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

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 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.

Is baclofen the least worst option for spasticity management in children?

“…However, there can be challenges with use of compounded baclofen. One challenge is that compounded baclofen can settle out of solution [12]. Thus, it must be vigorously shaken every time before administration or the amount given will not be the expected For this child, I would initiate diazepam due to his possible ongoing or undertreated seizure disorder, constipation, and likely need for liquid medication to ease administration.…”

“…However, there can be challenges with use of compounded baclofen. One challenge is that compounded baclofen can settle out of solution [ 12 ]. Thus, it must be vigorously shaken every time before administration or the amount given will not be the expected concentration.…”

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

“…The prepared in-hospital pre-products were stored under the following three storage conditions according to the previous study [4][5][6]11]: (1) "Bottle (closed)" condition: stored in polycarbonate bottles (Yamayu, Osaka, Japan), (2) "Bottle (in-use)" condition: 0.1 g weighed daily from the bottle condition, and (3) package condition: packaged in cellophane and polyethylene wrapping paper (TK-70W, Takazono, Tokyo, Japan), and then stored under light-shielded conditions at 25 • C ± 2 • C and 60% ± 5% relative humidity (RH). The samples were stored for 0 to 120 days.…”

“…Many in-hospital pre-products often lack quality assurance, such as the assurance of long-term stability and ingredient dissolution. The National Center for Child Health and Development (NCCHD) has been studying the standardization of preparation methods to ensure the quality of in-hospital preparation for pediatric drug therapy, and has examined preparation methods for baclofen, hydrocortisone, and clonidine [4][5][6]. Although the quality of the preparations prepared at the Department of Pharmacy of NCCHD was confirmed to be assured, the quality of products prepared in different environments and by different methods at other facilities is unclear.…”

In Vitro Profile of Hydrocortisone Release from Three-Dimensionally Printed Paediatric Mini-Tablets

“…The use of this native hormone is recommended over synthetic steroids (prednisolone and dexamethasone) due to its greater suppressive effect on growth [ 35 ]. According to the primary diagnosis, the HCT dose range is 7.5–15 mg/m 2 /day, given in three to four divided doses, with the first and slightly higher dose administered upon waking in the morning and the last dose administered 4 to 6 h before bedtime [ 36 ]. However, this regimen’s continuous administration poses challenges to patient compliance, particularly in children, who may need to disrupt their activities to adhere to their medication schedule, leading to discomfort and potential non-compliance.…”