Pediatric Formulation Optimization Using a Rational Design: Exploring Amorphous Solid Dispersion Technology with Terbinafine Hydrochloride as a Case Study
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Abstract
Developing orally administered pediatric formulations presents significant challenges due to the unique characteristics of pediatric patients. Terbinafine hydrochloride (TER), a powerful antifungal agent, is effective against various fungal infections, including Tinea capitis, which is common in children. However, its low aqueous solubility necessitates innovative pharmaceutical strategies to enhance its effectiveness. This study describes a rational approach to selecting suitable carriers, approved for use in children, to increase the apparent solubility of TER and to guide the development of amorphous solid dispersions containing this drug. Assessments of solubility parameters, equilibrium solubility measurements, and calculations of pediatric dose numbers guided formulation development using theoretical and experimental methodologies. Carriers like Plasdone S-360 ULTRA®, HPMCAS L, and Soluplus® demonstrated favorable solubility parameter values with TER, indicating potential for drug solubilization. The solubility of TER was strongly dependent on pH. In buffer pH 6.5 containing 10% (w/v) of Soluplus®, TER presented the highest solubility value. The solid-state characterization techniques employed to assess the precipitate formed after equilibrium solubility studies during preformulation demonstrated that there were no phase transitions and no significant interactions between the drug and the evaluated carriers. Furthermore, the results demonstrate that Soluplus® achieved the lowest dose number (0.23) for pediatric patients over 6 years old. So, it was selected for preparing the amorphous solid dispersion via spray drying, which significantly enhanced the apparent solubility of TER while maintaining prolonged supersaturation, offering a promising alternative for developing solid formulations of this drug, particularly for pediatric patients, as it aims to improve oral bioavailability.
期刊介绍：
AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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