Lecture 4: Packaging, formulation drug delivery Flashcards
Why use the parenteral route?
- To ENSURE adequate delivery (sustained??)
- To TARGET delivery e.g. to organ or malignancy
- Oral route unavailable…unconscious, elderly
- Low or NO oral bioavailability
- Unstable drug (pH)
- To give a LOCAL effect (anaesthesia)
- To give a rapid effect
- To give sustained effect (depot injection, implants)
- To assure compliance – administered by trained personnel
Parenteral routes
Intradermal (diagnostic tests)
Subcutaneous S/C (e.g. insulin)
Intramuscular I/M (e.g. vaccines)
Intravenous I/V (e.g. infusions, drugs, EMERGENCIES)
Intra-arterial I/A(EMERGENCY)
Spinal injections
Epidural (anaesthesia)
Intrathecal (into CSF)
Joints
Intrasynovial (e.g. anti-inflammatory, steroids)
Potential issues - parenteral route
- Dosage forms MUST be sterile
- Costs - drug prep & administration
- Effects (adverse) are almost immediate – no way back!
- Fear & pain of injections.
Formulation of Parenteral Products
Factors to consider:
1) Route
2) Volume of injection
3) Vehicle
4) Osmotic pressure (isotonic: 0.9% w/v NaCl)
5) Use of preservative
6) pH – transfer across biol. membranes
7) Stability of components
PHARMACEUTICAL CLOSURES
Essential part of primary and secondary packaging
types:
1. Physical compression
- plug-in e.g. rubber closure for injections
- push-over or “snap-fit”
- screw cap
- roll-on aluminium alloy caps
2. Heat sealing
Three Primary Modes of Drug
Delivery
- To provide for the insertion of a drug into one of the bodies orifices
- To provide for drug entry into the blood stream
- To provide for inhalation of drugs into the lungs
Medicine labels and what they must contain
Tell you what you are buying, what the medicine can do for you, and how to use it…
Active Ingredient
Uses of the medicine and Directions for Use
Warnings
Declarations (possible allergens etc)
Storage conditions
Expiry date
Batch number and company address
Australian Register of Therapeutic Goods (ARGT) number
What are ARTG numbers
The ARTG number not only identifies the product, but is a guide to how much examination the product has received before going on sale, including whether the TGA has
assessed the medicine for efficacy.
Medicines sold in Australia will have either an AUST R, an AUST L or an AUST L(A) number
“AUST R” numbers
registered medicines
are assessed for quality, safety and effectiveness before they can be sold.
include all prescription-only medicines, and many over-the counter medicines
An AUST R number means the medicine is tightly controlled and highly regulated.
“AUST L” numbers
listed medicines
are lower risk self-medication products
used for minor health problems
and are less regulated than AUST R
AUST L medicines include fish oils,
multivitamins, as well as herbal and
homoeopathic products
AUST L(A)
If AUST L are assessed for efficacy complimentary medicines are referred to as AUST L(A)
Purpose of medicinal packaging
- Provides protection against climatic, biological, physical and chemical hazards
- Provides product identification and information
- Assists patient compliance and convenient use of medication
etc
Metered dose inhalers (MDIs)
“sophisticated” pharmaceutical packaging
like puffers - they release a metered dose at a time obvi
Primary & Secondary Packaging
PRIMARY packaging:
Directly contains and comes into contact with the pharmaceutical e.g. bottle or closure.
SECONDARY packaging:
Provides additional physical protection to ensure safe warehousing and delivery to point where bulk quantities are broken down into individual units.
Physical or mechanical hazards
Shock or impact damage
Risk reduced by - use of cushioning
- restriction of pack movement
- careful handling
Vibration/abrasion during transport
Puncture due to sharp objects
Climatic or environmental hazards
Climatic conditions - arctic, temperate, tropical countries
Moisture - liquid or water vapour may result in:
* physical changes (e.g. softening or hardening)
* chemical changes (e.g. hydrolysis, effervescence)
Temperature extremes and cycling of temperature can cause deterioration in the product and pack
Light can cause discolouration and fading of printed or decorated packaging
Atmospheric gases
Oxygen promotes oxidation of the pharmaceutical
Biological Hazards
Microbiological
- General move towards improved microbial control for all pharmaceutical products
Infestation
- by insects, birds, rodents
Pilferage
- Need for ‘tamper proof’ packs and security seals.
- Increases consumer confidence in the product
Chemical Hazards
ADSORPTION of chemical entities on pack surface (loss of preservatives e.g. benzalkonium chloride)
ABSORPTION and evaporation through LDPE volatile preservatives e.g. chlorbutol
ADDITIVES in the plastic can enter the pharmaceutical product by
dissolution (‘extractives’)
DETACHMENT of glass spicules/splinters can occur when solutions of citrates, tartrates, chlorides salicylates are stored in ‘soda-glass’ bottles
ORGANOLEPTIC* changes may occur due to permeation of volatile or
odorous substances through plastic materials (e.g. solvents from printing inks)
CORROSION or erosion of the packaging material
PHARMACEUTICAL CLOSURES
- total hermetic seal
no exchange occurs between contents and outside environment
e.g. fused glass vial - microbiological seal
e.g. rubber bung with metal over seal - effective seal
minimally adequate for the product,
closure not hermetic nor a total guarantee against entry of bacteria
Two main types of closure:
- Physical compression
- Heat sealing
Closures: Physical compression systems
- Plug-in : friction or push-fit
e.g. rubber closure for injections - Push-over or ‘snap -fit’ e.g. LDPE
- Screw cap e.g. aluminium, PE, PP
- Rolled on (RO) aluminium alloy caps
Heat sealing closures
blister packs or packs for medical instruments
e.g. wax, PVC, LDPE
Sealants compatible : permanent heat seals ‘push through’ systems,
with lid firmly bonded to tray
Partly compatible : ‘peelable’ seals
Why use dosage forms?
- Mechanism for the safe and convenient delivery of dosage forms (accurate dosage)
- Protect drug from destructive influences of atmosphere & humidity e.g. aerosols/inhalers
- Protect from gastric acid (oral administration)
Key considerations in dosage
form selection
- Is the drug for a local effect (not entering blood circulation)
OR
Is it for a systemic effect (Localised graze to skin?) - Speed of onset
- Duration of action
- Patient factors e.g. age, disease
Speed of onset
I/V 30-60 seconds (FASTEST)
Inhalation 2-3 mins
Sublingual 3-5 mins
I/M 10-20 mins
S/C 15-30 mins
Rectal 5-30 mins
Oral 30-90 mins (SLOWEST)
Duration of action
Dependant upon whether effects are local or systemic (ADME):
* Half-life of drug
* 1st pass effect - enzymatic susceptibility
* Type of formulation administered (e.g. uncoated tab v CR tab)
Patient factors
Is patient conscious?
Epileptic seizures – risk of choking
Fear (or phobia) of a particular route
Age of patient?
Any surgery? e.g. partial vs full colonectomy…
Oral Dosage forms
- Oral route
- most frequently used
Advantages:
easy
simple
convenient
