Colonic Drug Delivery Challenges and Oppor tunities - An Overview
Jack Aurora , Naresh Talwar , Vinayak Pathak Director, Pharmaceutical Research and Development, Manager, Formulation Development and
Research Scientist, Pharmascience
The overall goal for optimum therapy is to match the needs of the patient while improving the efficiency and safety of the administered drugs. Various drug delivery approaches have always played a challenging and crucial role in ensuring and predicting the delivery of promising and successful drugs to the target site of delivery in the human body. Oral drug delivery is the preferred route of delivery, accounting for more than US$15 billion in annual global sales. Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal (GI) tract presents several formidable barriers to drug delivery. In addition, life-cycle management, patient compliance, improved stability and optimisation of the drug absorption process are some of the key drivers for developing alternative delivery systems for drugs. In the recent past, considerable interest has grown in targeting the delivery of drugs to the colon. The necessity of such delivery systems to protect the drug from absorption and/or the environment of the upper GI tract and then enable selective release of drugs in the proximal colon makes it very challenging for research scientists involved in this field. This article reviews the surge of research focus, potential opportunities and challenges available in the new area of colon-targeted drug delivery systems.
Introduction
Historically, the pharmaceutical industry has always maintained and enjoyed strong financial earnings and business growth. Such healthy growth is not only made possible by launching new products but also by life-cycle management of older, existing products, which is playing an increasingly significant role. This aspect becomes even more important once the revenue drops significantly from the existing molecule due to patent protection expiry. Controlled rate, slow delivery and targeted delivery are some of the focus systems that are being pursued very vigorously in light of patients’ needs and also to succeed in today’s competitive business world.
In the area of targeted delivery, the colonic region of the GI tract is the one that has been embraced by scientists and is being extensively investigated over the past two decades. Targeted delivery to the colon is being explored not only for local colonic pathologies, thus avoiding systemic effects of drugs or inconvenient and painful trans-colonic administration of drugs, but also for systemic delivery of drugs like proteins and peptides, which are otherwise degraded and/or poorly absorbed in the stomach and small intestine but may be better absorbed from the more benign environment of the colon.1,2 This is also a potential site for the treatment of diseases sensitive to circadian rhythms such as asthma, angina and arthritis. Furthermore, there is urgent need for delivery to the colon of drugs that are reported to be absorbable in the colon, such as steroids, which would increase efficiency and enable reduction of the required effective dose.3–5 The treatment of disorders of the large intestine, such as irritable bowel syndrome (IBS), colitis, Crohn’s disease and colon disease, where it is necessary to attain a high concentration of the active agent, may be efficiently achieved by colon-specific delivery. The necessity and advantages of a colon-specific drug delivery system (CDDS) have also been extensively reviewed elsewhere in the literature.7–9
Limitations and Challenges
As a site for drug delivery, the colon offers a near neutral pH, reduced digestive enzymatic activity, a long transit time and increased responsiveness to absorption enhancers; however, the targeting of drugs to the colon is very complicated.10 Due to its location at the distal portion of the alimentary canal, the colon is particularly difficult to access. In addition, the wide range of pH values and different enzymes present throughout the GI tract, through which the dosage form has to travel before reaching the target site, further complicate the reliability and delivery efficiency.
Successful delivery through this site also requires the drug to be in solution form before it arrives in the colon or, alternatively, it should dissolve in the luminal fluids of the colon, but this can be a limiting factor for poorly soluble drugs as the fluid content in the colon is much lower and it is more viscous than in the upper part of the GI tract. In addition, the stability of the drug is also a concern and must be taken into consideration while designing the delivery system. The drug could potentially bind in a nonspecific manner to dietary residues, intestinal secretions, mucus or faecal matter. The resident microflora could also affect colonic performance via metabolic degradation of the drug.11
