Design and evaluation of extemporaneous formulations for treating pulmonary hypertension in children

Abstract

Introduction: Children, being the most vulnerable group, whose health status require urgent attention, are constantly in need of extemporaneous formulations for the treatment of several clinical conditions, such as pulmonary hypertension (PH) Method: Amiloride hydrochloride / Hydrochlorothiazide (AH) combination, (1 mg / 10mg)/mL, and furosemide, 1 mg/mL, were separately formulated into liquid dosage forms using simple syrup BPC, commercially available ascorbic acid syrup, deionized water and deionized water: propylene glycol (ratios 75:25, 65:35 and 50:50) as solvents. The formulations were analyzed for stability over a 7-day period at different storage conditions (27±2°C protected from and exposed to sunlight, and refrigeration at 4±1°C) using physical parameters, pH analysis, UV spectrophotometry assay and microbial count as assessment parameters Results: Significant changes were observed for formulations exposed to sunlight (27°±2°C), while refrigerated formulations were the most stable to physical changes, but had increased viscosity. All formulations had reduction in pH values, however, formulations containing deionized water and propylene glycol were the most significant, with formulations protected from light at 27°±2°C providing the least pH changes. Refrigerated formulations retained higher medicament percentages within official limits, while formulations exposed to light (27°±2°C) had the highest loss of potency. Virtually all the formulations prepared with simple syrup BPC aided growth of lactose fermenters. Refrigerated formulations resisted microbial growth most. In terms of stability, the storage conditions can be ranked as 4°± 1 °C > 27°±2°C protected from light >27°±2°C exposed to light. Conclusion: The refrigerated extemporaneous formulations were the most physically stable. Deionized water: propylene glycol (75:25) is the most appropriate solvent for formulating the formulations and should be used only for a maximum of 6 days. It is recommended that extemporaneous formulations containing Amiloride hydrochloride-Hydrochlorothiazide (AH) combination or furosemide are preferably stored at 4°±1°C protected from light, as this offers good resistance to microbial growth.