Research

12 pages, 250 KiB

Open AccessArticle

Study on the Preparation Method of Quality-Assured In-Hospital Drug Formulation for Children—A Multi-Institutional Collaborative Study

by Jumpei Saito, Eiji Suzuki, Yosuke Nakamura, Takashi Otsuji, Hiroshi Yamamoto, Hideki Yamamoto, Yuiko Kai, Maiko Totsu, Sayuki Hashimoto, Hidefumi Nakamura, Miki Akabane and Akimasa Yamatani

Children 2023, 10(7), 1190; https://doi.org/10.3390/children10071190 - 10 Jul 2023

Viewed by 863

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Global Collaboration in Pediatric Drug Development and Formulation: Toward Better and Safe, and Appropriate Formulation for Children)

10 pages, 1377 KiB

Open AccessArticle

Drug Prescriptions Requiring Compounding at a Canadian University Affiliated Pediatric Hospital: A Cross-Sectional Study

by Émilie Kate Landry, Julie Autmizguine, Sophie Bérubé, Raphael Kraus, Marie-Élaine Métras, Denis Lebel and Catherine Litalien

Children 2023, 10(1), 147; https://doi.org/10.3390/children10010147 - 11 Jan 2023

Viewed by 1562

Abstract

Despite ongoing international efforts, many drugs administered to children must be compounded from dosage forms designed for adults because they remain unavailable in commercial formulations that suit their needs. Even though oral drug compounding is common in pediatrics, the extent of this practice [...] Read more.

Despite ongoing international efforts, many drugs administered to children must be compounded from dosage forms designed for adults because they remain unavailable in commercial formulations that suit their needs. Even though oral drug compounding is common in pediatrics, the extent of this practice has not been well described in recent years. This cross-sectional and retrospective study was conducted at a Canadian university-affiliated, 484-bed, tertiary care pediatric hospital and its rehabilitation centre on two randomly selected days. A total of 606 hospitalized children with 5465 prescriptions were included. Overall, compounded drugs for enteral administration (CDEA) represented 13% of all prescriptions (enteral and parenteral) and 23% of prescriptions for enteral administration. Of the 390 prescribed drugs, 122 required compounding. CDEA were mostly liquids (n = 478 [67%]) and mainly included drugs of the central nervous (35%), cardiovascular (21%), and gastro-intestinal (12%) systems. Nearly half (N = 298 [49%]) of children had at least one CDEA prescribed in their medical file. Many CDEA are available as commercial products in other jurisdictions. Collaboration is needed between all stakeholders to make these drugs available to Canadian children. Full article

(This article belongs to the Special Issue Global Collaboration in Pediatric Drug Development and Formulation: Toward Better and Safe, and Appropriate Formulation for Children)

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12 pages, 13855 KiB

Open AccessArticle

Investigation on the Usefulness of Sulfamethoxazole Trimethoprim Combination Small Tablets in Pediatric Pharmacotherapy: A Single Center Observational Study Using a Questionnaire

by Jumpei Saito, Miho Yamaguchi, Seiichi Shimizu, Kyoko Chiba, Tomoyuki Utano, Akinari Fukuda, Seisuke Sakamoto, Mureo Kasahara and Akimasa Yamatani

Children 2022, 9(10), 1598; https://doi.org/10.3390/children9101598 - 21 Oct 2022

Cited by 2 | Viewed by 1493

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Global Collaboration in Pediatric Drug Development and Formulation: Toward Better and Safe, and Appropriate Formulation for Children)

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15 pages, 2231 KiB

Open AccessArticle

Stability Study of Baclofen in an Oral Powder Form Compounded for Pediatric Patients in Japan

by Jumpei Saito, Takehisa Hanawa, Ayuna Ozawa, Takahiro Matsumoto, Nozomi Yoshikawa, Tsutomu Harada, Kana Iwahashi and Akimasa Yamatani

Children 2022, 9(9), 1313; https://doi.org/10.3390/children9091313 - 29 Aug 2022

Cited by 3 | Viewed by 2221

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Global Collaboration in Pediatric Drug Development and Formulation: Toward Better and Safe, and Appropriate Formulation for Children)

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13 pages, 6200 KiB

Open AccessArticle

Microparticulated Mefenamic Acid with High Dispersion Stability for Pediatric Dosage Form

by Moe Yamazaki, Emi Shimamura, Takehisa Hanawa and Yayoi Kawano

Children 2022, 9(6), 861; https://doi.org/10.3390/children9060861 - 09 Jun 2022

Viewed by 1513

Abstract

Mefenamic acid (MFA), a water-insoluble drug, is used as a suspension in the medical field, but it requires shaking before using to disperse MFA content in the suspension. In previous studies, trials to prepare MFA suspension with high dispersion stability by atomizing MFA [...] Read more.

Mefenamic acid (MFA), a water-insoluble drug, is used as a suspension in the medical field, but it requires shaking before using to disperse MFA content in the suspension. In previous studies, trials to prepare MFA suspension with high dispersion stability by atomizing MFA by the wet-milling method. However, HPC is used for atomizing MFA. Therefore, the optimum concentration and molecular weight for atomizing MFA have not been investigated. In this study, we investigated the optimum molecular weight and concentration of HPC for the micronization of MFA. As a result, MFA particles became fine particles by adding SDS, and the particle size was also smaller than that of HPC alone. In addition, the suspension with the highest dispersion stability can be obtained when a mixed solution of 1.0% HPC-SL and 0.12% SDS aqueous solution is used. Therefore, this study considers that the addition of SDS and 1.0% HPC-SL aqueous solution are optimal for improving the dispersion stability of the MFA suspension. Full article

(This article belongs to the Special Issue Global Collaboration in Pediatric Drug Development and Formulation: Toward Better and Safe, and Appropriate Formulation for Children)

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8 pages, 1496 KiB

Open AccessFeature PaperArticle

A Survey to Understand Parent/Caregiver and Children’s Views on Devices Used for the Administration of Oral Pediatric Medicines in Japan

by Jumpei Saito, Hidefumi Nakamura, Jennifer Walsh, Akimasa Yamatani and Smita Salunke

Children 2022, 9(2), 196; https://doi.org/10.3390/children9020196 - 03 Feb 2022

Cited by 7 | Viewed by 1882

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Global Collaboration in Pediatric Drug Development and Formulation: Toward Better and Safe, and Appropriate Formulation for Children)

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Review

Jump to: Research, Other

28 pages, 1117 KiB

Open AccessReview

The Current States, Challenges, Ongoing Efforts, and Future Perspectives of Pharmaceutical Excipients in Pediatric Patients in Each Country and Region

by Jumpei Saito, Anjali Agrawal, Vandana Patravale, Anjali Pandya, Samuel Orubu, Min Zhao, Gavin P. Andrews, Caroline Petit-Turcotte, Hannah Landry, Alysha Croker, Hidefumi Nakamura, Akimasa Yamatani and Smita Salunke

Children 2022, 9(4), 453; https://doi.org/10.3390/children9040453 - 23 Mar 2022

Cited by 9 | Viewed by 3839

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Global Collaboration in Pediatric Drug Development and Formulation: Toward Better and Safe, and Appropriate Formulation for Children)

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Other

Jump to: Research, Review

8 pages, 231 KiB

Open AccessCase Report

Acute Kidney Injury with SARS-CoV-2 Infection in Pediatric Patients Receiving High-Dose Methotrexate Chemotherapy: A Report of Three Cases

by Olga Nigro, Cristina Meazza, Elisabetta Schiavello, Veronica Biassoni, Nadia Puma, Luca Bergamaschi, Giovanna Gattuso, Giovanna Sironi, Virginia Livellara, Gabriele Papagni and Maura Massimino

Children 2023, 10(2), 331; https://doi.org/10.3390/children10020331 - 09 Feb 2023

Cited by 1 | Viewed by 1211

Abstract

Background. Methotrexate is renally excreted. HDMTX (high dose-methotrexate)-induced acute kidney injury (AKI) is a non-oliguric decrease in glomerular filtration rate (GFR) heralded by an acute rise in serum creatinine. Moreover, AKI is also a frequent complication of COVID-19. Among our patients treated with [...] Read more.

Background. Methotrexate is renally excreted. HDMTX (high dose-methotrexate)-induced acute kidney injury (AKI) is a non-oliguric decrease in glomerular filtration rate (GFR) heralded by an acute rise in serum creatinine. Moreover, AKI is also a frequent complication of COVID-19. Among our patients treated with HDMTX, some of these developed AKI during SARS-CoV-2 infection. Therefore, we wondered whether our patients’ kidney failure might have been triggered by their underlying SARS-CoV-2 positivity. Methods. Data were collected from the database at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori in Milan (Italy) regarding patients who matched the following selective criteria: (a) treatment with HDMTX during the pandemic period; (b) SARS-CoV-2 infection during the treatment; (c) development of AKI during HDMTX treatment and SARS-CoV-2 infection. Results. From March 2020 to March 2022, a total of 23 patients were treated with HDMTX; 3 patients were treated with HDMTX during SARS-CoV-2 infection and all 3 developed AKI. Conclusions. Clinical manifestations associated with this virus are many, so we are not yet able to lower our guard and rule out this infection as a cause of clinical manifestations with any certainty. Full article

(This article belongs to the Special Issue Global Collaboration in Pediatric Drug Development and Formulation: Toward Better and Safe, and Appropriate Formulation for Children)

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