Orphan Formulations for Pediatric Use: Development and Stability Control of Two Sildenafil Citrate Solutions for the Treatment of Pulmonary Hypertension
| Autor: | Silvana Vignaduzzo, Cecilia Casabonne, Darío Leonardi, Mauro Morri |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Sildenafil Drug Compounding Hypertension Pulmonary Pharmaceutical Science Vasodilation 02 engineering and technology Aquatic Science Pulmonary arterial pressure Pharmacology 030226 pharmacology & pharmacy Sildenafil Citrate 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Smooth muscle Drug Stability Drug Discovery medicine Humans Palatability Solubility Child Ecology Evolution Behavior and Systematics Ecology business.industry Drug administration General Medicine Middle Aged 021001 nanoscience & nanotechnology medicine.disease Pulmonary hypertension Solutions chemistry 0210 nano-technology business Agronomy and Crop Science |
| Zdroj: | AAPS PharmSciTech. 21(6) |
| ISSN: | 1530-9932 |
| Popis: | Sildenafil citrate causes vasodilatation, relaxation of the smooth muscle, and reduction of pulmonary arterial pressure. The latter property makes sildenafil citrate efficient for the treatment of cardiovascular diseases, including pulmonary arterial hypertension. Pediatric patients with pulmonary arterial hypertension are more susceptible to errors in drug administration than adults because of a lack of suitable drug dosages. Thus, the purpose of this study was to develop stable (chemically and microbiologically) sildenafil citrate drop liquid formulation, suitable for pediatric patients (including diabetics), ensuring safety during preparation and storing and improving palatability by using milk as a carrier for administration. The significant factors that affect the sildenafil solubility were evaluated by applying a Plackett-Burman design using two levels with six variables. The experiment showed that the type of buffer and glycerin content influenced the sildenafil solubility. The developed formulations proved to be stable for 6 months at all three assayed conditions (40± 2°C, 75 ± 5% RH; 25± 2°C, 60 ± 5% RH; and 4 ± 2°C). The microbiological tests fit with the requirement of the pharmacopeia at day 0 and 90 and even more at day 180. Finally, the palatability assay showed that 0.82 mL of the formulation containing buffer phosphate, 20% glycerin, and 4 mg mL−1 of sildenafil citrate diluted in 4.8 mL milk (which fits the medium pediatric dose) presented similar palatability to milk alone, and no precipitate or turbidity was observed. |
| Databáze: | OpenAIRE |
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