± 3.64%. The optimized gel formulation (FNTG3) exhibited superior transdermal delivery characteristics, achieving approximately 70% permeation within 15 h and a significant flux rate of 190 µg/cm2, which substantially outperforms current market alternatives. The comprehensive pharmaceutical evaluation included rigorous stability studies over 45 days, confirming consistent physical stability and sustained drug permeation. In vivo assessments using a UVB-induced hyperpigmentation rat model validated the formulation's dermal tolerability and depigmentation potential, demonstrating comparable or superior performance to commercial hydroquinone treatments. Histopathological analyses revealed pronounced depigmentation effects, attributable to the synergistic design of the nanocomposite system. The strategic integration of fluocinolone, chitosan, and graphene oxide facilitated enhanced drug release kinetics and improved skin penetration, highlighting the potential of rational pharmaceutical design in developing advanced topical delivery systems. This research provides a robust framework for developing sophisticated pharmaceutical dosage forms with enhanced therapeutic performance, offering significant insights into nanoscale drug delivery technologies for dermatological applications. The findings underscore the importance of systematic optimization and multifunctional component design in creating innovative pharmaceutical formulations. Graphical abstract
PubDate: 2025-04-02
- Investigation of Curcumin-β-Cyclodextrin Complex Release in Injectable
Hyaluronic Acid/Quince Seed Gum Hydrogel-
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Abstract: Injectable hydrogels play a crucial role in various biomedical applications, serving as fillers in tissue engineering, facilitating cell repair, and contributing to the development of drug delivery systems. This study aims to investigate the release of dissolved curcumin from a new injectable hyaluronic acid/quince seed gum (HA/QSG) hydrogel. Curcumin possesses numerous biological activities, including anti-cancer, antioxidant, antimicrobial, and anti-inflammatory properties. However, due to its very low water solubility, its bioavailability is poor. To address this, curcumin was encapsulated in three inclusion complexes: Cur 1:2 β-CD, Cur 1:4 β-CD, and Cur 1:6 β-CD. These Cur-β-CD inclusion complexes were lyophilized and converted into a water-soluble form. The curcumin, bisdemethoxycurcumin, and desmethoxycurcumin content of the obtained lyophilized Cur-β-CD complexes were analyzed using the HPLC method. HA-QSG hydrogels were loaded with Cur 1:2 β-CD inclusion complex in compositions of 0.75% (w/w), 0.50% (w/w), and 0.25% (w/w). The dissolution profiles of the HA-QSG hydrogels were examined in a pH 6.8 phosphate buffer medium, used as the swelling medium in intra-articular hydrogels. The initial burst of the 0.75% (w/w) hydrogel reached 9% release within the first 15 min, whereas the 0.25% (w/w) hydrogel exhibited only 6% release during the same period. The 0.75%(w/w) and 0.50% (w/w) hydrogels displayed very similar dissolution profiles, with a slightly faster release in the early stages of dissolutions, compared to the 0.25%(w/w) Cur β-CD-HA-QSG hydrogel. The 0.25%(w/w) Cur β-CD-HA-QSG hydrogel demonstrated a relatively slower release rate particularly during the initial stage of dissolution period. However, all three formulations reached approximately 98% release within 24 h. While the 0.75%(w/w) and 0.50%(w/w) curcumin-loaded HA-QSG hydrogels, with their rapid initial release, may be suited for intra-articular applications requiring quick drug availability, the 0.25%(w/w) curcumin-loaded HA-QSG hydrogel, with its slower release, may be more beneficial for sustained intra-articular delivery. Graphical Abstract
PubDate: 2025-04-01
- Biogenic Amino Acid Cross-Linked Hyaluronic Acid Nanoparticles Containing
Dexamethasone for the Treatment of Dry Eye Syndrome-
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Abstract: Ocular barriers, poor retention time, and frequent ocular discharge suppress the activity of Dexamethasone. Arginine (Arg) and hyaluronic acid (HA) are crucial for maintaining ocular health because of their unique biological benefits. In this study, we investigated the cationic properties of arginine to develop dexamethasone-loaded HA nanoparticles (ADHA NPs) and evaluated their therapeutic potential in alleviating dry eye syndrome using various reported in-vitro and in-vivo techniques. The ionic cross-linking method was used to prepare ADHA NPs. The ADHA NPs exhibited nearly 94.99 ± 4.16% drug release at the end of 6 h and followed the Korsemeyar-Peppas kinetic model (R2 = 0.9811). Moreover, the developed formulation exhibited a higher water retention capacity, i.e., 86.89 ± 1.41%, and revealed enhanced mucoadhesion characteristics. ADHA NPs also exhibited significant anti-inflammatory effects (p
PubDate: 2025-03-27
- Exploration of Conventional and FDM-Mediated 3D Printed Tablets Fabricated
Using HME-Based Filaments for pH-Dependent Drug Delivery-
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Abstract: Hot melt extrusion (HME) helps to improve the solubility of BCS class II and IV molecules. The downstream processing of the resulting filaments was crucial in developing the final dosage form. The present work investigates advantages of combining HME with fused deposition modelling (FDM) 3-Dimensional (3D) printing in delivering the naringenin to the colon to treat inflammatory bowel disease. HME filaments were made using a pH-sensitive polymer hydroxypropyl methylcellulose acetate succinate for the localized delivery of naringenin at the colonic pH. Polyethylene glycol (PEG – 4000) and Aerosil 200 were incorporated as plasticizer and flow modulator respectively, to facilitate the extrusion process. Naringenin was converted to amorphous form as confirmed by differential scanning calorimetry and powder x-ray diffraction. The optimized filament showed 0.03, 11.52 and 77.80% drug release at pH 1.2, 6.8 and 7.4 respectively. The tablets produced with the optimized filament by compression and 3D printing also confirmed the presence of naringenin in amorphous form and demonstrated pH-dependent release followed by zero-order release independent of the concentration. The dissolution profiles of FDM 3D printed (3DP) tablets with varying dimensions and infill densities suggested that both significantly influenced drug release from the tablets without altering the composition of tablets, indicating the potential application of 3D printing technology in developing personalized medicine according to patient requirements. These promising results may be valuable in evaluating the potential of naringenin in animal models, which may further facilitate clinical applications. Graphical Abstract
PubDate: 2025-03-27
- Harnessing Exercise-Like Benefits of Protonation prone Liposomal
Resveratrol in Differentiated Fat Cells: A Proof-of-Concept Study-
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Abstract: Obesity is a significant health issue resulting from a sedentary lifestyle and is linked to numerous other serious conditions, including cancer, diabetes, and cardiovascular diseases. Consequently, resveratrol (RES) is gaining attention as an emerging therapeutic agent due to its exercise-like effects. However, RES's instability and low aqueous solubility have limited its applications. This research report focuses on the loading, solubilization, and sustained delivery of RES using a dendrimer complex loaded liposomal formulation. The safety and efficacy of formulation was studied by performing various assays. The DEN-RES complex loaded liposomes were optimized using a Quality by Design (QbD) approach whereas particle size, PDI and zeta potential were found to be 159.29 ± 0.58 nm, 0.206 ± 0.008, and -7.2 ± 0.14 mV, which followed first-order release kinetics for sustained RES release. The mRNA levels of the SIRT1 and AMPK genes were found to be upregulated by more than two folds, whereas the LIPO-DEN-RES downregulated the mRNA expression of PPARγ in adipocytes. Therefore, the modulation of mRNA levels detected in 3T3-L1 cells post-treatment with the LIPO-DEN-RES validates the formulation's potential in addressing obesity. Graphical Abstract
PubDate: 2025-03-27
- Integrating Quantitative Methods & Modeling and Analytical Techniques in
Reverse Engineering; A Cutting-Edge Strategy in Complex Generic
Development-
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Abstract: Generic drugs are crucial for healthcare, offering affordable alternatives to brand-name drugs. Complex generics, with intricate ingredients, are gaining increasing importance in managing chronic conditions. However, prior to the regulatory market approval, they must demonstrate similarity in active ingredients, formulations, strength, and administration routes to ensure bioequivalence. The primary constraint lies in demonstrating bioequivalence with the innovator drug using traditional methods includes a lack of advanced technologies, and standardized protocols for analysing complex products. Given the multifaceted nature of these products, a single methodology may not suffice to establish in vitro/in vivo bioequivalence. Recognizing this, the USFDA conducts several workshops aiming advancement of complex generic drug product development. Notably, these efforts highlight the need to use Quantitative Methods and Modeling (QMM) approaches to support generic product development. QMM is a scientific approach used to analyze data and simulate drug development processes, ensuring safe, effective, and similar formulations of generic drugs using mathematical, statistical, and computational tools. QMM facilitates the design of formulations and processes, establishes a framework for in vivo BE studies, and suggests alternative ways to demonstrate BE. Appropriate utilization of the QMM approach can reduce the need for unwanted in vivo studies and bolster in vitro approaches for generic product development. Furthermore, use of orthogonal analytical techniques to characterize and decode innovator drugs can provide valuable insights into product attributes. Integrating this data into QMM enables the assessment of critical material attributes, or critical process parameters, thus demonstrating sameness. The combined application of QMM and analytical techniques not only supports regulatory decisions but also enhances the success rate of complex generic drug products. Graphical Abstract
PubDate: 2025-03-26
- Novel Methods Developed in Bioequivalence Assays: Patent Review
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Abstract: This study examines advancements in bioequivalence (BE) assessment methods, with a focus on in vitro-in vivo correlation (IVIVC) and dissolution testing technologies. A systematic patent search was conducted via Espacenet, following PRISMA criteria and the study objectives, revealing 216 relevant patents, of which 28 were selected based on their contributions to novel BE methodologies. Analysis indicates a rapid increase in patent filings from 2021 to 2022, with a significant concentration of contributions from China. Key innovations include enhancements in dissolution testing apparatus, application of physiologically based pharmacokinetic (PBPK) modeling for IVIVC, and advanced statistical approaches for BE assessment. In dissolution testing, ƒ1 and ƒ2 factors remain essential metrics for assessing similarity, especially in solid oral dosage forms. These innovations enhance the efficiency (streamline) of BE evaluations, optimizing the biowaiver process and minimizing the need for extensive clinical trials while ensuring greater precision and reliability. The dissolution test, particularly when combined with PBPK models, allows for predictive evaluation of formulation changes and population-specific responses, fostering efficiency in drug development. Overall, these novel BE assessment approaches provide a framework for regulatory compliance, cost-effective production, and assurance of therapeutic equivalence in generic formulations. While they may not always be implemented in practice, they contribute significantly to innovation in the field, driving advancements in bioequivalence evaluation. This review highlights the evolving landscape of BE and IVIVC methodologies and underscores the importance of incorporating innovative testing approaches to advance pharmaceutical science and regulatory practices. Graphical Abstract
PubDate: 2025-03-26
- Engineering pH-Dependent Orally Disintegrating Tablets for Modified
Indomethacin Release: A Polymer-Based Approach-
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Abstract: The application of pH-sensitive polymers has been widely explored in pharmaceutical industry because of their versatile properties. This work aims to delay the release of indomethacin (IND), a commonly used anti-inflammatory drug, using a pH-dependent polymer within orally disintegrating tablets (ODTs) and to investigate the effect of the polymer particle size on the ODTs. When developing delayed-release formulations for orally disintegrating tablets (ODTs), it's essential to balance the pellet's matrix properties to maintain integrity and delayed release. Different sizes of Eudragit L100 were used to create IND-containing pellets via extrusion spheronization, which were then embedded into the matrix of ODTs. The particle sizes displayed good elastic properties with low Young's modulus (YM) values, and there was no significant difference between the different sizes (45, 60, 93 µm; p > 0.05). The tensile strength of the pellets was directly proportional to YM (p
PubDate: 2025-03-26
- Treatment of Bleomycin-induced Pulmonary Fibrosis by Intratracheal
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Abstract: Idiopathic Pulmonary Fibrosis (IPF) is a rare and serious chronic interstitial lung disease that may endanger the lives of patients. The median survival time of patients with idiopathic pulmonary fibrosis is short, and the mortality rate is higher than that of many types of cancer. At present, pirfenidone (PFD) and nintedanib (NDNB) have been approved by FDA for IPF, but they can only delay the process of pulmonary fibrosis and cannot cure the disease. Therefore, it is urgent to develop other drugs with the effect of improving pulmonary fibrosis. Ellagic acid (EA) can inhibit the Wnt-signaling pathway and has an effect in treating pulmonary fibrosis induced by bleomycin (BLM) in mice. However, its solubility is poor, resulting in its low bioavailability and limited therapeutic benefits, so its clinical application has been limited. Herein, based on the characteristics of nano-drug lung delivery system, chitosan (CS) was selected as the carrier, and ellagic acid-loaded chitosan nanoparticles (EA-CS-NPs) were prepared by ionic gelation method. The EE% and DL% of prepared EA-CS-NPs was 73.73 ± 4.52% and 6.23 ± 1.09%, the particle size was 119.6 ± 5.51 nm (PDI = 0.234 ± 0.017), the zeta potential was 29.833 ± 0.503 mV. The morphology of the nanoparticles was observed by TEM microscope, which was round, uniform dispersion, indicating that the preparation process is stable and feasible. The toxicity experiment showed that EA-CS-NPs maintained 80% cell viability, significantly higher than that of the NDNB group, indicating lower toxicity and better inhibitory effects on TGF-β1-stimulated MLg and NIH-3T3 cells. Wound healing assay results showed that the inhibitory effect of EA-CS-NPs on cell migration was more pronounced than that of EA in the same amount of EA-containing drugs. Drug uptake experiments revealed that EA-CS-NPs significantly enhanced drug uptake in MLg and NIH-3T3 cells. In vivo, Cy7-CS-NPs exhibited higher fluorescence intensity in rat lungs compared to Cy7 solution, indicating better lung retention. The in vivo efficacy test showed that compared with the EA group, EA-CS-NPs could better reduce the area of pulmonary fibrosis and collagen deposition, improve lung function, and have a longer retention time in the lung. In summary, our results revealed that EA-CS-NPs may be a good choice for the treatment of pulmonary fibrosis. Graphical Abstract
PubDate: 2025-03-26
- Co-Delivery of Tacrolimus and Thymoquinone Topically by Nanostructured
Lipid Carrier Gel for Enhanced Efficacy Against Psoriasis-
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Abstract: Psoriasis is a chronic inflammatory skin disorder affecting 2–5% of the global population and is often characterized by skin thickening, scaling, and various epidermal changes. Current topical treatments have limitations in terms of efficacy, skin penetration, and side effects. The present study aimed to develop a novel nanostructured lipid carrier (NLC) gel that co-encapsulates tacrolimus (TAC) and thymoquinone (THQ) to enhance drug delivery and efficacy in the treatment of psoriasis. TAC-THQ-NLC was formulated using the emulsification solvent-evaporation technique and subsequently converted into nanogel using Carbopol Ultrez10 as a gelling agent. The prepared nanogel efficacy was evaluated through ex-vivo skin permeation, dermatokinetic analysis, and psoriasis-induced Balb/c mice model. The TAC-THQ-NLC-gel (TAC-THQ-NG) demonstrated significantly higher skin permeation compared to the TAC-THQ-suspension-gel (TAC-THQ-SG). Specifically, the permeation enhancement for the NLC-gel was 2.51-fold and 2.12-fold for TAC and THQ, respectively. These enhancements were confirmed using Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The dermatokinetic analysis showed that the TAC-THQ-NG had 2.78-fold and 2.37-fold higher maximum concentration (Cmax) and 2.93-fold and 2.40-fold higher area under the curve (AUC) for TAC and THQ, respectively, compared to the TAC-THQ-SG. Further, in the Balb/c mice psoriasis model, the TAC-THQ-NG formulation resulted in an 83.80 ± 3.62% reduction in the cumulative Psoriasis Area Severity Index (PASI) score of thickness, erythema, and scaling, compared to the TAC-THQ-SG formulation, which showed 57 ± 9.90% reduction. The results of the in vivo skin compliance study suggested that the developed TAC-THQ-NG was safe for topical application. Further histopathological examination showed no significant changes in the skin, spleen, and liver, indicating the efficacy and safety of the TAC-THQ-NG formulation. Based on these observations, it can be inferred that the developed TAC-THQ-NG exhibits superior therapeutic efficacy. Graphical Abstract
PubDate: 2025-03-26
- Development of Complex Generics and Similar Biological Products: An
Industrial Perspective of Reverse Engineering-
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Abstract: Generic drugs are developed to be bioequivalent to innovator formulation, matching them in dosage form, safety, strength, quality and efficacy. Known as "interchangeable multi-source pharmaceutical products," generics play a crucial role in reducing therapeutic costs and enhancing patient compliance. Over the past decade, generics have accounted for more than 90% of prescriptions in the U.S., which has driven down the average price of these drugs to nearly match production costs once market competition grows. Simple generics of small-molecule drugs are often produced through trial and error based on existing data, but complex generics require advanced techniques like reverse engineering to replicate the brand drug's release profile. These complex generics include sophisticated drug delivery forms that ensure the therapeutic agent is released gradually, maximizing effectiveness. Conversely, similar biological products highly similar to approved biologics-undergo rigorous analytical and clinical evaluations due to their complexity and the nature of biologic production. The increased demand for similar biological products is driven by expiring biologic patents, economic incentives, and regulatory advancements, with the market expected to grow significantly by 2026. The Biologic Price Competition and Innovation Act (BPCIA) enable abbreviated approvals for similar biological products, promoting affordability. Despite minor differences from original biologics, similar biological products undergo extensive testing to ensure safety and efficacy, following global regulatory guidelines that emphasize strict quality standards. This framework is essential for expanding patient access to effective therapies for conditions like cancer and autoimmune diseases while supporting healthcare sustainability. Graphical Abstract
PubDate: 2025-03-26
- Quantitative Analysis of Salmon Calcitonin Hydroxyapatite Nanoparticle
Permeation to substantiate Non-Invasive Bone Targeting via Sublingual
Delivery-
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Abstract: We earlier reported comparable efficacy in bone parameters of sublingually administered salmon calcitonin hydroxyapatite nanoparticles (SCT-HAP-NPs) compared to the subcutaneous injection, in the ovariectomy rat model, despite a bioavailability of barely ~ 15%. We ascribed this intriguing finding to targeted bone delivery, facilitated by translocation of significant quantity of intact NP into systemic circulation. In the present study we track the translocation of FITC-SCT-HAP-NPs (~ 100 nm) across porcine sublingual mucosa using the Franz diffusion cell to validate our hypothesis. Confocal Laser Scanning microscopy (CLSM) established that SCT-HAP-NPs permeated into the deeper layers of sublingual porcine mucosal tissue. We confirmed the nanoparticles were present in the receptor medium of the Franz diffusion cell by DLS and TEM. We also demonstrate for the first time quantification of the NPs (%) translocated across the porcine mucosa, using the Amnis Image StreamX Mk II imaging flow cytometer. Computation revealed transport of ~ 60% of the FITC-SCT-HAP-NPs across mucosa in 2 h, substantiated that high NP concentrations could reach systemic circulation. Such high NP concentration in systemic circulation coupled with the small size (~ 100 nm) and the high bone affinity of HAP, validate our hypothesis of targeted bone delivery following sublingual administration. Furthermore, quantification of translocated NPs, which we demonstrate for the first time, would permit rational development of optimal targeted nanoparticulate carriers for delivery by noninvasive routes. Graphical Abstract
PubDate: 2025-03-18
- Amorphous Solid Dispersion/Salt of Efavirenz: Investigating the Role of
Molecular Interactions on Recrystallization and In-vitro Dissolution
Performance-
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Abstract: Efavirenz (EFZ), a BCS (Biopharmaceutical classification system) class-II/IV drug, suffers from low oral bioavailability (40–50%) and significant inter/intra-individual variability due to its low solubility and poor dissolution properties. The present investigation aimed to prepare a stable amorphous system of EFZ to improve its dissolution using the slurry method with various polymers and examine the nature of the interaction between them and its impact on the stability (recrystallization) of the formed systems and their in-vitro dissolution performance. Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies proved the formation of a complete amorphous system of EFZ with Eudragit® E100, HPMC E5, and HPMCAS-LF up to 50% drug loading. During 90 days accelerated stability studies, amorphous systems prepared using Eudragit® E100 remained stable at 50% drug loading however those prepared with HPMC E5, and HPMCAS-LF only remained stable at 25% drug loading. The ability of Eudragit® E100 based system to stabilize the drug at higher drug loading was attributed to the formation of stronger ionic interaction as revealed by the Fourier-transform infrared spectroscopy (FTIR) study. During in-vitro dissolution study, Eudragit® E100 based amorphous system generated and maintained significantly higher supersaturation compared to those prepared with HPMC E5, and HPMCAS-LF due to the formation of ionic interaction between EFZ and Eudragit® E100 as revealed by solution 1H NMR study. Graphical Abstract
PubDate: 2025-03-18
- Development and Optimization of Eberconazole Nanostructured Lipid Carrier
Topical Formulations Based on the QbD Approach-
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Abstract: Eberconazole nanostructured lipid carrier (EBR-NLC) 1% w/w optimization was done using the Quality by Design (QbD) approach, employing a 23 Full Factorial Design (FFD) for experimental planning, followed by thorough physico-chemical, in-vitro, and ex-vivo evaluations. The 23 FFD assessed the impact of total lipid amount, surfactant amount, and sonication time on critical quality attributes such as particle size and % entrapment efficiency. In-vitrorelease testing (IVRT) validation was performed using vertical diffusion cells. IVRT, a compendial technique by pharmacopoeias, was for performing semi-solid formulations analysis. The optimized EBR-NLC 1% w/w was characterized for assay, organic impurities, amplitude sweep, viscosity, IVRT, ex-vivo permeation testing, and skin retention. The validated IVRT technique was meeting the acceptance criteria of regulatory guidelines. The results showed that in-vitro release, ex-vivo permeation, and skin retention were significantly higher (P
PubDate: 2025-03-18
- Unraveling the Effects of Filtration, Process Interruptions, and
Post-Process Agitation on Protein Aggregation-
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Abstract: Filtration is an essential process step for the manufacturing and filling of biopharmaceuticals. In filling operations, sterile filtration is typically achieved through dead-end filtration using fine membrane filters that completely retain colony-forming units per square centimeter of filter area. According to FDA and USP guidelines, sterilizing filters must be product-compatible and composed of non-fiber releasing materials, typically with a absolute pore size rating of 0.22 µm. However, it has been observed that protein interaction with filters and particle shedding from filter materials, can contribute to protein aggregation when exposed to routine stresses such as agitation during manufacturing, handling, storage or transportation. Since aggregates can cause severe immune responses upon parenteral application, it is crucial to understand the possible effects of various filter materials during different manufacturing and filling set-ups in order to choose the most suitable filter types and filtration processes. To address this, we investigated particle formation on the visible, subvisible and submicron scales as well as structural changes in a specific liquid glycoprotein (GP) formulation after constant and impulse filtration (i.e., stop and go mechanisms to assess possible film formation and film disruption on the filter material) with commonly used hydrophilic membrane materials, i.e., polyvinylidene fluoride (PVDF), polyether sulfone (PES), and cellulose acetate (CA) with a pore size of 0.22 μm. In addition, we exposed the material to stirring and heating to induce aggregation and investigate the filter performances in the case of initially high particle content. Graphical Abstract
PubDate: 2025-03-14
- Brazilian Green Propolis Extract-Loaded Poly(Ε-Caprolactone)
Nanoparticles Coated with Hyaluronic Acid: Antifungal Activity in a Murine
Model of Vulvovaginal Candidiasis-
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Abstract: Brazilian green propolis extract-loaded poly(ε-caprolactone) nanoparticles coated with hyaluronic acid (PE-NPsHA) were developed as a therapeutic strategy to treat vulvovaginal candidiasis (VVC) and combat the growing issue of fungal resistance. The chemical composition of PE was analyzed using UHPLC-MS/MS, revealing the presence of various bioactive compounds, such as phenolic acids, flavonoids, coumarins, and quinones. These compounds were encapsulated into the polymeric matrix of NPs, as indicated by FTIR and DSC. In addition, PE-NPsHA were characterized by DLS, AFM, encapsulation efficiency (EE), and in vitro release study. They displayed a spherical morphology with a hydrodynamic diameter of 170 nm, a low polydispersity index of 0.1, a zeta potential of -28.5 mV, and an EE of 78%. The in vitro release study indicated a controlled and sustained release of PE over a period of 96 h. The in vitro and in vivo PE-NPsHA biocompatibility were investigated as well as their antifungal activity in a murine model of VVC. PE-NPsHA did not impact the HaCaT cell viability and demonstrated no signs of in vivo vaginal toxicity. PE-NPsHA exhibited in vivo antifungal efficacy, effectively eliminating Candida albicans infection. PE-NPsHA could expand the available treatment options for VVC and counteract Candida resistance to antifungal drugs.
PubDate: 2025-03-14
- Characterizing the Complex Multi-Step Degradation Kinetics of Amphotericin
B in a Microemulsified Drug Delivery System-
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Abstract: Amphotericin B (AmB), a potent amphiphilic drug with antifungal and antileishmanial properties, exhibits reduced nephrotoxicity when delivered via lipid-based systems like microemulsions (ME). However, the complexity of these multi-phasic systems challenges the use of simple schemes and models for describing AmB degradation. The aim of this study was to establish a degradation scheme and model for AmB within a ME, alongside a control micellar formulation. AmB degradation pathways and models in both lipidic and aqueous systems were evaluated based on prior research. Experimental investigations into interface degradation pathways were conducted using a micellar approach. High-Performance Liquid Chromatography (HPLC) was employed for AmB quantification. Oxidation emerges as the principal degradation pathway within micelles, dependent on surfactant-induced aggregation. Considering AmB's behavior in distinct media (lipidic, aqueous, and micellar), an empirical degradation scheme is proposed, translated into a complex multi-pathway mathematical model capable of describing experimental data on AmB degradation in ME under dark conditions. Aggregation and oxidation played significant roles, and kinetic constants were calculated for AmB in ME. The model presented here represents a significant step toward accurately describing the non-linear degradation of AmB in prospective liquid lipid-based dispersions, potentially advancing its market prospects. Graphical Abstract
PubDate: 2025-03-12
- Towards Enhanced Solubility of Cannabidiol: Preparation and Evaluation of
Cannabidiol Solid Dispersions Using Vacuum Compression Molding-
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Abstract: The present study aims to develop and characterize cannabidiol (CBD) solid dispersions using Vacuum Compression Molding (VCM) to enhance the drug solubility and release profile. Solid dispersions of CBD and polymers were processed using VCM at 130 °C for 4 min after a prior physical mixing. Five percent w/w of CBD was used with 5% w/w of poloxamer 188 and 90% w/w of polymeric carrier (Polyethylene Oxide, PEO-N80 or Hydroxypropyl cellulose, HPCEF). Discs were collected and milled to obtain formulations (F1V, F2V). The degradation temperature of CBD was determined using Thermogravimetric Analysis (TGA). The formulations were further characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier-Transform Infrared Spectroscopy (FTIR). In vitro dissolution testing of pure CBD and formulations was evaluated using USP apparatus II. TGA showed that CBD degradation occurs after 200 °C. FTIR spectra of formulations indicate potential interactions between the drug and polymers. DSC thermograms of F1V showed a thermal peak at 65 °C that could correspond to PEO-N80. F2V did not show any of the thermal event peaks, which suggests the conversion of the drug to the amorphous state. Images from the SEM showed irregular surfaces for both formulations. The release profile showed an increase in the CBD dissolution rate by 4.75 folds for F1V and 3.63 folds for F2V in four hours. In this study, solid dispersions of CBD formulations were successfully achieved. The VCM technology has proven to be successful in formulating solid dispersions of CBD for early-stage drug development. Graphical Abstract
PubDate: 2025-03-11
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