IMPORTANCE OF SOLID STATE IN THERAPEUTIC ACITIVITY

The amorphous solid state possesses several advantages in comparison to the crystalline state which allow enhanced forms of drugs to be produced. Many drugs when generated as an amorphous form will exhibit one or more of the following properties:

Solubility

The amorphous state is thermodynamically the form with the highest solubility.
Consequently, amorphous forms will exhibit a greater solubility in a solvent than any crystalline form. Solubility advantages of factors >1000 have been observed between crystalline and amorphous drugs. The increased solubility of amorphous actives can lead to dramatically increased intrinsic dissolution rates when compared to crystalline forms.

Wettability

For a drug to dissolve, its surface has first to be wetted by the surrounding fluid.
Amorphous forms possess a chemically randomized surface which expresses equal amounts of hydrophobic and hydrophilic interactions which can lead to improved wettability expressed by a lower contact angle of the drug particle surface with a liquid. A lower contact angle represents a higher degree of hydrophilicity with consequently faster surface wetting and faster dissolution.

An amorphous form of Novobiocin is inactive when administered in crystalline form, but when they are administered in the amorphous form, absorption from the gastrointestinal tract proceeds rapidly with good therapeutic response.

Crystalline forms of drugs may be used because of greater stability than the corresponding amorphous form. The crystalline forms of penicillin G as K or Na salt is considerably more stable and result in excellent therapeutic response than amorphous forms. Crystalline Novobiocin poorly absorbed, whereas amorphous is readily absorbed.

Amorphous form of Insulin-Zinc suspension is rapidly absorbed, while crystalline Ultralente Insulin-Zinc is slowly absorbed. By combining the two types, intermediate-acting insulin of varying degree of onset and duration of action can be obtained. Lente Insulin, a mixture of 70% crystalline and 30% amorphous is a very good example of this category.

The crystal or amorphous forms and/or the particle size of a powdered drug have been shown to affect the dissolution rate, and thus the rate of absorption, for a number of drugs.

Therefore, selective control of the physical parameters of a drug is very important by which biologic response may be optimized

POLYMORPHISM 

Polymorphism (Greek word, Polus = many and morph = shape) is the phenomenon in which a substance exists in more than one crystalline forms. This can be happened under different conditions of temperature and pressure. Different crystalline forms are called Polymorphic.

For example; Mercuric iodide (Hgl2) and calcium carbonate (CaCO3) exist in two types of crystal forms like (a)Orthorhombic and (b) Trigonal. Polymorphous substances have similar chemical properties but different physical properties.

It essentially means that in different polymorphs, the same molecule exists in different ways.

If this difference is because of packing, it is termed as packing polymorphism and if it is due to difference in conformation, it is called conformational polymorphism. As a result of polymorphism, molecules have different arrangements in the unit cell of its crystal and thus display different physical properties.

These include different packing properties, thermodynamic properties such as solubility, free energy, melting point, etc., spectroscopic properties, kinetic properties such as dissolution rate, stability, and mechanical properties such as hardness, compatibility, tensile strength, etc.

In Pharmaceutical field, polymorphism is very important because full characterization of a material has an essential role in determining its ultimate use.

In polymorphism, chemical identity of the material is not changed from one polymorph to another, so that a direct correlation between activity and solid state structure may be established.

For example, paracetamol exists in different ways in solid state because of their free energy difference. The free energy difference may be from 0.5 to a maximum of about 8 kcal / mol.

Based on this, some forms of compounds are slightly unstable compared to others and we can have a functional classification based on this factor.

 TYPES OF POLYMORPHISMS

Polymorphs are categorized into two types depending upon their stability with respect to the range of temperatures and pressure.

Polymorphs which are stable at all temperatures below the melting point are called Monotropes.

When one of the polymorphs is stable (having lower free energy and solubility) over a certain temperature range and pressure, while the other polymorph is stable over a different temperature range and pressure, then the two polymorphs are said to be Enantiotropes.

Generally, it is possible to distinguish between monotropes and enantiotropes from their heats of fusion. An endothermic polymorphic transition indicates enantiotropes whereas an exothermic one indicates monotropes. Other than Differential Scanning Calorimetric (DSC) analysis, there are a number of efficient ways to characterize polymorphs.