Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome

Provenza, N.; Calpena, Ana Cristina; Mallandrich, Mireia; Pueyo, Blanca; Clares, Beatriz

doi:10.3109/10837450.2015.1055765

Cited by 3 publications

(3 citation statements)

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“…It should be note that the methadone analyzed with these methods was either found in concentrations different from 10 mg/ml, or they were preparations for intravenous administration, or they were compounded with other vehicles than water (sodium chloride [ 11 , 12 ], various drinks [ 13 ], syrups, suspension and sugar-free vehicles [ 14 ]) and none of the pharmaceuticals analyzed for oral administration contained exactly the same preservatives (only methylparaben) [ 9 ] used in our new formulation [ 15 ], so they really were not suitable for us. Furthermore, these methods use columns that are no longer used, such as µBondapak or Radpak-Novapak, a type A silica-based column with a lot of silanolic activity and therefore a high possibility of deformation tailing.…”

Section: Introductionmentioning

confidence: 99%

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Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies

et al. 2022

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Purpose The Pharmacy Service of the Infanta Leonor University Hospital acquires, compounds, distributes and dispenses more than 3000 L of methadone oral solution to Drug Addiction Patients Centers per year. Our purpose is to develop and validate an improved high performance liquid chromatography (HPLC) method to quantify methadone hydrochloride in a new oral solution with methylhydroxybenzoate (methylparaben) and propylhydroxybenzoate (propylparaben) to be implemented in physicochemical stability studies that allow to provide more information and even to increase the beyond-use date. Methods A HPLC-Agilent® 1100 equipment, comprising a quaternary pump and an ultraviolet diode-array-detector (DAD) was used. An analytical method development and validation was completed. The curve was constructed from methadone working concentrations of 75–125% (7.5, 9.0, 10.0, 11.0 and 12.5 mg/mL) to assess the linear relationship between the concentration of the analyte and the obtained areas. Precision and accuracy were calculated. Detection and quantification limit (LD, LQ) were estimated using the EURACHEM method. Forced-degradation studies were also performed. Results Chromatographic conditions were: flow rate 1.6 mL/min; mobile phase 55% acetonitrile and 45% sodium phosphate 25 mM (pH = 10); injection volume was 5 µL. The column was a Waters-XTerra™ RP18, maintained at 40 °C. DAD was λ = 254 nm. Retention times for methadone, methylparaben and propylparaben were 4.34, 0.70 and 0.88 min respectively. The method was linear (y = 284.3x − 97.8, r = 0.996). Instrumental precision was 0.33% for standards (n = 10); intra-assay precision 0.53% (n = 6) and inter-assay precision 1.95% (n = 12). The relative standard deviation percentage for accuracy was 1.28%. The recovery percentage was 101.5 ± 1.5%. LQ and LD were 2.18 µg/mL and 2.0 µg/mL respectively. The most destabilizing conditions were oxidizing and alkaline. The chromatograms confirmed no interference with the methadone signal. Conclusions The HPLC method has proved to be valid and reproducible for methadone quantification in a new oral solution with methylparaben and propylparaben. This assay is a rapid, simple and reliable technique that can be used in daily analysis and physicochemical stability studies.

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Section: Introductionmentioning

confidence: 99%

“…Therefore, there would not be suitable for our work. Methadone stability studies have also been described, but the methadone determination technique is either the USP one, those previously shown in the literature, GC [ 23 ] or spectrophotometry [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies

et al. 2022

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“…It should be note that the methadone analyzed with these methods was either found in concentrations different from 10 mg/ml, or they were preparations for intravenous administration, or they were compounded with other vehicles than water (sodium chloride [11,12], various drinks [13], syrups, suspension and sugar-free vehicles [14]) and none of the pharmaceuticals analyzed for oral administration contained exactly the same preservatives (only methylparaben) [4] used in our new formulation [15], so they really were not suitable for us. Furthermore, these methods use columns that are no longer used, such as µBondapak or Radpak-Novapak, a type A silica-based column with a lot of silanolic activity and therefore a high possibility of deformation tailing.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a HPLC-UV Method for Methadone Hydrochloride Quantification in a New Oral Solution with Preservatives to be Implemented in Physicochemical Stability Studies.

Álvaro-Alonso

Lorenzo-García

Rodríguez

et al. 2022

Preprint

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Purpose: The Pharmacy Service of the Infanta Leonor University Hospital acquires, compounds, distributes and dispenses more than 3,000 liters of methadone oral solution to Drug Addiction Patients Centers per year. Our purpose is to develop and validate an improved high performance liquid chromatography (HPLC) method to quantify methadone hydrochloride in a new oral solution with methylhydroxybenzoate (methylparaben) and propylhydroxybenzoate (propylparaben) to be implemented in physicochemical stability studies that allow to provide more information and even to increase the beyond-use date.Methods: A HPLC-Agilent® 1,100 equipment, comprising a quaternary pump and an ultraviolet diode-array-detector (DAD) was used. An analytical method development and validation was completed. The curve was constructed from methadone working concentrations of 75%-125% (7.5, 9.0, 10.0, 11.0 and 12.5 mg/mL) to assess the linear relationship between the concentration of the analyte and the obtained areas. Precision and accuracy were calculated. Detection and quantification limit (LD, LQ) were estimated using the EURACHEM method. Forced-degradation studies were also performed.Results: Chromatographic conditions were: flow rate 1.6 mL/min; mobile phase 55% acetonitrile and 45% sodium phosphate 25 mM (pH=10); injection volume was 5 µL. The column was a Waters-XTerraTM RP18, maintained at 40oC. DAD was λ=254 nm. Retention times for methadone, methylparaben and propylparaben were 4.34, 0.70 and 0.88 minutes respectively.The method was linear (y=284.3x-97.8, r=0.997). Instrumental precision was 0.33% for standards (n=10); intra-assay precision 0.53% (n=6) and inter-assay precision 1.95% (n=12). The relative standard deviation percentage for accuracy was 1.28%. The recovery percentage was 101.5 ± 1.5%. LQ and LD were 2.18 mg/mL and 2.0 mg/mL respectively. The most destabilizing conditions were oxidizing and alkaline. The chromatograms confirmed no interference with the methadone signal.Conclusions: The HPLC method has proved to be valid and reproducible for methadone quantification in a new oral solution with methylparaben and propylparaben. This assay is a rapid, simple and reliable technique that can be used in daily analysis and physicochemical stability studies.

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Physicochemical and Microbiological Stability of Two Oral Solutions of Methadone Hydrochloride 10 mg/mL

et al. 2022

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In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage conditions. For this, two oral solutions of methadone (10 mg/mL) were prepared, with and without parabens, as preservatives. They were packed in amber glass vials kept unopened until the day of the test, and in a multi-dose umber glass bottle opened daily. They were stored at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C. pH, clarity, and organoleptic characteristics were obtained. A stability-indicating high-performance liquid chromatography method was used to determine methadone. Microbiological quality was studied and antimicrobial effectiveness testing was also determined following European Pharmacopoeia guidelines. Samples were analyzed at days 0, 7, 14, 21, 28, 42, 56, 70, and 91 in triplicate. After 91 days of storage, pH remained stable at about 6.5–7 in the two solutions, ensuring no risk of methadone precipitation. The organoleptic characteristics remained stable (colorless, odorless, and bitter taste). The absence of particles was confirmed. No differences were found with the use of preservatives. Methadone concentration remained within 95–105% in all samples. No microbial growth was observed. Hence, the two oral methadone solutions were physically and microbiologically stable at 5 ± 3 °C, 25 ± 2 °C, and 40 ± 2 °C for 91 days in closed and opened amber glass bottles.

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Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome

Abstract: A correct dosage for the treatment of NAS was guaranteed.

Cited by 3 publications

References 28 publications

Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies

Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies

Development and Validation of a HPLC-UV Method for Methadone Hydrochloride Quantification in a New Oral Solution with Preservatives to be Implemented in Physicochemical Stability Studies.

Physicochemical and Microbiological Stability of Two Oral Solutions of Methadone Hydrochloride 10 mg/mL

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