Stability of extemporaneously compounded spironolactone suspensions.

Pharmaceutical Development, G.D. Searle & Co., Skokie, IL 60077.
American journal of hospital pharmacy 11/1989; 46(10):2040-2.
Source: PubMed

ABSTRACT The short-term stability of spironolactone in liquid formulations prepared from spironolactone tablets was studied at three temperatures. Suspensions of spironolactone at concentrations of 2.5, 5.0, and 10.0 mg/mL were prepared by grinding film-coated tablets to a fine powder, adding Purified Water, USP, triturating the mixture to form a fine paste, adding Cherry Syrup, NF, and homogenizing the suspension. Drug concentrations were immediately measured by a stability-indicating high-performance liquid chromatographic (HPLC) method. Samples were stored in amber glass prescription bottles at 5 and 30 degrees C in controlled environmental cabinets and at ambient room temperature (20 to 24 degrees C) under intense fluorescent light. After two and four weeks of storage the bottles were shaken, and samples were removed and assayed by HPLC. There was no appreciable loss of spironolactone from the cherry syrup formulations stored for two weeks under the conditions studied. Degradation was less than 5% for samples stored for four weeks. Color and odor of the samples did not change appreciably, and counts of bacteria and fungi remained within acceptable limits. Extemporaneously prepared suspensions of spironolactone in Cherry Syrup, NF, are stable for four weeks under the conditions studied.

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    ABSTRACT: In der vorliegenden Arbeit wurde der Bedarf an kindgerechten Arzneizubereitungen in der Bundesrepublik Deutschland in pädiatrischen Abteilungen von Krankenhäusern erstmalig flächendeckend erfasst und quantifiziert. Dabei zeigte sich, dass ein Bedarf fast ausschließlich für lange in die Therapie eingeführte Substanzen, deren Patentschutz meist seit langem ausgelaufen ist, besteht. Ein besonders hoher Bedarf wurde bei Arzneistoffen zur Therapie von Herz-Kreislauf-Erkankungen deutlich. Die Arzneistoffgruppe, die am häufigsten verordnet wurde, sind die Diuretika. Dazu gehören Hydrochlorothiazid, Spironolacton und Furosemid. Da neben den Arzneistoffen unter anderem auch deren Dosierung in Abhängigkeit von Lebensalter und Körpergewicht untersucht wurde, konnte für die Arzneistoffe Hydrochlorothiazid und Spironolacton ein Vergleich zwischen den tatsächlich verwendeten und den in der Literatur empfohlenen Dosierschemata gezogen werden. Neben zum Teil deutlichen Unterschieden zwischen verschiedenen in der Literatur gegebenen Dosierungsempfehlungen konnten auch deutliche Abweichungen zwischen der tatsächlichen Dosierung und den Empfehlungen aufgezeigt werden. Darüber hinaus wurden Daten zu den verwendeten Arzneiformen gesammelt. Dies ermöglichte einen Vergleich mit den in dem EMEA-Dokument „Formulations of choice for the paediatric population“ für die verschiedenen Altersgruppen empfohlenen Darreichungsformen. Während für Neugeborene, Kleinkinder und Vorschulkinder flüssige Zubereitungen empfohlen werden, erfolgt die Therapie auf den Kinderstationen der deutschen Krankenhäuser hauptsächlich mit Hartkapseln. Ausgehend von den aufgedeckten Versorgungsdefiziten wurde die Qualität von Rezepturarzneimitteln für die Diuretika Hydrochlorothiazid, Spironolacton und Furosemid vergleichend beurteilt. Während für die Arzneistoffe Spironolacton und Furosemid qualitativ hochwertige und hinsichtlich der Formulierung gut geeignete Rezepturen gefunden werden konnten, zeigen die Untersuchungen zu Hydrochlorothiazid-Rezepturarzneimitteln den besonderen Bedarf an einer neuen stabilen und kindgerechten Zubereitung. Defizite bestehen nicht nur bei den flüssigen Zubereitungen, sondern auch bei den im Neuen Rezeptur-Formularium monographierten Hydrochlorothiazid-Kapseln. Es wurde ein Hydrochlorothiazid-Saft entwickelt, der allen Anforderungen an eine kindgerechte Formulierung gerecht wird. Erstmalig wird es möglich, Neugeborene und Kleinkinder mit einem adäquaten Hydrochlorothiazid-Arzneimittel zu behandeln. Die entwickelte Formulierung wurde systematisch hinsichtlich ihrer Qualität untersucht. Ein pharmazeutischer Hersteller beabsichtigt, die Entwicklung des Saftes voranzutreiben und eine behördliche Zulassung als Fertigarzneimittel anzustreben. In the present investigations the need for child-appropriate drug formulations in paediatric wards of German hospitals was detected and quantified for the first time. It became obvious, that the most prominent need is for “old” drug substances without patent exclusivity. The highest demand has been found for the therapy of cardiovascular diseases. Thereof, diuretics are the most prescribed drugs, namely hydrochlorothiazide, spironolactone, and furosemide. Furthermore the dosage of the drug in dependency of age and body-weight was investigated, which enables the comparison of the actual dosage of hydrochlorothiazide and spironolactone with the recommendations given in the literature. In addition to partially considerable differences between different dosage recommendations given in the literature, considerable discrepancies between actual dosage and dosage recommendations could be demonstrated. In addition, data on the prescribed drug formulations were collected. This allowed a comparison with the formulations recommended in the EMEA document “Formulations of choice for the paediatric population” for the different age-groups. Whilst oral liquids are recommended for newborns, toddlers, and infants mainly hard capsules are used in the therapy on paediatric wards of German hospitals. Starting from the unmet needs, the quality of extemporaneously compounded drugs with hydrochlorothiazide, spironolactone, and furosemide was comparatively evaluated. Whilst formulations of high quality were found for spironolactone and furosemide, an urgent need was detected for hydrochlorothiazide in terms of a new, stable child-appropriate formulation. Deficiencies do exist for liquid formulations but also for the capsules specified by NRF. A new oral liquid formulation with hydrochlorothiazide was developed that meets all requirements for a child-appropriate formulation. Now it will become possible to treat newborns and infants with such an adequate hydrochlorothiazide formulation. The quality of the developed formulation was thoroughly investigated. A pharmaceutical company intends to continue the pharmaceutical and clinical development of the oral liquid and to apply for a marketing authorisation.