Background: Oral liquid solutions of the diuretic active ingredient furosemide (FUR) marketed across Europe do not comply with recent requirements for paediatric preparation owing to their ethanol content and, moreover, in some countries only tablet or injection dosage forms of furosemide are available. Objectives: To formulate extemporaneous paediatric ethanol-free solutions of FUR (2 mg/mL) with suitable solubility in the aqueous vehicle and an acceptable taste and to evaluate their stability under two different storage conditions during a 9-month study period. Methods: Our work presents two developed formulations of FUR ethanol-free paediatric oral solutions 2 mg/mL for easy extemporaneous compounding in a pharmacy. FUR solubility avoiding the use of ethanol was achieved using sodium hydroxide (formulation F1) or disodium hydrogen phosphate dodecahydrate (formulation F2). The preparations were stored at 25°C±3°C or at 40°C±0.5°C and protected from light. For FUR and preservative, methylparaben (MP), a stability assay was conducted by a high-performance liquid chromatography validated method and determination of pH stability. Results: The remaining FUR concentration was >90% of the initial concentration after 270 days in both formulations at both storage conditions, 25°C and 40°C. The concentration of MP decreased significantly in the formulation F2 stored at 40°C. Conclusions: Both formulations were stable when stored at room temperature for up to 9 months; formulation F1 was stable even at 40°C. MP used as an antimicrobial agent fully satisfied the recommended criteria for preservative efficacy in oral preparations according to the European Pharmacopoeia 9.0 (5.1.3).
- Publikační typ
- časopisecké články MeSH
This work describes a comparison of three types of commercial high-performance liquid chromatography silica monolithic columns with different inner diameters and generations of monolithic sorbent: a "classic" monolithic column, the first generation (Onyx™ monolithic C(18), 100 mm × 4.6 mm, Phenomenex); a "narrow" monolithic column for fast separation at lower flow rates (Chromolith® Performance RP-18e, 100 mm × 3 mm, Merck); and a recently introduced "high-resolution" monolithic column, the next generation (Chromolith® HighResolution RP-18e, 100 mm × 4.6 mm, Merck). Separation efficiency (number of theoretical plates, height equivalent to a theoretical plate and van Deemter curves), working pressure, the symmetry factor and resolution were critical aspects of the comparison in the case of the separation of ascorbic acid, paracetamol and caffeine. The separations were performed under isocratic conditions with a mobile phase consisting of 10:90 (v/v) acetonitrile-phosphoric acid (pH 2.80). Detailed comparison of the newest-generation monolithic column (Chromolith® HighResolution) with the previously introduced monolithic sorbents was performed and proved the advantages of the Chromolith® HighResolution column.
- MeSH
- adsorpce MeSH
- kofein chemie izolace a purifikace MeSH
- kyselina askorbová chemie izolace a purifikace MeSH
- paracetamol chemie izolace a purifikace MeSH
- vysokoúčinná kapalinová chromatografie přístrojové vybavení metody MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Cílem práce je formulace pediatrického perorálního přípravku s propranolol-hydrochloridem (PRO) 2 mg/ml pro magistraliter přípravu, určeného k terapii infantilního hemangiomu nebo hypertenze u cílové skupiny dětí od 1 měsíce do školního věku, a hodnocení jeho stability. K dosažení pH okolo 3, optimálnímu pro PRO, byl jako vehikulum využit roztok kyseliny citronové nebo citráto-fosfátový pufr. K maskování hořké chuti PRO byl použit prostý sirup. Všechny roztoky byly uchovávány v dobře uzavřené hnědé lékovce při 5 ? 3 °C a/nebo 25 ? 3 °C. V časových intervalech 0–180 dní byla hodnocena koncentrace PRO a protimikrobní látky, benzoanu sodného, validovanou HPLC metodou. Všechny přípravky byly stabilní při obou teplotách s hodnotou pH v rozmezí 2,8–3,2. V souladu s požadavky lékopisu byla prokázána účinnost protimikrobní látky, benzoanu sodného (Ph. Eur., 5.1.3). Podle našich zkušeností má přípravek s citráto-fosfátovým pufrem lepší chuť než přípravek s kyselinou citronovou. Klíčová slova: propranolol-hydrochlorid • pediatrický přípravek • magistraliter přípravek • roztok • testování stability • HPLC
The aim of this study is to formulate an extemporaneous pediatric oral solution of propranolol hydrochloride (PRO) 2 mg/ml for the therapy of infantile haemangioma or hypertension in a target age group of 1 month to school children and to evaluate its stability. A citric acid solution and/or a citrate-phosphate buffer solution, respectively, were used as the vehicles to achieve pH value of about 3, optimal for the stability of PRO. In order to mask the bitter taste of PRO, simple syrup was used as the sweetener. All solutions were stored in tightly closed brown glass bottles at 5 ? 3 °C and/or 25 ? 3 °C, respectively. The validated HPLC method was used to evaluate the concentration of PRO and a preservative, sodium benzoate, at time intervals of 0–180 days. All preparations were stable at both storage temperatures with pH values in the range of 2.8–3.2. According to pharmacopoeial requirements, the efficacy of sodium benzoate 0.05 % w/v was proved (Ph.Eur., 5.1.3). The preparation formulated with the citrate-phosphate buffer, in our experience, had better palatability than that formulated with the citric acid solution. Keywords: propranolol hydrochloride • pediatric preparation • extemporaneous preparation • solution • stability testing • HPLC
- MeSH
- dítě MeSH
- farmaceutické pomocné látky MeSH
- kojenec MeSH
- lékové roztoky MeSH
- lidé MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- příprava léků * MeSH
- propranolol * analogy a deriváty MeSH
- stabilita léku * MeSH
- vysokoúčinná kapalinová chromatografie normy MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- Publikační typ
- práce podpořená grantem MeSH
