Polymorphism the property of the solid substance to exist in two or more crystalline forms. These forms differ in their physicochemical properties like solubility, stability, dissolution, flowability and hygroscopicity. Crystalline polymorphs although having the same chemical composition, have different internal crystal structures or lattice structures or different molecular conformations. Hence they have different physicochemical properties. Organic molecules commonly form polymorphic structures and they are known to crystallize into different polymorphic forms. These polymorphic forms can decide upon the various factors pertaining to the drugs performance and can also affect the bioavailability, efficacy and toxicity.
The relative application of polymorphism can be studied on the basis of preparation, characterization of the drugs.
Significance of polymorphism studies in drug stability:
The polymorphism analysis services in India have influenced many drug manufacturers to propel the research towards the polymorph induced drug compound manufacturing to a higher level. The drug manufacturers have found tremendous application for the polymorphic forms of the drug because of the thermodynamic and physicochemical properties. Some of the properties are melting point, stability, solubility, density etc. The factors such as dissolution rate and manufacturability can affect the physicochemical properties of the drug. Hence it becomes necessary to identify, detect and characterize the polymorphic form of the drug molecule during the drug manufacturing process and drug discovery. It is also important for quality control and assurance.
Polymorphism studies help to understand whether a specific polymorph is relatively more stable physically than the other metastable polymorphs. This gives the information about the table polymorph being in the lowest energy state having high melting point and least aqueous solubility. The structure of the crystalline solid polymorph is crucial in understanding the efficacy of the drug and its impact on the human body system. The variations in the solubility profile of the polymorphs can decide whether the concerned polymorph will be therapeutically more successful than the others.
The factors influencing drug polymorphism:
There are various factors that can influence the crystallization process to develop the polymorphs. The common factors that can affect the drug polymorphism are crystallization temperature, heating, cooling and agitation rate, evaporation rate, degree of supersaturation, pH of the media etc.
When the polymorphic form of the drug compound is decided, it is important to verify the bioavailability and stability of the drug substance. The metastable polymorphs become thermodynamically more stable form in a relatively short period of time but they are found to be more soluble than corresponding stable polymorphic forms. Hence to ensure the bioavailability after drug administration, it is important to observe and note the polymorphic transformation during formulation, manufacturing and storage of dosage forms.
Drugs with low water solubility have poor and variable oral bioavailability and therefore appropriate formulation of the drug is required. The physicochemical stability of the drug compound is necessary to increase shelf life and bioavailability of the drug compound. Additionally it is necessary to identify and characterize polymorph crystal forms of every drug by using drug crystal engineering methods, high throughput seeing technology and use of combinatorial chemistry to identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs. This helps to overcome the risks involving bioavailability and clinical failures.
There has been considerable research and development done to increase the solubility, dissolution rate and thus oral bioavailability by salt formation method. Newer strategies are developed to increase the oral bioavailability and dissolution rates in the pharmaceutical industries for the increased production of the polymorphs of the drug compounds.
