1. Taking advantage of the amorphous form– the preparation and characterisation of solid dispersions Rakesh Dontireddy, UCC, Cork

3. crystalline A or h s m p o u

4. crystalline amorphous

5. crystalline amorphous

10. Solid dispersions + Drug particles Carrier particles Disrupt molecular arrangements and supermolecular structures Create solid particles with altered molecular arrangements and supermolecular structure Create a molecular mixture of drug and carrier molecules Drug -Carrier solid dispersion particle s Diffusion in solution Mix melt of drug and carrier Cool molten mixture Remove solvent Dissolve or melt or melt and dissolve Techniques

11. Solid dispersions Solid solutions are a resultant single phase upon dispersion of two compounds in each other, at their molecular level Eutectic mixture Crystalline drug Amorphous carrier Amorphous drug Amorphous carrier Solid Dispersion Solid State Two phase solid system Single phase solid system Crystalline Amorphous Substitutional Interstitial

14. Model drug: Hydrocortisone practically insoluble in water, sparingly soluble in acetone and in alcohol, slightly soluble in methylene chloride solubility behaviour due to some hydrogen bonding capability due to the presence of both C=O and OH groups but largely due to dispersion forces Crystalline in nature Model carrier: PVP High water solubility – improve wettability and enhance dissolution High glass transition point – improve stability Amide group participates in hydrogen bonding

16. Influence of drug:carrier ratio on solid dispersion behaviour XRD patterns of spray dried dispersions (from 96% ethanol) of drug with different ratios of carrier

17. MDSC thermographs of PVP and spray dried dispersions (from 96% ethanol) of drug with different ratios of carrier showing the glass transition temperatures

18. MDSC thermographs of spray dried (from 96% ethanol) and Hydrocortisone unprocessed

19. Moisture content of dispersions spray dried from 96% ethanol (n=3)

20. 40% PVP 50% PVP 60% PVP 75% PVP Moisture content of spray dried (96% ethanol)

21. Dissolution behavior of solid dispersions of spray dried dispersions (96% ethanol) of drug with different ratios of carrier (n=3)

23. Influence of solvent composition XRD patterns of spray dried dispersions prepared from a) 20% aqueous ethanolic mixtures and b) 96% ethanol with different ratios of carrier Influence of solvent behaviour on solid dispersion behaviour

24. MDSC thermographs of spray dried dispersions prepared from a) 20% aqueous ethanolic mixtures and b) 96% ethanol with different ratios of carrier showing the glass transition temperatures

25. Moisture Content of Spray Dried Systems (n=3)

26. Morphology of Spray Dried 20% Ethanol from Scanning Electron Microscopy Hydrocortisone 40% PVP 50% PVP 75% PVP

27. Dissolution behavior of solid dispersions of spray dried from a) 20% aqueous ethanolic mixtures and b) 96% ethanol with different ratios of carrier (n=3)

29. Influence of processing method + Drug particles Carrier particles Drug -Carrier solid dispersion particles Remove solvent Dissolve carrier and drug Process parameters Rate of solvent removal Temperature of material Humidity of air Volume of air Temperature of air etc

30. XRD patterns of both spray dried and freeze dried dispersions of drug and carrier at different ratios of carrier

31. Figure showing the MDSC scans of physical mixture ,spray dried HC sample and freeze dried HC sample

32. Moisture Content of Spray Dried and Freeze Dried Systems (n=3)

33. Hydrocortisone 40% PVP 50% PVP 75% PVP Morphology of Freeze Dried 20% Ethanol from Scanning Electron Microscopy

34. Dissolution Behaviour of Spray Dried and Freeze Dried Systems (n=3)