Challenges in the Oral Administration of Gastro-Resistant Formulations: The Role of Vehicles and Bottled Waters.

Background/

Objectives

Gastro-resistant multiparticulate systems are designed to protect drugs in acidic environments and to ensure intestinal release. In practice, the method of administration may need to be modified: pellet-containing capsules opened or tablets halved for patients with swallowing difficulties, yet the type of liquid used for administration is often not specified. This study examined the stability of gastro-resistant coated pellets after exposure to various aqueous media prior to ingestion.

Methods

To evaluate administration instructions, 103 Summaries of Product Characteristics of gastro-resistant products were reviewed. Pellets were produced using a bottom-spray fluidized bed process and coated with Eudragit L 30 D-55. Dissolution testing in pH 1.2 medium was performed after pre-soaking the pellets for 5, 15, and 30 min in beverages with various pH and conductivity. Drug release was measured by UV-VIS method, and morphological changes were assessed by image analysis. Marketed gastro-resistant products were also examined visually.

Results

SmPC review revealed that the beverage for intake was frequently unspecified. Among the tested beverages differences in pH and conductivity were observed. Alkaline medicinal mineral waters induced increased and time-dependent premature drug release compared to tap and filtered water. Image analysis indicated a reduction in surface area after exposure to alkaline media.

Conclusions

Contact with non-specified aqueous media before swallowing may weaken the protective function of gastro-resistant films. More explicit recommendations on suitable administration manipulation and media may improve therapeutic consistency.