Introduction In the recent years it is estimated that of

Introduction
In the recent years, it is estimated that 90% of the New Chemical Entities (NCEs) are poorly water soluble compounds which come under Biopharmaceutical classification system (BCS) class II or class IV (Filippos and Yunhui, 2008). According to BCS, dissolution is the rate limiting factor for the drug etizolam vendor rate of both class II and class IV compounds which result in poor bioavailability. Owing to their low poor water solubility and bioavailability, several potential drugs are abandoned in pharmacological screenings (Robinson, 1993; Rasenack and Muller, 2002a). It is a well-known major hurdle for the formulators to handle such poorly water soluble compounds. The chemical and physical properties of the poorly soluble compounds can be optimized to improve oral bioavailability of water insoluble compounds. Various formulation strategies have been reported to improve solubility and dissolution rate of poorly water soluble drugs such as inclusion of complexation with cyclodextrins, solid dispersion, salt formation, particle size reduction, use of surfactants, cosolvency, hydrotrophy, etc. Amongst above mentioned methods, the most reliable technique to improve the dissolution rate is micronization (Rasenack and Muller, 2004; Jalay, 2011).
Micronization is a term used to describe size reduction technique where the resulting particle size distribution is less than 10μ. Since the morphology of particles, particle size and size distribution produced in different industries are usually not appropriate for the subsequent use of such materials; particle design has been gaining importance in manufacturing advanced coating materials, microsensors, polymers, pharmaceuticals, and many other chemicals. The present article thoroughly reviews about in situ micronization as a novel micronization technique.

In-situ micronization is a novel particle engineering technique where micron sized crystals are obtained during its production itself without the need for any further particle size reduction (Rasenack and Muller, 2002a; Rasenack et al., 2002a). In contrast to other techniques where external processing conditions like mechanical force, temperature and pressure are required, the drug is obtained in micron size during the crystal formation. Hence this technique is described as in situ micronization. Each and every aspect of in situ micronization technique is discussed in the following sections.

Conclusion
Although many other techniques are available for micronization like spray drying and supercritical fluid technology, they are more complicated and require high processing conditions that make the resultant product highly expensive. Furthermore the stability of particles obtained by these techniques is less due to the formation of amorphous surfaces which limits their application in pharmaceutical industry. In-situ micronization is a new class of micronization technique which can overcome the limitations associated with the other techniques. It can be able to produce microcrystals of homogenous particle size distribution with improved flow properties, dissolution behaviour and stability. It reduces the cost of the final product because of simple process involved in the production of microcrystals. Further studies on the choice of stabilizing agents and the scale up techniques are required for the effective use of this technique in pharmaceutical industry.

Introduction
Chemotherapeutic research started with the identification of lead structures. These lead structures are unique for each target. Lead structures often need to be developed by incorporating desirable safety, efficacy and ADME characteristics required for a “drug”. For example- development of cimetidine (drug) and ranitidine (drug) was from brimmed drug candidate and N-α guanyl histamine (drug candidate), that were both developed from histamine (lead) (Ganellin, 1982; Bradshaw, 1993). Thus, we can say that in drug discovery we are concerned to select a suitable drug candidate with promising pharmacological activity for the development process. The main aim of the drug design process is to bring down the toxicity level of a drug candidate with improved activity as well as therapeutic index (Drews, 2000). But unfortunately, as the pharmacological activity of a drug increases, the toxic effects also increase and the therapeutic index remains unchanged. To improve the therapeutic index one has to separate activity and toxicity properties of a drug compound. The toxic or unwanted side effects are produced during the drug design process because new structural moieties are introduced into the drug candidate to enhance its activity and hence, the toxic or unwanted pharmacokinetic properties will further be enhanced during the drug design process. The high activity of a drug candidate is of no use if it has high toxicity as well and the only reason for the low success of a drug design process is the lack of toxicity consideration during such a process. One way to decrease the drug toxicity is to design metabolically stable drugs. At one glance, the idea looks very facilitating as one can avoid unwanted toxicity by avoiding the metabolism of the drug and a simpler pharmacokinetic route can be followed by a drug controlled by only renal excretion. These non-metabolic drugs are called as ‘hard drugs’ (Ariens and Simonis, 1977). But, the idea of designing ideal hard drugs is not achieved till date because living organisms have developed mechanisms to metabolize the endogenous substances as well as for the detoxification (Gillette, 1979; Mannering, 1981). Most metabolic processes aim at the transformation of foreign chemicals into more easily eliminated hydrophobic conjugates (Picot and Macherey, 1996).Thus, it is not enough for a molecule to just have good pharmacodynamic property but pharmacokinetic parameters also play a vital role for a molecule to become a drug because the in vivo administration of a drug becomes a troublesome process as it has to cross a number of biological barriers (Bodor, 1977). The pharmacokinetic factors which affect the in vivo administration of the drug are: absorption, distribution, metabolism and excretion (ADME). Thus, the basis of successful drug discovery is the incorporation of the ADME approach to the process. Out of four pharmacokinetic factors, metabolic studies play an important role in drug discovery because the study of metabolic clearance pathways as the major drug clearance pathway is very important in determining the drugability of the molecule (Bodor, 1984). In early drug discovery processes, the main role of drug metabolism is to provide a basis for choosing the chemical structures and lead compounds with desirable drug metabolism and pharmacokinetic properties but nowadays metabolic studies are mainly concerned to have a good safety profile of the drug (Bodor and Buchwald, 2000). Thus, it is necessary to take into consideration the metabolic as well as the toxicity profile of a molecule during the drug design process. The metabolism of a foreign compound by a given enzyme in the body can result in the formation of either toxic or non-toxic metabolites. The metabolic conversion of a drug can generate (as shown in Fig. 1):