Search Results (118)

Background: Twin-screw wet granulation (TSWG) is a promising continuous manufacturing technology, featuring high operational flexibility, short residence time and consistent quality. The process development of TSWG relies on the synergy of material characterization, screw configuration, and process parameter optimization. Objective: In order to fully combine various design variables, and to accelerate the process development of TSWG, a material–process–equipment integrated design (MPEID) methodology is first applied to the TSWG process of Guizhi Fuling capsule, a botanical drug product. Methods: First, an equivalent formulation was designed to save trial costs. Second, 3D printing technology was used to customize both conveying and kneading elements with the lead, with the kneading discs stagger angle (SA) and the thickness (thick) as screw element variables. The position of fabricated kneading elements was varied to generate different screw configurations. Then, the critical screw parameters (CSPs) and critical process parameters (CPPs) were identified by a two-step design of experiment (DOE) toward optimizing granule quality. Results: As a result, the SA and thick were identified as CSPs, and the liquid-to-solid ratio was the CPP. Under the optimal TSWG process conditions, the twin-screw granulator could be operated under low torque (i.e., average torque = 1.48 ± 0.06 Nm). The dried granules exhibited superior flowability, as well as highly consistent particle size distribution with industrial batches. After capsule filling, the dissolution test results showed the prepared Guizhi Fuling capsules reached 93.7% cumulative dissolution at 15 min, which approached that of commercial capsules (i.e., 93.0%). Conclusions: This study demonstrated the feasibility of proposed MPEID methodology, supporting the efficient and cost-effective process development of TSWG. Full article

Breast implants are among the most frequently used long-term implantable medical devices in aesthetic and reconstructive surgery. In addition to correcting anatomical deficits, they have significant psychosocial effects, influencing body image, self-esteem, and quality of life, particularly in patients undergoing postmastectomy reconstruction. This review provides a comprehensive overview of the historical development, biological interactions, material characteristics, and clinical outcomes of breast implants. Early reconstructive attempts using foreign materials and injectable substances were associated with severe complications, underscoring the need for safer technologies. The introduction of silicone gel implants in the 1960s marked a pivotal advancement, followed by the development of saline-filled devices and highly cohesive silicone gels with enhanced mechanical stability. Key surgical considerations, including incision type and implant placement plane (subglandular, submuscular, dual-plane, and subfascial), are discussed in relation to aesthetic outcomes and complication risk. Emphasis is placed on the implant–tissue interface and the foreign body response (FBR), a process involving protein adsorption, immune cell activation, fibrous capsule formation, and potential chronic inflammation. Persistent inflammatory stimulation, often associated with bacterial biofilm formation, contributes to capsular contracture, the most common long-term complication. Additional adverse events include implant rupture, silicone gel bleed, granulomatous reactions, infection, hematoma, implant malposition, and rare but clinically significant conditions such as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The review also summarizes implant classification according to construction, filling material, shape, and surface topography, highlighting the influence of surface characteristics on host response and clinical outcomes. Advances in biomaterials, cohesive gel formulations, and surface engineering aim to enhance biocompatibility and long-term safety, supported by standardized mechanical and biological testing protocols. Full article

Background/Objectives: The limited aqueous solubility of therapeutically active drugs remains a significant challenge in their pharmaceutical application. This study presents a novel solid dispersion matrix (NSDM) that utilizes the inverted thermoresponsive behavior of Pluronic F127 to enhance drug dissolution while addressing the industrial and ecological limitations of conventional methods. Methods: For comparative assessment, a solid dispersion formulation of dapagliflozin was formulated using the NSDM approach and three conventional approaches: heat fusion (HFSD), microwave (MWSD), and lyophilization (LPSD). Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) were used to characterize the prepared formulations. In vitro dissolution test was performed to compare the pharmaceutical performance of NSDM against conventional approaches. Results: The NSDM exhibited a unique thermal transition to the liquid state at 32.4 °C. Moreover, the physiological assessment revealed complete liquefaction within 81.7 s. DSC and XRD confirmed amorphization of dapagliflozin in all formulations. In addition, FTIR revealed that dapagliflozin was integrated within the formulation without any chemical interaction with the excipient. Dissolution studies showed remarkable superiority of NSDM, with 97.30 ± 2.26% dissolution efficiency and a mean dissolution time of 2.40 ± 0.80 min. A multi-criteria assessment of ecological impact, worker friendliness, industrial effectiveness, and pharmaceutical performance demonstrated NSDM’s comprehensive advantages. Conclusions: The present approach provides a sustainable paradigm compared to conventional solid dispersion approaches. It eliminates energy-intensive operations and post-processing steps through direct capsule filling. This affords superior pharmaceutical performance while supporting sustainability and industrial applicability. Full article

Hepatic hemangiomas are the most common benign liver tumors and are typically small and asymptomatic; however, pedunculated and exophytic variants are extremely rare and may mimic extrahepatic lesions on imaging, posing a potential diagnostic challenge. The aim of this study was to describe the multimodal imaging features of a pedunculated hepatic hemangioma arising from the left triangular ligament and to review the available literature with particular attention to MRI findings and diagnostic considerations. A 52-year-old man underwent contrast-enhanced thoracoabdominal CT for unrelated symptoms, which incidentally revealed a pedunculated hepatic lesion. Further evaluation was performed with multiparametric MRI at 1.5T, including diffusion-weighted imaging and dynamic contrast-enhanced sequences. A review of the English-language literature published up to 2025 focusing on pedunculated and exophytic hepatic hemangiomas was also conducted. CT and MRI demonstrated imaging features consistent with hepatic hemangioma, including peripheral nodular enhancement with progressive centripetal fill-in and marked T2 hyperintensity. Multiplanar MRI depicted a thin vascular pedicle connecting the lesion to the hepatic capsule, supporting its hepatic origin. Fewer than approximately 30 well-documented cases have been reported in the English literature. Recognition of these imaging findings may facilitate correct diagnosis and help avoid unnecessary invasive procedures. Full article

Background/Objectives: Poor aqueous solubility limits the oral absorption and bioavailability of many active pharmaceutical ingredients. Simple formulation approaches suitable for hospital and community pharmacy compounding are therefore needed. This study aimed to develop and evaluate melt-filled hard capsules containing nifedipine, a model of poorly water-soluble BCS class II drug, using polyethylene glycol (PEG) carriers to improve dissolution performance. Methods: PEG blends of different molecular weights (PEG 400, PEG 1500, and PEG 4000) were prepared by melt mixing, followed by incorporation of nifedipine and manual filling into hard gelatin capsules. The formulations were characterized regarding mass variation, drug content, in vitro dissolution, rheological behavior, and solid-state properties using Fourier transform infrared (FTIR) spectroscopy. Dissolution profiles were kinetically modeled and compared with pure nifedipine. Results: All capsules met pharmacopoeial requirements for mass uniformity and showed acceptable drug content. PEG-based melt-filled formulations exhibited markedly enhanced dissolution compared with crystalline nifedipine. Faster drug release was associated with lower-molecular-weight PEGs and reduced viscosity, with the PEG 400/PEG 1500 blend demonstrating the most rapid dissolution. Rheological analysis confirmed shear-thinning behavior, while FTIR findings suggested intermolecular interactions and partial amorphization of nifedipine within the PEG matrices. Conclusions: This study provides a translational adaptation of solid dispersion principles into a compounding-compatible melt-filling approach. Full article

Introduction: The growing demand for traditional medicines and health supplements (TMHS) in Malaysia has raised concerns regarding microbial contamination in hard-shell capsule products. Despite regulatory oversight, recurring recalls highlight persistent non-compliance with Good Manufacturing Practice (GMP) standards. This study examines the risks of microbial contamination, recall patterns, and encapsulation practices among TMHS hard-shell capsule manufacturers in Malaysia. Methods: A cross-sectional approach was employed, comprising a review of regulatory guidelines, analysis of NPRA recall data from 2020 to 2024, and a structured survey of 86 TMHS manufacturers on equipment and production parameters. Results: Review of GMP guidance indicated that greater automation and reduced manual handling in capsule-filling processes help minimise microbial contamination. In line with this, TMHS products were recalled at a rate of 4.73%, more than 4 times the pharmaceutical recall rate (1.09%). Among the 245 TMHS recalls, 68 involved hard-shell capsule products that failed microbial testing, primarily total aerobic microbial count (73.53%). Additionally, manufacturers with 50–100 registered products had significantly higher odds of recall (OR = 10.0, 95% CI: 2.35–42.47). However, no significant associations were found between recall status and equipment type, capsule size, or production frequency. Conclusions: Microbial contamination remains a critical issue in TMHS hard-shell capsule products. Regulatory efforts should focus on medium-scale manufacturers and reinforce risk-based GMP adherence to enhance product safety and public health protection. Full article

Conventional gelatin capsules deliver a rapid drug release in the stomach, which is suboptimal for therapies requiring controlled and delayed release, emphasizing the need for customizable drug delivery systems for precision medicine. This study’s objective was to optimize 3D-printed capsule shells formulated with pH-responsive polymer blends—hydroxypropyl methylcellulose acetate succinate (HPMC-AS), PEG-4000, and PVA—to achieve controlled and sustained drug release, comparing profiles against a commercial enteric capsule. Capsule shells were produced via fused filament fabrication (FFF) at two ratios (80:15:5 and 70:20:10), filled with acetaminophen (250 mg), and tested using a two-stage dissolution method (simulated gastric fluid (SGF) for 2 h followed by simulated intestinal fluid (SIF) for 4–5 h). Results showed negligible drug release in SGF (≤5%) for both printed and commercial capsules. However, in SIF, the commercial capsule released its payload rapidly (>80% within 15 min), while the 3D-printed capsules achieved a prolonged, gradual release. The higher HPMC-AS content significantly extended the release duration. All capsules met the pharmacopeial weight uniformity criteria. In conclusion, the 3D-printed shells provided a controllable, sustained drug release profile, underscoring 3D printing’s potential to create tunable, patient-specific dosage forms. Full article

Silicone-based implants have been widely used in breast reconstruction but have also been associated with poorly understood complications, including pathologic foreign body responses such as capsular contracture. In this study, we leveraged 3D-printing technology to generate silicone-based implants in a novel, anatomically relevant, prepectoral rat model. We used this model to evaluate the response to an extracellular matrix-based product: ovine-derived reinforced tissue matrix (RTM). Two-piece negative molds were developed through computer-aided design and 3D-printed. The molds were filled with various polydimethylsiloxane mixtures and dip-coated to fabricate implants. Implant material characterization revealed that the implants retained the original 3D-printed mold shape and qualitatively demonstrated a shell with an inner solid gel-like structure. Fabricated implants had smooth surfaces, as well as tunable features including implant stiffness (storage modulus). From initial studies in our rat model, placement of bilateral prepectoral implants allowed assessment of both muscle- and skin-facing capsules and were well-tolerated for at least 12 weeks. Comparison of the foreign body response between RTM-covered and uncovered (control) implants in this model revealed that the capsule thickness did not differ between groups at the 12-week endpoint. However, RTM reduced contractile fibroblasts (alpha-smooth muscle actin) and macrophages (Iba1) compared to the control. Our findings suggested that RTM may improve capsule quality by attenuating cells involved in fibrosis, even when total capsule thickness remains unchanged. However, these changes to cells involved in fibrosis were only observed at this early endpoint and may not predict long-term clinical outcomes. Full article

Objective: The purpose of this study was to explore the effects of an acute dose of cannabidiol (CBD) on physical and mental health, as well as running performance in a group of runners. Methods: This study used a randomized, cross-over design where individuals were given CBD (CBD-T) or placebo (PLA-T) capsules on two separate occasions. During their first visit, the subjects consumed 300 mg of either placebo or CBD capsules and were then instructed to sit quietly for 2 h. Then, participants filled out a State Trait Anxiety Inventory (STAI) and completed measures of resting systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), blood lactate (BL), and heart rate variability (HRV). Next, participants completed a 2-mile treadmill run as fast as possible. During each run, HR, rating of perceived exertion (RPE), and BL were measured during and after the run. Participants completed a gastrointestinal (GI) symptom questionnaire immediately after the 2-mile time trial. Results: Participants (N = 12; 4 males, 8 females) averaged 25.5 years ± 3.34 years of age. Mean CBD-T reported increased feelings of calm (21% p = 0.04) and relaxed (22%, p = 0.02) when compared to PLA-T. There were no differences in the severity of GI symptoms, SBP, DBP, or HRV between the treatments. The CBD-T experienced an 8% reduction in average RPE at mile 1 of the run compared with PLA-T (p = 0.05). There was no significant difference in run performance time. Conclusions: An acute dose of CBD (300 mg) taken 2 h before a 2-mile run may potentially benefit runners in shorter distance competitions by increasing calm and relaxed feelings and reducing perceived effort at the halfway point without impairing performance or increasing gastrointestinal upset. Full article

Background/Objectives: This study aims to investigate the underexplored impact of capsule type on the performances of capsule-based dry powder inhalers (cDPIs). It compares specific properties of hard gelatin-based capsules (Hard Gelatin Capsules (HGC), HGC including polyethylene glycol (HGC + PEG)) and hypromellose-based capsules, (Zephyr^® Vcaps^® (VC), Zephyr^® Vcaps^® Plus (VCP) and Vcaps^® Plus Zephyr Inhance™ (VCP-I)) with aerosolization performances of model carrier-based formulation, providing insights into their impact on pulmonary drug delivery efficacy. Methods: Aerosolization properties of a model phenytoin/lactose blend formulation filled in the different capsules was evaluated using a Next Generation Impactor (NGI) with RS01 device. Capsule shell characteristics were evaluated in terms of water activity, static charges, and inner surface aspect and roughness. Results: Hypromellose-based capsules, especially VC and VCP-I, exhibited significantly higher drug delivery performances compared to gelatin-based capsules. In particular, VCP-I demonstrated good results with excellent batch-to-batch reproducibility and 51% of the nominal dose available for lung absorption. Although capsule inner surface showed clear differences between both polymer families, no clear correlation could be found between cDPI performances and capsule roughness and density of charge. All capsules presented good mechanical properties in the conditions of the tests. Conclusions: Capsule type exerts a significant impact on cDPI performances. These findings highlight the importance of capsule selection as a critical material attribute in the design and optimization of inhalation products. Full article

Background and Clinical Significance: Fourth ventricular epidermoid cysts are among the least frequently encountered intracranial tumors (less than 1%). Their slow growth pattern along cisternal and subarachnoid spaces, and their close proximity to neurovascular structures (brainstem–cerebellar), create difficulty for surgical treatment. Total removal is often complicated by the capsule’s adherence to eloquent structures and requires a thoughtful surgical approach of weighing radical resection versus neurologic/function preservation. This case description provides an example of using careful clinical–radiological correlation and anatomy-dissecting microsurgery as a method of permanent decompression and neurologic recovery with low operative risk. Case Presentation: A 57-year-old female presented with impaired stability of gait, gaze-evoked nystagmus, appendicular ataxia, minimal ipsilateral hypotonia, and mild bulbar dyscoordination. Imaging (MRI, MRA) revealed a large, lobulated mass that was lobulated and avascular centered in the left cerebellar hemisphere, with an extension into the vermis and cisterna magna, and partial filling of the fourth ventricle with classic epidermoid imaging. Resection was performed via a midline suboccipital telovelar approach with microsurgery, relying on native arachnoid planes and quadrant opportunities of decompression, while preserving critical neurovascular structures. A thin rim of capsule intimately adherent to the floor of the ventricle was intentionally left to minimize irreversible cranial nerve injury. Histology showed keratinizing stratified squamous epithelium with laminated keratin and cholesterol clefts. Following resection, truncal stability, limb coordination, and ocular pursuit improved without additional deficits. Initial and 3-month postoperative MRI showed total decompression, re-established CSF pathways, and no recurrence. Conclusions: This case demonstrates that maximal safe resection (with function preservation) through natural anatomy corridors can achieve excellent neurologic results in fourth ventricular epidermoids. Lifelong MRI surveillance will be needed due to the srisk of delayed recurrence even after near-total resection. Full article

Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, S_mix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM. Full article

In this study, a production method for ceramic shell macrocapsules and a high-temperature-resistant, polymer agent-based self-healing system was developed. Two types of macrocapsules were created by filling hollow ceramic capsules with high-temperature-resistant diallyl phthalate (DAP) resin, known for its thermal stability, and a peroxide-based curing agent. These capsules were incorporated into epoxy and DAP matrix materials to develop polymer composite materials with self-healing properties The macrocapsules were produced by coating polystyrene (PS) sacrificial foam beads with raw ceramic slurry, followed by sintering to convert the liquid phase into a solid ceramic shell. Moreover, FTIR, TGA/DTA, and DSC analyses were performed. According to the thermal analysis results, DAP resin can effectively function as a healing agent up to approximately 340 °C. In addition, quasi-static compression tests were applied to composite specimens. After the first cycle, up to 69% healing efficiency was obtained in the epoxy matrix composite and 63.5% in the DAP matrix composite. Upon reloading, the second-cycle performance measurements showed healing efficiencies of 56% for the DAP matrix composite and 58% for the epoxy matrix composite. Full article

Background/Objectives: D-lysergic acid diethylamide (D-LSD) is under investigation as a potential therapeutic strategy for alcohol use disorder (AUD). However, the extreme light sensitivity of D-LSD presents a significant challenge in developing suitable pharmaceutical forms, particularly for clinical trial settings. This study proposes a liquid-filled capsule formulation designed to provide accurate dosing while protecting D-LSD from photodegradation. Methods: To support formulation development and ensure its suitability as an investigational medicinal product, a multi-tiered analytical strategy was employed. This included liquid chromatography coupled with ion mobility spectrometry and mass spectrometry (LC-IM-MS), along with quantum chemical calculations (density functional theory (DFT) and time dependent-DFT (TD-DFT)), to ensure robust and orthogonal structural characterization of degradation products. Results: Photostress studies demonstrated that while D-LSD in solution rapidly degrades into photoisomers and photooxidative byproducts, the capsule formulation markedly mitigates these transformations under ICH-compliant conditions. Conclusions: These findings highlight the essential role of orthogonal stability profiling in guiding formulation development and demonstrate that this approach may offer a viable, photostable platform for future clinical investigation of D-LSD in the treatment of AUD. Full article

Interest in pulmonary/nasal routes for local delivery has significantly increased over the last decade owing to challenges faced in the delivery of molecules with poor solubility, systemic side effects, or new modalities such as biologics. This increasing interest has attracted new stakeholders to the field who have yet to explore inhaled drug product development. Contract development and manufacturing organizations (CDMOs) play a key role in supporting the development of drug products for inhalation, from early feasibility to post marketing. However, a critical gap exists for these newcomers: a clear, integrated, and a CDMO-centric roadmap for navigating the complexities of pulmonary/nasal drug product development. The purpose of this publication is to highlight the key aspects considered in the product development of inhaled dry powder products from a CDMO perspective, providing a novel and stepwise development strategy. A roadmap for the development of inhalable drug products is proposed with authors’ recommendations to facilitate the decision-making process, starting from the definition of the desired target product profile followed by dose selection in preclinical studies. The importance of understanding the nature of the API, whether a small molecule or a biologic, will be highlighted. Additionally, technical guidance on the choice of formulation (dry powder/liquid) will be provided with special focus on dry powders. Selection criteria for the particle engineering technology, mainly jet milling and spray drying, will also be discussed, including the advantages and limitations of such technologies, based on the authors’ industry expertise. Lastly, the paper will highlight the challenges and considerations for encapsulating both spray dried and jet milled powders. Unlike existing literature, this paper offers a unified framework that bridges preclinical, formulation, manufacturing, and encapsulation considerations, providing a practical tool for newcomers. Full article