Current Issue : January-March Volume : 2026 Issue Number : 1 Articles : 5 Articles
Pediatric patients are at increased risk of exposure to potentially harmful excipients when receiving offlabel medicinal products primarily formulated for adults, raising concerns about adverse events. Based on data from a previously published study, this research focuses on the most frequently prescribed off-label medicinal products in order to assess the safety of their excipients. The aim was to identify Excipients of Mandatory Declaration (EMDs) that could pose additional safety risks in individuals under the age of 18. A descriptive, and retrospective observational population-based study in individuals under 18 was developed in the Spanish primary care setting between the years 2004–2005 and 2017– 2020. The main data source was proprietary database, with nationwide coverage of prescriptions. The analysis included 4,922,984 off-label prescriptions, accounting for 16 active ingredients and 37 medicinal products (18 oral, 16 topical and three inhaled) that were scrutinized for EMD composition. Neonates and infants up to five years old accounted for nearly 50% of all off-label prescriptions among the under-18 population, exposing them to additional safety risks from potentially harmful EMDs in these formulations, which may lead to severe adverse events, causing permanent or long-term harm. The degree of harm of EMDs was assessed overall as “severe” for nine out of 22 EMDs, mostly used for oral formulations, and “moderate” for six EMDs. No EMDs were categorized as “no harm”. Results on EMDs in oral medicinal products, for instance, highlight the urgent unmet needs in this regard, especially for young children; EMDs like sodium, sorbitol, propylene glycol and sweeteners often exceeded EMA-recommended thresholds. This study underscores the need to address risks linked to off-label use of medicinal products in children, particularly those related to EMDs. Integrating excipient risk warnings into prescribing systems and monitoring related adverse events is strongly recommended....
This study explored the functional and pharmaceutical properties of native and modified starches derived from rice bean (Vigna umbellata) using physical (pregelatinization) and chemical (phosphorylation, carboxymethylation) modifications. Native starch (NRBS) exhibited a 27.5% amylose content. Modifications significantly influenced physicochemical characteristics. Swelling power increased from 12.25 g/g in NRBS to 16.34 g/g (pregelatinized, PGRBS) and 18.91 g/g (carboxymethylated, CMRBS), while solubility reached 53.12% in CMRBS. X-ray diffraction study estimated degrees of crystallinity of 26.5%, 19.4%, 22.8%, and 14.5% for NRBS, PGRBS, phosphate crosslinked (CLRBS), and CMRBS, respectively. Oil absorption capacity was highest in CMRBS (1.67 g/g), while its free swelling capacity reached 6.12 g/g at 37 ◦C. In vitro digestibility showed resistant starch (RS) contents of 11.31%, 5.49%, 17.38%, and 21.65% for NRBS, PGRBS, CLRBS, and CMRBS, respectively. Flowability and compressibility analysis demonstrated that CLRBS had the best flow (Carr’s Index: 12.16%, Hausner ratio: 1.14), while CMRBS exhibited superior tablet hardness across compression forces. These findings highlight rice bean starch, particularly in its modified forms, as a sustainable and multifunctional excipient and ingredient for food and pharmaceutical applications....
The stability of amorphous drug substances is a crucial issue in the pharmaceutical field. This study examines the influence of polyvinylpyrrolidone as an excipient on the stabilization of the amorphous drug substance bicalutamide. Solid dispersions of the active substance and the excipient were prepared in different weight ratios using ball milling, then packed into aluminum sachets and stored in a climate chamber for one year. The results indicate successful amorphization of bicalutamide, as confirmed by the absence of crystalline structure in the diffractograms and improved dissolution in the 1:1, 2:1, and 4:1 weight ratio systems. However, the 10:1 drug-to-excipient composition remained crystalline. Our findings demonstrate that PVP effectively stabilizes bicalutamide in its amorphous form. The solid dispersions prepared in weight ratios ranging from 1:1 to 4:1 remained stable under both tested storage conditions throughout the entire study period....
Background/Objectives: Intrathecal drug delivery is essential for treating CNS disorders, but the safety of commonly used excipients such as citric acid/sodium citrate (SC) remains unclear. This study aims to systematically evaluate the potential neuropharmacological effects of repeated intrathecal SC administration. Methods: Multimodal approaches were applied across murine and lagomorph models. Doses ranged from 1.833–14.664 μg/g in mice and 0.104–3.290 mg/rabbit. Behavioral, neurophysiological, and fiber photometry analyses were conducted to assess sensorimotor function, cortical activity, and calcium dynamics. Results: SC induced dose-dependent sensorimotor deficits, including hypolocomotion (45.7% reduced distance, p < 0.001) and impaired coordination (latency reduction 48.3–64.1%, p < 0.001). Mortality increased with dosage and repeated exposure. Neurophysiological data revealed biphasic cortical modulation: acute c-Fos suppression followed by delayed hyperactivity. Fiber photometry confirmed calcium chelation-mediated attenuation and subsequent potentiation of Ca2+ signals. Rabbits exhibited similar neurological symptoms, correlating with transient CSF calcium/magnesium depletion, though no structural neural damage was observed. Conclusions: These results provide the first comprehensive evidence that SC buffers can significantly disrupt neuronal calcium homeostasis and induce functional impairments upon intrathecal delivery. The findings emphasize the need for reassessing excipient safety in CNS-targeted formulations....
Objective: This article investigated the structural characteristics, powder properties, and performance variations of co-processed pregelatinized starch (PS) and microcrystalline cellulose (MCC) at varying ratios. Methods: Scanning Electron Microscopy (SEM) revealed the embedding of MCC within the PS matrix. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis indicated no chemical interaction between the starch and MCC during processing. The physical properties of the co-processed materials were evaluated using multiple indicators, such as the Carr index, and their properties in pharmaceutical applications were evaluated using multiple indicators, such as tensile strength and dilution capacity. Results: The absence of new chemical substances during co-processing, as confirmed by FTIR/XRD analyses, coupled with SEM evidence of a physically interlocked MCC-PS architecture, conclusively demonstrates that structural reorganization occurred via physical mechanisms. An increase in the MCC proportion enhanced the tensile strength of the co-processed material while decreasing the Carr’s index, particle size, tapped density, bulk density, swelling, and water-soluble content. A co-processed sample (PS:MCC = 7:3) was selected for application in formulations. The coprocessed material exhibited superior compactibility compared to a physical mixture and demonstrated favorable dilution capacity in poorly compactible model drugs, including Linaoxin and Lingzhi spore powder, as well as higher biological inertness. Conclusions: These findings suggest that the co-processed PS and MCC possess excellent compactibility and dilution capacity. The co-processed excipient demonstrates applicability in direct compression manufacturing of oral solid dosage forms (e.g., tablets), offering distinct advantages for high drug-loading formulations....
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