Biopharmaceutical Classification Of Drugs
Oral route of drug administration is, still the route of choice for the formulators. The in vivo performance of orally administered drug depends upon its solubility and tissue permeability characteristics.
Based on these characteristics drug substances are divided into four classes and the classification system is called as Biopharmaceutical Classification System. This article focuses on the methods of determination of solubility and permeability of drug substance and its subsequent use in classification of drug in one of the four classes. The biopharmaceutical classification system acts as a guiding tool for development of various oral drug delivery technologies.
The oral route of drug administration is the route of choice for the formulators and continues to dominate the area of drug delivery technologies. However, though popular, this route is not free from limitations of absorption and bioavailability in the milieu of gastrointestinal tract. These limitations are even more prominent with the advent of protein and peptide drugs and the compounds emerging as a result of combinatorial chemistry and the technique of high throughput screening.
Whenever a dosage form is administered orally, the events that follow are depicted in Figure1. The drug in the dosage form is released and dissolves in the surrounding gastrointestinal fluid to form a solution. This process is solubility limited. Once the drug is in the solution form, it passes across the membranes of the cells lining the Gastro-Intestinal tract. This process is permeability limited. Then onwards the drug is absorbed into systemic circulation. In short, the oral absorption and hence bioavailability of drug is determined by the extent of drug solubility and permeability.
Determination of solubility:
Determination of permeability:
Fundamental to understanding of the nature of gastrointestinal permeability limitations are methods and techniques to both screen and grade these characteristics. Figure 2 summarizes these techniques with their complexities.
Absolute bioavailability studies
Intestinal perfusion methods
Biopharmaceutical Classification System:
The biopharmaceutical classification system was developed primarily in the context of immediate release (IR) solid oral dosage forms. It is the scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability (2). It is a drug development tool that allows estimation of the contributions of three major factors, dissolution, solubility and intestinal permeability that affect oral drug absorption from immediate release solid oral dosage forms. The interest in this classification system is largely because of its application in early drug development and then in the management of product change through its life cycle. It was first introduced into regulatory decision-making process in the guidance document on Immediate Release Solid Oral Dosage Forms: Scale Up And Post Approval Changes (3).
Dissolution number, defined as the ratio of mean residence time to mean dissolution time.
Dose number, defined as the mass divided by the product of uptake volume (250 ml) and solubility of drug (4).
Applications of BCS in oral drug delivery technology (5):
Once the solubility and permeability characteristics of the drug are known it becomes an easy task for the research scientist to decide upon which drug delivery technology to follow or develop.
A. V. Gothoskar1 , S. M. Khangaonkar2
2 Post graduate student NDMVP Samaj’s College of Pharmacy, Nashik, Maharashtra .
Dr Abhijit V Gothoskar has completed his graduation, post-graduation and doctorate from Pune University, India. He is the gold medalist at graduate and post graduate levels for his outstanding performance. His research areas include Oral Controlled Drug Delivery Systems and applications of polymers in the field of pharmaceuticals. He has worked as a Senior Lecturer in Pharmaceutics in Maharashtra Institute of Pharmacy, Pune for five years and is currently working as Modified Release Area Technical Manager at Colorcon Asia Pvt Ltd. His current job responsibilities include generation of applications data, development of platform technologies for OCRS and trouble shooting.