Biopharmaceutics

Route of Administration,Anatomy & physiology affecting absorption and

Transit of Drugs

Lec:2

Ali Y Ali BSc Pharmacy, MSc Industrial Pharmaceutical Sciences

Dept. of Pharmaceutics School of Pharmacy

University of Sulaimani 1

Overview

• Introduction • Routes of drug administration • Physiological factors affecting oral drug absorption • Transit of Pharmaceuticals in the GIT

• Barriers to Drug Absorption

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IntroductionPhysicochemical

properties

Dosage form Route of

Administration

Bioavailability(Rate & Extent)

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Introduction

Factors affecting bioavailability depends on • The route of the administration.

– IV (100 %)

– Other routes: Oral, dermal, pulmonary, rectal• Absorption

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Routes of Drug Administration

1. Parenteral

2. Enteral

3. Miscellaneous

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Parenteral

• Intravenous (IV) Bolus:• Bioavailability:

• Extent: 100 % systemic absorption • Rate: instantaneously in the blood

• IV infusions • Extent: 100 % systemic absorption • Rate: controlled by the rate of infusion

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Parenteral

• Intramuscular (IM)• Bioavailability:

• Rapid absorption rate is rapid from aqueous solution • Slow absorption form oily based solution (Depot)

• Subcutaneous (SC): • Bioavailability:

• Rapid absorption from aqueous solution • Slow absorption form repository formulations

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Enteral

• Buccal or sublingual(SL)• Rapid absorption for lipid soluble drugs

• Oral (PO)• Absorption may vary • Slower than fast parenteral like IM and IV bolus

• Rectal (PR)• Absorption may vary from suppository• More reliable from enema (solution)

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Miscellaneous

• Transdermal • Slow absorption • Rate of absorption varies

• Inhalation and Intranasal • Rapid absorption • Total amount absorbed varies

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Oral route

• Most popular• Natural and convenient for patient• Relatively easy to manufacture oral dosage forms

• Compact• Not sterilized• Inexpensive

• https://www.youtube.com/watch?v=GtZm4Iyb_Mo

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Gastrointestinal Tract (GIT)

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Dosage forms in GIT

• Solid dosage forms • Tablet

• Liquid • Solution, Suspension

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Rate-limiting step

1. Dissolution rate limited

2. Permeability limited

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Rate Limiting step

• Others

• Release from the dosage form

• Gastric emptying rate

• Metabolism

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Anatomy and physiology

• 6 meters length • Muscular • Luminal surface is rough• Increases surface area -----> absorption

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Mucus

• Secreted by GIT • Covers majority of GIT (Continuous in stomach and Duodenum)

• Functions • Protective

• Composition;• Water (95%)• Mucin (large glycoprotein)

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Oral cavity

• Portal • pH = 7 • Saliva • Amylase

• Mucin

• Oral dispersing tablets (ODT)• Aripiprazole discemelt®

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Oesophagus

• Links oral cavity to the stomach• Length 25cm and 2 cm diameter

• Mostly covered by epithelial cells

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• Mucus secretion • Food lubrication • Protect lower part from gastric acid

• pH : 5-6• Movement:

1. Peristalsis 2. Gravity

• Dosage from transit < 15 seconds • Absorption is rare

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Stomach

• 4 regions: Fundus, Body, pylorus, pyloric sphincter

• Function:a) Reservoir b) Food reduction to smaller mass and juicy like

structure called chyme

• Capacity:1.5 Litre

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Fasting State

• Gastric juice 1. Acid: parietal cells

2. Gastrin hormone; stimulates acid secretion, in response of presence of proteins and peptides

3. Pepsin: pepsinogen converted at low pH pepsin to break down small peptides

4. Mucus: protection

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Stomach

• Absorption ?

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Small intestine

• 4-5 metres

• Doudenum, jejunum and ileum

• Functions:1. Digestion

2. Absorption

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Contents

• Ph: 6-7.5

a) Mucus b) Bicarbonate c) Pancreatic juice d) Enzymes: • Protease, hydrolase, lipase

e) Bile: cholesterol and fatty acid (fat absorption)

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Enterohepatic circulation

• Bile is secreted from gall bladder via common duct into the intestine

• Bile acids are absorbed by an active transport in the terminal ileum and returned to the liver via portal vein

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Small Intestine

• Absorption ?

• Major site ?

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• Large surface area

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• Highly supplied with blood and lymphatic vessels

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Colon

• 1.5 meters

• No villi

• Functions • Absorption (little)• Storage and compaction of faeces

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Colon

• Bacteria:• Permanently colonized

• Capable of metabolic reactions

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Transit of drugs in the GIT

• How long does a drug take to stay in the whole GIT ?

• 0.4-5 days

• Most of the drugs are absorbed from the intestine• time drug takes to the site do absorption is

important as it defines the onset of action

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Oesophagus Transit

Transit

Posture Dosage form

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Oesophagus Transit

• A person in supine position and taking a solid dosage form, it might lodge in the oesophagus and by dehydration adhesion and forming of a gel might occur.

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Oesophagus Transit

• Consequences: 1. Delay in effect 2. Irritation and ulceration of the oesophagus

e.g. KI tablets and NSAIDs.

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Stomach transit

Gastric Emptying Rate (GER)

• The time taken by dosage form to transit stomach.

• 5 minutes to 2 hours

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Factors affecting GER

1. Dosage form • Solid vs liquid

2. Postural position:• lying on the left decrease GER

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Factors affecting GER

3. Fasted/fed state

4. Composition of food:• Fatty food decrease GER

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Factors affecting GER

5. Effect of drugs• Anticholinergics and ethanol

6. Disease states:• Decrease GER: some diabetics, local pyloric lesion, Hypothyroidism• Increase GER: Hyperthyroidism

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Cycle at fasting state

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• The discrimination between dosage forms is not found in the fasted state.

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Fed State

A. The proximal part dilates to receive food and then contracts to move the food down B. Peristalsis: contraction of the distal stomach

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Small intestine

• Major site of absorption:– high surface area and– rich blood and lymphatic supply.

• Transit from stomach to the caecum( 3-4 hours) , Small Intestine Transit time (SITT)

• Movement – Propulsive – Mixing

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• No discrimination:

1. Dosage forms

2. Fed and fasted state.

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Intestinal transit time importance

1. Controlled release and sustained release

2. Enteric coated tablet

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3. Drugs dissolve slowly in the intestinal fluid- Dissolution Rate limited

4. Drugs absorbed by intestinal carrier-mediated transport

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Colon Transit

• Long and variable (2- 48 hours)

Depending on: • Dosage form• Diet • Disease state

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Colon Transit

• Example:• Metoprolol • Theophylline

• Good candidates for an oral sustained-release dosage form.

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Further readings

• Aulton, M. E. and K. M. Taylor (2013). Aulton's pharmaceutics: the design and manufacture of medicines, Elsevier Health Sciences.• Shargel, L., S. Wu-Pong and A. B. Yu (2007). Applied biopharmaceutics

& pharmacokinetics, McGraw-Hill.• Fleisher, D., B. Sweet, A. Parekh and J. Boullata (2010). Drug

Absorption with Food. Handbook of Drug-Nutrient Interactions. J. I. Boullata and V. T. Armenti, Humana Press: 209-241.

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