Overview
This lecture introduces the fundamental concepts of the physicochemical characteristics of drugs, with a focus on solids, crystal forms, and their pharmaceutical significance.
Introduction to Pharmaceutics
- Pharmaceutics is the study and design of drug formulations, including manufacturing and delivery systems.
- Drugs can exist in solid, liquid, or gas states, but most drugs and excipients are solids at room temperature.
Types and Forms of Solids in Pharmacy
- Solid dosage forms include powders, effervescent preparations, capsules, tablets (conventional, coated, sustained-release), and suppositories.
- Solids are characterized by their crystal structure and unit cells, such as cubic, tetragonal, hexagonal, rhombic, monoclinic, triclinic, and rhombohedral.
Crystalline Solids and Crystal Lattices
- Crystalline solids have a well-ordered arrangement of molecules, atoms, or ions in a repeated unit cell pattern forming a crystal lattice.
- There are seven primitive unit cells and 14 Bravais lattice types in crystalline solids.
Crystal Habits and Properties
- Crystal habits (shape) depend on crystallization conditions like solvent, temperature, concentration, and impurities.
- Examples include needle-like (acicular), prismatic, pyramidal, tubular, columnar, and lamellar shapes.
- Crystal habit affects the flow, compaction, and dissolution characteristics of powdered drugs.
Factors Affecting Crystal Formation
- Crystal formation is influenced by supersaturation, crystal nuclei formation, and crystal growth around nuclei.
- Supersaturation can be achieved by cooling, evaporation, or adding precipitant or seed crystals.
Polymorphism and Solid State Characteristics
- Polymorphism is the existence of more than one crystal form for a substance, affecting drug properties like solubility and dissolution.
- Isotropic solids have identical properties in all directions; anisotropic solids vary with orientation.
Solvates and Hydrates
- Crystals can entrap solvents (solvates); hydrates specifically contain water.
- Anhydrous forms dissolve faster than hydrate forms, affecting drug absorption and bioavailability.
Analytical Techniques for Solid State Characterization
- Powder X-ray Diffractometry (PXRD) and Single Crystal XRD identify crystal phases and structures.
- Bragg’s Law relates X-ray diffraction patterns to crystal structure.
- Other techniques: DSC/MDSC (phase transitions), TGA (solvate/hydrate stoichiometry), IR/NIR/Raman spectroscopy (phase identification), Solid State NMR, HSM, and sorption analysis.
Key Terms & Definitions
- Pharmaceutics — Study of drug formulation and delivery.
- Crystal lattice — Repeating three-dimensional structure of a crystal.
- Unit cell — Smallest repeating unit of a crystal lattice.
- Polymorphism — Existence of different crystal forms for the same substance.
- Solvate/Hydrate — Crystal containing solvent (hydrate if water).
- Amorphous solid — Lacks long-range order or crystal structure.
- PXRD — Technique to characterize the crystalline phase.
- Bragg’s Law — Law describing X-ray diffraction in crystals.
Action Items / Next Steps
- Review crystal structures, crystal habits, and methods of crystallization.
- Study analytical techniques for solid state characterization.
- Prepare for discussion on the pharmaceutical implications of polymorphism and solvates.