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Solubility Method

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The first method of increasing drug solubility is reduction of particle size, solubility of drug is often related to drug particle size; reducing the particle size results in increasing the ratio of the surface area to volume, which allows more interaction with the solvent leading to an increase in solubility. (Savjani, Savjani, Gajjar, 2012). Several conventional methods are used for particle size reduction, including comminution (milling and grinding), spray drying and micronization (Chaudhary, Nagaich, Gulati, Sharma, & Khosa, 2012). Micronization increases the dissolution rate of drugs through increased surface area. Decreasing the particle size of these drugs has an advantage in improving their rate of dissolution (B, P, S, & G, 2014) . Drug micronization technique is carried out by milling techniques using jet mill, rotor stator colloid mills (Vimalson, Parimalakrishnan, Jeganathan, & Anbazhagan, 2016). Regarding the advantages of particle size reduction, it is usefull for extraction and drying of drugs, it improves the rate of absorption as well as physical stability and dissolution rate and increasing the surface area, while the disadvantages include drug degradation and poor mixing (Patel, Baria, & Pate, 2008). Griseofulvin (GF) (C17H17ClO6 ) is a drug which solubility can be increased by particle size reduction. Griseofulvin is an antifungal medication which belongs to a class of drugs called antifungal agents and it is used to treat fungal infections of the skin and nails. (Hsu & Arndt, 2007)

The second technique used to increase drug solubility is crystalline modification. Generally solid drugs may exist either as a form a regular repeating three-dimensional structure called a crystal lattice, thus producing a crystalline solid which are characterized by their hardiness its sharp and high melting points (Ferraz, Carpentieri, & Watanabe, 2007), or they can aggregate with a lack of three dimensional order framework and they are called amorphous solid drugs (Sivasankar, 2008). Both forms of solid drugs have different biological and physicochemical properties such as shelf life, melting point, vapor pressure, solubility, morphology, density and bioavailability. These properties can affect the stability and activity of the drug within the formulation. (Jadhav, Pacharane, Pednekar, Koshy, & Kadam, 2012). Moreover the necessary energy for molecule separation in the amorphous form is less than that of the crystalline form which provides the amorphous solids with greater solubility, dissolution velocity and bioavailability than the crystalline structure. These properties in turn make the amorphous form of a drug is more affective therapeutically than the corresponding crystalline form. (Ferraz, Carpentieri, & Watanabe, 2007)

Amorphous drug form can be formed by certain methods or techniques including cryogenic techniques, followed by various drying processes such as: spray Freezing onto Cryogenic Fluids, spray Freezing into Cryogenic Liquids (SFL), spray Freezing into Vapor over Liquid (SFV/L) and Ultra-Rapid Freezing (URF). (Savjani, Savjani, Gajjar, 2012). A main advantage in the amorphous form of drug is providing higher experimentally determined solubility values compared to the crystalline form. While an important disadvantage represents in low molecular weight, thus thermodynamic and physical instability. (Vimalson, Parimalakrishnan, Jeganathan, & Anbazhagan, 2016). Chloramphenicol palmitate (C11H12Cl2N2O5) is an example of an amorphous form drug; it is an antibiotic effective for the treatment of several bacterial infections. It has been used in the treatment of thyroid fever, meningitis and cholera. It is administered either orally or by injection. (Ferraz, Carpentieri, & Watanabe, 2007).

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