POLYMORPHISM

POLYMORPHISM : 

POLYMORPHISM Presented by Shilpi Bhatnagar M.Pharm (Q.A) 1st sem

INTRODUCTION : 

INTRODUCTION A polymorph is a solid material with atleast two different molecular arrangements that give distinct crystal species. These differences disappear in the liquid or the vapour state. POLYMORPHISM: Ability of a compound to crystallize as more than 1 distinct crystalline species with different internal lattices. These species are polymorphs and this phenomenon is called polymorphism. Polymorphs generally have different melting points, x-ray diffraction patterns, and solubilities, even though they are chemically identical. Differences in the dissolution rates and solubilities of different polymorphic forms of a given drug are very commonly observed.

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When the absorption of a drug is dissolution rate limited, a more soluble and faster-dissolving form may be utilized to improve the rate and extent of bioavailability. For drugs prone to degradation in the solid state, the physical form of the drug influences degradation. Selection of a polymorph that is chemically more stable is a solution in many cases. Different polymorphs also lead to different morphology, tensile strength and density of powder bed which all contribute to compression characteristics of materials. Their existence can be determined by optical crystallography, x-ray diffraction, DSC (Differential Scanning Calorimetry), Thermal analysis

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Although a drug substance may exist in two or more polymorphic forms, only one form is thermodynamically stable at a given temperature and pressure. The other forms would convert to the stable form with time. In general, the stable polymorph exhibits the highest melting point, the lowest solubility, and the maximum chemical stability.  Polymorphism is remarkably common, particularly within certain structural groups: 63% of barbiturates, 67% of steroids & 40% sulphonamides exhibit polymorphism.

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Amorphous>Metastable>Stable

Pseudopolymorphism : 

Pseudopolymorphism Before the preformulation study begins, the presence of false polymorphs or pseudopolymorphs, should be indentified since most polymorphs can be obtained by changing the recrystallizing solvent. The pseudopolymorphism is confused with the true polymorphism. Pseudopolymorphism includes hydrates (water) & solvates (e.g., methanolate, ethanolates). These are molecular addition to the crystals & change its habit.

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The distinction between these false forms & true polymorphs can be obtained by observing the melting behaviour of the compound dispersed in silicone by using hot stage microscopy. Pseudopolymorphs will evolve a gas (stream or solvent vapour) causing bubbling of the oil. True polymorphs merely melt forming a second globular phase. The temperature at which the solvent volatilizes will be close to the boiling point of the solvent & can be used for identification.

True Polymorphism : 

True Polymorphism Many polymorphs are obtained by solvent manipulation. Other are produced without the presence of solvent by thermal techniques. The initial difficulty is to measure the melting point of the metastable form, and here heating rate, either DSC or hot stage , is critical. Too rapid heating rate will obscure the endotherm, while too slow heating rate may allow transition or encourage decompostion. Often therefore comparison at two rates, e.g., 2º and 20º min -1 is necessary.

Conclusion : 

Conclusion Polymorphism is important in the development of pharmaceutical ingredients. Many drugs receive regulatory approval for only a single crystal form or polymorph. E.g., Cefdinir is a drug appearing in 11 patents from 5 pharmaceutical companies in which a total of 5 different polymorphs are described. Polymorphism in drugs can also have direct medical implications.

References : 

References Wells J.I and M.E Aulton, The Drug Delivery System, p. 237-238 Martin Alfred, Physical Pharmacy, 4th edition, p.36-38 www.wikipedia.com www.authorstream.com

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