Physical Pharmacy

1. Physical Pharmacy Frank M. Etzler LECOM Fall 2012

2. Introduction • Instructor Contact Info • Room A4-354 • 814-860-5184 • fetzler@lecom.edu • Exams • 2 Exams (100 pts ea.) • 1 Final Exam (100 pts) • Classroom conduct • Distractions from cell phones, computers, newspapers, etc. are disrespectful to the instructor and your classmates.

3. Textbook

4. Suggested Reading

5. Purpose • Provide a basic knowledge of physical pharmacy, pharmaceutics and biopharmaceutical principles as they apply to the development and assessment of various types of drug delivery systems . • Develop critical thinking and problem solving required to address related to dosage form design and effective use. • Acquire technical vocabulary to discuss pharmaceutical problems.

6. Physical Pharmacy Fall 2012 Review of Basic Concepts

7. Greek Alphabet It is expected that you will be familiar with the Greek alphabet used in mathematics.

8. Review of Basic ConceptsSI Units (International System of Units)Base Units N.B. Names are not capitalized. Symbols are capitalized only for units named after a person. All other units are derived from these base units.

9. Review of Basic ConceptsSI Units (International System of Units)Prefixes

10. Review of Basic ConceptsSI Units (International System of Units)Derived Quantities

11. Unit Conversions You should be able dimensional analysis in problem solving

12. Review of Basic ConceptsLogarithms

13. Review of Basic ConceptsFormulas from Geometry

14. Review of Basic ConceptsPlotting Data Linear Plot

15. Review of Basic ConceptsPlotting Data

16. Log Graph Paper

17. Review of Basic ConceptsSignificant Figures • The number of significant figures represent the approximate error of the measurement. • In performing a series of calculations it is best to retain at least an extra digit then rounding appropriately the final answer.

18. Review of Basic ConceptsSignificant Figures • Addition and Subtraction • Include only as many figures to the right of the decimal point as the number with the least such figures. • 442.78+58.4+2.684 = 503.9 • Multipilcation and Division • The number with the least number of significant digits determines the number of significant figures in the result. • 2.67 x 3.2 = 8.5 • Rounding rule • If first insignificant digit is less than 5 last significant digit is not changed; if greater than 5 then last significant digit is increased by 1. • If exactly five then digit increased if last significant digit is odd.

19. Review of Basic ConceptsSignificant Figures • Examples. • 32.451 x 10.02 =325.15902 ~ 325.2 • 4.2500 + 10.1 = 14.3500 ~ 14.3

20. pH Neutral Acid Base 0 14 7

21. Temperature Dependence of Kw

22. Thermodynamic Principles

23. Thermodynamic Principles

24. Free Energy

25. Free Energy

26. Basic Thermodynamic Relations

27. Basic Thermodynamic Relations

28. Things you need to know • Recognize greek characters • SI units / perform unit conversions • Logarithms - define and convert between bases • Significant figures • pH and Kw definitions • Define basic thermodynamic functions E,H,S and G • Know the value of ΔG for and equlibrium and spontaneous process. • The relation between ΔG and K

29. Physical Pharmacy Fall 2011 Chapter 1 - Solids

30. Crystal Structure • All crystalline materials composed of repeating units called unit cells. • There are 7 types of primitive unit cells. Some of these cells can be divided into sub classes bringing the total number of types of cells to 14. • Various planes in the crystal are described by Miller indices

31. Fundamental Bravis Lattices

32. Fundamental Bravis Lattices

33. Miller Index Miller indices are a notation system in crystallography for planes and directions in crystal (Bravais) lattices. In particular, a family of lattice planes is determined by three integers ℓ, m, and n, the Miller indices. They are written (hkl), and each index denotes a plane orthogonal to a direction (h, k, l) in the basis of the reciprocal lattice vectors. By convention, negative integers are written with a bar, as in for −3. The integers are usually written in lowest terms, i.e. their greatest common divisor should be 1. Miller index 100 represents a plane orthogonal to direction ℓ; index 010 represents a plane orthogonal to direction m, and index 001 represents a plane orthogonal to n.

34. Miller Index Miller directions

35. Miller Index

36. Miller Indices for Crystal Planes in Cubic Lattice

37. Crystal Habit

38. Some Common Crystal Habits • Some common crystal habits are as follows. • Cubic - cube shapes • Octahedral - shaped like octahedrons, as described above • Tabular - rectangular shapes. • Equant - a term used to describe minerals that have all of their boundaries of approximately equal length. • Fibrous - elongated clusters of fibers. • Acicular - long, slender crystals. • Prismatic - abundance of prism faces. • Bladed- like a wedge or knife blade • Dendritic- tree-like growths • Botryoidal- smooth bulbous shape

39. Quantitative Methods for Describing Particle Shape

40. Wulff Theorem • Crystal shape is determined by minimizing the ΔG for forming the crystal faces. This is done by adjusting areas of the faces to minimize ΔG • The shape can be influenced by degree of saturation, solvent, and adsorption of surfactants or other substances on crystal surfaces.

41. What is Particle Size? The size of a sphere can be described by a single number, r r

42. What is Particle Size?Irregular Particles Size no longer described by single number. Equivalent sphere diameter used to describe size. Equivalent sphere diameters may be based on volume, surface area, mass or linear dimension. Various calculated equivalent diameters are only equal for spheres These diameters differ to a greater degree when the particle shape deviates more from that of a sphere.

43. Comparison of Various Measures of Particle Size da = projected area dp= perimeter dsa = surface area dv = volume (mass)

44. Presentation of Particle Size Data Data can be presented as number, volume(mass) or surface area distributions Data can be presented as histogram, cumulative or differential distribution

45. Particle Size Analysis • Particle size is expressed as an equivalent spherical diameter. • There a number of different ways to calculate equivalent diameters each giving a different result. • Particle size distributions may be number, surface area or volume (mass) weighted. • Various methods for determining particle size exist. These are divided into two classes ensemble methods (e.g. sieves, light scattering) and number counting methods ( e.g. microscopy) • When comparing particle sizes the same type of distribution and method must be used.

46. Pharmaceutical Importance of Particle Size and Shape • Particle size and shape influence a number of parmaceutical processes. • Powder flow (smaller size worse flow) • Aerosolization (dry powder inhalers) • Dissolution (small size better) • Mixing and blending.

47. Crystal Forms and Polymorphism Polymorphism – The ability of a solid to exist with more than one crystal structure. (e.g. ROY) Pseudopolymorphs- hydrates or solvates that have their own crystal structure. Allotropes – solid chemical elements which exist in different crystalline forms. ( diamond, graphite and fullerenes are allotropes of carbon)

48. Crystal Forms and Polymorphism • Other crystal forms • Salts ( often exhibit improved solubility) • co-crystals - crystalline solids composed of at least two components that form a unique crystal structure. Salts differ from cocrystals in the complete proton transfer occurs in the case of salts.

50. Factors Affecting Which Polymorph is Formed • Various factors affect which polymorph is formed. • These factors include: • Choice of solvent • Level of supersaturation • Presence of impurities • Temperature • Stirring conditions.