The word 'new' in relation to drug delivery system (DDS) is a search for something out of necessity. The objective is to minimize the disadvantages associated with existing dosage form (DF) and optimizing therapy while maximizing patient comfort. Drug delivery system is relatively modern term used in place of 'dosage form' to describe a system carrying a drug. The ideal form of DDS would be the 'magic bullet' envisioned by the 1908 Nobel Laureate Paul Ehrlich. His aim was, as he put it, to find chemicals which have special affinities for pathogenic organisms, to which they would go, and would be, as Ehrlich expressed it, 'magic bullets' which have very little affinity for non-target cells.
What are the drawbacks of oral controlled release (CR) dosage forms (DFs)? Historically, oral drug administration has been the predominant route for drug delivery due to the ease of administration, patient convenience and flexibility in formulations. However, it is a well accepted fact today that drug absorption throughout the GI tract is not uniform. Using currently utilized release technology, oral drug delivery for 12 or even 24 hours is possible for many drugs that are absorbed uniformly from GI tract. Nevertheless this approach is not suitable for a variety of important drugs, characterized by narrow absorption window in the upper part of GI tract i.e. stomach and small intestine. In addition drugs that are poorly soluble in intestinal fluid, act locally in the stomach and have stability problems in lower intestine will not be good candidates for conventional CRDFs.
Gastroretentive drug delivery system (GRDDS): Therefore the real issue in the development of oral CRDFs is not just to prolong the delivery of drugs for 12 hours or more, but to prolong the presence of DFs in the stomach or upper GI tract until all the drug is released for the desired period of time. A novel DF that is retained in the stomach for a prolonged and predictable period of time, known as GRDDS, would definitely enable extended absorption phase of narrow absorption window drugs. After oral administration, of such a DDS would be retained in the stomach and release the drug in a controlled manner for prolonged period of time. Controlling the residence time of a DDS in the stomach can be achieved by various approaches. These include low density DDS that causes buoyancy above gastric fluid; high density DDS that is retained in the bottom of stomach; polymeric bioadhesion to the stomach mucosa; expansion by swelling or unfolding to a large size and other delayed gastric emptying devices.
Floatable GRDDS: This approach has recently become one of the leading methodologies in gastroretentivity. The approach, also known as floating DDS, is convenient and utilizes simple technique to prolong gastric residence time (GRT). All floating DDS have the common property of possessing density lower than that of gastric fluids so that they can float in the stomach for prolonged period of time. While the system is floating on gastric contents, the drug is released slowly at the desired rate from the system. The problem arises when the stomach is completely emptied of gastric fluid. Therefore, besides a minimal gastric content needed to allow buoyancy, a minimal level of floating force is also required to keep the dosage buoyant. The intragastric position of the DDS, far distant from the gastroduodenal junction, protects them from a random, early and erratic emptying during their digestive phase even if their size is smaller than pylorus opening. Many drugs are being considered today as possible candidates for GRDDS, especially floating DDS. Examples of some of drugs are acyclovir, alendronate, atenolol, captopril, cinnarizine, ciprofloxacin, cispride, furosemide, ganciclovir, glipizide, ketoprofen, L-dopa, melatonin, metformin, minocyclin, misoprostol, nicardipine, riboflavin, sotalol, tetracycline, verapamil, vitamin E etc.
The buoyant systems utilize matrices prepared with either swellable polymers like HPMC, HEC or effervescent components like sodium carbonate and citric acid. The former is known as hydrodynamically balanced systems, HBS (non-effervescent) since it is able to maintain their low apparent density while the polymer hydrates and builds a gelled barrier at the outer surface. Buoyant materials are incorporated to enable the device to float. The second approach for preparing buoyant systems involves gas-generating materials such as carbonates and incorporated in the dosage forms. These materials react with gastric acid or acid present in the formulation and produce carbon dioxide, which allows them to float. The gas is trapped to achieve low density. The gas generating system may be present either as a part of formulation or may consist of separate layer in the formulation.
Better drugs: GRDSS will bring about new and important therapeutic options of existing CRDFs. To date, seven drugs have been successfully incorporated into GRDDS for commercial use. Research is in progress to develop GRDDS for a number of drugs including mentioned earlier. Many pharmaceutical manufacturers in the west are undertaking extensive research anticipating huge opportunities for such development of DDS. From economic point of view, the development of DDS can potentially prove profitable for a modest investment. While the control of drug release profiles has been main aim of pharmaceutical research in the past years, the control of GI transit profiles is the focus of research in coming years. It is expected using scintigraphic images of both GRDDS and gastric motility may yield a deeper insight into the mechanisms of gastroretentivity. This could lead to a more rational design of GRDDS.
World medicine situation report 2004, mentions though investment in drug research has increased over the years the outcome has not been encouraging. R and D costs have almost tripled from 1990 to 2000 but number of NCE fell from 50 in 1996 to 32 in 2000. Although, invention of NCE is necessary, that continue to offer improvements to medical care, development of new techniques of delivery of comparatively safer existing drugs is receiving more attention than ever before. Floatable GRDSS is one such emerging technique. It is being used not only to improve therapeutic efficacy, but also a method to extend drug life cycle after its patent expiry.
(The author is selection grade lecturer in Pharmacy, Annamalai University, Annmalainagar. e- mail: cdl_scbasak@sancharnet.in)