Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan

Abstract

Background Clonidine hydrochloride is used to treat sedative agent withdrawals, malignant hypertension, and anesthesia complications. Clonidine is also prescribed off-label to pediatric patients at a dose of 1 μg/kg. The commercially available enteral form of clonidine, Catapres® tablets, is often compounded into a powder form by pharmacists to achieve dosage adjustments for administration to pediatric patients. However, the stability and quality of compounded clonidine powder have not been verified. The objectives of this study were to formulate a 0.2 mg/g oral clonidine hydrochloride powder and assess the stability and physical properties of this compounded product in storage. Methods A 0.2 mg/g clonidine powder was prepared by adding lactose monohydrate to crushed and filtrated clonidine tablets. The powder was stored in polycarbonate amber bottles or coated paper packages laminated with cellophane and polyethylene. The stability of clonidine at 25 °C ± 2 °C and 60% ± 5% relative humidity was examined over a 120-d period in “bottle (closed),” “bottle (in use),” and “laminated paper” storage conditions. Drug dissolution and powder X-ray diffraction analysis were conducted to assess physicochemical stabilities. Validated liquid chromatography-diode array detection was used to detect and quantify clonidine and its degradation product, 2,6-dichloroaniline (2,6-DCA). Results Clonidine content was maintained between 90.0 and 110.0% of the initial contents in all packaging and storage conditions. After 120 d of storage, 2,6-DCA was not detected, and no crystallographic and dissolution changes were observed. Conclusions Compounded clonidine powder stability was maintained for 120 d at 25 °C ± 2 °C and 60% ± 5% relative humidity. This information may contribute to the management of clonidine compounded powder in community and hospital pharmacies in Japan.

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.…”

“…For drug stability, the samples were obtained from each storage condition at days 0, 30, 60, 90, and 120, diluted according to previously published methods [4][5][6] and analyzed using an HPLC system Ultimate 3000 (Thermo Fisher Scientific, Tokyo, Japan) containing an autosampler, a column oven, and a diode array detector (Table 2). The concentration changes were calculated as (measured concentration/initial concentration) × 100 (%), and within 10% of the initial concentration were considered acceptable changes [12].…”

“…Dissolution tests were performed under the same conditions as previously reported [4][5][6] according to ICH Japanese Pharmacopoeia 17.6.10. (paddle method; NTR-6400AC; Toyama Sangyo, Tokyo, Japan) using 900 mL of dissolution solution stirred at 37 • C ± 0.5 • C and 50 rpm.…”

“…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.…”