pharmaceutical eye drops

PHARMACEUTICAL EYE DROPS-BY KYEBAVUMA ROBERT

Eye drops: are oily/aqueous sterile preparationscontaining active medicaments for instillation intothe conjunctiva sac, without particulate matter.

Sterile product: it’s a preparation completely freefrom any particulate matter.

Properties of an ideal eye drop.

- Must be sterile.- Should be non-toxic and non-irritant to the eye.- Should be free from any foreign particles.- Chemically stable.- Be isotonic to the lachrymal secretions.- Should retain sterility within the prescribed

period of use.- Its P.H should be stable for a particular drug.- Should contain suitable preservatives.

Components used in their formulation.

- Active ingredients - Buffers e.g. sodium citrate, boric acid, sodium

phosphate.- Preservatives e.g. BAC, PMN- Anti-oxidants e.g. sodium metabisulphate, sodium

thiosulphate.- Thickening agents/ tonicity modifiers.- Tonicity modifiers e.g. sodium chloride.- Chelating agents e.g. sodium EDTA, disodium

adetate.- Vehicle.

By Kyebavuma Robert.

a)ACTIVE INGREDIENTSThey are included in eye drops to producepharmacological effects. Examples of these activeingredients can include;

- Anaesthetic purposes e.g. amethocaine eye drops.- Antimicrobial purposes e.g. chloramphenicol eye

drops.- Miotics e.g. physostigmine- Mydriatics e.g. atropine.- Anti-inflammatory e.g. hydrocortisone- Diagnostic purposes e.g. fluorescein and

artificial tears (hypromellose eye drops BPC)

b)CHELATING AGENTS.- These form soluble co-ordination compounds with

heavy metal ions which could have been in non-ionisable forms. ETHYLENE DIAMINE TETRA ACETICACID (EDTA) is the most common and is usually asdisodium or tri-sodium salts.

- The most popular compound is disodium adetate(the disodium salt of EDTA) forms complexes withdi and trivalent metals and effectiveconcentration which ranges from 0.01% w/v to 0.3%w/v are harmless to the eye and are compatiblewith most common eye drop medicaments.

- They are contained in prednisolone eye drops BPCand their addition to neomycin eye drops BPC isallowed.

c)VISCOSITY ENHANCERS

These increase the residence time of the drop inthe eye and result in increased penetration and


therapeutic action of the drug. Most are adjustedto be within a range of 15-25 milli Pascal seconds(maps). They include;

i) HYPROMELLOSEIt’s a hydroxypropyl derivative of methylcellulose.Has good optical clarity.Used as 0.5-2.0% w/v.High concentrations usually form crusts on theeyelids.Most used viscosity enhancer.

ii) POLYVINYL ALCOHOLUsed as 1.4% w/v.Has a good contact time on the eye surface.Good optical qualities i.e. gives a clearsolution.Can withstand autoclaving and can be filteredthrough a 0.22um gauge.Compatible with most antimicrobial agents (PMN,BAC)

Other viscosity modifiers include; polyvinylpyrrolidane, poly ethylene glycol, dextrin.

NB; Thickening agents are not used in eye drops forsurgical purposes because of adverse drug effects dueto the prolonged contact time in the eye.

a)BUFFERS.

These include; citrate buffers e.g. sodium citrateused in eye drops of phenylephrine (PH 2.5-6.5),idoxuridine (PH 6.0), and benzyl penicillin (PH 6.0).


Borate buffers e.g. boric acid (PH 6.8-9.1) used ineye drops of chloramphenicol (PH 7.5), Hypidmellose(PH 8.4).

Phosphate buffers e.g. sodium phosphate in eye dropsof prednisolone and sodium phosphate (6.6) andneomycin.

PH of eye drops should be stable and hence they areadjusted for the following reasons;

- To reduce discomfort e.g. irritation, excessivetear secretion which may wash away themedicament.

- To maintain chemical stability: most medicamentsin eye drops are salts of strong acids and weakorganic bases and hence are most stable at a lowP.H.

- To improve clinical response; This is becausemost salts are absorbed in their un ionised freebase form from which it is fat soluble andreadily diffuse through the lipid bi-layer ofcell membranes into the cornea. Hence clinicalefficiency of these salts is improved if thesesolutions are adjusted to neutrality and slightalkalinity reduces their stability. However it’simportant that eye drops are buffered at low P.Has this opposes adjustment by the tears andreduces the quantity of free bases available forrapid absorption.

Factors considered in PH adjustment.

i) PH offering best stability during preparation,use and storage.

ii) The PH should offer best therapeutic activity.iii)It should also provide comfort to the patient.


d)TONICITY MODIFIERS

Tonicity; this refers to the osmotic pressure exertedby solutes e.g. salts in a solution.

A solution is isotonic with another when themagnitude of the colligative properties are equal.Colligative properties are physical properties ofsolutions which are dependent on the number of units’solutes in a solution and are dependent on the natureof the solute. The eye can tolerate a wide variationin osmotic pressure equivalent to 0.7-1.5% sodiumchloride.

Colligative properties of interest in eye dropsinclude;

a)Depression of freezing point.b)Osmotic pressure.

An ophthalmic solution is said to be isotonic withthe lachrymal secretion when its tonicity is equal tothat exerted by 0.9% w/v aqueous solution of NaCl. Ahypotonic solution causes temporally oedema of theeye resulting to impaired vision. A hypertonicsolution produces discomfort due to the inability ofthe tears to rapidly dilute the solution. Usually toadjust the tonicity of hypotonic eye drops, NaCl isadded. Paratonic solutions do not have the sameosmotic pressure as lachrymal solution, they areeither hypotonic or hypertonic e.g. sulphacetamide.The eye can accommodate a PH of around 0.7-1.5%sodium chloride.

e)ANTI-OXIDANTS


Reducing agents should be included in preparationssince the medicaments may be liable to oxidation.They include;

- Sodium metabisulphate; Preferred at acidic PH.Enhances the activity of phenyl mercuric nitrateat acid PH. It is used at concentrations of 0.05-0.5% according to the medicaments in solution.

- Sodium thiosulphate; Used at concentrations of0.1-0.2% w/v. It’s more stable and commonly usedin solutions containing sulphacetamide solution.It’s mostly preferred for alkaline products.

f)VEHICLE

It is the medium in which the active ingredients andother additives are incorporated. Examples include;

- Water; water for injection and distilled water isused.

- Oil; sterile castor oil is mostly used.- Solutions for eye drops: these are provided in

the BPC containing, ethyl hydroxyl benzoate 0.02%w/v and propyl hydroxyl benzoate over 0.01%w/v.

- Self-sterilising vehicles. Prepared usingpreservatives like PMN or PMA which arebactericidal and fungicidal.

- Boric acid vehicle; Contains 1.9% w/v boric acidand PMN(A) 0.01% w/v. Suitable for eye drops ofmethocaine, cocaine, phenylephrine and zinc salts

- Special boric acid vehicles; contain 1.9% w/vboric acid and sodium sulphite 0.1% w/v. Suitablefor salts of adrenaline.

- Isotonic phosphate vehicle; contains anhydroussodium acid phosphate 0.8% w/v and anhydroussodium phosphate 0.9%w/v.


- Produces solutions with PH 5.9-8.0. Incompatiblewith zinc salts and have a low stability withhyoscine, homatropine and pilocarpine.

g)PRESERVATIVES.

They should be able to withstand the test forefficacy of preservatives of the BP. Eye drops forthe use of intraocular surgery should not containpreservatives because of the risk of damage ofinternal eye surfaces.

Properties of an ideal preservative.

- Should be capable of preventing the developmentof micro-organisms introduced during the use ofthe eye drop.

- Non-irritant.- Chemically stable and non-volatile.- Compatible with other ingredients, closures and

container.- Should be within their solubility to avoid

crystallisation at low temperatures.- Should not be affected by PH.- Should withstand efficacy tests stipulated in the

BP.- Free from foreign particles.- Effective in small concentrations.- Have no pharmacological effect.- Should be bactericidal but not bacteriostatic.


Should be completely dissolved in the self-sterility solution to ensure anti-bacterialactivity.

Examples of preservatives used include;

- Benzalkonium chloride- Cetrimide- Methylhydroxy benzoate- Chlorhexidine acetate or gluconate- Chlorbutol- Phenyl mercuric salts- Thiomersal- Phenylethyl alcohol & benzyl alcohol.

1.Benzalkonium chloride.

It is a quartenary ammonium compound. Contraindicated for incompatibility and sensitivityreasons. It is not a pure material, but it exists asa mixture of alkyl benzyl dimethyl ammoniumcompounds. The higher the carbon chains it has, thegreater the anti-bacterial properties but the lessthe solubility. Its antibacterial properties areenhanced by aromatic alcohols e.g. benzyl alcohol, 2-phenyl ethanol, 3-phenyl propanol. Its activityagainst gram –ve bacteria is increased by presence ofchelating agents e.g. disodium adetate because theychelate the divalent cations (principally Mg 2+ ofgram negative bacteria). They are not supposed to beused with anaesthetics because it abolishes theblinking reflex and the preservative solubility.

It’s used in preparations of; atropine sulphate,carbachol, cyclopentolate, phenyl ephrine,


prednisolone sodium phosphate (concn of 0.04%required).

Conditions that reduce its anti-bacteria properties.

- Presence of multivalent cations e.g. Mg2+, Ca2+

these compete with the preservative for negativelycharged sites on the bacterial cell surface.- Presence of fluorescein and nitrates because theyare large ions and it’s incompartible with them.

NB: i) Benzalkonium BP contains 50% w/v Benzalkonium.

iii)Benzalkonium is well tolerated on the eye up toa concentration of 0.02% w/v but usually usedas 0.01%

Advantages

- Rapid bactericidal action in clean conditions.- Stable to sterilisation by autoclaving.- It destroys the external bacteria cell envelope

when used in combination with EDTA.- It’s active in controlled aqueous environments

and PH of ophthalmic solutions.- Its surface activity may be used to enhance the

trans-corneal passage of non-lipid solubledrugs e.g. carbachol.

Incompatibilities.

- With soaps and anionic substances.- Boric acid 5% and not 2% w/v.- High concentrations of non-ionic compounds and

hydrocortisone.2.Cetrimide.

Used as 0.001% w/v. Soluble in two parts of water,stable in solution, non-irritant, non-toxic and non-


volatile. Compatible with most ophthalmic drugs butnot with anionic surface active agents e.g. iodide,phenyl mercuric nitrate, phenol and chlorocresol. Aconcentration of 0.005% w/w is used in ophthalmicsolutions.

3.Methyl hydroxyl benzoate.

Used as 0.1% w/v and is effective as a self-sterilising fluid though irritant to some extent.

4.Chlorhexidine acetate or gluconate.

It is a cationic bi-guanide bactericide in aqueoussolutions similar to Benzalkonium chloride. Itsactivity is reduced by other formulation ingredients.Applications include; cocaine eye drops, homatropineeye drops BPC. Should not be used in eye drops of;atropine sulphate, neomycin, serine and zincsulphate.

- Used at 0.01% concentration. - Bactericidal even against gram negative

bacteria (enhanced by the presence of aromaticalcohols and disodium adetate)

- Ineffective against spores and its activity isantagonised by multivalent cations.

- Stability greatest at PH of 5-6 but less stableto autoclaving. Boric acid can be used toadjust the PH to 5-6.

- Incompatible with anionic compounds.5.Chlorbutol.

It’s chlorinated and used at 0.5% w/v and iseffective against bacteria and fungi. Compatible withmost ophthalmic preparations.


Disadvantages.

- Volatile and slowly soluble.- Absorbed by plastic containers and high PH

affects its stability.- Unstable at high temperatures therefore not

autoclaved. Not recommended for eye drop use.6.Phenyl mercuric salts.

They are organic mercurial and are used as 0.001-0.04% w/v. The usual eye drop concentration is 0.002%w/v.

- Active over a wide PH range.- Activity is increased with phenyl ethanol. And

decreased by sodium adetate.- Incompatibilities with halides, hydrobromide of

hyoscine and homatropine.- Heavy metals are not suitable preservatives

except when as a substitute.- Should not be used in eye drops of prolonged

usage because this leads to intra-occulardeposition of mercury/ mercury poisoning.

7.Thiomersal.

It is an organic mercurial and used at aconcentration of 0.005-0.01%w/v. Its action isbacteriostatic and fungi static. Absorbed byrubber. Allergy to this preservative is possiblebut no mercurialness is caused. Used insulphacetamide eye drops. Sensitive to light andunstable at a PH of 9.

8.Phenyl ethyl alcohol and benzyl alcohol.


The concentration used ranges from 0.25-0.5% w/v.usual strength is 0.5% w/v.

Advantages.

- Wide range of compatibility and effectiveagainst gram negative bacteria.

- Non-irritant- Does not destroy the natural lysosome found in

the eye.- Effective against pseudomonas.

Disadvantages.

- Has little action against gram positiveorganisms.

- Used in ophthalmic preparations usually withother bactericides.

The solubility of chlorobutol is improved with theuse of phenyl ethyl alcohol which is a liquid.

9.Self-sterilising vehicles.

The recommended substances include; methyl hydroxylbenzoate (0.1% w/v), phenyl mercuric nitrate (0.004%w/v). It can be formulated in the followingmedicaments;

a)Methyl hydroxyl benzoate.

Chloramphenicol, ethyl morphine, homatropine,adrenaline, amethocaine, antazoline, hydrochloride,atropine, sodium iodide, streptomycin, methylnitrate, hydrocortisone, hyoscine, lachesine,lignocaine, neomycin sulphate, penicillin, potassiumiodide, sulphacetamide, zinc sulphate eye drops.

b)Phenyl mercuric nitrate


Atropine, copper sulphate, escrine, dubiosin,fluoeserine, glycerine, methyl cellulose,pilocarpine, sulphacetamide.

These solutions should also be made with the samestrict precautions (aseptic techniques)

METHOD OF COMPOUNDING EYE DROPS.

I) Using aqueous vehicle.II) Using an oily vehicle.

Points to consider when compounding eye drops.

- Prescribed drug present in terms ofcompatibility with adjuncts.

- Solution sterility to prevent re-infection.- Solution should be free of visible particles- The solution should be isotonic to body fluids.

Types of eye drops; i) Solutions e.g. hydrocortisoneeye drops but they can easily be washedaway from the site of application.

ii)Suspensions. The particles should besmall enough not to cause irritation.

iii)Ointments; have a long contact time butcan cause a coating on the eye hence aweaker vision for some time.

Method of preparation.

1.Preparation of a solution (bactericidal) or onemay use a self-sterilising vehicle, add in the


other ingredients in the formulation and top upwith the vehicle.

2.Clarification of the solution. Particulate mattershould be removed by use of a sintered glassfilter, membrane filters 0.45-1.21 micro metres.

3.Filling; the solution is filled into finalcontainers prior to heat sterilisation and aresealed off.

4.Sterilisation; The methods of sterilisationinclude autoclaving filtration and dry/moist heatsterilisation. But for oily vehicles, we use dryheat sterilisation.After sterilisation, the eye drop container iswell covered with a readily breakable seal, pack,polish and label suitably.

ASEPTIC TECHNIQUESAseptic is the complete absence of bacteria,fungi and other living micro-organismsAseptic techniques are a set of specificpractices or procedures performed under carefulcontrolled conditions with intention ofminimising pathogen contamination. OR is atechnique for manipulations of compounded sterileproducts and parenteral preparations whichprevents contamination

Sources of contamination.

- Air/ breath.- The skin.- The hair.

- Clothing.- Working surfaces.

Minimisation factors.


- All items in a sterile field must be sterileand sterile packages must be opened as close aspossible to their time of use.

- Contaminated items must be removed from thesterile field.

- The areas that can be seen by the clinician areconsidered sterile and those not seen,unsterile thus must not be touched.

- Air borne contamination must be guarded againstby working in a room fitted with a fan forlaminar air current flow.

- An entrance porch fitted with doors at each endis usually provided to prevent sudden rush ofair.

- Edges should be avoided when designing a roomso as to prevent dust accumulation on them.

- Extensive scrubbing of the skin to avoidcontact contamination.

- Before any aseptic operation; hands and nailsshould be scrubbed with a detergent to avoidcontamination.

- Hair and clothing contamination is avoided bycovering with freshly laundered material,overalls and gowns which should be rolled upabove the elbows.

- Cotton cap should be worn over the head.- Long hair should be lied back to avoid

contaminating the products.- Working surfaces should be scrubbed with a

bactericidal agent.- Wall surfaces above the working area should be

repeatedly cleaned and the floor repeatedlyswabbed.


- Equipment should be stored in dust freecupboards and the exposed parts should be wipedbefore use.

- Tables are considered to be sterile only atabove the table.

- There should be no talking, sneezing andlaughing across a sterile field.

- Edges of sterile fields should not beconsidered sterile. Discard potentiallycontaminated items and sterilise again.

- A safe space/margin of safety is maintainedbetween sterile and non-sterile objects andareas.

- The lips of the pouring and receiving containercaps should not touch each other when pouringfluids.

- Inspection for expiry and defects should bedone.

- Materials essential for preparing the sterileproduct should be placed in the laminar airflow chamber of work place or barrier Isolator.

- Overcrowding in the work area may interferewith laminar air flow.

- The number of personnel preparing sterileproducts should be minimised.

- Materials used in aseptic preparation should bearranged in the critical area within thelaminar air flow work place/ barrier.

Cautions to be taken by personnel in the work area.

1.No eating or drinking from the work area.2.No smoking.3.No touching pens, paper within the working area.


PACKAGING

The usual type of container for eye drops is avertically fluted amber green glass bottle fittedwith a Bakelite cap carrying a dropping tube withinit.

Types of the containers used;

1)Single application packs; they contain a single unitdose. Consist of disposable tube applicationsmade of polypropylene. The container has a capusually enclosed in heat sealed envelope with itsfront made of polypropylene and its back made ofpaper. The mode of application is by firstpeeling away the back paper, applicator isremoved, cap of the container is twisted off, anddrops prescribed are gently squeezed into the eyeand the residue solution thrown away.

2)Multiple dose container; Contains several doses appliedat a specific time. They are made of flexibleplastic material and contain a dropping tipusually covered by the cap of the bottle.

PROPERTIES AND MODE OF APPLICATION.

- The glass should protect the contents fromlight.

- They should be neutral and contain grooves toindicate that the contents are not takenorally. (flutted)

- The rubber lid should resist heat duringautoclaving.

- The glass should not shed alkaline intosolution or the rubber teats to absorb thepreservative.


Application; squeeze the rubber teat while thedropper is inside the bottle and release it atonce, apply gently the drop into the eye bysqueezing the rubber teat, care should be takenso as the teat not to touch the eye as it cancontaminate the eye drop.

Multiple dose containers include;

- Traditional eye dropper bottles and a removabledropper.

- Screw capped bottle with a separate dropper.- Plastic bottles with embedded droppers.

Disadvantages of plastic containers for eye drops.

- Less resistant to heat hence impossible tosterilise the medicament.

- Rubber teats absorb the medicament.- They liberate plasticisers into the medicament.- Can allow passage of gases and water through

the walls of the container.

IDEAL PROPERTIES OF A CONTAINER.

1.They comply with the test for limit of alkalinityof glass.

2.Should protect the contents from light.3.Must have a satisfactory seal.4.Tests for materials that are absorbent should be

impregnated with any preservative in the eye dropsolutions for which they are employed.

5.They must have a dropper ready for use andprotected against breakage and contamination.

6.They must comply with the poisons regulations.7.Non-glass container should not react with the

medicaments.


8.The container should have minimised heatconduction.

9.The container should be easily collapsible.

METHOD OF STERILISATION OF EYE DROPS.

a)Dry heat sterilisation.

This is usually carried out in a hot air oven inwhich heat is transferred from the source to theload by radiation, convection and to a lesserextent conduction. All vegetative pathogens arekilled in 11/2 hrs at 100oc.The oven has a reflectinginner surface, the lagging and the gasket toprevent heat loss and to make use of the heatingcapacity of the hot air, circulating the air with afan ensures that all articles no matter where it isplaced is at the same temperature.

The following should be considered when using a hotair oven;

i) Contents should be well spaced.

ii) The spacing should not obscure the centre itemsfrom wall radiation.

iii) Contact with walls and floor must be preventedbecause these are even hotter than the hot air.

iv) The screw caps of the container should beloosened half a turn to prevent distortion of theclosure or bursting of the container from theexpansion of the contents and the trapped air.

Applications;

-oily solutions and suspensions, glass ware e.g. flasks, beakers, pipettes.These must be de-greased by washing with in hot waterand a detergent and rinsing well followed by three


more rinses in pyrogenic free distilled water. Theyare then dried in a drying oven at about 65oC.

- Powders e.g. starch.

Advantages.

- Can be used for substances that are harmed bymoisture e.g. powders.

- Suitable for assembled equipment e.g. all glasssyringes.

- Provides sufficient time for penetration.- It is less damaging to glass compared to

moisture at high temperature and can provideclouding, alkali extraction and rusting.

Disadvantages.

- Thermolabile agents like rubber, somemedicaments and plastics cannot be sterilisedby this method.

- It is unsuitable for surgical dressing andhydrous medicaments.

- Time consuming.- Expensive.- Dead micro-organisms remain in the preparation.

b) HEATING WITH A BACTERICIDE.

Applied where low temperatures are used to killspores without harming heat sensitive medicaments.During this method, an appropriate amount ofbactericide is included in the solution which afterclarification is transferred to the final containerand these after sealing heated at 98-100oC for 30minutes.


The apparatus used can be a simple electric steameror electric water boiling steriliser. Without these,the process can be carried out in a deep cylindricalvessel containing water and which has a lid toprevent escape of heat/steam to the surrounding. Thecontainer should be completely covered. Timing isstarted as soon as the steam starts getting out.

Advantages.

- Comparatively, lower temperatures are used.- The apparatus is less expensive.- There is double effect from the bactericide and

the steam.

Disadvantages.

- Can’t be used for substances unstable at 98oC.- A substance is ideally added.- Bactericides have a number of

incompatibilities.- It is unsuitable for oily solution and

suspensions.- It can’t be used for intravenous of the dose

greater than 15ml for intra-theca,intracisternal injection of any size.

c) MOIST HEAT STERILISATION (AUTOCLAVING)

Can kill micro-organisms at a comparatively lowertemperature in a shorter time than dry heat.Organisms in a moist atmosphere are subjected to araising temperature and will die at a point wheretheir cell proteins coagulate. Latent heat liberatedcondenses on a cool surface and raises thetemperature of the cool area. Destruction of thebacterial spores also follows a similar pattern


whereby the steam condenses on the wall of the sporeand increases the water content with ultimatehydrolysis and breakdown of the bacterial spores.

Methods of exposing microbes to moist heat.

a) Hot water (pasteurisation).

Exposures are done at 56oC for 1hr for three days orseveral successful days. This destroys vegetativebacteria but it’s not satisfactory because the sporesare present. A modified form of pasteurisation refersto as low temperature. Sterilisation is used in thelaboratories for body fluids e.g. serum, vaccinesetc.

b) Boiling water.

Non sporing or vegetative bacteria are killed almostimmediately at temperatures of 90-100oC for about 5minutes. The materials to be sterilised are fullyimmersed and the lid of the steriliser should not beopened during this time. Not recommended in modernhospital settings. Sporing bacteria are destroyed attemperatures above 100oC.

c) Steam at atmospheric pressure (tyndallisation).

Steam at atmospheric pressure is used to steriliseculture media that may decompose once it is subjectedto higher temperatures and may be carried out in aknock or anorld steamer. Exposures of 1 and halfhours at 100oC (steam) usually ensures completesterilisation of nutrient bloats but it is tooprolonged for media containing sugar or gelatin andfor this, exposures at 100oC for 20 minutes on each ofthe successive days is used. It uses the principlethat the first exposure kills all the vegetative


forms of bacteria. Any spores present being infavourable medium will germinate and be killed duringthe subsequent heating.

d) Steam under pressure (autoclaving).

Steam under pressure is a means of elevatingtemperature. The principle upon which it works isthat water boils when its vapour pressure equals tothat of the surrounding atmosphere and if pressureinside a closed vessel increases so the temperaturerises above 100oC. When the steam comes in contactwith the cooler surface, it gives up its latent heatand condenses into water. The drop in pressure willresult in more steam being applied to this area untilthe temperature equals to that of steam. It is thecontraction in volume at the point of condensationthat gives up rise to permeation of steam throughoutthe entire load and the liberation of latent heatthat destroys any more micro-organisms.

When sterilising aqueous solutions, the temperatureused ranges between 108-126oC. Heat is conductedthrough the walls of the seal containers until thetemperature of the fluid is in equilibrium with thesteam and the micro-organisms will be destroyed bymoist heat sterilisation.

If the fluids are non-aqueous such as liquidparaffin, the method is not satisfactory as theeffect is comparable with dry heat sterilisationexcept the temperature would not rise above 126oC.

Factors affecting thermal destruction of microbes.

- PH; Thermal resistance of bacteria mostlyoccurs at a PH of 6-8. This is because the


growth rate at that PH range causes resistance.- Inhibitory medicaments; Some medicaments are

harmful to bacteria hence making their thermaldestruction simple.

- Anti-bacterial agent; The most commonbacteriocides are more effective at assistingheat to destroy bacteria.

- Those with protective substances like proteinsand carbohydrates are hard to destroy.

- Initial number of microbes; the longer theexposure, the less the number of the survivors.

Production of steam.

-On small scale, generated from water within thesteriliser and this steam is known as wet saturatedsteam due to presence of water in it.

- For large sterilisers, dry saturated steam may befrom a separate boiler.

DESIGN AND OPERATION OF A STEAM STERILISER(AUTOCLAVE)

The apparatus is called an autoclave. They areclassified as follows;

a) PORTABLE STERILISER.

These are used for laboratory works and for smallscale production. They are also classified into;

i) Pressure regulated; the pressure gauge is the soleindicator of the internal condition and therefore allthe air must be removed before the sterilisingexposure time begins.

ii) Temperature regulated; a thermometer orthermostat is used to indicate or ensure that the


correct sterilising temperature is used. Therecommended time/temperature is 121oC for 15 minutesachieved at a pressure of 200Kpa.

b) LARGE STERILISERS.

The essential features are the common basic featuresto all types of sterilisers.

General procedure of operation.

- Load material to be sterilised and close thelid.

- Expell the residual air.- Admit dry saturated steam.- Allow for heating up and expose for required

duration.- Cut off steam supply.- Allow to cool

APPLICATION OF MOIST HEAT STERILISATION.

1.Sterilisation of vaccines.2.Pasteurisation.3.Tyndallisation4.Injection solutions.5.Surgical dressing and fabrics.6.Closures.

ADVANTAGES OF AUTOCLAVING.

i. Destroys microbes more efficiently than dryheat sterilisation and allows short exposuretime.

ii. Can be used for large portion of the officialinjection.

iii.Porous material can be sterilised withoutdamage in a steriliser supplied with dry


saturated steam.iv. Equipment of rubber, plastics e.g. nylon and

PVC withstand the conditions.

DISADVANTAGES.

i. Not good for anhydrous material.ii. Can’t be used for injections and articles such

as plastics that detoriate at 115oC.

DEFINITION OF TERMS.

Sterilisation; this is the subjection ofpharmaceutical products to a process whereby allviable microbial life forms are either killed orremoved.

Validation; is the extent to which sterilisation testmeasurements are carried out.

Monitoring; Observation and evaluation ofsterilisation process and sterilisation testmeasurement.

Bio-burden or bio-load; Is the initial number ofviable organisms.

Viable organisms; Are those which when transferred toa culture medium can form a colony.

D-value; is the time in minutes at any definedtemperature to destroy 90% of viable organisms.

Z-value; is the number of degrees of the temperaturechange to produce a tenfold change in the D-value.

Bacterial cells have a Z-value range of 10-15oC whilemost non-Sporing organisms have a Z-value of 4-6oC.

F-value; This is the measure of lethality of thetotal process of sterilisation and equates to the


heat treatment at any particular temperature with thetime in minutes at a designated reference temperaturethat would be required to produce the same lethalityin an organism of stated Z-value.

Fo value of a saturated steam process is thelethality expressed in terms of the equivalent timein minutes at 121oC delivered by the process to theproduct in its final container with reference tomicrobes possessing a Z-value of 10oC. One F unit isequivalent to heating the load for 1 minute at 121oC.


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