Pharmaceutical Development and Technology最新文献

The aim of this study was to develop an amorphous solid dispersion system utilizing meglumine (MG) as an alkalizing matrix to improve the dissolution rate and oral bioavailability of gambogic acid (GA). Solid dispersion of GA with MG (GA/MG-SD) was fabricated via solvent evaporation using an equal molar of quantity of GA/MG. Physicochemical characterization was conducted through FT-IR spectral analysis, DSC thermograms, PXRD patterns, and SEM imaging, and the contact angle and dissolution profiling also were determined. Pharmacokinetic evaluation was performed in SD rats to assess bioavailability enhancement. DSC analysis indicated disappeared crystal of GA and MG as no distinct peaks were observed. This was further evidenced by PXRD analysis. The dissolution of GA from GA/MG-SD reached 76.1% after 1 h in media (pH 6.8), compared to only 22.2% for free GA. The solubility and drug dissolution rate of GA/MG-SD were significantly higher than those of free GA (p < 0.01), and drug dissolution behavior fit in the Higuchi model. Furthermore, pharmacokinetic assessment demonstrated a 2.0-fold increase in AUC_0-24 values compared to free GA, confirming improved systemic exposure. Overall, the MG-based dispersion strategy effectively transformed GA into an amorphous state with superior wettability, achieving concurrent enhancement of dissolution efficiency and oral bioavailability.

Zn²⁺/Ca²⁺ synergistic crosslinking was engineered in chitosan-alginate semi-interpenetrating networks (semi-IPNs) to establish crosslinking density (15.2-58.3 mol/m³) as a predictive parameter for multi-scale hydrogel performance. Fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) analyses confirmed Zn²⁺ ions coordination bonding with chitosan amines, synergizing with Ca²⁺-alginate ionic bridges to significantly enhance thermal stability (initial decomposition temperature increased to 255.8 °C; final decomposition temperature elevated to 490.6 °C) and mechanical properties (tensile strength improved 615% to 12.9 MPa; compressive strength increased 350% to 1.8 MPa). Morphological refinement reduced pore size to 24.3 μm and porosity to 56.9%, enabling pH-responsive swelling where the equilibrium swelling ratio at pH 5.5 exceeded pH 7.4 values by 52%. Anomalous non-Fickian drug release (Korsmeyer-Peppas exponent n = 0.47-0.66) facilitated infection-targeted delivery, with metformin release at pH 5.5 reaching 78.2% compared to 58.7% at pH 7.4. In vivo, the optimized 10 mM Zn²⁺ ions/10 mM Ca²⁺ ions system (F5) accelerated wound healing to 94.2% closure by day 14, eliminated infection incidence, and promoted immunomodulation (38.2% reduction in TNF-α; 2.1-fold increase in IL-10) through degradation-matched tissue regeneration. Validated via multi-technique characterization, this dual-ion platform resolves historical trade-offs in natural polymer hydrogels, offering a predictive design paradigm for advanced wound dressings and stimuli-responsive drug delivery. HIGHLIGHTSA quantitative correlation (R² > 0.94) was established between dual-ion crosslink density and hydrogel mechanical strength, enabling rational engineering of natural-polymer dressings.Achieved unprecedented thermal stability (initial decomposition 255.8 °C), surpassing autoclave requirements and solving a long-standing translational barrier.pH-triggered anomalous transport accelerated metformin release by 19.5 % at pH 5.5 (infected wound) versus pH 7.4, outperforming commercial Aquacel® Ag.In vivo rat model showed 94 % wound closure in 14 days, zero infection incidence, and favorable immunomodulation (38 % TNF-α reduction, 2× IL-10 increase).

Anal fissures (AF) are painful anorectal disorders for which topical calcium-channel blockers (CCBs), such as amlodipine besylate (AMD), are recommended to avoid systemic adverse effects associated with oral therapy. However, the topical use of AMD has been limited by its poor aqueous solubility and chemical instability.This study focused on developing and characterizing a 1% w/w AMD-loaded microemulsion (ME) for topical application. Optimal composition was selected using solubility screening and pseudo-ternary phase diagrams. The lead formulation, M5, demonstrated favorable properties: nanometric scale (size ≈ 34 nm, PDI 0.45), pseudoplastic rheology (viscosity ≈20 Pa·s), and high interfacial stability (ζ - potential +8.7 mV).Franz diffusion cell assays confirmed sustained permeation (steady-state flux ≈14.4 µg·cm-2·min-1), while differential scanning calorimetry evidenced partial plasticization of AMD by the surfactant matrix. The final product was manufactured at pilot scale under GMP guidelines to ensure long-term stability. AMD potency decreased by only 7.7% over 24 months under refrigerated storage. In vitro safety evaluations confirmed a non-irritant profile and low acute toxicity.Compared with other reported topical CCB preparations, this AMD-loaded ME provides superior physicochemical stability, reproducible permeation, and dermal compatibility. These results establish a translational platform for future GMP-scale validation and clinical assessment in AF management.

Ivermectin (IVM), a broad-spectrum antiparasitic agent that has been extensively used in both human and veterinary medicine for decades. Conventional formulations of IVM are challenged by poor aqueous solubility, low bioavailability, and limited tissue targeting, which can limit its therapeutic potential, despite its clinical success. The investigation of novel dosage forms and drug delivery technologies has been facilitated by recent advancements in pharmaceutical sciences, with the objective of improving the pharmacokinetic and pharmacodynamic profiles of IVM. Innovative systems, including lipid-based drug delivery systems, nanoparticles, polymeric carriers, solid lipid nanoparticles, and nanostructured lipid carriers, have demonstrated significant potential in terms of their ability to enhance solubility, facilitate controlled and targeted drug release, and reduce systemic toxicity. Additionally, these advanced systems open new possibilities for repurposing IVM in therapeutic areas beyond parasitic infections, including antiviral and anticancer applications. This review highlights the current progress and future prospects of modern dosage forms designed to optimize IVM delivery and broaden its clinical utility. Thereby providing an in-depth and critical evaluation of advanced IVM dosage forms, with a particular emphasis on their design rationale, pharmacokinetic enhancements, and capacity to address the limitations associated with conventional formulations.

A semisolid oral formulation of carvedilol microemulsion-loaded oleogel (CARV-MEOG), filled in hard gelatin capsules, was developed and investigated for in vitro dissolution at different physiological pH levels. In vitro dissolution studies were conducted on CARV-MEOG and the reference product, Coreg^® CR, in dissolution media that simulate the gastrointestinal fluid and cover its physiological pH range. The stability of CARV-MEOG was assessed both chemically and physically. Results showed that CARV formed intermolecular forces with oleic acid, the oil phase of the microemulsion, through the N-H bond of CARV, which disappeared in the CARV and oleic acid mixture. In 0.1 M HCl dissolution medium, CARV release attained 102.5 ± 2.66% after 24 h. In pH 4.5, 6.8, and 7.5 dissolution media, CARV release was significantly lower, achieving 65.6 ± 2.73%, 20.1 ± 1.32%, and 26.3 ± 1.67%, respectively, after 24 h. Compared to Coreg^® CR, the release of CARV after 24 h was lower than that from CARV-MEOG, attaining 91.2 ± 1.03%, comparable to CARV-MEOG in pH 4.5, where it reached 76.8 ± 1.32%, and it was higher than CARV-MEOG in pH 6.8 and 7.5, attaining 59.0 ± 0.88% and 54.2 ± 1.01%, respectively. CARV-MEOG remained stable for 6 months when stored at 5-8 °C. Therefore, the development of CARV-MEOG successfully enhanced the dissolution rate of the poorly soluble drug carvedilol, aiming to improve its oral bioavailability.

The rapid growth in the number of patients with psychological disorders puts immense pressure on the economy, society, and healthcare systems. Various classes of drugs have been approved for different psychological disorders; however, a vast number of these medicines experience first-pass metabolism and low bioavailability, plasma level fluctuations, side effects, and the need for frequent daily doses, which all lead to poor patient compliance. Besides, the mental condition of these patients makes it hard for them to use drugs in oral dosage forms, frequently. Transdermal delivery systems have drawn attention to the treatment of different psychological disorders, including psychosis, depression, anxiety, attention-deficit hyperactivity disorder (ADHD), and sleep disorders. These systems offer a substitute route to address mentioned issues and improve patient adherence, particularly in long-term administration. Different devices have been designed to facilitate the administration of drugs through transdermal routes, such as patches and microneedles. Moreover, to enhance the absorption of medicines, chemical penetration enhancers, iontophoresis, radiofrequency, and nanotechnology are integrated with these transdermal delivery systems, which is the basis of the development of generations of transdermal delivery systems. In this review, we will focus on more novel generations of transdermal delivery systems and their applications for psychological disorders.

This study presents the first evaluation of the shelf life of a novel three-dimensional (3D) printed formulation of Mexiletine Hydrochloride (HCl) over a six-month storage period. Mexiletine HCl was incorporated into a patient-personalized solid oral dosage form using a Semi-Solid Extrusion (SSE) 3D printing technique, and was then subjected to a preliminary stability assessment. We evaluated physical and chemical stability under ICH-recommended storage conditions, taking an important first step toward future full ICH-compliant studies. 3D-printed tablets were stored in a climatic cabinet, at 25 ± 2 °C and relative humidity 60 ± 5% (RH). The tablets were then evaluated for drug content analysis and impurities at 0 and 6 months of storage. Throughout the evaluation period, the printed tablets retained their physical characteristics, including shape and color, and exhibited no significant deviation in drug content and weight. Moreover, no detectable levels of degradation products or impurities were observed, as confirmed by validated analytical methods. These findings collectively indicate that the 3D-printed Mexiletine HCl formulation demonstrates excellent stability under room temperature storage conditions-information that is essential for advancing the formulation along regulatory and commercial pathways. Our data address the common trade-off between printability and stability, demonstrating that a formulation optimized for SSE printing can maintain stability under standard storage conditions.

Peucedanum praeruptorum Dunn has long been used in traditional Chinese medicine (TCM) for the treatment of respiratory diseases, its active constituent praeruptorin A (PA) has multiple anti-inflammatory activities. However, its bioavailability and therapeutic effect is not satisfactory in clinic owing to many physicochemical and physiologic barriers. Herein, this work highlights the successful development of an inhalable PA dry powder (MIL-100(Fe)-PA), which is facilely constructed through the optimization of the formulation between PA and a metal-organic framework (MIL-100(Fe)) carrier. Moderate pore and particle size distribution endow the dry powder with excellent loading efficiency and resistance to degradation. All ingredients and their interactions endow MIL-100(Fe)-PA favorable flowability, and pulmonary deposition, as well as direct lung drug delivery and release. These attractive characteristics enable the dry powder to effectively enhance alveolar epithelial cell penetration, improve anti-inflammatory activity, promote lung accumulation, and reduce the side effects of PA. Thus, this PA dry powder may open a new avenue for the inhalation treatment of diseases, greatly advancing its clinical application.

Bone metastasis is commonly observed in cancer patients, necessitating high-dose chemotherapy for effective treatment. Repurposing mebendazole (Meb) has shown promise in inhibiting cancer progression. To overcome its poor solubility and enhance tumor targeting, nanocrystals were employed as a delivery platform. The current work aimed to develop optimized Meb nanocrystals with improved bone metastasis therapeutic potential via passive targeting. Optimization was achieved through high shear homogenization and stabilizer selection (HPMC E15) to produce nanocrystals with enhanced colloidal stability and size uniformity. In vitro characterization and in-vivo assessment were conducted to compare the selected optimized formulation with the Meb solution. Two Meb nanocrystal formulations, homogenized (NC4) and unhomogenized (NC*), were compared to determine the importance of particle size reduction. The results revealed that NC4, prepared using anti-solvent precipitation combined with high shear homogenization, exhibited a promising particle size (121.20 ± 6.20 nm) and higher drug release in the acidic pH, favorable for passive targeting. The in vivo results confirmed the superior effects on tumor growth inhibition (90.01%), pain remission, and bone tumor markers of NC4 over NC*. NC4 showed an absence of kidney and liver toxicity. In conclusion, these comprehensive findings strongly support the clinical relevance of NC4 in treating bone metastasis. Its ability to passively target the drug, inhibit tumor growth, alleviate pain, and exhibit favorable biomarker profiles and safety make it a promising candidate for improving the management and outcomes of patients with bone metastasis.

Rhein (RH) is a promising phytochemical with well-documented pharmacological effects in several types of cancer. However, its pharmacological activity in skin cancer has not been studied. Moreover, RH suffers from numerous limitations that handicap its clinical applications, such as its poor aqueous solubility and dermal bioavailability. Herein, this study highlights, for the first time, RH application on skin cancer human melanoma cell line A375 and determines its IC50, the development of a novel rhein-loaded transferosomes; hyaluolimosomes, and its evaluation as a free drug and nano-drug. The formation of the RH-PL complex (RH-PLC) was verified by infrared spectroscopy, thermal analysis via differential scanning calorimetry, and structural examination through X-ray powder diffraction. Studies on in-vitro release and ex-vivo permeation and skin deposition showed the superiority of hyaluolimosomes to significantly improve RH release, skin permeation, and deposition compared with the free drug. Cell viability studies on A375 revealed a significant reduction in IC50 of hyaluolimosomes at 31.3 µg/mL compared to 434.8 µg/mL of rhein (12.89 fold) with safety profiles. The present study successfully achieved its primary objective by demonstrating cytotoxic activity against the melanoma cell line. On the other hand, an important issue of concurrent cytotoxicity was observed on HDFa cells, highlighting the need for incorporating active targeting strategies in future preclinical investigations.