Formulation Development of Ambroxol Hydrochloride Soft Gel with Application of Statistical Experimental Design and Response Surface Methodology

Abstract

The purpose of present work was to develop ambroxol hydrochloride soft gel formulation with the application of statistical experimental design and response surface methodology (RSM). A two-factor, three-level (3²) full factorial design of experiment with RSM was run to evaluate the main and interaction effect of two independent formulation variables that included the amount of low-acetylated gellan gum and sodium citrate. The dependent variables included viscosity (Y₁), amount of drug release at 10 min (Y₂) and 30 min (Y₃), and gelation time (Y₄). In order to obtain a formulation having the maximum amount of drug release at 10 min and minimum gelation time, RSM optimization was used. The prepared formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. All the formulations showed a gelation time in the range of 6 to 48 min. The drug content in all the formulations was within limit (99.6 ± 1.56%). The viscosity of all the formulations was found in the range of 1872–12,182 cP. Dissolution studies of the formulations showed drug release in the range of 40.56–72.46% within 10 min and 80.2–100.5% within 30 min. Human evaluation tests revealed that all the gels possessed acceptable characteristics. This study showed that the soft gel formulation GA5, containing 0.3% of gellan gum and 0.4% of sodium citrate, has potential use as an immediate release soft gel for oral drug delivery.

LAY ABSTRACT: The objective of this investigation was to develop a new, immediate-release, soft gel dosage form for ambroxol hydrochloride, an oral expectorant and mucolytic agent. This novel soft gel dosage form needs to be suitable for pediatric and geriatric patients as well as patients with dysphagia. A statistical technique was used for optimization of the gel formulation. The methodology, called a design of experiment with response surface methodology, evaluated several independent formulation variables, including the amount of two ingredients, low-acetylated gellan gum and sodium citrate. Their effects were studied by comparing physical properties of the gel such as viscosity, amount of drug release at 10 and 30 min, and gelation time. The final optimized formulation (0.3% of gellan gum and 0.4% of sodium citrate) was chosen to maximize the amount of drug release at 10 min, minimize gelation time, and optimize viscosity in a reasonable range. After this optimization exercise, the prepared ambroxol hydrochloride soft gel formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. Human evaluation tests revealed that all the gels possessed acceptable organoleptic characteristics.