Influence of Polylmorphism Exhibited by Selected Antibiotics on Development of Rational Dosage Forms

Abstract

The pharmaceutics scientist must formulate this material into a dosage form that is homogeneous, callable, stable, and bio available. Since most of the dosage forms are solids such capsules/tablets the focus will be on the processing parameters that are operative in the production of solid dosage forms. Solution dosage forms are generally independent of the polymorphic problems. If there is a less soluble form, it will appear on temperature cycling stability testing. Temperature cycling is the most severe challenge to solubility and if one should generate seed crystals of a less soluble form of a compound during cooling, then equilibrium will rapidly be established. The final stage of this scenario will be precipitation or crystal growth. The classic cases in industry are the soluble anhydrous materials converting to an insoluble hydrate upon stability testing, or moisture leakage into a delivery system. In solid dosage forms, the first opportunity for a change in crystallinity will be in the blending and milling of drug with excipient to produce a homogeneous blend. The excipients in the formulation can exert a strong influence on polymorphic conversion and may create new pathways that did not exist for the pure drug substance. One should expect polymorphs with similar thermodynamic energies to be prone to substantial conversion during a milling operation. The key parameters that cause polymorphic conversion or dehydration of hydrates at the formulation stage are milling, granulation wetting. All these parameters can become more important during prolonged processing times if the batch size become sufficiently large. In the light of the results of the present study, it is concluded that the crystalline forms of the selected drugs Cefuroxime axetil and aztreonam prepared by ammonia diffusion method did not undergo any phase transition by either formulation variables or manufacturing processes as shown by no changes in their stability and essential physico-chemical properties dependent on crystalline behavior.