Viva A(i, ii)

This viva refers to  Section A(i) and Section A(ii) of the 2017 CICM Primary Syllabus. Section A(i) reads cryptically "A more detailed knowledge would be expected for more commonly used drugs.", which is not a learning objective in any meaninful sense. But, something needed to be concocted to help prepare for possible future vivas. 

What is the definition of pharmaceutics?

Pharmaceutics is the study how to best present the pure drug molecule in order to achieve the therapeutic goal.

"Pharmaceutics... is the discipline of pharmacy that deals with the process of turning a new chemical entity (NCE) or old drugs into a medication to be used safely and effectively by patients. It is also called the science of dosage form design."

- Wikipedia

What is involved in presenting a chemical in a useable form, as a  medication?
  • Presenting the drug in a usable and durable form
    • Bulking agents
    • Stability modifiers
    • Preservatives
  • Changing the physico-chemical properties of the drug to ensure its delivery
    • Complexing the drug
    • Changing its solubility
    • Modifying the absorption mechanisms, eg. in controlled-release formulations
  • Improving the safety of the drug to the person administering it
    • Making a cytotoxic drug less volatile
    • Presenting a radioactive isotope in  shielded packaging
    • Ensuring the ampules break correcly without lacerating fingers
  • Controlling the risk of incorrect drug administration, eg
    • Labelling the packaging and making it sufficiently distinct
    • Naming the drug unambiguously
    • Appropriatly using warning labels and cautionary signs
  • Improving the tolerability or appeal of the drug
    • Flavours and colours, eg. syrup for children
    • Easily swallowed pill coating
    • pH-adjusted intramuscular injectable formulation
    • Cosmetic appearance of the packaging
What are the characteristics of an ideal drug name?
  • Unambiguous, i.e. identifies the substance
  • Simple
  • Unique (i.e. not duplicate or sound-alike)
  • Standardised, i.e. recognisable as a member of a class of drugs
What types of names are there, for each drug?
  • Brand name:, eg Diprivan
  • Generic name: propofol
  • Molecular name: 2,6- diisopropylphenol
What are the safety principles involved in drug labeling?
  • Use explicit text to describe dosage and interval in instructions.
  • Use a universal medication schedule (UMS) to convey and simplify dosage and use instructions.
  • Organize labels in a patient-centered manner.
  • According to need, include indication for use.
  • Simplify language, avoiding unfamiliar words or medical jargon.
  • Improve typography, use larger, sans serif font.
  • When applicable, use numeric versus alphabet characters.
  • Use typographic cues (bolding and highlighting) for patient content only.
  • Use horizontal text only.
  • Use a standard icon system for signaling and organizing auxiliary warnings and instructions.
What is the importance of safe drug labeling? Why do we need to think about this?
  • 25% of all medication errors are attributed to name confusion
  • 33% to packaging and labeling confusion
  • That adds up to approximately 500,000 medication errors per year in the US
  • The total cost of this is though to be approximately $300 million

To determine how this could be happening, Shrank et al (2007) evaluated a pile of drug labels from pharmacy-dispensed preparations. The following issues were identified:

  • On 84% of the labels, the most prominent item was the pharmacy's logo (average font size 13.6 points)
  • The font size of the drug name was much smaller (8.9 points on average)
  • The instructions for use were also small (9.3 point)
  • The warnings and instruction stickers were unreadably tiny (6.5 point)
What national standards are you aware of in drug labeling?

The Australian TGA has introduced new clearer labeling rules in 2016, as a legal act (Therapeutic Goods Order No. 91 - Standard for labels of prescription and related medicines.

What is the purpose of drug packaging?

Protective purpose

  • Temperature protection
  • Water-sealed, to protected from degradation by humidity
  • Air-sealed to prevent degradation by oxygen
  • Sterile packaging to prevent contamination by microorganisms
  • Photoopaque packaging to protect drugs from degradation by light
  • Radioopaque packaging to prevent radiation exposure of the personnel handling the substance
  • Durable protective packaging to protect glass ampoules from shattering in transport
  • Role in dosing (eg. the plastic body of a metered dose inhaler can be viewed as a form of packaging)

Safety purpose

  • Tamper-resistance
  • Child-proofing
  • Protection against counterfeiting
What factors play a role in the choice of materials for drug packaging?
  • The packgaing has to be inert
  • Interaction of drug packaging with the drug needs to be minimised
  • Leeching of active ingredient into the packaging needs to be minimised
  • Adsorption or absoprtion of packaging components into/onto the drug may occur

Excellent example of major packaging problems are drugs like sodium nitroprusside (which should not be exposed to light) and paraldehyde (which will happily dissolve its way out of any plastic container). 

References

Aulton, Michael E., and Kevin MG Taylor, eds. Aulton's Pharmaceutics E-Book: The Design and Manufacture of Medicines. Elsevier Health Sciences, 2017.

Banker, Gilbert S., Juergen Siepmann, and Christopher Rhodes, eds. Modern pharmaceutics. CRC Press, 2002.

Bernardo, Peter D., and Emanuel J. Russo. "Pharmaceutical sciences—1968. A literature review of pharmaceutics.Journal of pharmaceutical sciences 58.7 (1969): 777-812.

Kenagy, John W., and Gary C. Stein. "Naming, labeling, and packaging of pharmaceuticals.American Journal of Health-System Pharmacy 58.21 (2001): 2033-2041.

Hoffman, James M., and Susan M. Proulx. "Medication errors caused by confusion of drug names." Drug Safety 26.7 (2003): 445-452.

King, Caroline, and Lakshmi NP Voruganti. "What's in a name? The evolution of the nomenclatureof antipsychotic drugs." Journal of Psychiatry and Neuroscience 27.3 (2002): 168.

George, C. F. "Naming of drugs: pass the epinephrine, please." BMJ: British Medical Journal 312.7042 (1996): 1315.

WHO: Guidelines on the Use of INNs for Pharmaceutical Substances (1997)

Shrank, William H., et al. "The variability and quality of medication container labels." Archives of internal medicine 167.16 (2007): 1760-1765.

Paine, Frank A., and H. Lockhart. Packaging of pharmaceuticals and healthcare products. Springer Science & Business Media, 2012.

Feenstra, Peter, Michael Brunsteiner, and Johannes Khinast. "Prediction of drug-packaging interactions via molecular dynamics (MD) simulations."International journal of pharmaceutics 431.1 (2012): 26-32.

Feenstra, Peter, Michael Brunsteiner, and Johannes Khinast. "Investigation of Migrant–Polymer Interaction in Pharmaceutical Packaging Material Using the Linear Interaction Energy Algorithm." Journal of pharmaceutical sciences103.10 (2014): 3197-3204.