Solid Dosage 3

8/6/2019 Solid Dosage 3

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Dissolution

Dissolution is defined as the process by

which solid substances enter in a solventto yield a solution


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Factors affecting dissolution rate

1. Physicochemical properties of a drug

2. Drug product formulation

3. Processing factors4. Dissolution test parameters

5. Miscellaneous factors


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1. Physicochemical properties

Effect of solubility

Aqueous solubility of a drug is a major factor

that determines the dissolution rate

Drug solubility data could be used as a rough

predictor of the possibility of any problems

with bioavailability.


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Effect of particle size Dissolution rate is directly proportional to the

surface area of the drug.

Surface area increases with decrease inparticle size, thus reduction in particle sizeresults in increased dissolution rate.

Micronization of certain poorly soluble drugs

has resulted in improved dissolution rates. E.g. chloramphenicol, tetracycline, sulfadiazine

etc.


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Effect of solid phase characteristics Amorphicity and crytallinity are 2 important

characteristics that affect drug dissolution

rate. Studies have confirmed that amorphous form

exhibits higher dissolution rate than crystallineform.

E.g. phenobarbitol exhibits higher dissolutionrate and bioavailability in amorphous form.

One contradictory example is that oferythromycin.


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2. Factors related to drug product

formulation Effect of granulating agents and

binders.

Phenobarbital tablets granulated with gelatinexhibit higher dissolution rate than those

granulated with CMC or PEG

Even gelatin obtained from different

processes and sources has shown to affectthe dissolution rate.


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2. Factors related to drug product

formulation Effect of disintegrants and diluents

Increasing the amount of starch in a

formulation has shown to improve the

dissolution rate.

Effect of lubricant

The nature, quality and quantity of a lubricant

can affect dissolution rate


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3. Processing factors

Method of granulation

Wet granulation has been shown to improve

dissolution rate by imparting hydrophillicity.

Compressional force

High compression force can increase tablet

hardness and consequently decrease solventpenetrability, thus decreasing the dissolution

rate.


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4. Factors related to dosage form

Drug excepient interaction

This can occur during any unit operation like

mixing, blending, drying or granulation.

E.g. the effect of magnesium stearate on

disintegration time of tablets containing potato

starch.


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5. Effect of test parameters

Stirring device

Eccentricity of the stirring device needs to be

minimized.

Vibration

Vibration is a common variable introduced

due to numerous causes and it needs to beeliminated.


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5. Effect of test parameters

Alignment of the stirring element

temperature

Dissolution medium

pH of the medium Viscosity


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Miscellaneous parameters

Adsorption

Humidity

Detection errors

Compendial method


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Compendial dissolution testing

apparatuses BASKET APPARATUS (I)

PADDLE APPARATUS (II)

RECIPROCATING CYLINDER (III)

FLOW-THROUGH CELL (IV)

PADDLE OVER DISK (V)

CYLINDER (VI)

RECIPROCATING HOLDER (VII)


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Basket apparatus

The assembly consistsof: vessel

motor metallic drive shaft

cylindrical basket. The vessel is partially

immersed in a suitablewater bath of anyconvenient size

A suitable heating devicethat permits holding thetemperature inside thevessel at 37 0.5 C


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Basket apparatus

The vessel is cylindrical, with ahemispherical bottom.

A speed-regulating device (motor) isused that allows the shaft rotation

speed to be selected andmaintained at the specified rategiven in the individual monograph,within 4%

Cover may be used to retardevaporation.


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Basket apparatus

Useful for capsules

delayed release /

entericcoated dosage forms

floating dosage forms

Standard volume 900/1000 ml

1, 2, 4 liter vessels


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Advantages

Breadth of experience (more than 200

monographs)

Full pH change during the test

Can be easily automated which is important

for routine investigations


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Weaknesses of the basket method

Hindered visual inspection Disintegration-dissolutioninteraction

Poor homogeneity of the bulk fluid due to insufficientstirring or agitation

Sensitivity against external vibration, wobble, eccentricity

limited volume

Inconvenience for cleaning the set-up after testing


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Paddle apparatus

Use the assembly fromApparatus 1, except that apaddle formed from a bladeand a shaft is used as thestirring element.

The distance of 25 2 mmbetween the bottom of theblade and the inside bottom ofthe vessel is maintained duringthe test.

The metallic or suitably inert,rigid blade and shaft comprisea single entity.


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Paddle apparatus


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Sinker types

JP/ USP / Ph. Eur.5.3 Sinker


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Paddle apparatus

Useful for tablets

capsules

delayed release / entericcoated dosage forms

Standard volume

900/1000 ml

Method of first choice !!!


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Advantages of paddle apparatus

easy to use

robust

can be easily adapted to apparatus 5 long experience

pH change possible

can be easily automated

which is important for

routine investigations


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Weaknesses of paddle apparatus

Problems with floating dosage units

The use of spiral for holding capsules is subject

to variability with operators.

The non-dispersion of disintegrated tablets can

lead to non-reproducibility of test

Coning


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Documents

Solid Dosage 3