The lower gastro-intestinal tract plays an important role in optimizing bio-availability and drug absorption – and therefore the effectiveness of many therapies. But delivering sensitive APIs to the right location is a challenge. In a series of ‘real world’ questions, we explore the options and solutions when it comes to the targeted delivery of acid-sensitive APIs.
Question: What is the best capsule-coating agent for colon targeting?
Answer: Scientific development of colon-targeted oral drug delivery systems has gained increasing interest in recent years. Various formulation approaches have been explored to determine colon-targeted drug delivery. Colon targeting involves components that interact with one or more of the following: pH differences along the gastro-intestinal tract (GIT), the presence of colonic microflora, and enzymes. Like drug delivery systems that enhance absorption in the small intestine, acid-labile colon-targeted drugs and therapies such as fecal microbiota transplantation and biologic agents need protection to safely transit the hostile acidic milieu of the stomach. To achieve this, a capsule offering acid resistance is essential to ensure the initial phase of entering the distal small intestine fully intact.
Traditionally, acid resistance was achieved through the additional manufacturing step of enteric coating the filled capsule, which often involves the use of solvents and heat treatment. By combining the Innovaform® Accelerator expertise with the unique polymer bi-layered Capsugel® Enprotect® capsule, full compendial acid resistance without the need for additional treatment of the capsule is achieved, protecting the active pharmaceutical ingredients (APIs) from degradation during these processes. Bespoke forms of this capsule can also be made with particular targeted-release profiles, such as targeting the distal intestinal tract or the proximal colon.
In addition to acid resistance, the design of colon-targeted drug delivery systems has to overcome a number of other challenges, such as pH variations throughout the GIT, the presence of enzymes that can degrade drugs, variations in transit time, and the presence of a mucus barrier and rhythmic contractions in the colon that can alter the residence time of the formulation. Various approaches, such as pH-dependent, time-dependent, microbially triggered and ligand- or receptor-mediated systems, have all been explored in the design of these systems.1
Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases, such as ulcerative colitis, Crohn’s disease, irritable bowel syndrome, chronic pancreatitis and colonic cancer.2 Because of the unique challenges involved, designing CDDS often involves the application of a range of formulation technologies. To support formulators, Lonza has established Innovaform® Accelerator, a formulation center of excellence to support formulators in the development of bespoke oral delivery systems.
Learn more about Innovaform® Accelerator and the Capsugel® Enprotect® capsule, and how they could help solve your oral-dosage challenge.
Sources:
1. S.H. Lee, R. Bajracharya, J.Y. Min, J.W. Han, B.J. Park, H.K. HanStrategic approaches for colon targeted drug delivery: An overview of recent developments Pharmaceutics, 12 (2020), p. 68;
2. Amidon S, Brown JE, Dave VS. AAPS PharmSciTech. 2015;16(4):731–741.