First Development, Optimization, and Stability Control of a Pediatric Oral Atenolol Formulation

Abstract

Liquid formulations can be used in children of different ages by varying the volume of the administered dose in order to ensure an exact dosage. The aim of this work was to develop and to optimize a safe liquid atenolol formulation and to carry out the corresponding chemical and microbiological stability studies. A Plackett-Burman design was used to determine the factors that could be critical in the development of the formulations, and a central composite design was used to determine the optimal working conditions. As a result of these analyses, three formulations were selected and their stability studied in three storage conditions, 4, 25, and 40°C. After 6 months of stability testing, the optimal systems showed no pH change or atenolol loss; however, only glycerin-based formulations showed no microbial development. These systems, employing excipients in a range that the EMA has recommended, showed chemical and microbiological stability for at least 6 months even at the worst storage conditions.

Miconazole Nitrate Microparticles in Lidocaine Loaded Films as a Treatment for Oropharyngeal Candidiasis

“…The different compositions of the systems are shown in Table 1. High-Performance Liquid Chromatography was carried out using an Agilent Technologies 1200 Series chromatograph (Santa Clara, CA, USA) comprising a SiliaChrom C18 column (5 µm, 150 × 4.6 mm, S/N S11410) thermostatted at 40 • C [8] and a diode array detector. The amounts of MN and LDCH released were obtained spectrophotometrically by measuring the absorbance at 230 [9] and 265 nm [10] using ammonium acetate buffer (50 mM, pH 4): acetonitrile (35:65) as the mobile phase in isocratic mode with a flow rate of 1.5 mL min −1 .…”

Stability of Oral Liquid Dosage Forms in Pediatric Cardiology: A Prerequisite for Patient’s Safety—A Narrative Review

“…Such cases have demonstrated, by extrapolation, chemical stability for at least 850 days. The limitations would be represented by the microbial enumeration tests, which failed to meet the specifications after 180 days [12].…”

“…The EMA also issued an inventory of pediatric therapeutic needs [11]. In the cardiovascular therapeutic area, several substances, such as clonidine, atenolol, bisoprolol, carvedilol, sotalol, amiodarone, flecainide, and nicardipine have been listed, with a particular focus on information required regarding safety and pharmacokinetics and the need for developing age-appropriate formulations [11][12][13]. Nonetheless, there are still few medications that have been approved for children's use, especially regarding age-appropriate formulations.…”

A quality by design approach for optimization of Lecithin/Span® 80 based nanoemulsions loaded with hydrophobic drugs

“…However, the poor aqueous solubility of drugs may leads to a low/erratic bioavailability, affecting the invivo performance of such systems 2 . In this regard, several strategies have been explored to overcome such drawback including the supercritical antisolvent technique [3][4][5] , amorphous and crystalline solid dispersions [6][7][8] , cyclodextrin complexes [9][10][11] , cosolvency [12][13][14] and microencapsulation [15][16][17] . Particularly, the reduction of the particle size from microto nanometer scale is as a valuable and widely applied approach to improve the apparent saturation solubility, dissolution rate and bioavailability of hydrophobic molecules 18 .…”