Routes of Administration

Question 1

The aim of pharmaceutics is to get the drug?

Answer 1

i. to the site of action
ii. at the required concentration
iii. for the desired duration
iv. with minimal side effects

Question 2

What is the difference between a DRUG and a MEDICINE?

Answer 2

DRUG = a substance that affects the structure or functioning of a living organism.
Used for the prevention, diagnosis or treatment of disease or for the relief of
symptoms.

MEDICINE = a drug delivery system that is used to administer drug to the body
efficiently, safely, reproducibly and conveniently.

Question 3

What is a dosage form?

Answer 3

A term for the physical characteristics of a drug product. Typically contain a mixture of
active drug and non-drug components known as excipients.

Question 4

Types of dosage forms?

Answer 4

Liquids: solutions (mixtures, linctuses, gargles, lotions), suspensions, emulsions

Semi-solids: creams, ointments, gels, pastes, suppositories, pessaries

Solids: powders, granules, capsules, tablets

Question 5

Therapeutic aspects to consider in dosage form design?

Answer 5

 Nature of the clinical indication
 Local or systemic therapy
 Duration of action
 Emergency situations
 Age of patient

Question 6

Drug factors to consider in dosage form design?

Answer 6

 Solubility
 Dissolution
 Particle size and surface area
 Partition coefficient and pKa
 Crystal properties
 Stability
 Organoleptic

Question 7

What is Pharmacokinetics?

Answer 7

The study of Absorption, Distribution, Metabolism and Excretion
(ADME).

Question 8

First Pass Metabolism?

Answer 8

All drugs given by the oral route undergo a degree of first pass metabolism either in the gut or the liver.

Drugs administered by the oral route are absorbed from the stomach and the small intestine into the hepatic portal vein. Blood flows via the hepatic portal vein into the liver before reaching the general systemic circulation.

Question 9

What is Parenteral Drug Delivery?

Answer 9

When a drug is administered into the body other than through the gastrointestinal (GI) tract. The drug is injected via a hollow needle into the body at various sites and depths.

Question 10

What are the main routes of Parenteral Drug Delivery?

Answer 10

1. Intravenous (i.v.)-Injected into vein.
2. Intramuscular (i.m.)-Injected into muscle.
3. Subcutaneous (s.m.)-Injected into subcutaneous tissue.
4. Intradermal (i.d.)-Injected into dermis.

Question 11

When is Parenteral route preferred?

Answer 11

 Rapid absorption is essential (emergencies).
 Patient unconscious and unable to take oral medications.
 Drug is unsuitable for the oral route.

Question 12

Why is water an ideal vehicle?

Answer 12

Ideal vehicle as it is well tolerated and will not cause irritation at the injection site.

Question 13

When is Water + miscible solvent used as a vehicle?

Answer 13

Used to increase the aqueous solubility of a drug

o E.g. Propylene glycol, ethanol

Question 14

When is Water + Immiscible oil: used as a vehicle?

Answer 14

Used when drug is prone to hydrolysis or has poor
aqueous solubility.
o E.g. Almond oil, isopropyl myristate

Question 15

What is an Intravenous injection?

Answer 15

An aqueous solution injected directly into a vein as either a single small volume (bolus) injection or as a large volume slow drip infusion. There is no absorption step as the drug is already in solution and thus you achieve a rapid onset of action.

However, the drug must remain in solution upon injection into the blood stream, as precipitation of the drug could result in an embolism and the solution must be isotonic with blood.

Question 16

What is an Intramuscular injection?

Answer 16

An aqueous or oily solution or suspension injected deep into the skeletal muscles. Absorption is required, so the onset of action may be slightly slower compared to i.v. The rate of drug absorption can be tailored based on the type of injection (suspension or solution) and choice of vehicle (aqueous or oily).

Question 17

What affect does Aqueous solutions: e.g. Diazepam (Valium™) have?

Answer 17

Rapid absorption.

Question 18

What affect does Aqueous suspensions: e.g. Fluspirilone (Redeptin™) have?

Answer 18

Medium absorption.

Question 19

What affect does Oily solutions: e.g. Zuclopenthixol decanoate (Depixol™) have?

Answer 19

Slow absorption, depot effect.

Question 20

What affect does Oily suspensions: e.g. Benzathine benzylpenicillin (Bicillin LA™) have?

Answer 20

Sustained drug release.

Question 21

What are the Potential sites for intramuscular injection?

Answer 21

Deltoid muscle of th arm.
Ventrogluteal muscle of the hip.
Dorsogluteal muscles of the buttocks.
Vastus lateralis muscle of the thigh.

Question 22

What is a Subcutaneous injection ?

Answer 22

An aqueous solution or suspension injected into loose
subcutaneous tissue. They must be isotonic solutions to reduce pain at site of administration and the rate of absorption is dependent on the molecular weight and
lipophilicity of the drug; the greater the molecular weight and lipophilicity the slower the rate of absorption. Like I.M, absorption may also be modified by changes to the formulation.

Question 23

What is are Intra-arterial injections?

Answer 23

An Injection directly into an artery and like I.V. injections they must be a sterile, isotonic aqueous solution, however, they are rarely used.

Examples include, vasodilators for vasospasm and thrombolytics for embolisms.

Question 24

What is are Intraperitoneal Injections?

Answer 24

An injection into the peritoneal cavity (the abdomen) that can be used to administer both hydrophilic and lipophilic drugs. It provides a faster onset of action compared to oral drug delivery; however, it is rarely used.

Question 25

What is an Intradermal injection?

Answer 25

Small volume of drug solution (<0.2 mL) is injected between the epidermal and dermal layers of the skin causing a characteristic bump. Drug
absorption is slow, so useful when limited absorption from the injection site is required. It is primarily used for vaccination e.g. the BCG vaccine for tuberculosis.

Question 26

What is an Intracardiac injection?

Answer 26

An injection directly into a heart chamber e.g. adrenaline in the case of cardiac arrest.

Question 27

What is an Intrathecal injection?

Answer 27

An injection of a high concentration of drug directly into the cerebrospinal fluid for delivery to the brain and spinal cord e.g. methotrexate for meningeal leukaemia or baclofen for spinal spasticity.

Question 28

What is an Intraarticular injection?

Answer 28

A direct injection into the synovial cavity of a joint, to obtain a local therapeutic effect e.g. corticosteroids to treat inflammation.

Question 29

What is an Intravitreal injection?

Answer 29

An injection into the vitreous humour of the eye. The inside of the eye is filled with a jelly-like fluid (vitreous) and injecting directly into it can treat certain eye problems that can’t be treated with eye drops.

Question 30

What are the 3 main absorption sites in the GI tract?

Answer 30

1. Stomach: pH 1 to 3.5 and a small surface area
    Weak acids may be absorbed
2. Small intestine: pH 6 to 7.5 and a very large surface area
    Major site of drug absorption
    Weak acids and weak bases well absorbed
3. Large intestine: pH 5.5 to 7.5 and a very large surface area
    Some slow absorption

Question 31

Advantages of Oral Drug Delivery?

Answer 31

1. Natural and convenient for the patient.
2. Good patient compliance.
3. Least complicated route of administration.
4. Safest route of administration.
5. Extensive absorption occurs along the GI tract.
6. Wide range of dosage forms available.

Question 32

Disadvantages of Oral Drug Delivery?

Answer 32

1. Slow onset of drug action.
2. Possibility of irregular absorption.
    Presence/absence of food and food type
3. Exposure too harsh stomach environment.
    Low pH and enzymes
4. First pass metabolism of susceptible drugs.
5. Need to consider organoleptic properties.

Question 33

Solutions

Answer 33

The drug is dissolved in the solvent, which is usually water. Solutions allow for faster absorption and a quicker onset of action as the drug is already in
solution. As well as the drug and solvent solutions may also contain co-solvents other than water to improve drug solubility, buffers to control pH, colours and
flavourings to improve patient compliance and use, preservatives to prevent microbial contamination.

Question 34

Suspensions

Answer 34

Finely divided drug particles are suspended in the liquid phase (vehicle). For this to occur, the drug must be insoluble in the vehicle. Suspensions are useful for delivering a liquid dose of a poorly or insoluble drug, where formulation into a solution or tablet is not appropriate due to solubility issues. Suspensions tend
to have slower absorption that solutions as the drug particles need to solubilise in the GI fluid before being absorbed. As well as the drug and vehicle, suspensions may also contain wetting agents, suspending agents, organoleptic and preserving agents.

Question 35

Emulsions

Answer 35

Consist of two (or more) immiscible liquids, one of which is dispersed as small droplets (0.1-10µm in diameter) within the other. Such emulsions are
thermodynamically unstable since they tend to separate. Therefore, emulsifying agents are included. The drug is contained in the dispersed phase either as a solution or a suspension. Two types of emulsions exist; oil-in-water (o/w) or waterin-oil (w/o).

Emulsions are intrinsically unstable and creaming occurs when globules of the
disperse phase accumulate at the top or bottom of the system (depends on
densities). Cracking occurs when coalescence of the disperse phase globules leads
to complete phase separation.

Question 36

Capsules

Answer 36

Solid dosage forms containing drug in a hard or soft gelatin shell. Excipients can include diluents, lubricants and glidants, wetting agents and
disintegrants.

Question 37

Soft gelatine capsules

Answer 37

Soft gelatin capsules are pharmaceutically elegant, one-piece units that can be coloured and flavoured, and virtually any shape (oval and oblong most popular).
They contain liquids or semi-solids and can be coated to prevent degradation in the stomach or to delay release of the contents.

Question 38

Hard gelatine capsules

Answer 38

Hard gelatin capsules consist of two cylinders closed at one end, the shorter of which (the cap) fits over the open end of the other (the body). They are available in
a range of sizes and can be coloured with the majority filled with powders or granules, but may contain pastes, capsules or tablets Their filling with powder
requires good powder flow, no adhesion and good cohesion properties.

Question 39

Tablets

Answer 39

Solid dosage form that contain a drug and are formed by powder compression. Excipients can include diluents, disintergrants, binders, glidants, lubricants, sorbants, flavours, coulourants and antiadherents.

Tablets may be swallowed whole, chewed then swallowed, dissolved or dispersed in water then swallowed. They can be plain or coated (e.g. sugar, film, gelatin, enteric coats) and intended for immediate-, modified- or delayed-release of the drug.

Question 40

Alternative Routes of Drug Delivery?

Answer 40

 Rectal
 Vaginal
 Nasal
 Ocular
 Aural
 Oral cavity
 Pulmonary
 Topical
 Implants

Question 41

Rectal Drug Delivery

Answer 41

Dosage forms that are administered via the anus into the rectum. Suppositories are the most common dosage form used for rectal drug delivery. However, solutions and suspensions (enemas) and liquid-filled gelatin capsules may also be used.

Is used to achieve a local effect to relieve pain and itching from haemorrhoids through the administration of local anaesthetics, vasoconstrictors, antiinflammatories, astringents, antiseptics and/or providing soothing or protective properties. They can also be used for a laxative effect e.g. bisacodyl, docusate sodium, glycerol or for a systemic effect, such as sustained pain relief e.g. diclofenac sodium and nausea and vomiting relief e.g. prochlorperazine.

Question 42

Vaginal Drug Delivery

Answer 42

Mainly used for the treatment of local conditions such as trichomonas and candida infections or spermicidal contraceptives. Some drugs can
be administered via this route for systemic effect such progesterone for Premenstrual Syndrome (PMS) and Hormone Replacement Therapy (HRT).
There are a range of vaginal dosage forms available such as creams, gels, pastes, foams, tablets, pessaries and vaginal rings.

Question 43

Nasal Drug Delivery

Answer 43

Used for local effect e.g. ephedrine (decongestant) or systemic effect e.g. sumatriptin (anti-migraine agent). It is an easily accessible route, with good blood supply and there is rapid absorption from nasal membranes, while it avoids first pass metabolism. Nasal dosage forms are usually aqueous solutions e.g. Rynacrom™ and Otrivine™, but can also be aqueous suspensions e.g. Beconase™ or creams and ointments e.g. Naseptin™, Bactroban™.

Question 44

Ocular Drug Delivery

Answer 44

Used for local treatment of the eye e.g. infection, inflammation or glaucoma. However, the bioavailability of the drug is usually low due to the barrier
properties of the conjunctiva and cornea as well as loss of drug due to tear turnover. A range of dosage forms such as solutions, ointments, gels and suspensions are
available and the preparations need to be isotonic and sterile to reduce pain and the risk of infection.

Question 45

Aural Drug Delivery

Answer 45

Administered into the ear canal and used solely for local treatment. The formulations are usually quite viscous, to prolong contact with the affected area. Used to treat:
 Ear wax: e.g. Otex™ ear drops
 Earache: e.g. EarCalm™ ear spray
 Infection: e.g. Canesten™ solution
 Inflammation e.g. Tri-Adcortyl Otic™ ear ointment

Question 46

Buccal Delivery

Answer 46

The dosage form is placed against the inner cheek. The buccal mucosa (inside of the cheek) is thin, has a rich blood supply and avoids first pass
metabolism, however, there is little to no agitation and the mucus level is limited. Therefore, the formulation must remain in contact with the buccal mucosa to allow
absorption of drug. Taste becomes an important factor and bioadhesive excipients may be required. Examples include:
 Buccastem™: buccal tablets
 Nicorette™: chewing gum

Question 47

Sublingual Delivery

Answer 47

The dosage form is placed under the tongue. The sublingual epithelium is thinner than buccal tissues, and is immersed in saliva, which will aid rapid absorption. First pass metabolism is again avoided, however, taste and bioadhesive issues remain. Examples include:
 Nitrolingual™ Pump spray
 Temgesic™ sublingual tablets

Question 48

Pulmonary Drug Delivery

Answer 48

Drug are delivered to the lungs usually for the
treatment/prophylaxis of airway diseases such as asthma and cystic fibrosis. The lungs are a huge, moist area for available for drug absorption that avoids first pass metabolism, so it does have the potential for delivering systemically-acting drugs such as insulin and morphine.

Question 49

Topical Drug Delivery

Answer 49

The drug is applied to the skin for either local (e.g.
hydrocortisone for anti-inflammatory) or systemic (e.g. estradiol for HTR) effect, however, absorption can be low and erratic. Dosage forms used include creams,
ointments, pastes, gels, solutions, lotions, emulsions and transdermal patches. Transdermal patches release drug to the skin at a controlled rate and have an adhesive layer to attach the patch to the skin. They can cause sensitivity reactions.

Question 50

Implantable Drug Delivery Devices

Answer 50

Sterile, solid dosage forms designed to be
inserted (usually) under the skin to provide continuous long term drug therapy through slow drug release. Examples include Zoladex™ for prostrate and breast
cancer and Implanon™ for contraception. A health professional is required for insertion and removal.