PHS 3207: Industrial

Pharmacy
BIOPHARMACEUTICS 3
SEM II 2019
Concentration of drug in blood plasma
Dependent on:
• Relative amount of administered dose that enters systemic circulation
• Rate at which drug enters systemic circulation
• Rate and extent of drug distribution between systemic circulation and
other tissues and body fluids
• Rate of elimination from the body
Drug must be absorbed in sufficient quantity and at sufficient rate so
as to achieve a blood concentration capable of producing
appropriate concentration at the site of action to elicit desired
therapeutic response

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Bioavailability
• The fraction of administered dose of drug that reaches systemic
circulation in unchanged form is the bioavailable dose for the given
dosage form.
• systemic circulation (=venous blood and arterial blood which caries intact
drug to the tissues; excludes hepatic portal blood via which drug passes
during absorption)
• Normally, the unchanged form is the active form of the drug, used to assay
bioavailability
• In the case of a prodrug, which must first be converted to the active form
before or on reaching the systemic circulation, the active metabolite is used.
• Bioavailability is both rate and extent or quantity at which the intact
form of drug appears in systemic circulation upon administration of a
dose of the drug in a given dosage form.
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Rate limiting steps/factors to drug
absorption
In a series of kinetic or rate processes, the rate at which drug reaches
systemic circulation is determined by the slowest of various steps
involved in the sequence of events following administration= rate
limiting step.
Dissolution and solubility:
Gastric emptying

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Dissolution and solubility
• dissolution is the process by which a drug substance becomes
dissolved in a solvent,
• solubility is the mass of solute dissolved in a specific mass or volume
of solvent at a given temperature. Solubility is a static parameter,
dissolution is dynamic. Drug dissolution in aqueous medium is vital for
predicting systemic drug absorption in vivo.

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Dissolution and solubility
• The rate at which drugs with poor aqueous solubility dissolve from an
disintegration dosage form controls the rate of systemic absorption of drug
• Dissolution tests may be used to predict bioavailability
• Drug dissolution steps begin with process of drug dissolution at the surface
of the solid particle, forming a saturated solution around the particle
• Dissolved drug in the saturated solution (=the stagnant layer) diffuses to the
bulk of the solvent from high to low concentration regions
• The overall rate of dissolution may be described by the Noyes-Whitney
equation:
• dC/dt=DA (Cs-C)/h
Where: D= diffusion constant; A=Surface area of particle; Cs= concn of drug in
stagnant layer; C=concn of drug in bulk solvent; b=thickness of the stagnant
layer
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Dissolution and solubility
• dC/dt = rate of dissolution, rate of drug dissolved per time expressed
as a change in concentration in the dissolution medium
• The equation shows that dissolution can be influenced by the drug’s
physicochemical characteristics
• Dissolution of drug in GIT fluids can be considered as in aqueous
environment
• Permeation of drug across the gut wall if affected by its ability to
diffuse (D) and to partition between the lipid membranes
• A drug with a favourable partition coefficient Kwater-oil will have
better absorption
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Factors that affect drug dissolution
• Drug physicochemical characteristics:
• Drug solubility
• Salt form
• Particle size
• Nature of excipients in the formulation:
• Diluents
• Disintegrants
• Binders
• surfactants

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Factors that affect drug dissolution…
• Method and process of manufacture:
(i) Method of granulation
• Comminution
• Granulation
• Mixing
(ii) Drug-excipient interactions
(iii) Compression force
• Dissolution test conditions:
• Agitation: Basket, paddle methods
• temperature
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Gastric emptying
• The passage of drug from the stomach to the small intestine is called
gastric emptying
• It can be a rate limiting step in drug absorption given that the
intestine is a major absorption site
• Rapid gastric emptying is desirable:
• for rapid onset of action
• Enteric dissolution (enteric coated)
• Instability of drug in gastric fluids e.g. penicillin and erythromycin
• Gastric emptying promoted by administration on empty stomach

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Gastric emptying…
• Delayed gastric emptying is desirable:
• When food promotes drug dissolution and absorption
• Disintegration and dissolution of dosage form is promoted by gastric fluids
• Drugs irritate gastric mucosa
• Factors influencing gastric emptying:
• Volume of meal
• Type of food ingested
• Temperature of meal
• Body posture
• Exercise
• Other drugs
• Gastrointestinal pH
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The Biopharmaceutical Classification
System (BCS)
• Is an experimental model that measures permeability and solubility
under prescribes conditions.
• An in vitro regulatory guide on oral generic drug delivery systems (majority)
• Waivers permission to skip in vivo bioequivalence studies
• Now a tool of drug product development: e.g.
• Class II compound; permeable but relatively insoluble : is not a good clinical candidate
without enhanced formulation techniques to improve solubility or rate dissolution.
• BCS places an API in one of the 4 categories

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The Biopharmaceutical Classification
System..
Class Solubility Permeability Absorption Rate limiting Example
Pattern Step in
absorption

I High High Well absorbed Gastric Diltiazem

emptying

II Low High Variable Dissolution Nifedipine

III High Low Variable Permeability Insulin

IV Low Low Poorly absorbed On case by case Paclitaxel

basis (Taxol)

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The Biopharmaceutical Classification
System

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Product Ranking in order of promptness of
response and duration of action
• IV injection> injections> oral Solutions> oral
suspensions> oral solid dosage forms

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Modification of response characteristics to
product
• Biological: e.g. co-administration of adrenalin with lignocaine to cause
vaso-constriction and minimize transfer of anaesthetic from site thus
prolonging its action.
• Chemical: (Home work)
• Pharmaceutical: e.g. drug in a wax-base slows release and prolongs
drug activity

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