EXTEMPORANEOUS PREPARATIONS - PowerPoint Presentation

Slide1

EXTEMPORANEOUS PREPARATIONS

BY

SANA

GHAYASSlide2

LEARNING OBJECTIVES:

At the end of this lecture, students will be able to:

Know about extemporaneous dispensing.

Define different dosage forms

Classify different dosage forms on the basis of their use with examples (solutions, suspensions, creams, emulsions, ointments, paste, gels, suppositories,

pessaries

, powders, granules, oral unit dosage forms)

Contrast different dosage forms

Dispense different dosage forms extemporaneously with labels.

Evaluate dispensed dosage forms and their labels.

Provide special labels and advice for patients.Slide3

Dispensed products grouped into

Solution

Suspension

Emulsion

Creams

Powders and oral unit-dosage forms

Ointments

Pastes & jellies

Suppositories &

pessariesSlide4

SOLUTIONS:

Homogenous liquid preparations

Containing one or more dissolved ingredients

Designed for internal & external use.

FORMULATION OF SOLUTION:

Following should be determined before formulating a solution:

Vehicles

Solubility

additivesSlide5

VEHICLES:

Medium in which ingredients of medicine are dissolved or dispersed.

Water

Syrup

Ethanol

Glycerol

Propylene glycol

Acetone

Solvent etherSlide6

SOLUBILITY:

“The no. of parts of solvent (by volume) that will dissolve one part (by weight of a solid or volume of a liquid )of the substance.

For oral solutions, ethanol, glycerol and propylene glycol may be used in various combinations with water as

cosolvent

.

Surfactant can be used for

solubilization

of poorly water soluble medicaments. E.g.

polysorbates

.Slide7

ADDITIVES

GIT

can tolerate solutions with a wide range of pH values.

Hypertonic solutions (potassium citrate mixture BP) should be well diluted before taking orally.

Solutions prepared for mucosal surfaces (nasal drops) usually include sodium chloride to increase tonicity to that of body fluids.

Stabilizers

preservative

Colours

FlavoursSlide8

SOLUTIONS AS ORAL DOSAGE FORMS:

Elixirs, mixtures & oral solutions contain one or more ingredients dissolved in a suitable vehicle.

If dose less than 5 ml prescribed, oral liquid usually diluted.

Choice of

diluent

is critical as their inclusion can adversely affect

flavour

, stability or appearance.

Extemporaneously dispensed products usually diluted with water or syrup, appears as last line in the formula.Slide9

SHELF LIFE:

SUPPLY OF PRODUCT WITH SHORT HALF LIFE:

Quantity of product supplied to patient must not exceed that which would be expected to be used with in the shelf life.

CONTAINERS, LABELS AND ADVICE FOR PATIENTS:Slide10

MOUTHWASHES AND GARGLES:

These are usually diluted with warm water before use

Most are not intended to be swallowed in significant amounts.

Long shelf life

Stable products

Prepared from stock.

Extemporaneously prepared or poured preparations are supplied in amber colored fluted bottles or medicine bottles for products intended to be swallowed.Slide11

SOLUTIONS INSTILLED INTO BODY CAVITIES:

Nasal drops and sprays formulated as

iso

osmotic with nasal secretions.

Buffered

Shelf life of extemporaneous products

Dispensing:

extemporaneous nasal drops supplied in hexagonal, amber fluted glass bottles with a rubber teat and dropper closure.

Nasal sprays packed in flexible plastic bottles or pressurized containers.

For decongestant drops, patient should “AVOID EXCESSIVE USE” and “AVOID USE IN VERY YOUNG BABIES UNLESS UNDER MEDICAL ADVICE”Slide12

EAR DROPS:

Water, glycerol and propylene glycol may be used as vehicles.

They are supplied in glass bottles with a teat and dropper closure or plastic squeeze bottles.

ENEMAS:

Used for cleansing, therapeutic or diagnostic purposes.

shelf life

Amber fluted glass bottles used for enemas and disposable bags sealed to a rectal nozzle are for commercial use.

Label is marked as “FOR RECTAL USE ONLY”Slide13

SOLUTIONS FOR EXTERNAL USE:

Liniments, lotions and paints

are usually stable.

Shelf-life of liniments, lotions and paints

Containers for liniments, lotions and paints

Special labels and advice for patients .

Antiseptic and disinfectant solutions

Shelf-life of antiseptic and disinfectant solutions

Containers for antiseptic and disinfectant solutions

Special labels and advice for patientsSlide14

PHARMACEUTICAL SUSPENSION:

Suspensions are classified as:

Coarse suspensions.

Colloidal suspensions.

FORMULATION OF SUSPENSION:

Water is usually vehicle of choice.

Non aqueous vehicle like fractionated coconut oil are occasionally used.

Other additives are buffers, stabilizers, preservatives, colors and flavors.

PROPERTIES OF A GOOD PHARMACEUTICAL SUSPENSIONSlide15

FACTORS AFFECTING PROPERTIES OF A PHARMACEUTICAL SUSPENSION:

Diffusible solids

Stokes law

Control of particle size

Flocculation

poorly

wettable

solids

In diffusible solids

THICKENING AGENTS:

Polysaccharides i.e. acacia gum,

tragacanth

, sodium alginate, starch.

Water soluble celluloses i.e. methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose.Clays i.e.

bentonite

,

aluminium

magnesium silicate,

hectorite

.

Synthetic thickeners

i

. e.

carbomers

, colloidal silicon dioxide.Slide16

BASIC TECHNIQUES FOR PREPARING PHARMACEUTICAL SUSPENSIONS

SUSPENSIONS AS ORAL DOSAGE FORMS

MIXTURES:

Advantages of suspensions as oral dosage forms

Disadvantages of suspensions as oral dosage forms

Shelf life of oral suspensions

Containers for oral suspensions

Special labels and advice for patientsSlide17

SUSPENSIONS FOR EXTERNAL USE

LOTIONS:

containers for lotions

Special labels and advice for patients

INHALATIONS

Containers for inhalations

Special labels and advice for patients

OTHER TYPES OF DISPENSED PRODUCT

SUSPENSIONS AS 'EMERGENCY' FORMULATIONSSlide18

EMULSION:

An emulsion is a disperse system consisting of two immiscible liquids, one of which(disperse phase) is finely divided and distributed through the other (continuous phase).

DETERMINATION OF EMULSION TYPE

To distinguish between O/W and W/O emulsions, following tests may be used:

Miscibility test

Microscopic examination after staining with a oil soluble dye

Microscopic observation under UV radiation

Conductivity measurementsSlide19

FORMULATION

Emulsifying agents facilitate the production of a dispersion by reducing interfacial tension and maintain the separation of the droplets of the dispersed phase by forming a barrier at the interfaces.

For oral/

parenteral

administration, O/W emulsions are required

For external use both O/W and W/O systems may be used.

TYPES OF EMULSIFYING AGENTS

Synthetic or semi synthetic substances

Natural products

Finely divided solids

Many of the substances described as thickening agents also act as

amulgents

.Slide20

SYNTHETIC OR SEMI SYNTHETIC SUBSTANCES

They are further classified depending on their ionization in aqueous solution as follows:

Anionic surfactants e.g. alkali metal and ammonium soaps, amine soaps, soaps of

di

valent

& tri

valent

metals, alkyl phosphate and alkyl

sulphates

.

Cationic surfactants e.g.

quarternary

ammonium compounds like

cetrimide

Non ionic surfactants e.g. glycol and glycerol esters,

sorbitan

esters,

polysorbates

,

macrogol

ethers and esters

Ampholytic

or

amphoteric

surfactants which are not widely used as emulsifiers in pharmacy.

NATURAL PRODUCTS

FINELY DIVIDED SOLIDSSlide21
Slide22

Choice of an emulsifying agent

Selection of appropriate emulsification system depends on active ingredients incorporated into product and on use of final product and based on theoretical con­siderations and on experience.

Formulation by the

HLB

method

emulgents

with high numbers (8-18) produce o/w emulsions and with low numbers (3—6) give w/o emulsions. Slide23
Slide24

OTHER ADDITIVES

Antioxidants:

e.g.

butylated

hydroxyanisole

(

BHA

) or

butylated

hydroxytoluene

(

BHT). Ethyl, propyl or dodecyl

gallate

may also used.

Preservatives

Desirable properties of a preservative for emulsions

Preservatives commonly used in emulsions

Organic acids.

Parahydroxybenzoic

acid esters.

Chlorocresol

.

Phenethyl

alcohol.

Quaternary ammonium compounds.

Chloroform.

Colour

and flavor

Additional color is rarely necessary.

Flavors are used for oral emulsions.Slide25

STABILITY OF EMULSIONS :

The main difficulties encountered in practice are listed here.

Creaming

This is separation of the emulsion into two regions, one containing more of the disperse phase, e.g. cream on milk.

Cracking

This involves coalescence of dispersed globules and separation of the disperse phase as a separate layer.

Phase inversion

The most stable range of disperse phase concentrations is 30-60%.

If amount of disperse phase increased until it approaches or exceeds the theoretical maximum of 74% of the total volume then phase inversion may occur, i.e. from o/w to w/o, or from w/o to o/w. Slide26

COMPOUNDING OF EMULSIONS AND CREAMS

Basic techniques are:

Weighing

Measuring of liquids

Mixing

On small scale mortar and pestle are used producing globule size larger than 10 µm.

Homogenizers are used for extemporaneously prepared emulsions.

EMULSIONS AS ORAL DOSAGE FORMS

Shelf-life of oral emulsions

Containers for oral emulsions

Special labels and advice for patientsSlide27

EMULSIONS FOR EXTERNAL USE:

Liniments and lotions are liquid or semi liquid emulsions designed for application to skin.

Shelf-life of applications, liniments and lotions

Containers for applications, liniments and lotions

Special labels and advice for patientsSlide28

CREAMS:

They are viscous semi solids for external use.

They may be W/O or O/W emulsions.

GENERAL COMPOUNDING PROCEDURE FOR CREAMS

DILUTED CREAMS

SHELF-LIFE OF CREAMS

CONTAINERS FOR CREAMS

SPECIAL LABELS AND ADVICE FOR PATIENTSSlide29

OINTMENTS PASTES AND GELS:

Ointments are greasy preparations.

Gels are transparent or translucent, non greasy, aqueous preparations.

Pastes contain a higher proportion of finely powdered medicament than ointments or gels

BASES FOR OINTMENTS AND OINTMENT TYPE PASTES

They may be classified into four main groups:

HYDROCARBON BASES

ABSORPTION BASES

WATER MISCIBLE BASES

WATER SOLUBLE BASESSlide30
Slide31

OTHER ADDITIVES FOR OINTMENTS AND PASTES

These include:

Antioxidants like

BHT

,

BHA

,

EDTA

and must be compatible with the medicaments incorporated into the base.

Preservatives, which may not be required in anhydrous ointments. Examples are

sorbic

acid, quaternary ammonium compounds etc.Slide32

FORMULATION OF GELS:

Gelling agents are either organic hydrocolloids or hydrophilic inorganic substances.

Slightly viscous gels may be used as replacement solutions for body secretions i.e. artificial saliva and tears.

More viscous gels may be used as lubricants for catheters, examination gloves and surgical instruments.

Those designed for surgical or ophthalmic use must be supplied sterile.Slide33

TRAGACANTH

GELS:

Concentration of

tragacanth

from 2%-5% produce gels of increasing viscosity.

SODIUM ALGINATE GELS:

A concentration of 1.5% produces fluid gels and 5-10% gels are suitable as dermatological vehicles.

PECTIN GELS

CELLULOSE DERIVATIVES:

POLYVINYL ALCOHOLS:

The required concentration is usually between 10% and 20%, depending on the grade of

PVA

and the desired viscosity. Slide34

OTHER ADDITIVES FOR GELS:

HUMECTANTS:

Like glycerol, propylene glycol or

sorbitol

solution may be added to retain water, otherwise skin formation may occur.

PRESERVATIVES:

like methyl and

propyl

hydroxybenzoates

either alone or in combination are suitable for gels containing pectin,

carmellose

sodium, sodium alginate,

tragacanth, etc.

CHELATING AGENTS:

like

EDTA

may be used for protection against heavy metals.Slide35

COMPOUNDING OF OINTMENTS AND PASTES

The basic techniques are weighing, measuring of liquids, size reduction, size separation and mixing.

MIXING BY FUSION

PREPARATION OF MEDICATED OINTMENT AND PASTES BY FUSION

MIXING BY

TRITURATIONSlide36

SHELF LIFE OF OINTMENTS, PASTES AND GELS

CONTAINERS FOR OINTMENTS, PASTES AND GELS

Extemporaneously prepared ointments and pastes are usually packed in screw capped amber glass or plastic pots.

SPECIAL LABELS FOR OINTMENTS, PASTES AND GELS

Store in a cool place.

Sterile.

The labels for collapsible tubes should be fixed to the upper(

nozle

) end of the tube.Slide37

SUPPOSITORIES:

They are solid medicated preparations designed for insertion into rectum.

They melt, dissolve or disperse and exerts a local or systemic effect.

Pessaries

similar solid medicated preparations designed for insertion into the vagina.

Usually used to provide local effect.

FORMULATION OF SUPPOSITORIES AND

PESSARIES

:

There are two main classes of suppository base:

Fatty bases designed to melt at body temperature.

Water soluble or water miscible bases designed to dissolve or disperse within the body.Slide38

PROPERTIES OF IDEAL SUPPOSITORY BASE:

FATTY BASES:

Theobroma

oil (cocoa butter):

Advantages of

theobroma

oil include:

Disadvantages of

theobroma

oil include:

Polymorphism

Adherence to the mould

Softening point too low for hot climates

Melting point reduced by soluble ingredients

Rancidity on storage

Poor water-absorbing ability

Leakage from the body

expense Slide39

(b) Synthetic hard fat:

They include mixture of mono-,

di

- and tri-

glycerides

of saturated fatty acids.

Advantages of these bases over

theobroma

oil:

Disadvantages of synthetic bases include:Slide40

(2)Water soluble and water miscible bases:

glycero

-gelatin

Mixture of glycerol and water gelled by the addition of gelatin.

(b)Gelatin

Two type of gelatin are used in pharmaceutical preparations:

Type A which behaves as a cationic agent and most effective at pH 3.2.

Type B which behaves as a anionic agent and most effective at pH 7-8.

(c)

Macrogols

(polyethylene glycols)

Mixtures of

macrogols

can be used as bases for suppositories and

pessaries

.Slide41

OTHER ADDITIVES

Antioxidants

can be added to prevent oxidation which must be compatible with the medicament.

Water miscible or water soluble bases

should include preservative which must be challenged with appropriate micro organisms to test its efficacy.

Emulsifying agents (wool fat,

macrogols

)

may be included to facilitate incorporation of aqueous solutions or polar liquids but with caution.

Hardening agents

are added to the base to raise the melting point.

Viscosity modifiers

reduce the sedimentation rate.Slide42

CHOICE OF SUPPOSITORY OR

PESSARY

BASE

COMPOUNDING OF SUPPOSITORY OR

PESSARY

BASESlide43

SUPPOSITORY OR

PESSARY

MOULDS

For small scale, metal moulds are used having 6 cavities usually.

Normal capacities of commonly used moulds include 1, 2, 4 and 8 g.Slide44

DISPLACEMENT VALUES

Use of displacement values (Method for determining displacement value)

Using a nominal 1 g mould, Prepare and weigh six suppositories of

unmedicated

base =

ag

Prepare base containing 30% medicament, fill six moulds and weigh six suppositories =

bg

Calculate the amount of base, cg and medicament d g in the six suppositories c = 70% b and d = 30% b

Therefore the amount of base displaced by

displacement value = __d______

a-c

For example:

Weight of six

unmedicated

suppos

. = 6.0 g

Weight of six

suppos

. Containing 30% drug = 7.5 g

Base = 70% of 7.5 = 5.25

Drug = 30% of 7.5 = 2.25

Base displaced by 2.25 g = 6 - 5.25 = 0.75 g

Therefore the displacement value of the drug = 2.25/0.75 =3

Method for using displacement value

Required: to prepare for 8 suppositories each containing 300 mg drug of displacement value 3 using a nominal 1 g mould.

Total amount of drugs required = 8 x 300 mg = 2.4 g

This will displace 2.4/3= 0.8 g of base

Therefore amount of base required = 8-0.8 = 7.2 gSlide45

MOULD LUBRICATION

Preparation of suppositories with a fatty base

Calculate the quantities required.

Prepare the mould.

Prepare the base.

Prepare the medicament.

Melt the base.

Incorporate the medicament.

Fill the mould.

Remove the excess.

Open the mould.

Preparation of suppositories with a

macrogol

baseSlide46

Preparation of suppositories with a

glycero

-gelatin base

Calculate the quantities required.

Prepare the mould.

Prepare the medicament.

Prepare the base.

Heat treatment of the base

.

Adjustment of base to weight.

Incorporate any medicament

.

Fill the mould.Slide47

SHELF LIFE:

Stable preparations if the packaging provides adequate protection and that the storage temperature is low.

CONTAINERS

LABEL AND ADVICE

Store in a cool place.

For rectal use only.

For vaginal use only.

EXAMPLES

Compound bismuth

subgallate

suppositories BP

Dimenhydrinate

suppositories

Glycerol suppositories BPSlide48

POWDERS:

Undivided oral powders.

Divided oral powders.

Granules for oral administration.

Dusting powders for external use.

FORMULATION OF POWDERS AND GRANULES:

COMPOUNDING:

Basic techniques of compounding of powders and granules are:

Weighing

Size reduction

Size separation

MixingSlide49

PREPARATION OF UNDIVIDED ORAL POWDERS:

PREPARATION OF DIVIDED ORAL POWDERS:

WRAPPING DIVIDED POWDERS:

PREPARATION OF GRANULES:

On small scale, granules are made with a mortar and pestle and suitable sieves.

PREPARATION OF DUSTING POWDERS:

They are prepared using method as for undivided oral powders.

Sieve size should be 180 µm.Slide50

ORAL POWDERS AS DOSAGE FORMS:

1. UNDIVIDED POWDERS AS ORAL DOSAGE FORMS:

Relatively few medicaments are formulated as undivided/divided powders.

ADVANTAGES AND DISADVANTAGES OF UNDIVIDED POWDERS:

SHELF LIFE OF UNDIVIDED POWDERS:

Undivided powder are suitably packaged and stored.

Remain stable over a long period.

CONTAINERS OF UNDIVIDED POWDERS:

Plain glass jars with close fitting closures and a 5 ml measuring spoon should be supplied for undivided powders.

SPECIAL LABEL AND ADVICE FOR PATIENTS:

2. DIVIDED POWDERS AS ORAL DOSAGE FORMS:

SHELF LIFE OF DIVIDED POWDERS:

CONTAINERS OF DIVIDED POWDERS:

SPECIAL LABEL AND ADVICE FOR PATIENTS:Slide51

3. GRANULES AS ORAL DOSAGE FORMS:

Bulk granules can be used to deliver medicaments of low potency.

Granules packed in individual sachets.

SHELF LIFE OF GRANULES

CONTAINERS OF GRANULES

SPECIAL LABEL AND ADVICE FOR PATIENTS:

GRANULES FOR MIXTURES:

Some antibiotics are unstable in solution or suspension, which are formulated by manufacturers as dry granules containing medicaments and various adjuncts.

4. BULK POWDERS FOR EXTERNAL USE

SHELF LIFE OF DUSTING POWDERS

CONTAINERS OF DUSTING POWDERS

SPECIAL LABEL AND ADVICE FOR PATIENTSSlide52

ORAL UNIT DOSAGE FORMS

have accurately measured amount of medicaments in a single dosage unit

Easily handled by the patient.

Major oral unit dosage forms are tablets and capsules

.

ADVANTAGES

OF ORAL UNIT DOSAGE FORMS:

Accurate release

Release characteristics of drug can be controlled

Uniform product

Stable & attractive product

Easy to administer

Unpleasant tastes can be masked

Simple to pack, Convenient to carryDISADVANTAGES OF ORAL UNIT DOSAGE FORMS:

Difficult to swallow

Unsuitable for the young

Excipients

may produce unwanted effects

Release characteristics may not be idealSlide53

DISPENSING OF TABLETS:

Mostly packaged by manufacturer into unit packs suitable to issue to the patient with out re-packing by the pharmacist.

Role

of pharmacist in dispensing of these

tablets

SUPPLY OF TABLETS FROM BULK PACK:

Required number of tablets must be counted from the bulk container.

Tablets must remain untouched by hands.

Cross contamination of different tablets must not occur.

Counting devices must be cleaned after each usage

.

CONTAINERS FOR TABLETS

SPECIAL LABELS FOR TABLETS AND ADVICE FOR PATIENTS:Slide54

CAPSULES:

These are dosage forms in which the medicaments are enclosed within a hard or soft gelatin shell.

Soft gelatin

capsules

H

ard

gelatin

capsules

Hard

gelatin capsules are available in a range of sizes.

Approximate capacities of hard gelatin capsule shells, based on lactose:

Cap. 000 00 0 1 2 3 4 5

Content 950 650 450 300 250 200 150

100

ADVANTAGES OF HARD GELATIN CAPSULE:

M

ask

unpleasant taste.

E

asy

to swallow.

R

equire

fewer

excipients

and can be made light resistant.

Give rapid & uniform release of medicaments. Slide55

FORMULATION OF CAPSULES:

COMPOUNDING

OF CAPSULES:

Hand filling of hard gelatin capsules is rarely carried out in a community pharmacy but can be done in hospital pharmacy.

Two methods are suggested:

(a)filling from a powder mass

(b)filling with weighed aliquots

SHELF LIFE OF CAPSULES

CONTAINERS FOR CAPSULES AND ADVICE FOR PATIENTSSlide56
Slide57

OTHER PRODUCTS IN CAPSULE SHELLS:

INSUFFLATIONS:

They are fine powders prepared for inhalation from a suitable insufflators.

EYE

OINTMENTS AND RECTAL OR VAGINAL DOSAGE FORMS:Slide58

REFERENCES:

Pharmaceutical Practice by D M

Collett

and M E

Aulton

.

Solutions - Pg: 87

Suspensions - Pg: 99

Emulsions/Creams - Pg: 109

Ointments, pastes, gels - Pg: 125

Suppositories and

pessaries

- Pg: 135

Powders and granules - Pg: 145oral unit dosage forms - Pg: 151Slide59

EXTRA REFERENCES:

COOPER & GUNN’S, DISPENSING FOR PHARM. STUDENTS BY S. J. CARTER-

12

TH

EDITION.

Dispensed preparations - Pg: 8

Solutions - Pg: 67

Suspensions - Pg: 100

Emulsions/Creams - Pg: 120

Powders and oral unit dosage forms - Pg: 168

Ointments, pastes, jellies - Pg: 192

Suppositories and

pessaries

- Pg: 232