Search Results (327)

Corn husk-derived cellulose (CHC) was incorporated into gelatin–cassava starch (CS) capsule formulations to evaluate its effectiveness as a sustainable reinforcing agent. The addition of CHC enhanced the structural cohesion of the films and improved their resistance to storage-related temperature–humidity stress, while maintaining desirable flexibility. Consistent with this, the films retained mechanical performance and appearance under ICH-aligned storage conditions, indicating better endurance during storage and processing. Disintegration performance remained within pharmacopeial requirements in both acidic and neutral media, confirming the suitability of the capsules for oral delivery applications. Surface assessment revealed more uniform morphology and fewer irregularities in the capsule matrix when CHC was present, suggesting strong compatibility among the cellulose, gelatin, and starch components. Collectively, these findings demonstrate that CHC is an effective plant-based reinforcement capable of strengthening gelatin capsules without compromising functional performance. The use of corn husk, an abundant agricultural residue, also highlights a sustainable pathway for the development of halal-compliant capsule shells and contributes to the broader advancement of eco-friendly biopolymer systems in pharmaceutical applications. Full article

Background/Objectives: Given the persistent threat of war and nuclear accidents, and the global reliance on marketed Prussian blue capsules manufactured in only a few countries without an openly accessible quantitative formulation, there is a critical need for robust tablet alternatives that ensure stability, scalability, and rapid deployment. This study focuses on the design and development of PB tablets for oral administration as decorporation agents for radioactive and toxic species, particularly for treatment in nuclear and radiological emergencies. Methods: Advanced tableting processes, including direct compression, wet granulation, and dry granulation, were employed to develop innovative Prussian blue tablet formulations and to provide significant flexibility for industrial-scale production. Comprehensive physicochemical and pharmacotechnical characterizations were performed to support the formulation and to ensure both the safety and efficacy of the PB tablets. Stability studies were conducted in accordance with ICH guidelines to evaluate product performance over time and to confirm that quality and performance attributes remained within specification. Results: Among the formulations evaluated, the direct compression (DC5) was recommended for industrial production due to its simplicity, short cycle time, and high throughput. Stability studies up to 18 months confirmed that the PB tablets remained within specification, and the program is ongoing at 24, 36, 48, and 60 months. Conclusions: This research provides a promising advancement in countermeasures for nuclear and radiological incidents by delivering a robust, scalable PB tablet formulation that can be rapidly manufactured and deployed in emergency situations. 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

Asiatic acid is an ursane-type pentacyclic triterpenoid compound extracted from the Umbelliferae plant Centella asiatica. Studies have shown that asiatic acid exhibits a wide range of pharmacological activities, including anti-tumor, anti-inflammatory, hypoglycemic, antimicrobial, neuroprotective, and wound healing effects. Asiatic acid is currently used in clinical settings in the form of tablets, capsules, and ointments, primarily for treating inflammation as well as burns, keloids, and other skin disorders. However, its poor water solubility, rapid metabolism, and low oral bioavailability have limited its clinical application for other diseases. Therefore, improving its water solubility and bioavailability is a prerequisite for addressing the limitations of asiatic acid in clinical use. This review summarizes the pharmacological mechanisms of action of asiatic acid and explains the reasons for its limited clinical application. This review describes methods to improve bioavailability through structural modifications of asiatic acid and the development of new formulations. It also focuses on enhancing the pharmacological effects of asiatic acid through the development and utilization of novel formulations such as nanoformulations and hydrogel formulations, providing a theoretical basis for the clinical translation of asiatic acid and the further research and development of asiatic acid-based drugs. Full article

Berberine, a natural isoquinoline alkaloid, has been shown to improve glycemic control, lipid metabolism, and blood pressure regulation. However, its poor bioavailability has limited widespread clinical use. ToBeRock^® is a self-emulsifying formulation designed to enhance the bioaccessibility of berberine. This retrospective, real-world pilot study conducted through community pharmacies with pharmaceutical care services aimed to evaluate the metabolic and hemodynamic effects of ToBeRock^® in adults with impaired fasting glucose (IFG). Sixty adults with IFG (FPG 100–125 mg/dL) were enrolled through territorial pharmacies offering pharmaceutical services. Patients were retrospectively grouped into two cohorts: a Low-Dose Group (ToBeRock^® 1 capsule/day) and a High-Dose Group (ToBeRock^® 2 capsules/day). Capillary blood sampling and in-pharmacy blood pressure measurements were recorded at baseline (T0), 4 weeks (T1), and 8 weeks (T2). Evaluated parameters included fasting glucose, HbA1c, lipid profile (total cholesterol, LDL, HDL, triglycerides), systolic and diastolic blood pressure (SBP/DBP), and oxidative stress markers (FORT, FORD). Both cohorts showed statistically significant reductions in fasting glucose (p < 0.001), LDL (p = 0.036 Low-Dose/p = 0.039 High-Dose), and triglycerides (p = 0.012/0.009) after 8 weeks of treatment. The High-Dose Group experienced a greater improvement in HbA1c (−0.26%, p = 0.041) and a mild but statistically significant increase in HDL (p = 0.049). Improvements in oxidative balance were observed with significant reductions in FORT (p = 0.019/0.011), increases in FORD (p = 0.033/0.008), and a favorable shift in the REDOX index (p = 0.012/0.006). Systolic blood pressure decreased by −6.3 mmHg in the Low-Dose Group (p = 0.031) and −7.6 mmHg in the High-Dose Group (p = 0.048), while diastolic pressure dropped by −3.9 mmHg (p = 0.044) and −4.2 mmHg (p = 0.051), respectively. This real-world, retrospective analysis highlights the potential clinical benefit of ToBeRock^® in improving glycemic, lipid, oxidative, and hemodynamic profiles. The High-Dose Group demonstrated more consistent and significant results, supporting the dose-responsive efficacy of the bioavailable formulation and the value of pharmacy-based monitoring of nutraceutical interventions. Full article

Dry powder inhalers (DPIs) are the mainstay in the treatment of obstructive pulmonary diseases. However, the performance of DPI formulations is highly dependent on the used inhaler device and the patient’s inspiratory effort. This study aimed to evaluate and compare the aerosolization behavior of three commercially available capsule-based DPI medications—formoterol (Foradil^®), glycopyrronium (Seebri^® Breezhaler), and tiotropium (Spiriva^®)—delivered using three different capsule-based inhalers (Aerolizer, Breezhaler, and Handihaler), under varying flow conditions. Methods: The aerodynamic performance of each formulation–inhaler combination was assessed using the Next-Generation Impactor (NGI) and Dosage Unit Sampling Apparatus (DUSA) methodology. Fine particle dose (FPD) and aerodynamic particle size distribution (APSD) were determined at fixed flow rates of 15, 30, 60, and 100 L/min, as well as at inhaler-specific flow rates corresponding to a 4 kPa pressure drop. Chromatographic quantification of active ingredients was performed using validated HPLC methods specific to each drug. Results: The FPD values increased consistently with higher flow rates across all tested formulations and inhalers. At a 4 kPa pressure drop, Aerolizer and Breezhaler achieved significantly higher FPDs compared to Handihaler. Notably, in some instances, non-dedicated inhalers produced greater respirable fractions than the originally intended devices. APSD profiles revealed that drug deposition shifted toward smaller NGI stages at higher inspiratory flows, supporting enhanced deep lung delivery potential under optimal conditions. Conclusions: Device resistance, capsule orientation, and piercing mechanics substantially influence drug aerosolization. Although non-dedicated inhalers may offer improved FPDs in vitro, clinical use should adhere to approved drug–device combinations, as these have been validated for efficacy and safety under real-world conditions. Full article

Objectives: Anagrelide, an oral phosphodiesterase-3 inhibitor, is widely used to treat thrombocythemia. Evaluating the bioequivalence of low-dose formulations is essential to ensure consistent therapeutic outcomes while minimizing adverse effects, particularly cardiovascular events such as palpitations, tachycardia, and potential arrhythmias, which are known concerns with anagrelide therapy. This study aimed to compare the pharmacokinetics and bioavailability of a newly developed 0.5 mg anagrelide capsule with the reference product under fasting conditions y. Materials and Methods: In a randomized, open-label, two-period crossover design, 42 healthy Turkish male volunteers received a single oral dose (0.5 mg) of either the test or reference anagrelide capsule, with a seven-day washout period between treatments. Serial blood samples were collected over a 10 h post-dose period. Plasma concentrations of anagrelide were analyzed using a validated LC-MS/MS method. Key pharmacokinetic parameters (AUC₀–t, AUC₀–∞, Cmax, tmax, λz, t½, AUC–extrapol) were calculated and subjected to ANOVA-based bioequivalence analysis. Results: A total of 42 healthy male participants (mean age: 34.1 ± 8.9 years; BMI: 25.7 ± 2.9 kg/m²) completed the study without any protocol deviations. Pharmacokinetic analysis demonstrated that the test and reference formulations of anagrelide 0.5 mg were bioequivalent. The mean AUC₀–t values were 4533.3 ± 2379.3 pg·h/mL for the test formulation and 4515.0 ± 2392.3 pg·h/mL for the reference (p > 0.05), while the mean Cmax values were 1997.1 ± 1159.2 pg/mL and 2061.3 ± 1054.0 pg/mL, respectively (p > 0.05). The 90% confidence intervals for the geometric mean ratios of AUC₀–t (94.09–104.75%), Cmax (85.62–104.03%), and AUC₀–∞ (94.50–105.10%) were all within the predefined bioequivalence range of 80–125%, with corresponding point estimates of 99.28%, 94.37%, and 99.66%, respectively. Intra-subject variability was 14.68% for AUC₀–t and 26.98% for Cmax. No statistically significant differences were observed between the formulations for any of the primary or secondary pharmacokinetic parameters (ANOVA, p > 0.05). Regarding safety, 13 treatment-emergent adverse events were reported in 11 participants (26.2%), mostly moderate-intensity headaches, all of which resolved without complications. No serious adverse events occurred, confirming the tolerability of both formulations. Conclusions: This study demonstrates that the test and reference formulations of low-dose 0.5 mg anagrelide are bioequivalent under fasting conditions, with similar safety and tolerability profiles. The findings support the use of the test product as a safe and effective alternative. Full article

This study aimed to develop a novel cream formulation incorporating pectin-based microcapsules loaded with lemon essential oil (LEO), with the goal of enhancing both sensory attributes and microbiological quality. The capsules were added at increasing concentrations (0%, 0.25%, 0.5%, 0.75%, and 1%) to assess their impact. Physicochemical analysis revealed that higher capsule content significantly improved consistency and viscosity. Microbiological evaluations confirmed the absence of key foodborne pathogens, including Salmonella spp., Listeria monocytogenes, Staphylococcus aureus, and Enterobacteriaceae, in all formulations. Additionally, the antibacterial efficacy of the encapsulated LEO was validated against Escherichia coli and Staphylococcus aureus strains. Sensory analysis using paired comparison, ranking, and hedonic tests demonstrated a clear preference for samples enriched with the 0.5% and 0.75% capsules, noted for their enhanced creaminess, pleasant lemon aroma, and well-balanced flavour. Statistical analysis (ANOVA and principal component analysis, PCA) confirmed significant differences among samples, particularly in texture and aroma attributes. These findings highlight the potential of LEO-loaded pectin capsules as a clean-label strategy to improve both the sensory appeal and microbial safety of cream formulations. Full article

Background: Aneratrigine, a potent selective Nav1.7 inhibitor, faced challenges in developing a clinically viable oral formulation due to its poor aqueous solubility in acidic gastric conditions (0.06 mg/mL at pH 1.2), leading to limited bioavailability in Phase 1 studies. Methods: To address this, a capsule formulation containing sodium bicarbonate (NaHCO₃) was developed to enhance dissolution via in situ pH modulation. However, production-scale wet granulation led to stability issues, such as capsule content discoloration and excessive degradant formation, attributed to NaHCO₃ decomposition under thermal and moisture stress. This raised the content pH and triggered degradation products not seen in initial compatibility tests. Consequently, dry granulation was adopted to minimize heat and moisture exposure. Results: The dry granulation process proved scalable, maintaining chemical integrity across laboratory (1.5 kg), pilot (5.4 kg), and commercial (25.9 kg) batches. The optimized formulation showed enhanced stability (total impurities < 0.05%) and improved dissolution (>80% at 30 min, pH 4.0). Conclusions: This work establishes a robust manufacturing platform that overcomes stability challenges in alkalizer-containing formulations, facilitating the successful advancement of aneratrigine to Phase 2a and providing a model for developing heat- and moisture-sensitive compounds. Full article

Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural hearing loss. Methods: The first phase methodology comprised preformulation studies (DSC, FTIR, and PXRD) to assess compatibility among active substances and excipients. Subsequently, four formulations were prepared and tested for flowability, dissolution behavior in acidic and neutral media, and stability under oxidative, thermal, and photolytic stress. Quantification of the active substances and flavonoids was performed using validated spectrophotometric and HPLC-UV methods. Results: Among the tested variants, the F1 formulation (4.5 mg NIC, 200 mg PIR, 50 mg HE, 2.5 mg magnesium stearate, 2.5 mg sodium starch glycolate, and 240.5 mg monohydrate lactose per capsule) displayed optimal technological properties, superior dissolution in acidic media, and was further selected for evaluation. The antioxidant activity of the formulation was confirmed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Trolox Equivalent Antioxidant Capacity (TEAC), and iron chelation tests, and was primarily attributed to the flavonoid content of the HE. Acute toxicity tests in mice and rats indicated a high safety margin (LD₅₀ > 2500 mg/kg), while ototoxicity assessments showed no adverse effects on auditory function. Conclusions: The developed formulation displayed good stability, safety, and therapeutic potential, while the applied workflow could represent a model for the development of future fixed-dose combinations. Full article

Background: Prebiotics are selectively used by host microorganisms to promote health. Because effective prebiotic doses (1.5–30 g/day) often require inconvenient delivery formats, this study aims to explore whether capsule-compatible doses of galacto-oligosaccharides (GOS) can effectively modulate the gut microbiome. Methods: The impact of Bimuno^® GOS (Reading, UK) at 0.5, 0.75, 1.83, and 3.65 g on the adult gut microbiome was assessed using the ex vivo SIFR^® technology (n = 8), a clinically validated, bioreactor-based technology. Results: The GOS were rapidly fermented and significantly increased beneficial Bifidobacterium species (B. adolescentis, B. bifidum, and B. longum), even at the lowest tested dose. In doing so, GOS strongly promoted SCFA production, particularly acetate (significant from 0.5 g) and butyrate (significant from 0.75 g). Gas production only mildly increased, likely as Bifidobacterium species do not produce gases. Based on the ability of the SIFR^® technology to cultivate strictly anaerobic, hard-to-culture gut microbes, unlike in past in vitro studies, we elucidated that GOS also enriched specific Lachnospiraceae species. Besides Anaerobutyricum hallii, this included Bariatricus comes, Blautia species (B. massiliensis, Blautia_A, B. faecis), Oliverpabstia intestinalis, Mediterraneibacter faecis, and Fusicatenibacter species. Finally, GOS also promoted propionate (significant from 0.75 g), linked to increases in Phocaeicola vulgatus. Conclusions: GOS displayed prebiotic potential at capsule-compatible doses, offering greater flexibility in nutritional product formulation and consumer convenience. Notably, the strong response at the lowest dose suggests effective microbiome modulation at lower levels than previously expected. Full article

Ginger (Zingiber officinale Roscoe) has been widely recognized for its antioxidant properties, primarily attributed to its phenolic compounds such as gingerols and shogaols. However, limited data exist regarding how different pharmaceutical forms influence the bioaccessibility and antioxidant efficacy of these compounds. This study aimed to evaluate the antioxidant capacity and bioaccessibility of ginger in different pharmaceutical forms—capsules (20 mg, 40 mg, and 80 mg), a pure powdered extract, and a liquid formulation—standardized to ≥6% gingerols. The phenolic profile of each formulation was characterized using HPLC-DAD (High-Performance Liquid Chromatography with Diode Array Detection), followed by the evaluation of antioxidant capacity through DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ORAC (Oxygen Radical Absorbance Capacity) assays, and the assessment of bioaccessibility via an in vitro digestion model. The results demonstrated that antioxidant activity was positively correlated with extract concentration and was highest in the liquid formulation (426.0 ± 0.05 µmol Trolox equivalents (TE) and 11,336.7 ± 0.20 µmol TE in the DPPH and ORAC assays, respectively). The bioaccessibility of 6-gingerol and 6-shogaol significantly increased in the liquid form, reaching 23.44% and 11.31%, respectively, compared to ≤4% in the pure extract. These findings highlight the influence of the formulation matrix on compound release and support the use of liquid preparations to enhance the functional efficacy of ginger-derived nutraceuticals. This standardized comparative approach, using formulations derived from the same extract, offers new insights into how the delivery matrix influences the functional performance of ginger compounds, providing guidance for the development of more effective nutraceutical strategies. Full article

Background/Objectives: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit^® oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. Methods: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. Results: After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). Conclusions: Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment. Full article

The fast-disintegrating capsules rapidly disintegrate in various physiological environments, ensuring therapeutic efficacy. The formulation of plant-based capsules with balanced mechanical and fast disintegration characteristics continues to present technical challenges in pharmaceutical development. In this study, natural marine polysaccharides were utilized to achieve both rapid disintegration and excellent mechanical properties by combining κ-Carrageenan (κ-C) and ι-Carrageenan (ι-C). Additionally, the selection of KCl + NaCl mixed coagulants, along with the evaluation of their types, mass fractions, and ratios, enhanced the mechanical properties and transmittance of the capsules. FTIR analysis revealed that the membrane with a 5:5 κ-C/ι-C ratio formed hydrogen bonds, which were beneficial to its fast disintegration. SEM analysis revealed a dense microstructure in this formulation, contributing to its improved mechanical properties. Finally, this study hypothesizes that the disintegration behaviors of the capsules exhibited significant pH dependence, with ion exudation predominating in pH 1.2 and pH 7.0 media, while swelling dominated under pH 4.5 and pH 6.8 media. The prepared carrageenan blend-based capsules exhibited fast disintegration properties while maintaining excellent mechanical and barrier properties, thereby broadening the application of plant-based capsules in the field of medicine. Full article

Background/Objectives. Flavonoids are a vast class of phenolic substances. To date, approximately 6000 plant-origin flavonoids have been discovered, with many of them being used in drug therapy. Therapeutic flavonoids are commonly formulated to conventional “one-size-fits-all” dosage forms, such as conventional tablets or hard capsules. However, the current trends in pharmacy and medicine are centred on personalised drug therapy and drug delivery systems (DDSs). Therefore, 3D printing is an interesting technique for designing and preparing novel personalised pharmaceuticals for flavonoids. The aim of the present study was to develop aqueous polyethylene oxide (PEO) gel inks loaded with rutin for semisolid extrusion (SSE) 3D printing. Methods. Rutin (a model substance for therapeutic flavonoids), Tween 80, PEO (MW approx. 900,000), ethanol, and purified water were used in PEO gels at different proportions. The viscosity and homogeneity of the gels were determined. The rutin–PEO gels were printed with a bench-top Hyrel 3D printer into lattices and discs, and their weight and effective surface area were investigated. Results. The key SSE 3D-printing process parameters were established and verified. The results showed the compatibility of rutin as a model flavonoid and PEO as a carrier polymer. The rutin content (%) and content uniformity of the 3D-printed preparations were assayed by UV spectrophotometry and high-performance liquid chromatography (HPLC). Conclusions. The most feasible aqueous PEO gel ink formulation for SSE 3D printing contained rutin 100 mg/mL and Tween 80 50 mg/mL in a 12% aqueous PEO gel. The 3D-printed dosage forms are intended for the oral administration of flavonoids. Full article