Q. Disintegration: It is a physical process that occurs when a dosage form (e.g.

tablet or gelatine capsule)

breaks up into smaller particles.

Q. Factor affecting disintegration

1. Effect of fillers: soluble fillers increase the viscosity of the penetrating fluid which tend to reduce the
effect of the swollen disintegrating agent which tend to dissolve rather than disintegrate. Insoluble fillers
disintegrate more rapidly.
2. Effect of lubricants: as lubricants are hydrophobic, they inhibit wetting and consequently disintegration
of tablets. Na starch glycolate remains unaffected as disintegrant.
3. Effect of binders: Increase in the concentration of the binder increases the disintegration time.
4. Effect of Surfactants: The speed of water penetration is increased by addition of surfactants

Q. Dissolution: Dissolution is the process by which a solid drug substance becomes dissolved in a solvent.
Solubility is the mass of solute that dissolves in a specific mass or volume of solvent at a given. Solubility
is a static property; wheareas dissolution is a dynamic property.

Q. Noyes and Whitney (1897) and other investigators studied the rate of dissolution of solid drugs.
According to their observations, the steps in dissolution include the process of drug dissolution at the
surface of the solid particle, thus forming a saturated solution around the particle. The dissolved drug in the
saturated solution, known as the stagnant layer, diffuses to the bulk of the solvent from regions of high drug
concentration to regions of low drug concentration ().

The overall rate of drug dissolution may be described by the Noyes–Whitney equation (Eq. 14.1),

Where dC/dt = rate of drug dissolution at time t, D = diffusion rate constant, A = surface area of the particle,
C S = concentration of drug (equal to solubility of drug) in the stagnant layer, C = concentration of drug in
the bulk solvent, and h = thickness of the stagnant layer. The rate of dissolution, dC/dt, is the rate of drug
dissolved per time expressed as concentration change in the dissolution fluid.

Q. Factor affecting dissolution: The Noyes–Whitney equation shows that dissolution in a flask may
be influenced by the physicochemical characteristics of the drug, the formulation, and the solvent.
Permeation of drug across the gut wall (a model lipid membrane) is affected by the ability of the drug to
diffuse (D) and to partition between the lipid membrane. A favorable partition coefficient (K oil/water) will
facilitate drug absorption.
In addition to these factors, the temperature of the medium and the agitation rate also affect the rate of drug
dissolution. An increase in temperature will increase the kinetic energy of the molecules and increase the
diffusion constant, D.
Factors that affect drug dissolution of a solid oral dosage form include (1) the physical and chemical nature
of the active drug substance, (2) the nature of the excipients, and (3) the method of manufacture.
Q. Factor affecting drug absorption

 Physicochemical properties of drug: a. Drug solubility and dissolution rate b. Particle size and
effective surface area c. Polymorphism and amorphism d. hydrates or solvates e. Salt form of the
drug f. Lipophilicity g. Drug stability h. Stereochemical nature
 Formulation factors: a. disintegration time b. manufacturing variables c. nature and type of dosage
form d. pharmaceutical ingredients
 Patient related factors: a. age b. gastric emptying time c. intestinal transit time d. gastrointestinal
pH e. diseased states f. blood flow through the GIT g. gastrointestinal contents
 other drugs , food fluids, other normal G.I contents , pre systemic metabolism

Q. Absorption pattern

Q. Factor affecting bioavailability

 Particle Size: The rate at which a drug is dissolved can be increased by increasing its surface area
by decreasing its particle size. –
 Salt Form: The rate at which a particular salt dissolves differs from its parent compound. • Salts
of weakly acidic drugs are highly water soluble
 Crystal Forms: The rate of absorption and bioavailability of a drug also depends on its crystalline
form
 Water of Hydration: If water molecules are already present in a crystal structure, the tendency of
the crystal to attract additional water to initiate dissolution process is reduced, compared to
anhydrous forms.
 Nature of Excipients and Adjuvants: Some of these excipients are wetting agents, which enhance
solvent penetration and ensures faster dissolution and in turn absorption
  Degree of ionisation: Non-ionised, lipid soluble drugs are better absorbed, increasing their
bioavailability, compared to strongly acidic or strongly basic drugs or highly ionised drugs.
 Gastric Emptying and Gastrointestinal Motility
 Gastrointestinal Diseases: There are many gastrointestinal diseases which have an effect on drug
absorption
 Food and Other Substances: In general, GI absorption rate is reduced after ingestion of food,
although it has no effect on extend of absorption. • Both rate and extend of absorption of certain
antibiotics like rifampicin is reduced after meals.
 First Pass Metabolism: It means that drug degradation occurs, reducing its bioavailability, when
it passed through GIT wall and then through portal system, before it reaches systemic circulation
Drug-
 Drug Interactions: Drug-drug interactions can also cause difference in bioavailability.

Q. Dosage Form Selection: The properties of the drug and required dosage are important in formulating
an extended-release product. For example, a drug with low aqueous solubility generally should not be
formulated into a non-disintegrating tablet, because the risk of incomplete drug dissolution. a drug with low
solubility at neutral pH should be formulated, so that most of the drug is released before it reaches the colon.
Erosion tablets are more reliable for these drugs because the entire tablet eventually dissolves.
A drug that is highly water soluble in the acid pH in the stomach but very insoluble at intestinal pH may be
very difficult to formulate into an extended-release product. Too much coating protection may result in low
bioavailability, while too little protection may result in dose dumping in the stomach. The osmotic type of
controlled system may be more suitable for this type of drug.
In addition, with most single-unit dosage forms, there is a risk of erratic performance due to variable
stomach emptying and GI transit time. Selection of a pellet or bead dosage form may minimize the risk of
erratic stomach emptying, because pellets are usually scattered soon after ingestion. Disintegrating tablets
have the same advantages because they break up into small particles soon after ingestion

Q. Kinetics of extended release dosage form: Drug release from conventional dosage forms, like the
other processes of ADME, are governed by the first-order kinetics model. In First-order model, drug release
is dependent on the amount of drug available for release and therefore the rate of release declines
exponentially with time.

Extended release dosage forms are governed by zero-order kinetics in which the rate of release is
independent of amount of drug remaining in the dosage form. Therefore a constant amount of drug will be
released over time from extended release dosage forms
Q. The matrix system
The matrix system is the mixture of materials with the drug, which will cause the drug to slow down.
However, this system has several subcategories: hydrophobic matrices, lipid matrices, hydrophilic matrices,
biodegradable matrices, and mineral matrices.
A hydrophobic matrix is a drug mixed with a hydrophobic polymer. This causes SR because the drug, after
being dissolved, will have to be released by going through channels made by the hydrophilic polymer.
A hydrophilic a matrix is a mixture of drug with a gelling agent. This system is well liked because of its
cost and broad regulatory acceptance. The polymers used can be broken down into categories: cellulose
derivatives, non-cellulose natural, and polymers of acrylic acid.
A lipid matrix uses wax or similar materials. Drug release happens through diffusion and erosion of the
wax and tends to be sensitive to digestive fluids.
Biodegradable matrices are made with unstable, linked monomers that will erode by biological compounds
such as enzymes and proteins.
A mineral matrix which generally means the polymers used are obtained in seaweed.

Q. Need for dissolution testing:

 Evaluation of bioavailability.
 Batch to batch drug release uniformity.
 Development of more efficacious and therapeutically optical dosage forms.
 Ensures quality and stability of the product.
 Product development, quality control, research and application

Q. klein solvmeter method

Carrier device surrounded by flat and is immersed in dissolution medium. When dosage form is placed in
the boat the bar moves and as dosage form dissolves it moves upwards. Amount of dosage form dissolved
is revealed from the difference in height of bar movement.
Q. Tumbling Method

The Drug/ Dosage form with the dissolution medium is placed in test tube that is in turn clamped to the
revolving drum which is rotated at the speed of 6- 12rpm in water bath at 37 C. The test tubes are removed
and the medium is assayed at regular time points for the dissolved drug amount

Q. USP rotating basket

DESIGN:

Vessel: Made of borosilicate glass. Semi hemispherical bottom .Capacity 1000ml

Shaft: Stainless steel 316. Rotates smoothly without significance wobble (100 rpm) and Speed regulator
Water bath:-Maintained at 37±0.5ºC

USE: Tablets, capsules, delayed release suppositories, floating dosage forms.

Q. Advantages of USP rotating basket

 Full pH change during the test

 Can be easily automated which is important for routine investigations.

Q. Disadvantages USP rotating basket

 Basket screen is clogged with gummy particles.

 Hydrodynamic „dead zone“ under the basket
 Degassing is particularly important
 Mesh gets corroded by HCl solution.