INTRODUCTION

Oral route of administration is usually the most acceptable way of self- due to enhanced patient convenience and compliance. It has limitations because of the way a drug typically moves through the digestive tract. After oral administration of drug, absorption may begin in the mouth and stomach. Drug absorption through the (GIT) is deeply hampered by different biological barriers (biochemical and/or physical), of which the first pass metabolism occurring in liver is a good example [Lennernäs et al.,1998]. Various promising are poorly soluble in aqueous media. The formulation of these drug substances into effective and safe pharmaceuticals has always been a challenge, in particular if the drugs have to be administered into the bloodstream [Westesen et al., 2000]. As a consequence of modern drug discovery techniques (i.e. advances in in vitro screening methods, the introduction of combinatorial chemistry), there has been a consistent increase in the number of poor soluble drug candidate compounds, and currently, more than 40% of new pharmacologically active chemical entities are lipophilic and exhibit poor water solubility. These molecules often suffer from low oral , and despite their pharmacological activity, they fail to proceed to advanced stages of research and development. A great challenge facing the pharmaceutical scientist is making these molecules into orally administered with sufficient bioavailability[ Martinez M.N. et al., 2002] The Biopharmaceutical Classification System (BCS) classifies drug according to their solubility and permeability .The Biopharmaceutical Classification System provided new quantitative data of importance for modern drug development, especially within the area of drug solubility and permeability. It gives clear and easy applied rules for determining the rate limiting factors of GI absorption process A drug substance is consider highly soluble when the highest strength is soluble in 250 ml or less of aquesous media over the pH range of 1.0-7.5. Otherwise, the drug substance is consider poorly soluble. The permeability classification is based on the

2 extent of intestinal absorption of a drug substance in human. The BSC guidance for permeability that “ in the absence of evidence suggesting instability in the gastrointestinal tract, a drug substance is consider to be highly permeable when gastrointestinal absorption in human is determined to be 90% or more of an administered dose based on mass balance determination or in comparison to an intravenous reference dose.” Solubility and permeability classifications results in four classes of drug substances. According to BCS , drug substance are classified as follows.

Class 1: High solubility – High permiabilty

Class2 : Low solubility – High permeability

Class3 : High solubility – Low permiabilty

Class4 : Low solubility – Low pwermiabilty

According to the Biopharmaceutical Classification System poorly water soluble compounds are classified as either class-II or class-IV compounds. For BCS class-II compounds, which have high intestinal permeability properties but very low solubility, absorption level is dictated by the dissolution properties of the molecule in the gastrointestinal fluids[ Amidon GL et al., 2003] Formulation plays a major role in determining the rate and extent of absorption of such drugs from the gastrointestinal tract, when water-solubility is less than 1mg/mL these drugs can be successfully formulated for oral administration, but care needs to be taken with formulation design to ensure consistent bioavailability. Essentially the options available involve either reduction of particle size (of crystalline drug) or formulation of the drug in , as an amorphous system or lipid formulation [Colin W et al., 2006]. Colloidal drug carriers investigated for many years include oil-in-water (O/W) , , microparticles and nanoparticles based on synthetic polymers or natural macromolecules. Solid lipid microparticle/ nanoparticle are one of the lipid based carrier systems having more advantages than other colloidal delivery systems with regard to biocompatibility and scale up [Muller, R.H. et al., .2000]

3 To increase the solubility of BCS class-II drug there are several approaches .One of the most popular approaches to improve the oral bioavailability of these molecules is the utilization of a lipid based particulate system .Particulate drug delivery system for therapeutic purposes has been the area of recent focus in the field of targeted drug delivery. Solid lipid based particulate drug delivery system have been widely studied because of their advantages of being biocompatible, biodegradable, nontoxic and stable against coalescence. Drug leakage, hydrolysis and particle growth often observed in lipid emulsions, liposomes and nanoparticles are rare with solid lipid microparticle (SLM) Moreover, they have the potential to release the drug over a prolonged period and they possess the ability to entrap lipophilic drugs with high entrapment efficiency. Solid microparticles in dispersion are usually obtained using melt dispersion method and solvent evaporation method. The advantage in the melt method is that it avoids the use of organic solvents.[ Savolainen M et al.,2003]

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