Exocrine Pancreatic Insufficiency (EPI), induced by conditions such as cystic fibrosis, chronic pancreatitis, and Crohn's disease, is a frequently overlooked and underdiagnosed gastrointestinal disorder. It leads to inadequate intestinal digestion due to insufficient secretion of pancreatic juice, resulting in discomfort, pain, and ultimately severe malnutrition. Despite numerous treatments proving ineffective over the past three decades, a strictly hydrophobic solid lipid formulation, administered orally, is proposed in this study to restore digestive function. This technology relies on the hydrophobic nature of the matrix to physically protect the hydrophilic active principle from the gastric environment while enabling its immediate release in the duodenum by targeting the amphiphilic nature of bile salts. Results demonstrate that this formulation effectively protects an acid-sensitive active ingredient during gastric passage (Simulated Gastric Fluid or SGF), facilitating its rapid release upon entering an artificial duodenal environment (Simulated Intestinal Fluid or SIF). Furthermore, it has been demonstrated that the preservation of a protein-based active ingredient extends beyond its primary protein structure to include its functional aspects, such as enzymatic activity. This drug delivery technology could enable the protection of hydrophilic active biomolecules, such as pancreatin, which are sensitive to gastric acidity, while promoting their immediate release upon contact with bile salts in the proximal duodenum, with the ultimate goal of correcting the digestive defect induced by EPI.