Electrochemical and scanning probe studies of active pharmaceutical ingredient release from polymer-coated multiparticulate oral dosage forms

This thesis explores the application of novel electrochemical and scanning probe techniques to study the dissolution of taste masking polymer, Kollicoat® Smartseal 30 D (KCSS, BASF) and how it controls the release of model active pharmaceutical ingredient (API) acetaminophen from a multiparticulate (MP) oral dosage form under the pH conditions of the GI tract. MP drug delivery systems consist of small API-containing particles, beads, often coated in a protective or taste masking polymer layer. These polymers are typically pH responsive, allowing release of the API only in specific pH conditions e.g., in the stomach. Understanding such polymer dissolution is a crucial quality control procedure in pharmaceutical science, as that determines the rate at which an API is released the from the formulation and, consequently, the rate at which it becomes available for absorption in the gastrointestinal (GI) tract. Traditional dissolution testing typically analyses the resultant dissolution media at specific time intervals, requiring the use of an ex situ analytical technique, such as HPLC. As a result, a continuous, in situ, dissolution profile is not obtained, and valuable information regarding the start of dissolution may be lost. This thesis focuses on the implementation and development of electrochemical methods for dissolution testing on the micro- (single bead, ultramicroelectrode) and macro- (MP dose, rotating disc electrode) scale, to investigate the rate of API release from a taste masking polymer-coated MP, in situ under pH conditions of the GI tract in real time. Additionally, this thesis investigated the effectiveness of taste masking polymer under simulated oral conditions. A variable temperature study resulted in the kinetic analysis of the API dissolution. The effects of physiological buffers were also explored. These studies led to the further investigation of the microstructural and morphological changes occurring in the KCSS polymer film in an acidic environment using ex situ atomic force microscopy (AFM). This was complemented by scanning ion conductance microscopy (SICM) to investigate in situ the charge distribution of the polymer layer of MP beads under a range of pH conditions. Overall, the development and application of electrochemical methods for real-time dissolution measurements are demonstrated and the mechanisms associated with dissolution under different pH conditions are discussed with reference to scanning probe microscopy data