the medicine Flashcards

Question

What other safety concerns are there with the long term use of NSAIDs such as naproxen?

Answer 1

Salt and water retention  increase BP and precipitate/worsen heart failure Reno-toxic Increased risk of thrombotic events (MI and stroke) GI Toxicity

Answer 2

Damage to joints is irreversible; can lead to gross deformity and functional impairment

Answer 3

Inhibits dihydrofolate reductase. Most likely mechanism is that MTX leads to an accumulation of an inhibitor of the enzyme adenosine deaminase  accumulation of adenosine which has anti-inflammatory effects via its receptors. Also action against various cytokines including IL1, 2 and 6 are more likely to be of significance Usual first line choice of DMARD for RA – most effective and quickest acting

Answer 4

Nausea, stomatitis Blood disorders Liver and lung toxicity Kidney damage

Answer 5

Not an analgesic – takes time to work Once a week dose (choose a day) Side effects, including blood disorders and lung function warning Need for follow up and blood tests Limit alcohol Avoid OTC NSAIDs and aspirin; inform all HCPs taking MTX

Answer 6

MTX inhibits dihydrofolate reductase leading to lower serum folate. Supplementation counteracts this, reducing incidence of mouth ulcers, stomatitis and nausea Different regimens depending on hospital Trust – usually once a week the day after MTX

Answer 7

Symptoms Side effects DAS28 score Health Assessment Questionnaire

Answer 8

Initial dose: 3mg/kg, so 3 x 82 = 246 mg

Answer 9

Close monitoring for hypersensitivity reactions Resus equipment available, anaphylaxis kits

Answer 10

Infliximab inhibits the activity of the inflammatory cytokine, tumour necrosis factor  (TNF)

Answer 11

Osteoarthritis (OA) is the most common type of arthritis and is often referred to as degenerative joint disease. It primarily affects the cartilage, the protective tissue that covers the ends of bones within a joint. OA is characterized by the breakdown of cartilage, leading to pain, stiffness, and decreased range of motion in the affected joint(s).

Answer 12

OA: Degenerative joint disease, cartilage breakdown, aging, wear-and-tear. RA: Autoimmune disease, chronic synovial inflammation, systemic symptoms, rapid onset. OA: Gradual onset, affects weight-bearing joints, hands. RA: Can develop at any age, affects multiple joints symmetrically. OA: Not primarily inflammatory, minimal elevation in inflammatory markers. RA: Significant inflammation, elevated inflammatory markers. OA: Manage symptoms, improve joint function, lifestyle modifications. RA: Suppress inflammation, alleviate symptoms, prevent joint damage, use of DMARDs and biologics.

Answer 13

No specific blood tests for OA  Usually based on Hx and clinical examination

Answer 14

Try to lose weight Physical activity Supportive footwear Signpost to Arthritis Action website Topical NSAID and/or regular paracetamol If not effective, oral NSAID (with PPI cover)

Answer 15

Hairs and mucous in each nostril act as filters/barriers for air-borne particles and microorganisms Warms and moistens incoming air Nasal mucosa connected to the conjunctiva of the eye, middle ear. Also, only location in the body that provides direct connection between brain and outside Bypasses Blood Brain Barrier (BBB) !!

Answer 16

olfactory tract olfactory bulb olfactory nerves (fingerlike structures) cribriform plate (nexr to / aside olfactory)

Answer 17

local systemic delivery to the CNS

Answer 18

conventional use

Answer 19

Absorption happens from nasal mucosa after ingestion and absorption from the gastrointestinal tract

Answer 20

Olfactory neurons located in olfactory bulb Supporting cells and capillary bed Directly to cerebrospinal fluid

Answer 21

These are the main delivery devices used. Mainly non-pressurised systems, operated by mechanical pump. They produce a spray plume made of drops of pre-determined size

Answer 22

For the treatment of various conditions such as decongestion, sinusitis and rhinitis. E.g. Beconase® Aqueous Nasal Spray Contains beclometasone dipropionate 50 micrograms Inflammation in the lining of nose (rhinitis) due to seasonal allergies, such as Hayfever. Droplets/drug particles are deposited topically on the mucosal tissues. Drug action through local absorption/effect at target tissue (not systemic). XHANCE® nasal spray Contains fluticasone propionate (93 mcg) Aqueous suspension of microfine fluticasone propionate having a particle size distribution (0-5 um)

Answer 23

However, local product sometimes can result in: 1- some systemic absorption depending on drug/formulation properties. 2- dripping down the throat into the GIT and undergoes oral absorption. Exhalation helps elevate and seal the soft palate. This may limit medication from dripping down the throat and helps guide the exhaled breath to pass behind the nasal septum and out the opposite nostril.

Answer 24

Onzetra Xsail® Sumatriptan nasal powder (11 mg per nosepiece) For acute treatment of migraine Onzetra Xsail® Powder targets highly vascularised upper posterior area of nose (Fig B) Note that TRUE nose-to-brain delivery via the olfactory nerve is yet to be commercialised! However, there are preclinical and clinical trials happening currently to explore this route. For Alzheimer’s and Parkinson’s disease as well as other CNS diseases.

Answer 25

Zomig® Nasal Spray Contains 5 mg zolmitriptan Spray contains only one dose. Fast absorption through the nasal mucosa May result in faster headache relief compared with oral formulations. Miacalcin® Calcitonin nasal spray for postmenopausal osteoporosis Synthetic peptide -Absorbed rapidly by nasal mucosa (max plasma conc. achieved in 13 min) Replaces injectable calcitonin Reduces risk of new vertebral fractures

Answer 26

1- Rapid absorption and onset of action as a result of the highly vascularised nature 2- Avoidance of first-pass metabolism 3- Non-invasive route for systemic delivery (convenience) 4- Potential route for delivery of peptides or other large molecules 5- Delivery to the brain through olfactory nerve.

Answer 27

1- Short retention time as a result of mucociliary clearance (happens every 20 min) 2- Challenging to deliver sustained formulations 3- May require solubility enhancers for poorly soluble drugs 4- May require permeation enhancers if drug absorption is poor or large molecules (>1000 Da in Mwt.) 5- Molecule susceptibility to degradation by enzymes (e.g. proteolysis)

Answer 28

Nasal formulations are often liquids and mostly liquid solutions. solutions - all patricles are dissolved suspention - all particles are suspended emulsion - o/w or w/o

Answer 29

Mucoadhesive excipients to improve retention (e.g. HPMC) Solvents/co-solvents to improve drug solubility (e.g. PEG) pH buffers (e.g. citric acid buffer) Penetration enhancers (e.g. liposomes and surfactants) Suspending agents or viscosity modifiers (e.g. CMC-Na) Antioxidants (e.g. Butylated Hydroxytoluene) and preservatives (e.g. Benzalkonium Chloride) Osmolality and tonicity agents (e.g. Mannitol)

Answer 30

Important to recognise that the prime purpose of nasal airway is to protect the lungs from hazardous materials. So need to consider factors such as: - Droplet size (solution and suspension) - Particle size (suspension) - Stability and compatibility between device and formulatio

Answer 31

To avoid lung inhalation of drugs intended for nasal delivery. Droplets < 10 μm may travel through the nasal cavity and be deposited in the lung. Droplets > 300 μm might drip back out of the nose Particle size of suspended particles (0-5 um)  affects dissolution and absorption Volume per dose: The delivered volume for nasal sprays typically lies within the 25–100 μL range.

Answer 32

Issues are similar to those of oral solutions or suspension. E.g. Suspensions: Precipitation issues leading to Caking (closely packed sediment at base of container) Leachables from plastic containers. Drug-Plastic/device container interaction For emulsions, coalescence of droplets is the main issue. Spray device mechanical failure.

Answer 33

Issues are similar to those of oral solutions or suspension. E.g. Suspensions: Precipitation issues leading to Caking (closely packed sediment at base of container) Leachables from plastic containers. Drug-Plastic/device container interaction For emulsions, coalescence of droplets is the main issue. Spray device mechanical failure.

Answer 34

Nasal delivery presents great opportunity to deliver medicines where oral bioavailability is poor. A potential alternative to deliver large molecules without inconvenience of injectables. Careful selection of device, formulation type/excipients and consideration of impact on lung/oral exposure.

Answer 35

economic value of the pharmaceutical industry contnues to rise

Answer 36

To establish safety … … and efficacy of new drugs. To compare existing treatments to find out which is best. To study different ways of using standard treatments so that they will more effective, easier to use and/or decrease side effects. To learn how best to use a treatment in a different population, such as children, in whom the treatment was not previously tested.

Answer 37

drug discovery - targets and rcepetors, small molecules, macromolecules drug development - ADME, toxicology, delivery systems Clinical trials in humans product locence application marketed drug

Answer 38

Drug metabolism and pharmacokinetics determine Absorption, Distribution, Metabolism and Excretion (ADME) in various test species Pharmaceutical development formulations for biological testing dosage forms for administration Safety assessment safety pharmacology in vitro and in vivo toxicology

Answer 39

Safety assessed throughout the life of the product During preclinical investigations During pre-registration clinical trials During post-marketing surveillance Not uncommon for drugs to be withdrawn after being in clinical use owing to unforeseen side-effects e.g. terfenadine, rofecoxib, cerivastatin

Answer 40

Core tests CNS – motor activity, behavioural changes, coordination, reflex responses, temperature CVS – BP, pulse, ECG Respiratory – rate, tidal volume Follow-up tests (examples) memory, cardiac output, blood gases Supplementary tests (examples) Monitoring renal function, nervous system, GI system

Answer 41

Exploratory toxicology rough estimate of compound toxicity when given acutely indication of major organs/systems affected Regulatory toxicology performed to GLP standards required before drug may be administered to humans 28-day repeated-dose studies in two species, one of which is non-rodent (usually dog) In vitro and in vivo genotoxicity tests Safety pharmacology Reproductive toxicity assessment Chronic 3-12 month toxicological studies 18-24 month carcinogenicity and reproductive toxicity testing Drug-drug interaction testing

Answer 42

Exaggerated pharmacological effects dose related, generally predictable Side effects pharmacological effects due to action of drug on receptors other than that intended Toxic effects dose related effects unrelated to intended action Idiosyncratic reactions rare, sometimes serious, reactions that occur in certain individuals not dose related

Answer 43

Approximately 80% of the cost of bringing a drug to market is incurred during clinical development Only 1 in every 5 compounds will get approved for clinical use Of the drugs that fail during clinical development, 30% fail of lack of efficacy 25% fail for safety reasons

Answer 44

Objective – what do you want to achieve Hypothesis – how we decide if we’ve achieved the objective Method Inclusion criteria – who will go in Exclusion criteria – who don’t you want Visits – what will you do Assessments – what will you measure Analysis – how will you test your hypothesis Administration

Answer 45

Administration of new, potentially therapeutic substances to man Controlled conditions to enable determination of: bioavailability, efficacy, safety, tolerability and acceptability Legal requirement before a new drug can be sold or any claims for its therapeutic benefit Studies are subject to international, national and local regulation, to meet requirement of the three major pharmaceutical development regions USA, EU, Japan

Answer 46

First administration and safety evaluation in man usually healthy (male) volunteers cytotoxic drugs tested in cancer patients Key aim is to collect preliminary information: safety tolerability bioavailability Pharmacokinetics

Answer 47

Single dose trials First Dose in Man – hugely critical time for drug development process Usually 4-8 cohorts of 6-8 subjects subsequent cohorts receive higher doses dose escalation stopped if tolerability issues provides Maximum Tolerated Dose data Each volunteer usually receives one dose only placebos are administered to some volunteers

Answer 48

Repeated dose trials tests safety, tolerability and PK following repeated administration frequency of dosing designed to maintain necessary PK profile for therapeutic effect Two or three-step dose escalations Successive groups of 12-24 volunteers take drug repeatedly for several days at each dose level

Answer 49

Early exploratory and dose-finding studies in patients Phase IIa studies proof of concept and go/no-go decision making “First in Class” and “Follower” drugs Phase IIb studies confirmatory, dose-finding studies Clinical surprises at this are bad news

Answer 50

Large-scale studies in patients demonstrate efficacy compared to placebo demonstrate advantages over existing treatments safety, tolerability, efficacy, acceptability, compliance, cost-effectiveness Commonly designed to compare new drug’s performance against competitor product Often multi-region studies

Answer 51

Post-marketing studies to monitor safety of drug in very large numbers of patients not all adverse effects detected before drug is marketed denying promising new drugs is not in patients’ best interests Around 1 in 5 new drugs may be ultimately recalled or cause serious side effects hence requirement for Phase IV studies

Answer 52

Single Arm Trial: No control group, all receive investigational treatment. Placebo-Controlled Trial: Randomly assign to investigational treatment or placebo, assesses beyond placebo effect. Positive Controlled Trial: Randomly assign to investigational treatment or active comparator, compares to standard care. Open Trial: Both participants and researchers aware of treatment, evaluates real-world effectiveness. Single-Blinded Trial: Participants unaware, researchers aware, reduces outcome bias. Double-Blinded Trial: Neither participants nor researchers aware, minimizes bias. Cross-Over Trial: Sequentially receive multiple treatments, compares efficacy and safety. Clinical Trials in Humans: Evaluate new treatments in humans, informs clinical practice.

Answer 53

side effects

Answer 54

European & National Law outline the basis of medicine regulation

Answer 55

The anti-syphilis drug, Salversan 606 contained toxic impurities. Each batch of product was submitted to the Medicines Research. Council for assessment before release for marketing in UK.

Answer 56

First launched in West Germany. Marketing and distribution rights sold to other countries, e.g. USA, UK. May 1961 licensees reported 75-90 cases of polyneuritis, then phocomelia (sealed limbs). Nov 1961 Withdrawn from W German market. The Ministry of Health issued a statement that thalidomide was a major factor in causing phocomeila (a teratogen). It was withdrawn from UK market. Thalidomide, marketed as "Distaval" in the UK, caused severe birth defects when prescribed to pregnant women in the late 1950s and early 1960s. Withdrawn in 1961, the UK implemented stricter regulations for drug approval and monitoring. Thalidomide survivors receive support from the Thalidomide Trust. Today, it's used under strict controls for conditions like leprosy and multiple myeloma.

Answer 57

Voluntary agreement by the Ministers of Health to look at the safety of new drugs. The Committee on Safety of Drugs consisted of scientists, physicians and pharmacists (Chairman; Mr Dunlop), they checked the “reasonable safety of a drugs intended purpose”. Products already on the market were granted a provisional Licence of Right.

Answer 58

Approved by the UK Government in 1968. Came into force in 1971. AIM: to assess evidence of the safety, quality, efficacy of all medicinal products (new and old).

Answer 59

1965 65/65/EC EEC directive to “safeguard public health” 1973 UK JOINED THE EEC UK required to comply with all EEC directives. Most important ones: 75/318/EC and 75/319/EC, a harmonised view of what should be in a Licence Application. i.e. Physicochemical, biological, microbiological tests Toxicological and pharmacological and clinical tests 1994 UK Medicines Act updated by SI 1994/3144 Legislation to bring UK into line with Europe. (except for Clinical Trials, sale and supply controls, ML/WDL and advertising)

Answer 60

Any substance or article (not being an instrument, apparatus or appliance) …manufactured, sold, supplied, imported or exported for use… by being administered to … human beings for a medicinal purpose

Answer 61

1. Treating or preventing disease 2. Diagnosing disease or ascertaining the existence, degree or extentent of a physiological condition 3. Contraception 4. Inducing Anaesthesia. 5. Otherwise preventing or interferring with the normal operation of a physiological function.

Answer 62

Except in accordance with a Licence granted for the purposes of this section (“a product licence”) no person shall in the course of business sell, supply or export any medicinal product SECTION 8(2): No person shall in the course of business manufacture or assemble any medicinal product except in accordance with a Licence granted for the purposes of this section NOTE: there are exemptions to this rule…...

Answer 63

1. PHARMACISTS, MIDWIVES, CHIROPODISTS, ETC. 2. VITAMINS - classed as a food not a medicinal product 3. IMPORT - for administration to the person importing product (at the specific request of a doctor)

Answer 64

MA- Qaulity, safety, efficacy NOT CONSIDERED for the granting of license:- medical need or price NB. UK has other controls beyond the simple granting of a licence e.g. Local Formularies, National Institute of Clinical Excellence (NICE)

Answer 65

The Common Technical Document (CTD) is a set of specification for application dossier for the registration of Medicines. Designed to be used across Europe, Japan and the United States. Developed by: European Medicines Agency (EMA, Europe), Food and Drug Administration (FDA, U.S.) Ministry of Health, Labour and Welfare (Japan). The CTD is maintained by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

Answer 66

module 1 - administrative and prescribng information module 2- quality overall summary, nonclinical overview, nonclinical summary, clinical overview, clinical summary module 3 - quality data module 4 - non clinical study reports module 5 - clinical study reports

Answer 67

Assessing a poor-quality Marketing Authorization Application (MAA) takes three times longer than assessing a high-quality one.

Answer 68

Label use packaging components labelling Summary of Product Characteristics (SPC) Patient Information Leaflet (PIL) User leaflet for products used by Health Care Professionals (HCP)

Answer 69

Mutual Recognition Centralised National (pre-1/1/98)

Answer 70

Mutual Recognition First application is made to one EC Member State AuthorityNational Authorisation grantedMutual recognition of this authorisationby other Concerned Member StatesAuthoritiesEach member state issues anAuthorisation

Answer 71

One single application is made to the EMATwo Member State Authorities act asrapporteurs with other Member StateAuthoritiesOne single European Authorisation isgranted by EMA

Answer 72

(Product Launch/Promotion) Renewals Variations Pharmacovigilance

Answer 73

Pharmacovigilance involves monitoring and assessing the safety of medications after they're approved. It aims to detect, assess, and prevent adverse effects and other drug-related problems, ensuring safe medication use.

Answer 74

ADR monitoring stability data production modifications QC procedures updated new clinical trial data modification synthetic route of active pack changes formulation modificatons new manufacture assembler

Answer 75

Line extensions new formulations (e.g. modified release) new indications Legal status (switches) POM to P (e.g. Simvastatin, chloramphenicol) Generics

Answer 76

1. False application details 2. Contravention of licence terms 3. Actual product does not comply with product licence /MA 4. Failure to provide requested information 5. Unsuitable premises 6. Not on the market within 3 years of grant 7. No longer safe/satisfactory risk/benefit balance 8. No longer manufactured to a suitable standard

Answer 77

Soften on heating to a viscous fluid and harded on cooling Autoclavable (for injections) High density polyethylene (HDPE) Poor visual clarity Polyvinylchloride (PVC) Poor flexibility Plasticisers have to be added to form infusion bags Polypropylene (PP) Higher heat resistance than PE

Answer 78

polystyrene General purpose and impact modified Tablet bottles for dispensing

Answer 79

polytetrafluoroethene High chemical resistance Very Expensive Coatings or liners

Answer 80

polyester Increasingly popular for oral liquids Inert Low temperature resistance

Answer 81

Large material choice Broad range of physical and chemical properties Large Number of fabrication processes Range of decorative and printing options Numerous design options Simple squeezable bottles for eye medication Complex valve systems for MDI’s Clean Process Light and robust

Answer 82

Possible extraction of chemical additives from the plastic PVC plasticisers Interaction with medicament diazepam absorbed onto PVC Absorption of components of the pharmaceutical formulation Lightweight All plastics permeable to some extent to moisture, oxygen and CO2 Most plastics build up electrostatic charge Transmit light unless pigmented

Answer 83

Stress cracking Caused in LDPE by certain agents detergents and volatile oils Surface crazing Fine-scales cracking especially in PS caused by exposure of amorphous plastics to certain chemicals Poor printability Polyolefins in PE and PP require pre-treatment to enable ink to “key” to surface Additives in plastics can migrate to the surface interfering with printing Poor impact resistance with PS and PVC Can be improved by inclusion of impact modifiers eg Rubber BUT permeability of plastic increased Gamma irradiation of LDPE Induces cross-linking and leads to brittleness Negative aspects of plastics for pharmaceutical packaging can be overcome or minimised by suitable design Loss of preservatives from by dissolution in LDPE can be reduced by enclosing bottle in PVC blister pack. PVC impermeable to volatilised preservative Equilibrium of volatile preservative forms in air space between formulation, bottle and pack air space

Answer 84

Simulate in-use conditions and examine for: Sensory, chemical, physical changes Changes in weight or volume Plastic permeability pH changes Effect of light Effect of extractables on the injection plasticiser from PVC bags detected in IV fluid Permeability of gases and solvent vapours through plastic into injection Cyclohexane - solvent for PVC - extracted from infusion bags Absorption of active, bactericides and other components Drug absorption - diazepam on PVC

Answer 85

Polymer Residues associated with polymerisation Additives used to modify properties Process aids Knowledge of constituents of plastic essential May be extracted from plastic into the medicament

Answer 86

Residues in plastics refer to any substances or materials that remain within the plastic after it has been manufactured or used. These residues can come from various sources

Answer 87

property modifiers Additives in plastics are substances added during manufacturing to modify properties. Types include plasticizers, stabilizers, flame retardants, colorants, fillers, and processing aids. They enhance performance, appearance, and manufacturability.

Answer 88

Process aids in plastics are additives used during manufacturing to improve processing characteristics. They enhance flow properties, reduce friction, prevent sticking, and improve mold release, optimizing production efficiency and product quality. Examples include lubricants, flow enhancers, and mold release agents.

Answer 89

monomers catalysts accelerators

Answer 90

fillers anti-static agents anti-oxidants plasticisers pigments dyes mhitners opacifiers UVabsorbers flame retardants Additives can change other properties of the plastic eg fillers (chalk and talk) increase moisture permeation

Answer 91

solvents release agents emulsifiers lubricants stabilisers

Answer 92

PE : low in residues, small quantity of anti-oxidant

Answer 93

The plastic fabrication process involves several steps to transform raw plastic materials into finished products. Options far greater than glass Injection moulding Blow moulding Thermoforming Vacuum forming Extrusion Solid phase pressure forming Basic Moulding Operations Plastic heated to melt or soften the material Material shaped in a mould Cooling to solidify plastic

Answer 94

Multi-layer, co- extruded polyolefine based material with inert polyethylene layer in contact with solution Polypropylene / Polyamide over wrap

Answer 95

Metals widely used 10 to 20 years ago for rigid containers Tablets, capsules, powders and liquids Example Product Collapsible tubes (Eye ointment or cream) Aluminium, tin or tin coated lead Manufactured by “impact extrusion” Replaced by plastic Modern Applications Mainly aluminium and its alloys Foils Facings for “wadded closures” Pressurised containers Aerosols including MDI’s Closures Particularly ROPP (Rolled on Pilfer Proof) Important for security and tamper evidence

Answer 96

Remains a significant part of SECONDARY pharmaceutical packaging Labels, cartons, bags, information, shrink wrap trays Cartons traditionally used for a high percentage of pharmaceutical products Increase product display area Improve stacking Physical protection Collapsible tubes Information Inside and out Protection from light

Answer 97

End uses Sachets, bottle seals, strip packs, blister packs, liners, over-wraps Blister packs Lid Board, paper, foil*, coated film Thermoformed Tray PS, PVC, PET, foil, PE (Or combinations of above) Push through systems Lid firmly bonded to the tray Peelable system Lid easily pulled back Foil blisters or foil overwrap Provides a hemetic pack – excludes virtually exchange of gases between product and surroundings

Answer 98

Essential part of primary and secondary pack Possible functions Totally hermetic seal Fused glass ampoule No exchange occurs between contents and outside environment Microbiological Seal Rubber bung with metal over-seal Effective seal Adequate for the product, closure not HERMETIC nor a total guarantee against entry of bacteria

Answer 99

Ideal Properties and Requirements Good aging properties and oxidation resistance Hardness and elasticity should allow needle to pass through without blunting Puncture should close immediately on withdrawing needle (Does not core) No change in properties during sterilisation Impermeable to air and moisture Penicillin is water sensitive

Answer 100

2 main types of closure Physical Compression Heat sealing 1. Plug in : friction or push in (eg rubber closure for injections) 2 Push-Over or “snap-fit (eg LDPE) 3. Screw Cap (eg Aluminium PE, PP) 4. Rolled on (RO)aluminium alloy caps Rolled on pilfer proof (ROPP) aluminium alloy caps Popular for security of export products

Answer 101

butyl rubber nitrile rubber chloroprene rubber silicone rubber More resistant to high temperature and ageing than natural rubber More expensive Latex Free

Answer 102

Components of injection can be extracted by rubber Bactericide absorption Chlorocresol and phenyl mercuric nitrate strongly attracted to and absorbed by rubber Treat closures in solutions containing bactericides Twice concentration of product solution Volatilisation of Bactericide from closure after equilibrium attained Loss limited by Sealing closure with less permeable material such as paraffin wax (consider fragmentation of wax) Reduction of upper surface area Increase closure thickness Reduction of antioxidant activity Sodium metabisulphite or sulphur dioxide can be absorbed from injection solutions Particulate contamination by “Rubber Coring” during withdrawal of dose Rubber is, to some extent, permeable to moisture and gases Seal may not be strictly hermetic

Answer 103

Greater emphasis must be placed on the packaging material and effects of sterilisation process 1. Discoloured 2. Rubber generally will not withstand dry heat (cf silicone rubber) 3. Unacceptable physical & chemical changes can occur by molecular cross-linking 4. Only suitable for a few plastics 5. Ethylene oxide treatment – degassing is essential to remove TOXIC residues of ethylene oxide, ethylene glycol (hydrolysed ethylene oxide), epichlorhydrin (if Cl- ions present)

the medicine Flashcards

(128 cards)