The first and foremost target of pharmaceutical technology is to attain better therapeutic effect using lowest quantity of drug administered by the most appropriate route. The oral route is most accepted and preferred route for drug administration because it is simple, convenience and easy to ingestion. Drawbacks for using this route include delay response so not suitable in emergency and unconsciousness. When drug administered orally in solid dosage (tablet, capsule), it undergo dissolution in the GI fluids and later get absorbed. Low aqueous solubility and reduced dissolution rate are a common property of many drug candidates. For various poorly soluble drugs, bioavailability is limited by the dissolution rate. This is a measure of the rate and amount of an administered dose/drug that reaches the systemic circulation. Many factors are responsible for low bioavailability including release of the drug from its dosage form, stability of drug and the pre-systemic metabolism in the intestinal wall and liver. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities and with the generic development. Approximately 40% drugs among all newly discovered chemical entities are hydrophobic and fail to reach therapeutic range due to their poor water solubility (solubility less than 100 ?g/ml). Low water solubility cause slow dissolution rates, usually show incomplete absorption that results in low bioavailability when administered orally.. The lack of good aqueous solubility has also been frequently identified as a key obstacle in the use of anticancer drugs.1-3
The Biopharmaceutic Classification System (BCS) a scientific framework has given description on the significance of the solubility for orally administered drugs, that has been approved by FDA. BCS classified drugs into four groups after a comprehensive analysis of the solubility and permeability through the biological membranes.
Table 1.- Biopharmaceutical classification system of Drugs
Biopharmaceutical Classification System
Due to insufficient solubility in the case of Class II and Class IV drugs, the dissolution rate happen to the limiting step in the absorption process. Bioavailability of Class II drugs can be achieved after improving their solubility. In addition, Class IV drugs also display low permeability and further alterations are required to get proper absorption through membranes.4 Limited solubility is a problem to all administration routes as only the highly soluble drug molecules are be able to permeate through biological membranes. Many formulation techniques have been developed in pharmaceutical industries to improve the solubility that cause the poor absorption and bioavailability are complexation with cyclodextrins, lipid-based formulations, solid dispersion technologies, nanosuspensions, pH-adjustment, co-solvents, encapsulation into nanodelivery systems (nanocarriers).5, 6
Nanotechnology, is the future of multidisciplinary science comprises manipulation, formation and utilization of materials or devices at the nanometer scale i.e, the scale of atoms and molecules. The exclusive and novel application provided by nanotechnology has been accepted relatively in all aspects of routine life. Nanotechnology has became a prerequisite research area of 21st century, may also be called as ‘nano-century’ as has been used in almost all fields.7 Nanoparticles or nanostructure are solid particles with a size range of 10-1000 nm, comparatively smaller than prokaryotic and eukaryotic cell, equivalent to antibody or virus. A nanometer is one-billionth of a meter, too small to be seen with a conventional laboratory microscope. It is at this size scale – about 100 nanometers or less that biological molecules and structures inside living cells operate. Therefore, nanotechnology is engineering and manufacturing at the molecular scale. 8