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The quality-assured preparation of crushed and diluted preparations for children is a challenge. In this study, a multicenter study was conducted to validate the preparation method for the quality assurance of baclofen powder, clonidine powder, and hydrocortisone powder prepared from tablets according to a previously established method. In-hospital preparations were prepared at five medical facilities under different crushing and mixing conditions. After storage in closed bottles, in-use bottles, and laminated paper for 120 days, ingredients stability, drug elution, and content uniformity after packaging were evaluated. All three ingredients were maintained at between 90% and 110% of their initial content for 120 days under packaging conditions of 25 ± 2 °C and 60 ± 5% relative humidity, with no change in dissolution in all formulations made at all five facilities. The content uniformity was also acceptable. The established method may contribute to quality-assured pediatric dosage form modification. [ABSTRACT FROM AUTHOR]

Sulfamethoxazole trimethoprim (ST) combinations are used to prevent infection in immunocompromised patients. In pediatric patients, conventional ST combination tablets (cTab) are large and granules are not preferred due to their rough and bitter taste in the mouth. Since a new formulation of smaller tablets (sTab, 1 cTab = 1-gram granules = 4 sTab) was approved, a study regarding the usability of sTab in pediatric patients was conducted. Children who started taking sTab of the ST combination at our hospital between August 2021 and August 2022 were included. Using an anonymous questionnaire, the dosage of ST combinations, the child's response (3-point visual scale: positive, neutral, or negative), preparation and administration time, and method of taking the drug were asked. Twenty-two patients (median age: 11.0 years) receiving cTab. Median (range) number of tablets per dose was 1 (0.5–1.5) tablet, and was 4 tablets (1.0–4.0) after switching to sTab. Twenty patients (median age: 5.0 years) receiving granules. Median (range) single dose was 0.75 (0.2–2.0) gram, and was 2.0 (1.0–4.0) tablets after switching to sTab. Post-dose reactions were positive in 5, neutral in 7, and negative in 10 cases for cTab, and positive in 1, neutral in 7, and negative in 12 cases for granules. After switching to sTab, 9, 13 and 0 cases, and 10, 9 and 1 cases were positive, neutral, and negative, respectively. Median preparation and administration times were decreased after switching to sTab in both cTab and granules groups. The frequency of dosage manipulations was also decreased. The switch to sTab improved acceptability, and decreased burden of administration, suggesting that sTab is a user-friendly formulation in pediatric medications. [ABSTRACT FROM AUTHOR]

Baclofen is used as a skeletal muscle relaxant for multiple sclerosis patients and pediatric patients with cerebral palsy and is prescribed to pediatric patients at 0.3 to 1.0 mg/kg/dose. Baclofen tablets, an oral drug, are usually administered as a powder in pediatric wards after a formulation change by the pharmacist. However, there is no information about stability and assurance of quality for compounded products. The purpose of this study was to design a 10 mg/g oral powder of baclofen and to investigate the stability and changes in the physical properties of this compounded product. A 10 mg/g baclofen powder was prepared by adding extra-fine crystal lactose hydrate to crushed and filtrated baclofen tablets and was stored in a polycarbonate amber bottle with desiccant or in a coated paper laminated with cellophane and polyethylene. The stability of baclofen at 25 ± 2 °C/60 ± 5%RH was tested for 120 days in 'bottle (closed)', 'bottle (in use)', and 'laminated' storage conditions. Baclofen concentrations ranged from 90.0% to 110.0% of the initial concentration under all storage conditions. No crystallographic or dissolution changes were observed after storage. This information can help with the management of baclofen compounded powder in pharmacies. [ABSTRACT FROM AUTHOR]

A major hurdle in pediatric formulation development is the lack of safety and toxicity data on some of the commonly used excipients. While the maximum oral safe dose for several kinds of excipients is known in the adult population, the doses in pediatric patients, including preterm neonates, are not established yet due to the lack of evidence-based data. This paper consists of four parts: (1) country-specific perspectives in different parts of the world (current state, challenges in excipients, and ongoing efforts) for ensuring the use of safe excipients, (2) comparing and contrasting the country-specific perspectives, (3) past and ongoing collaborative efforts, and (4) future perspectives on excipients for pediatric formulation. The regulatory process for pharmaceutical excipients has been developed. However, there are gaps between each region where a lack of information and an insufficient regulation process was found. Ongoing efforts include raising issues on excipient exposure, building a region-specific database, and improving excipient regulation; however, there is a lack of evidence-based information on safety for the pediatric population. More progress on clear safety limits, quantitative information on excipients of concern in the pediatric population, and international harmonization of excipients' regulatory processes for the pediatric population are required. [ABSTRACT FROM AUTHOR]

Administration devices are crucial for the correct dosing of medicines to children. In countries outside Japan, oral droppers and syringes are reported to be preferred for the administration of oral liquid medicines to neonates and infants, whilst spoons and cups are more frequently used for older children. However, in Japan the majority of oral medicines are powders and the use of dosing devices in each pediatric age group is not well known. This study was performed as an observational anonymous questionnaire survey on devices for oral medicines in children aged 10 to less than 18 years and parents/caregivers on behalf of children aged from birth to less than 18 years. The results from 336 respondents showed that powders were most frequently prescribed in children aged less than 10 years old followed by liquids. Unlike previous reports, droppers were most frequently used in patients less than 12 months old, while household spoons were most frequently used in older children. Oral syringes were perceived as easy to use, which was in line with previous studies. Further cross-regional multi-countries study for establishment the guidelines on the choice of device will be needed. [ABSTRACT FROM AUTHOR]

Minitablets have garnered interest as a new paediatric formulation that is easier to swallow than liquid formulations. In Japan, besides the latter, fine granules are frequently used for children. We examined the swallowability of multiple drug-free minitablets and compared it with that of fine granules and liquid formulations in 40 children of two age groups (n = 20 each, aged 6–11 and 12–23 months). We compared the percentage of children who could swallow minitablets without chewing with that of children who could swallow fine granules or liquid formulations without leftover. The children who visited the paediatric department of Showa University Hospital were enrolled. Their caregivers were allowed to choose the administration method. In total, 37 out of 40 caregivers dispersed the fine granules in water. Significantly more children (80%, 95% CI: 56–94%) aged 6–11 months could swallow the minitablets than those who could swallow all the dispersed fine granules and liquid formulations (22%, 95% CI: 6–47% and 35%, 95% CI: 15–59%, respectively). No significant differences were observed in children aged 12–23 months. Hence, minitablets may be easier to swallow than dispersed fine granules and liquid formulations in children aged 6–11 months. [ABSTRACT FROM AUTHOR]

Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it is crucial to consider all these different aspects for assessing this multi-faceted concept and designing or prescribing a medicine in order to reach adequate acceptability in the target population. [ABSTRACT FROM AUTHOR]

Hydrocortisone has been utilized in the management of adrenal insufficiency. For pediatric patients, the commercially available enteral form of hydrocortisone tablets (Cortoril®) is administered in powder form after being compounded by a pharmacist. However, the stability and quality of compounded hydrocortisone powder have not been verified. In this study, we formulated a 20 mg/g oral hydrocortisone powder by adding lactose monohydrate to crushed and filtered hydrocortisone tablets and assessed the stability and physical properties of this compounded product in polycarbonate amber bottles or coated paper packages laminated with cellophane and polyethylene. Stability was examined over 120 days in three storage conditions: closed bottle, in-use bottle, and laminated paper. Drug dissolution and powder X-ray diffraction analysis were conducted to assess its physicochemical stabilities. Validated liquid chromatography-diode array detection was used to detect and quantify hydrocortisone and its degradation products. Although impurity B (cortisone) and G (hydrocortisone-21-aldehyde) were found after 120 days of storage, no crystallographic and dissolution changes were noted. Hydrocortisone content was maintained between 90% and 110% of initial contents for 120 days at 25 ± 2 °C and 60 ± 5% relative humidity in all packaging conditions. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is a common health care-associated adverse event and the leading nosocomial complication following pediatric urological surgery. While continuous antimicrobial prophylaxis effectively reduces the risk of UTI following such a surgery, non-adherence is common and represents a distinct clinical entity that is associated with renal scarring. Acceptability is likely to have a significant impact on patient adherence. Herein we used a validated data-driven approach—the ClinSearch acceptability score test (CAST)—to investigate the acceptability of cefaclor, an oral antibiotic widely used for the prevention of pediatric UTI in Japan. Standardized observer reports were collected for 58 intakes of cefaclor 10% fine granules in patients aged from 0 to 17 years. The medicine was classified as positively accepted on the acceptability reference framework. According to the percentage of the prescribed dose taken reported at the end of the treatment, patients exhibited good adherence to this well-accepted medicine. Nonetheless, requirements for greater dosing frequency or poor acceptability in certain patients could affect adherence. Acceptability should be established to ensure patient adherence to medicines used for long-term prophylaxis and consequently guarantee the safety and efficacy of the treatment. [ABSTRACT FROM AUTHOR]