1. Rheology of Biological Systems Ref. Book: Applied Physical Pharmacy. Ed. Mansour M. Amiji, Beverly J. Sandmann, McGRAW-Hill, 2003 Rheological properties of blood Blood rheology has been used in diagnosing and treating different types of diseases. Blood from a normal person exhibit a fairly unique rheological profile in that it is non-Newtonian at lower shear rates and become Newtonian beyond the shear of 100/sec. At lower share rate the viscosity is higher as a result of aggregates of the erythrocytes. Above the shear rate of 100/sec, the viscosity of blood remains constant (about 3.0 cps). The rheologic profile of blood affected drastically by disease states in which the concentration of cells and protein changes. Fore example in the case of polycythemia, the viscosity of blood increases sharply while the oppsite is observed in patients of lower erythrocyte counts such as patients with anemia. In certain congenital disease where the patients suffers from both polycythemia and high fibrinogen concentration in the blood, the peripheral circulation is completely impaired and their blood has the consistency of a paste.

2. Rheological properties of Mucus Mucus is a gel – like material secreted by the epithelial cells on the mucosal surfaces of the respiratory tract, gastrointestinal tract, genitourinary tract and the eye. Primarily, mucus serves a protective function guarding the underlying mucosal tissue against digestive enzymes and preventing infectious organisms from coming in contact with the host at the first site exposure. Mucus also has other functions such as lubrication (the eyes). The mucus gel is a heterogeneous mixture of mucus glycoproteins (that are made up of subunits that are covalently bonded through disulfide linkages), phospholipids, enzymes and water. The normal function of the mucus is very much dependent on the rheologic properties that changes from gel-like to fluid consistency upon increase in the shear rate. In the respiratory tract, one of the complications of the cystic fibrosis, a congenital disease, is abnormality in the secretion and consistency of the bronchial mucus leading to childhood disorders of the respiratory tract. Due to the decreased ionic content and water, the mucus becomes extremely viscous, leading to obstruction of the airflow into the lungs which might cause upper respiratory infections and other complications. Mucolytic drugs should be taken to break the disulfide bond of the mucus allowing the patient to expel the mucus. In the G.I.T, it has been suggested that helicobacter pylori secreted an substance that decreases the viscosity of the stomach mucus allowing the enzymes and acid to diffuse into the tissue resulting in ulcer formation.

3. Rheological properties of Synovial fluids Synovial fluid is viscous (egg-white consistency) liquid present in all the skeletal joints of the body. It is composed mainly of hyaluronic acid, proteins such as albumin and water. The volume of the synovial fluid is about 0.2-0.5 ml even in large joints such as the knee. Hyluronic acid is a mucopolyssacharide that forms highly viscous aqueous solution. The function of the synovial fluid is to protect the skeletal joints through lubrication and provide a medium that acts as a shock absorber. In inflammatory conditions such as rheumatoid arthritis, the molecular weight and concentration of hyaluronic acid decreases sharply leading to a decrease in the consistency of the synovial fluid. To restore the joint function, intraarticular injection of hyaluronic acid has been found to be effective.

4. Rheologic properties of biological fluids substitute Example: tear substitute in dry eye syndrome High molecular weight (MW) polymers with water binding properties and high viscosity have increasingly been used as hydrogels for ophthalmic applications. Their use has three advantages. Firstly, in artificial tears, they soothe, protect and lubricate the ocular surface, thus relieving the symptoms of dry eye syndrome. Secondly, in solutions for contact lens wearers, they also provide better and prolonged comfort to contact lens wearers through moisturizing, lubrication, and reduction of the blink frequency. Thirdly, in viscous eye drops loaded with a drug, they increase the contact time with the ocular surface, and thereby improve the bioavailability of drugs. Bioadhesive properties of some polymers contribute also to the improvement of the bioavailability. The main polymeric materials that serve the aforementioned functions include cellulose derivatives (e.g., hypromellose, carmellose, hydroxyethyl cellulose), poly(vinyl alcohol) (PVA), carbomer, poly(vinyl pyrrolidone), polyethylene glycol, and dextran. These lubricating and rewetting agents are generally well tolerated at the concentration level found in commercial eye drops. However, some of the most viscous formulations are uncomfortable and lead to blurred vision, stickiness, and formation of a crusty residue. In addition, some of these polymers are Newtonian and do not shear thin by eye blinking, which limits their spreadability on the ocular surface and thus their efficacy.

5. To ease discomfort and overcome these limitations, growing attention has thus been paid to non-Newtonian and particularly to pseudoplastic polymers such as hyaluronic acid (HA) HA is a high molecular weight, natural and linear polysaccharide. This biocompatible, nonimmunogenic and biodegradable polymer is one of the most hygroscopic molecules in nature and hydrated hyaluronic acid can contain up to 1000-fold more water than its own weight. These exceptional water retention properties result in enhanced hydration of the corneal surface. Moreover, applications of ophthalmic formulations containing hyaluronic acid reduce tear elimination and enhance precorneal tear film stability, which is a useful property against dry eye syndrome. Its non-Newtonian and shear thinning properties grant HA solutions with a high viscosity at low shear rate (when the eye is open) and a low viscosity at high shear rate (during blinking) thus allowing an even distribution of the solution, improving lubrication of the ocular surface, retarding drainage, improving bioavailability, and reducing discomfort. Another important feature of this high molecular weight and anionic biopolymer is its muco-adhesivity, which provides effective coating and long-lasting protection of the cornea as well as extended residence times on the ocular surface. Finally, when topically instilled on the eye, hyaluronic acid has been shown to promote physiological wound healing by stimulating corneal epithelial migration and proliferation of keratocytes and to reduce the healing time of corneal epithelium.

6. Topical ophthalmic solutions should exhibit a certain degree of viscosity to prevent immediate drainage from the ocular surface and to provide there high efficacy and long residence time. However, the solutions should not be too viscous to avoid blurred vision and to ease their manufacturing process including their sterile filtration. Fig. 1. Change in viscosity of sodium hyaiuronate solutions with increasing shear rate.