Kulliyyah of Pharmacy, IIUM

PHM3133 Dosage Design 1

Laboratory Practical

Polymorphism of L-glutamic acid

This experiment uses optical microscopy to look at crystals grown from aqueous solution, and uses crystal morphology as evidence for polymorphism.

Objectives

  1. To grow single crystals of the α- and β- polymorphs of L-glutamic acid.
  2. To investigate the effects of temperature and stirring rate on the polymorphic form.

Introduction

Crystalline powders generally reveal little detail to the naked eye about the particles that make them up. However, when magnified under the optical microscope much more can be learned. In this case, a stage micrometer,or a microscope equipped with a software and sizing capability, enables size estimates to be obtained for crystal dimensions ranging from ca. 10μm to 1mm. Thus, crystal can be characterised by its shape, its length and breadth, and its aspect ratio (length÷breadth). Since the shape of a crystal is dependent on its internal lattice structure, shape can be used as evidence for the existence of polymorphism. In this case, crystals are obtained by preparing a saturated solution of L-glutamic acid, and then supersaturating by lowering the temperature.

Experimental Procedure

  1. Saturating the solution

Prepare 50ml of an aqueous solution containing ca. 2.4g L-glutamic acid at 80°C. Ensure that all solids dissolved. Otherwise, you may have to filter. Pour equal amount into four (4) warm beakers.WARNINGBe extremely careful when handling hot solutions. Use a pair of glove.

  1. Supersaturating the solution
  2. MethodA - Rapid cooling with stirring
    Stir vigorously at room temperature.
  3. Method B - Rapid cooling without stirring
    Leave it sitting unstirred at room temperature.
  4. Method C - Slow cooling with stirring
    Switch OFF the hotplate, but leave the beaker sitting on it with the solution stirring.
  5. Method D - Slow cooling without stirring
    Leave it sitting unstirred on the hotplate (OFF)

Hint:

  1. Monitor temperature as the solutions cool and the time taken for the first appearance of crystals.
  2. Use fast filter paper. Otherwise, crystals may form during filtration. Check availability with your lab technician.
  1. Observeand record the following:
  2. the time taken for crystalline product to appear from the solution.
  3. temperature of the solutions at crystallisation point.
  4. crystal morphology, using the optical microscope.
    Take a picture with a scale included. Record the:
  5. optical microscope model
  6. objective lens used
  7. total magnification
  8. estimate size of particles.

LABORATORY REPORT

The report should include the following:

  1. Experiment title, date of experiment, date of report submission
  2. Abstract
  3. Aim/Objective
  4. Introduction
  5. Methods/Experimental details i.e. weights, volumes, temperatures, procedures.
  6. Results/Experimental observation
  7. Discussion. Include:

(a)Chemical structure of L-glutamic acid

(b)Description of the morphology of the α- and β- crystals.

(c)Which is the more thermodynamically stable phase?

(d)What effect does temperature and stirring rate have on polymorphic form?

  1. Conclusion

Figure1 Prismatic -form (left) and needle-like -form of a model compound, L-Glutamic acid(C5H9NO4). Both orthorombic.

Figure 2 Temperature profile employed in the crystallization experiment of L-Glutamic acid:I, nucleation region; II, Trans-formation region.

References

Check the following at library red-spot:

  1. M Kitamura, T Ishizu, Growth kinetics and morphological change of polymorphs of L-Glutamic Acid, J. Crystal Growth 209 (2000) 138-145
  2. M Kitamura, Polymorphism in the Crystallization of L-Glutamic Acid, J. Crystal Growth96 (1989) 541-546
  3. T. Ono,J. H. ter Horst and P. J. Jansens, Quantitative Measurement of the Polymorphic Transformation of L-Glutamic Acid Using In-Situ Raman Spectroscopy, CrystalGrowth & Design 4 (2004) 465-469

Prepared by: Kausar Ahmad

Source: Dr. Tanveer Ahmad Khan

Date revised: 6-July-2006

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