Parental Products

Question 1

What is a parental product?

Answer 1

Sterile preparation intended for administration by injection, infusion or implantation in the human or animal body

Question 2

What are the different parental products available?

Answer 2

Solution, Emulsion, Suspension, Concentrate, powder, gel, implant, injection, infusion or direct implantation

Question 3

What happens to red blood cell in a HYPERtonic solution?

Answer 3

Higher solute concentrations (low H20 conc) - higher osmotic pressure than blood plasma = water driven out of cells by osmosis = SHRINK
always have to dilute prior to administration

Question 4

What happens to RBC in an isotonic solution?

Answer 4

“ideal”. Same conc of solute in solution as blood plasma = no net or water movement. e.g. NaCl solution

Question 5

What happens to RBC in HYPOtonic solution?

Answer 5

Lower solute concentration (higher H2o conc) - lower osmotic pressure than blood plasma = water driven out of cells by osmosis = CELLS BURST. Add NaCl, dextrose or mannitol this can quickly restore cell plasma volume e.g saline

Question 6

What are the advantages of Parental Products?

Answer 6

IV - bypasses first metabolism so absorption is 100% bioavailability.
Oral Route is unavailable (i.e patient cant swallow, unconscious, GI tract doesn’t work, Effective (predictable response), rapid drug effect in emergency situation, delayed, prolonged or controlled effect.

Question 7

Disadvantages of Parental Products?

Answer 7

Patience compliance, painful/stressful (needle phobia), Expensive, Stringent requirements for manufacture, requires professional for administration.

Question 8

What is volumes are small and large volumes?

Answer 8

LVP (100-1000mL) and SVP (<100mL)

Question 9

What are the four main routes for administration of parental products?

Answer 9

Intravenous (IV) – into an easily accessible prominent vein near the skin’s surface.
Subcutaneous (SC) – into the loose connective and adipose tissue beneath the dermis.
Intradermal (ID) – into the skin between the epidermal and dermis layers.
Intramuscular (IM) – into relaxed muscle tissue, commonly buttocks, thigh, shoulder muscles.

Question 10

6. Why are parenteral products required to be sterile?

Answer 10

Parenteral products bypass the body’s natural defence system and barriers directly into the blood stream or body tissue and thereforehave the opportunity to introduce infection. Additionally, patients receiving parenteral products may be immunocompromised, require nutrition and be age compromised (young / old) and therefore be more susceptible to infection.

Question 11

7. what is the most common vehicle which is used when designing parenteral products, what can be used to inc solubility and carry poorly soluble drugs and what allows a prolonged release of a drug

Answer 11

Water for injection (WFI) is used to dilute or reconstitute medicinal products for parenteral administration, it is the most commonly used vehicle in parenteral products and because it is well tolerated by the body.
Co – solvents can be used to aid solubility of poorly soluble drugs examples of co-solvents include ethanol, glycerol.
Solubilizing agents can also be used to aid dissolution of drugs with poor aqueous solubility e.g. cyclodextrins.
Oil in water (o/w) emulsion is used to carry water insoluble drugs
Oils (intramuscular injections) – these can allow drug release over a prolonged period of time.

Question 12

8. Explain the purpose of buffer systems within the formulation of parenteral products and give examples of buffer ingredients which could be used.

Answer 12

Buffers are added to parenteral products to maintain their pH at the desired optimum value (between 3.0 – 9.0 – ideally 7.4). Examples of buffers include citric acid, sodium citrate, sodium acetate.

Question 13

9. Explain why a viscosity enhancer may be used in a parenteral product?

Answer 13

Viscosity enhancers are used in suspensions for injection to ensure the drug is readily and uniformly suspended prior to administration. E.g. Water-soluble cellulose derivatives (methylcellulose)

Inc duration of action e.g artificial tears

Question 14

10. Preservatives may be incorporated into parenteral products in certain circumstances. State when this would be appropriate and the purpose for which they would be included.

Answer 14

Preservative are included in multi-use parenteral products. These injections are packaged in vials which have a self-sealing synthetic rubber septum which allows a needle to withdraw volumes of the injection on a number of occasions. Introduction of the needle into the vial can increase the risk of microbial contamination. Microbial preservatives inhibit the growth of microroganisms which may be inadvertently introduced into the product.

Question 15

11. Antioxidants can be incorporated into parenteral products (with a few exceptions), what are their purpose and give an example of an excipient which can be used as an antioxidant?

Answer 15

Antioxidants can be added into products where the drug is susceptible to degradation by oxidation. These are used to reduce the degradation rate and the shelf life / expiry date of the product. These have a lower oxidation potential than the drug and will react with the oxygen in the product. E.g. vitamin C, vitamin E, Ascorbic acid.

Question 16

What are the requirements of containers used to package parenteral products?

Answer 16

Containers should ideally be transparent so that the products can be examined prior to their use – for example during reconstitution of powders for injection to determine if the drug is fully dissolved. Containers must be tightly sealed as to maintain the sterility and integrity of the product. The container should be inert - there should be no interaction between the container and the product. The container should be robust to withstand further processing, transportation and handling.

Question 17

Define Osmosis

Answer 17

a. Osmosis - movement of water from high solute concentration to a low solute concentration across a semi permeable membrane

Question 18

Define Tonicity

Answer 18

b. Tonicity – the ability of an extracellular solution to make water move into or out of a cell by osmosis.

Question 19

Define Hypotonic solution

Answer 19

c. Hypotonic solution – A hypotonic solution has a lower solute concentration compared to another solution

Question 20

Define isotonic solution

Answer 20

e. Isotonic solution – An isotonic solution has the same solute concentration than another solution

Question 21

Define hypertonic

Answer 21

d. Hypertonic solution – A hypertonic solution has a higher solute concentration compared to another solution.

Question 22

How do you package parental product?

Answer 22

Vials, they are glass with synthetic closure, multiple use, require a preservative within them.
Ampules - tap the top to get the product at the bottom snap top and withdraw product. Glass or plastic. Single use unpreserved.
Prefiled syringes, glass or plastic, refilled with specific dose, patient can administer themselves, accurate, not expensive, sterile and safe to use.
Infusion bags, Larger volume. glass and plastic. Collapsible bags, with additional tap. Make up doses specific to patients chemotherapy.

Question 23

Define sterility?

Answer 23

Free from viable micro-organisms and pyrogens

Question 24

What are some errors of administration that can occur?

Answer 24

Omission of drug - wrong drug administered. Wrong route IV rather than IM, SC rather than IM. Wrong preparation - diluted with the wrong solvent
wrong drug administered
wrong dose - decimal point error or calculation
wrong time - out with required time frame

Question 25

Define and give an example of an implant

Answer 25

Contraceptive nexplanan replaced every 3 years. Sterile solid preparation containing one or more active ingredient, provides release of the active ingredient over an extended period of time.

Question 26

Define gels and give an example

Answer 26

Gels have enhanced viscosity suitable to guarantee a modified released of the active substance at site of injection. e.g. hydraulic acid injections for knee pain (osteoarthritis), cosmetic dermal filler (atrigel). Polymerises forming a semi-solid allowing extended release over time.

Question 27

What are particulates?

What is the difference between solution and suspension?

Answer 27

Microbe carrying particles (MCP) and inert particles. Solutions are free of visible particles + low number of sub-visible particles. Suspensions - particles permitted but not delivered intravenous - particles can lodge into capillaries resulting in a pulmonary embolism.

A solution is a homogeneous mixture, and a suspension is a heterogeneous mixture

The particles in a solution are much smaller and are dissolved in a solvent, therefore staying mixed together. In a suspension, the particles are large, do not dissolve, and will separate.

Question 28

Powders and give an example

Answer 28

Dry solid state powders sealed in their final container, unstable in aq solutions, they are diluted prior to administration and are freeze dried. e.g MMR vaccine (PRIORIX) Flucloxacillin (many antibiotics)

Question 29

What are infusions, how are they delivered, what are they contained in give example, how many times can they be used?

Answer 29

they are large volumes >100ml-1000mL. delivered intravenously, sterile solution or emulsion, no preservatives (single use), glass or plastic bottles or collapsible bags with additive parts e.g saline 0.9% NaCl and total parenteral nutrition (TPN) Intralipid, CLINOLEIC

Question 30

what are Injections, how are they administered, how are they contained and give example

Answer 30

They are small volumes <100mL, various routes of administration (IV, IM,SC), sterile solution, emulsion or suspension. The drug and excipients are in the vehicle. Can be in ampules, vials, refilled syringes. e.g. soluble insulin (Humulin S), Profofol (Diprivan), Isophane Insulin (Humulin)

Question 31

What complications can occur when with parental products? HINT physical, chemical, contamination

Answer 31

Physical:
Mixing of drug prior to administration
Insolubility, colour change, precipitation, gas formation, cloudiness

Chemical:
Oxidation, hydrolysis, photolysis
Changes potency (10% loss is considered incompatible)
Increase in toxicity
Drug degradation (e.g. norepinephrine in alkaline solution)
pH changes (precipitation)
Packaging Incompatibility

Microbial
bacteria, fungal, viral

Particulate
dust, fibres, metals, rubber, glass, precipitants

Question 32

What Administration complications are there?

Answer 32

Extravasation: Leakage of intravenous (IV) medications into the extravascular tissue around the site of infusion
Air Embolism: Blood vessel blocked with injected air
Hypersensitivity: Patient allergy to medication
Thrombosis: Blood clot
Phlebitis: Vein irritation

Question 33

What excipients are there? give examples

Answer 33

pH adjustment and buffers
pH of plasma and extracellular fluid 7.4
pH must be between 3.0 – 9.0 (> 9=tissue necrosis / <3 = pain/phlebitis in tissue)
Stability and solubility – also pH dependant
Acidifying or alkalizing agents (e.g. hydrochloric acid / sodium hydroxide)
Buffers – to maintain pH (e.g. citric acid, sodium citrate)
Suspending agents
Ensures drug us readily and uniformly suspended prior to administration
e.g. Water soluble cellulose derivatives (methylcellulose)

Question 34

What Tonicity adjusting agents are there?

Answer 34

Injection and infusions should be made isotonic with human plasma
0.9 % Sodium chloride solution (osmolarity of 286 mmol / L) = Isontonic with human plasma (osmolality of 280 – 295 mmol / kgThe ability of an extracellular solution to make water move into or out of a cell by osmosis.

related to osmolarity/osmolality (total concentration of all solutes in the solution)