Definitions and Concepts

Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

Department of PharmaceuticsFaculty of Pharmacy

Omer Al-Mukhtar UniversityTobruk, Libya.

E-mail: nanjwadebk@gmail.com

2014/01/25 1Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

2014/01/25 2Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

Definitions• Biopharmaceutics• Absorption• Bioavailability• Drug disposition• Drug distribution.• Elimination a. Biotransformation(Metabolism) b. Excretion

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Definitions• Pharmacokinetics• Clinical pharmacokinetics• Pharmacodynamics• Equivalence.• Bioequivalence.• Pharmaceutical Equivalence.• Pharmaceutical Alternatives.• Therapeutic Equivalence.• Bio-Inequivalence.• Bioequivalences studies.

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Biopharmaceutics

Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of drug products.

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Biopharmaceutics

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Absorption

Definition :• The process of movement of drug from its site

of administration to the systemic circulation is called as absorption.

• The process of movement of unchanged drug from the site of administration to systemic circulation.

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Absorption

There always exist a correlation between the plasma concentration of a drug & the therapeutic response & thus, absorption can also be defined as the process of movement of unchanged drug from the site of administration to the site of measurement.

i.e., plasma.

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G. I. T.

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Buccal

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Sublingual

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Skin (Dermal)

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Skin (Dermal)

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Skin (Dermal)

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Eye (Ophthalmic)

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Nasal (Nose)

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Lung (Respiratory)

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G. I. T.

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Bioavailability• Bioavailability is defined as the rate and extent

(amount) of drug absorption.

• The relative amount of an administration dose of a particular drug that reaches the systemic circulation intact and the rate at which this occurs is known as the bioavailability.

• The fraction of an administration dose of the drug that reaches the systemic circulation in the unchanged form is known as the bioavailable dose.

2014/01/25 19Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk, Libya.

Absolute Bioavailability

Absolute Bioavailability :- If the systemic availability of a drug

administered orally is determined by doing its comparison with I.V. administration, it is known as absolute bioavailability.

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Relative Bioavailability

Relative Bioavailability :- If the systemic availability of a drug

administered orally is determined by doing its comparison with that of an oral standard of the same drug, it is known as a relative bioavailability.

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Drug disposition

• Any alternative in the drug’s bioavailability is reflected in its pharmacological effects. Other processes that play a role in the therapeutic activity of a drug are distribution and elimination. Together, they are known as drug disposition.

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Drug distribution

• The movement of drug between one compartment and the other (general blood and the extra-vascular tissues) is referred to as drug distribution.

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Elimination

• Elimination is defined as the process that tends to remove the drug from the body and terminate its action.

• Biotransformation(Metabolism): Which usually inactivevates the drug.

• Excretion:Which is responsible for the exit of drug/metabolites from the body.

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Biotransformation(Metabolism)

• Biotransformation(Metabolism):Which usually inactivates the drug.

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Excretion

• Which is responsible for the exit of drug/metabolites from the body.

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Pharmacokinetics

• Pharmacokinetics is defined as the study of time course of drug ADME and their relationship with its therapeutics and toxic effects of the drug.

• Simply speaking, pharmacokinetics is the kinetics of ADME or KADME.

• Pharmacokinetic is a study of what the body does to the drug, whereas.

• Pharmacokinetics relates changes in concentration of drug within the body with time after its administration, whereas.

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Clinical pharmacokinetics

• The use of pharmacokinetic principles in optimising the drug dosage to suit individual patient needs and achieving maximum therapeutic utility is called as clinical pharmacokinetics.

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Pharmacodynamics

• Pharmacodynamic is a study of what the drug does to the body.

• Pharmacorelates response to concentration of drug in the body.

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Equivalence

• This term compares the drug products to the characters or functions to the set of standards.

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Bioequivalence

• It refers that the drug substance in two or more identical dosage forms, reaches systemic circulation at the same rate and to the same relative extent. i.e. their plasma concentration time profiles will be identical without significant statistical differences.

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Pharmaceutical Equivalence

• Drug products in identical dosage forms that contains the same active ingredients, use the same route of administration, and are identical in strength or concentration, quality, purity, content uniformity, however they may differ in containing excipients.

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Pharmaceutical Alternatives

• Drug products that contain the same therapeutic moiety but as different salt, ester or complex. For e. g. tetracycline phosphate or tetracycline hydrochloride equivalent to 250 mg tetracycline.

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Therapeutic Equivalence

• It indicate that two or more drug products that contain same therapeutically active ingredients, elicit identical pharmacologic effect and can control the disease to the same extent.

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Bio-Inequivalence

• When statistically significant differences are observed in the bioavailability of two or more drug products called as bio-inequivalences.

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Bioequivalences Studies

Bioequivalence studies are performed by comparing the bioavailability of, to-be-marketed Generic product with that of the Brand product. Pharmacokinetic studies are conducted whereby each of the preparations are administered in a cross-over study to volunteer subjects, generally healthy individuals but occasionally in patients.

Serum/Plasma samples are obtained at regular intervals and assayed for parent drug (or occasionally metabolite) concentration.

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Drug Administration and Therapy

1. The Pharmaceutical Phase.2. The Pharmacokinetic Phase.3. The Pharmacodynamic Phase.4. The Therapeutic Phase.

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The pharmaceutical Phase

• It is concerned with-a. Physicochemical properties of the drug, and b.Design and manufacturing of an effective drug

product for administration by a suitable route.

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The Pharmacokinetic Phase

• It is concerned with the ADME of drugs as elicited by the plasma drug concentration-time profile and its relationship with the dose, dosage form and dosing frequency and route of administration. In short, it is the sum of all the processes inflicted by the body on the drug.

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The Pharmacodynamic Phase

• It is concerned with the bio-chemical and physiological effects of the drug and its mechanism of action. It is characterized by the concentration of drug at the site of action and its relation to the magnitude of effects observed.

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The Therapeutic Phase

• It is concerned with the translation of pharmacological effect into clinical benefit.

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Concept of Bioavailability• Be completely released from the dosage form.• Be fully dissolved in the gastrointestinal fluids.• Be stable in solution in the gastrointestinal

fluids.• Pass through the gastrointestinal barrier into

the mesenteric circulation without being metabolized.

• Pass through the liver into the systemic circulation unchanged form.

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Concept of Biopharmaceutics

• In the same type of dosage form by different routes of administration, e.g. an aqueous solution of a given drug administered by the oral and intramuscular routes.

• By the same routes of administration but different types of dosage form, e.g. a tablet, a hard gelatin capsule and an aqueous suspension administered by the peroral route.

• In the same type of dosage form by the same route of administration but with different formulations of the dosage form, e.g. different formulations of an oral aqueous suspension.

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Poor biopharmaceutical properties

• Poor and variable bioavailability.• Difficulties in toxicological evaluation.• Difficulties with bioequivalence of

formulations.• Multi-daily dosing.• The requirement for a non-conventional

delivery system.• Long and costly development times.2014/01/25 Faculty of Pharmacy, Omer Al-Mukhtar University,

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References1. “Biopharmaceutics & pharmacokinetics”, D.M.

Brahmankar & Sunil B. Jaiswal, Vallabh prakashan.

2. “Text book of Biopharmaceutics &pharmacokinetics”, Dr. Shobharani R. Hiramath.

3. “Applied Biopharmaceutics & pharmacokinetics”, Leon Shargel & Andrew B.C.

4. www.google.com2014/01/25 45Faculty of Pharmacy, Omer Al-Mukhtar University,

Tobruk, Libya.

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E-mail: nanjwadebk@gmail.com