Pharmacuetics Exam IV

  1. Preparation of Syrups with heat
    • heat may hydrolyze sucrose, must be done quickly
    • Sugar is added to purified water and heated until sugar dissolves
    • Other heat stable components are added
    • The mixture is cooled and the volume is adjusted to the proper level with purified water
  2. Preparation of Syrups w/out heat
    • Sugar and other components dissolved in purified water by agitation
    • volume is adjusted with purified water
    • more time consuming, good stability
  3. Preparation of Elixirs
    Aqueous phase added to alcoholic phase to maintain highest possible alcohol strength at all times to prevent separation of alcohol soluble components
  4. Opium Tincture
    only give by drops
  5. Administration of oral liquid dosage forms
    • teaspoon or tablespoon
    • calibrated devices
    • follow with a glass of water
    • no syrups for diabetic patients
    • no elixirs with drugs that have antabuse properties
    • elixir may cause drowsiness
  6. Artificial sweetners
    • sweeter tgab sycrise
    • less than 0.2% concentration required
    • good for use in elixer
    • saftey concern: Cancer
  7. Advantages of TDDS
    • avoid GI tract
    • non-invasive
    • greater patient compliance
    • extended therapy
    • delivery of drugs with short half-life
    • therapy can be terminated rapidly
  8. Disadvantages of TDDS
    • Only potent drugs are candidates
    • Skin irritation
    • Poor adhesive
  9. Skin structure
    • Epidermis
    • Dermis
    • Sub-cutaneous
  10. Epidermis
    • major barrier for transdermal drug absorption
    • 5 layers
  11. stratum corneum
    • primary barrier to drug absorption across the skin
    • 15-20 layers of dead, flattened stacked cornified cells
    • impermeable and dense
    • rich in cholesterol, no phospholipids
    • changes in lipid composition =different permeability
    • lipid extraction with organic solvents increase permeability
  12. Transdermal drug absorption
    • transcellular route: drug moves through cells, hydrophilic drugs
    • paracellular route: drug moves between cells, lipophilic drugs
    • most drugs use both routes
    • Intercelluar is the major pathway and barrier
  13. Factors affecting transdermal absorption
    • physical and chemical properties of the drug
    • drug concentration
    • temperature and pH
    • formulation (liposomes improve absorption)
    • Exposure time; longer time = greater absorption
  14. Fick's First law of diffusion

    • dM/dt = total flux transported through a unit area of skin per unit time
    • A= area of skin
    • P=permeability coefficient
    • /\C=drug concentration gradient
  15. Which of the following layers is the primary barrier to drug absorption across the skin?

    C. Stratum Corneum
  16. It is generally difficult to get drugs to cross the skin at a sufficient rate (T/F)
  17. Epidermis is thicker than dermis (T/F)
  18. Which are true about drug epidermal transport?
    1. hydrophillic drugs prefer intercellular route
    2. most drugs pass the stratum corneum only by intercellular route
    3. Intercellular route is also called paracellular route
  19. Explain why stratum cornium is the primary barrier for transdermal drug absorption
    • 15-20 layers of dead, flattened, stacked cornified cells
    • "brick wall" architecture
    • unique lipids
    • impermeable and dense
  20. transdermal absorption of most drugs follows Fick's First law of diffusion. Briefly describe the meaning of A, P and /\C.
    • A= area of skin
    • P= permeability coefficient
    • /\C= drug concentration gradient across skin
  21. Effect of hydration on transdermal absorption
    • increases the penetration of most active compounds
    • opens up compact structure of stratum corneum
    • swelling of stratum corneum
    • apply water to skin or prevent water loss from skin
  22. Chemical penetration enhancers
    • increase skin permeability by reversible damaging or altering physiochemical nature of the stratum corneum
    • >275 chemicals
    • not enhancing enough for macromolecule delivery
  23. Criteria for chemical penetration enhancers
    • no pharmacological effect
    • specific in action
    • reversible action
    • stable
    • compatible with components of TDDS
    • odorless and colorless
    • inexpensive
  24. Classes of chemical penetration enhancers
    • extraction of lipids from the stratum corneum
    • alters the structure of skin lipids, decreasing diffusion resistance
    • enhances solubility of drug within the skin
    • loosening of stratum corneum cells (swelling and hydration)
  25. Examples of chemical penetration enhancers
    • Ethanol: cosolvent, extracts stratum corneum lipids
    • Azone: 1st chem. enhancer, effective at [low], lipophilic
    • DMSO: /\ keratin conformation from a-helix to b-sheet, extracts lipids
  26. Physical enhancement techniques
    • skin abrasion
    • iontophoresis
    • electroporation
    • sonophoresis
    • thermal ablation
    • microneedles
    • microchannels
    • needleless injection
  27. Which of the following penetration enhancers is called the "universal solvent" in pharmaceutical sciences?

    C. DMSO
  28. Which methods use electricity to enhance the transdermal drug delivery?
    1. Sonophoresis
    2. Iontophoresis
    3. electrophoresis
    2 and 3
  29. Which methods can enhance transdermal delivery of macromolecules (peptides/proteins)?
    1. Sonophoresis
    2. Iontophoresis
    3. Electrophoresis
    1, 2 & 3
  30. Iontophoresis only delivers charged molecules into the skin. (T/F)
  31. Microdermabrasion removes all stratum corneum cells to enhance transdermal drug absorption (T/F)
  32. Which of the following methods create transit small pores in the cell membrane of the stratum corneum?

    C. Electrophoresis
  33. RF-MicroChannel Technology
    • densely spaced array of microelectrodes
    • high frequency current
    • penetrates only outer layer of skin
    • micro channels generated in miliseconds
    • microchannels remain open for more than 24 hr
    • supports relatively high dosage of drug
  34. Structure and components of passive TDDS
    • Matrix
    • Reservoir
    • Backing
    • Adhesive
    • Protective Liner
  35. Criteria for backing material
    • contains formulation througout shelf life and during wear period
    • compatible with formulation
    • occlusive
    • laminate structure
    • printable
    • 2-3 mm thick
  36. Adhesive criteria
    • Pressure sensitive
    • safe
    • compatible with api and excipients
    • adheres to skin tightly
    • easily removable
    • excellent contact with skin
    • must not leave residue on skin
  37. Scopolamine
    • first TDDS
    • prevents n/v associated with motion sickness
    • four layers: backing, reservoir, membrane, adhesive
    • 0.2 mm thick
    • 1.5 mg scopolamine
    • initial dose 200mcg in adhesive layer
  38. Assesment of skin penetration
    • in vitro
    • ex vivo
    • in vivo

    most use franz diffusion chamber
  39. Franz Diffusion Chamber
    • Donor compartment
    • Membrane
    • Acceptor compartment
    • water jacket/ sampling port
  40. Clinical considerations in the use of TDDS
    • absorption varies with site of application (rotate locations)
    • TDDS should be applied to clean, dry skin
    • TDDS should not be physically altered
    • TDDS should be folded in half when disposed of
  41. Major components of a reservoir patch
    • backing
    • membrane (rate controlling)
    • drug reservoir
    • adhesive
    • protective lining
  42. Which of the following TDDS controls drug release by the polymer matrix?

    C. Layered
  43. Wich statements about the TDDS adhesives are true?
    1. printable
    2. compatible with API and other excipients
    3. must not leave residue on skin
  44. The most relavant animal model for human skin is

    A. Porcine
  45. The most commonly used animal model for transdermal study is

    D. Rat
  46. Importance of biotechnology in pharmaceuticals
    • ability to develope better drugs
    • utilize new drug targets
    • future of pharmaceutical industry
    • cancer patients benefit
    • speed development of new medicines
  47. small molecule drug
    • MW<500
    • conventional
    • high toxicity/side effects
    • "shot in the dark" development
    • saturated market
  48. Biotech drug
    • Large molecules
    • high efficiency
    • poor stability
    • treat cause of disease
    • delivery?
  49. Central Dogma
    • DNA is transcripted in to mRNA in the nucleus and translated into Proteins in the cytoplasm
    • mRNA is converted to DNA via reverse transcription in the nucleus
    • DNA is replicated in the nucleus
  50. Recombinant DNA Technology (6)
    • 1. Isolate interested gene and plasmid separately
    • 2. Cut plasmid and gene fragment with restriction enzymes
    • 3. Ligate gene fragment with restriction enzymes
    • 4. Transform ligated plasmid to bacterial cells
    • 5. select the transformed cells for propagation
    • 6. purify expressed protein
  51. Restriction enzyme
    nuclease which cleaves DNA at very specific site
  52. Ligase
    enzyme used to link the two ends of DNA
  53. Bacterial Transformation
    insertion of cloned plasmid into bacterial cells
  54. Antigen
    macromolecules recognized by the immune system as foreign objects
  55. Epitope
    particular groups on the antigen which signal the antibodies
  56. Antibody Structure
    • Y shaped molecue
    • 4 polypeptide chains
    • 2 identical heavy chains
    • 2 identical light chains
    • connected by disulfide bonds
  57. Heavy Chains
    • Constant region: identical in all antibodies of the same isotype
    • Variable region: differs in antibodies produced by different B cells; same fore all antibodies produced by a single B cell.
  58. Light Chains
    two successive domains, constant and variable
  59. Polyclonal antibody
    • derived from different B cells
    • mixture of immunoglobulin molecules produced against a specific antigen
    • each recognizes a different epitope
    • may be generated rapidly, with low cost and skill
  60. Monoclonal Antibody
    • derived from a single B cell
    • identical immunoglobulin molecules produced against a single epitope
    • homogeneity and consistency are advantages
    • small change in epitope can affect recognition
  61. Monoclonal antibody production
    • 1. Inject antigen into mouse. B cells will produce antibodies against antigen.
    • 2. Isolate B cells from the mouse spleen
    • 3. Normal B cells will die in culture w/in a few days
    • 4. Hybridoma screened and best cell will be cultured for MCAB production
  62. Applications of antibody
    • diagnosis and imaging
    • theraputics
    • targeting agents
    • purification and other applications in research
  63. Antibodies in Therapeutics
    Antibodies can cause apoptosis, recruit killer cells and block signal pathways of tumor cells.
  64. Challenges in protein drug development
    • high MW large molecules: difficulty in cellular uptake
    • Poor stability
  65. Why proteins cannot be administered in the oral route
    low pH denatures proteins
  66. Why can protein drugs be administered via the pulmonary route?
    • Highly vascularized tissue
    • Low enzymatic activity
    • Large absorptive surface
    • High permeability of alveoli
    • Greater tolerance to foreign substance
  67. Importance of freeze drying protein formulations (lyophilization)
    • convenient storage & shipment
    • less degredation of proteins
    • cost effective
    • best for long term storage
    • allows protein to be stored at room temperature
  68. Lyophilization process
    • 1. Freeze soln at -50~-80C
    • 2. Primary Drying
    • low pressure, high heat, several days
    • 3. Secondary Drying
    • low pressure, higher heat ~0C
    • 4. Vacuum broken with inert gas
    • 5. Final humidity ~2%
  69. Structure of Liposome
    • aqueous core, lipid sphere
    • 20nm-10mm
  70. Configuration of Liposomes
    • SUV: small unilamellar vesical
    • LUV: large unilamellar vesicle
    • LMV: large multilamellar vesicle
    • MVV: mulivesicular vesicle
  71. Conventional Ampho B
    • Dose 0.3 to 1 mg/kg/day
    • Overdose 1.5mg/kg/day
  72. AmBisome (liposomal)
    • decreased side effects
    • prolonged drug exposure
    • dose: 3-5 mg/kg/day
  73. Conventional Liposome
    neutral or negatively charged
  74. stealth liposome
    • sterically stabilized; polymer coatings (hydrated groups)
    • Interacts with blood components
    • Blocked recognition by macrophages
    • prologned circulation time
    • Higher uptake by tumor cells
  75. Immunoliposome
    • antibody modified liposome
    • recognize or bind specific cells in the body
  76. cationic liposome
    positive charged, for nucleic acid delivery
Card Set
Pharmacuetics Exam IV
Oral Solutions, Syrups, Elixers Part II