Parenteral Formulations with tonicity

TONICITY (PARENTERAL FORMULATIONS)

LOs:

• Understand and explain tonicity

• Why tonicity in certain formulations is important

• How to calculate tonicity

• Understand and explain the concepts of osmolarity and osmolality

  1. Explain what tonicity is

  2. Define osmotic pressure

  3. Discuss osmosis in a closed system and how pressure affects this system.

  4. Discuss osmosis in an open system and the effect of added pressure

  5. Colligative property is…

  6. Osmolarity is used to express ….

  1. Define Solution

A solution is a homogenous mixture in which two or more substances are mixed. They consist of a solute and a solvent in which the molecules or ions have a uniform composition throughout the mixture.

  1. Define Solvent

A solvent is the component in a solution that is present in the largest amount e.g. water in a NaCl solution.

  1. Aqueous solution is

Water as a solvent

  1. Define solubility

Essentially The ability of a solvent to dissolve a solute.

The maximum amount of a substance that will dissolve in a given amount of solvent at a specified temperature

  1. Factors that determine solubility

Various factors such as;

  • Solvent interactions

  • Temperature

  • Pressure

  • Polymorphic form of the solid

  1. Why is understanding aqueous solutions important?

  • Water is the solvent in all body fluids

  • The water content of the human body is about 60& by weight

  • Therefore all drugs, whatever route they are administered must exhibit at least limited aqueous solubility for therapeutic efficiency

  1. Unsaturated solution is when

  • More solute dissolves

  1. Saturated solution is when

No more solute dissolves

  1. Supersaturated solution

When max solute dissolves, the solute becomes unstable and crystals form

  1. What are parenteral formulations?

They are sterile, pyrogen-free liquids such as emulsions, or solid dosage forms packaged in either single-dose or multidose containers. Parenteral formulations are formulations that do not involve passage through the digestive tract

  1. How are parenteral formulations administered?

Parenteral formulations are administered through the skin or mucous membranes into internal body compartments.

  1. Give Advantages of parenteral formulations

  • The drug is not absorbed orally which is good for drugs that are unstable in GIT

  • First pass metabolism is avoided

  • Rapidly absorbed so are good when patients need rapid drug action in emergency situations

  • Able to achieve 100% drug bioavailability

  • Prolonged drug action is possible

  • Problems with patient compliance can be avoided

  1. Give Disadvantages of parenteral formulations

  • There may be pain upon injection

  • May require help from a trained professional and self administration is only option following training

  • Requires strict aseptic procedures

  • Danger of blood clot formation

  • The drug cannot be recovered in adverse conditions.

  1. List the four main forms of parenteral formulations.

  • Injections

  • Intravenous infusions

  • Powders for injections

  • Implants

  1. List the possible routes of parenteral administration

  • Intravenous

  • Intramuscular

  • Subcutaneous

  • Intradermal

  • Intracerebral

  • Sublingual

  • Intrasynovial

  1. What are some common injection sites?

  • Intramuscular ; into the muscle such as the gluteous maximus & upper arm

  • Subcutaneous; just under the skin this may be in the thigh, delatoid area or abdominal wall

  • Intravenously; directly into the patients vein.

  1. List the requirements for parenteral formulations 6

  • Sterility

  • Particulate material

  • Stability

  • Pyrogen free

  • Stability

  • Ph

  • Osmotic pressure

  1. What are the pH requirements for parenteral formulations?

They should be as close to physiological pH which is 7.4 as possible.

  1. pH requirement for IntraMuscular administration

3-11

  1. pH requirement for Subcutaneous administration

3-6

  1. Effects of administering a parenteral formulation with a pH of more than > 9 ?

Risk of NECROSIS - premature death of cells in living tissue

  1. Effects of administering a parenteral formulation with a pH of less than < 3?

Risk of PAIN & PHLEBITIS - an inflammation of a vein, usually in the legs

  1. Requirements that allow excipients to be added to a parenteral formulation

Excipients such as : Antibacterial preservatives, Buffers, Solubilizers, Antioxidants

are only to be added if:

  • They intend to increase stability or usefulness

  • They are not harmless in the amounts administered

  • They do not interfere with the therapeutic efficacy of the preparation or with specified assays and tests.

  1. Give examples of excipients

  • Antibacterial preservatives,

  • Buffers

  • Solubilizers

  • Antioxidants

  1. What techniques are done to ensure sterility?

  • Aseptic techniques

  • Special clothing like gowns, masks, gloves and hair nets

  • Laminar flow hoods placed in special rooms

  1. Define sterilisation and give methods of sterilisation

Sterilisation = destruction of all living organisms and their sports or their complete removal from the preparation

Methods of sterilisation = By using;

  • Steam

  • Dry heat

  • Filtration

  • Chemical sterilisation with gas or liquid chemical sterilant

  • Radiation using gamma radiation

  1. Define isosmotic

Isosmotic = two solutions with the same number of solutes or osmolarity

  1. Define Isotonic

Isotonic = when a solution has the same salt concentration as the blood and cells of the human body.

It refers to two solutions having the same osmotic pressure across a semipermiable membrane.

  1. Define hypertonic

Hypertonic = when there is a Higher Solute concentration

  1. Define Osmolarity

Osmolarity = an estimation of the osmolar concentration of plasma and is proportional to the number of particles per litre of solution, it is expressed as mmol/L or mol/L

  1. Give two factors that affect osmolarity

  • Temperature

  • Pressure

31. Define Osmolality

Osmolality = An estimation of the osmolar concentration of plasma and is proportional to the number of particles per kilogram of solvent, it is expressed as mOsmol/kg

  1. What change to the volume of a cell do Isotonic Solutions have?

Isotonic solutions do not change the volume of a cell

  1. What change to the volume of a cell do Hypotonic Solutions have?

Hypotonic solutions cause a cell to swell (the conc of solutes outside the cell is lower than the conc inside the cell so water moves in and causes the cell to swell)

  1. What change to the volume of a cell do Hypertonic Solutions have?

Hypertonic solutions cause a cell to shrink. ( the concentration of solutes outside the cell is more than the inside and due to osmosis, so water moves out cell and cell shrinks)

Note: aka less water outside so water moves from high (inside) to low (outside).

  1. The movement of molecules from an area of Higher Concentration to an area of Lower Concentration

A. Diffusion

B. Osmosis

C. Hypotonic

D. Isotonic

A

  1. An equal amount of solute and solvent in and out of a cell is called.

A. Isotonic

B. Hypotonic

C. Hypertonic

D. None of the above

A

  1. Water is a hypotonic solution in comparison to plasma

A. True

B. False

A - water has less solutes than plasma which has a lot.

  1. If a cell is placed in a HYPOTONIC solution, the water will move into the cell, causing it to swell.

A. True

B. False

A

  1. Soda drinks are what kind of solution?

A. Hypertonic

B. Hypotonic

C. Isotonic

D. None

A

  1. If a RBC is placed in sucrose there will be no movement of water

  2. True

  3. False

41. If a RBC is placed in water, water will move into the cell causing the cell to swell and burst

  1. True

  2. False

A

42. What is the normal serum osmolality?

Normal serum osmolality = 285mOsm/kg

43. What is the range of acceptable osmolality for solutions for nose, eye and injections?

Range = between 275-300 mOsm/L