Routes of Drug Administration
Presented by:
Marcia Williams
Routes of Drug Administration Introduction
May be classified asENTERAL and
PARENTERAL.
Enteral means has to do with the GI tract and includes oral, buccal, and rectal. Parenteral means not through the alimentary canal and commonly refers to injections such as IV, IM, and SC; but could also include topical and inhalation. IV can be distinguished from the rest, as with all others at least one membrane must be crossed, thus an absorption process is involved in the administration and the pharmacokinetics.Buccal/Sublingual
Route
Buccal/Sublingual
Route
Factors affecting oral mucosal delivery:
Lipophilicity of the drug:Slightly higher lipid solubility required than for GI absorption
Salivary secretion:Absorption is delayed if mouth is dry
Drug must be soluble in aqueous buccal fluid.
pH of the salivaUsually around 5
Favourable absorption rate for unionized drug
Factors affecting oral mucosal delivery (contd)
Binding to oral mucosaBinding decreases bioavailability
Thickness of oral epitheliumSublingual faster than buccal
Advantages of buccal sublingual administration
First pass - The liver is by-passed thus there is no loss of drug by first pass effect for buccal administration. Bioavailability thus is higher. Rapid absorption - Because of the good blood supply to the area absorption is usually quite rapid. Drug stability - pH in mouth relatively neutral (cf. stomach - acidic). Thus a drug may be more stable.Disadvantages of buccal sublingual administration
Holding the dose in the mouth may be inconvenient. If any is swallowed that portion must be treated as an oral dose and subject to first pass metabolism. Only small doses can be accommodated easily.Isosorbide concentrations after a 5 mg oral or sublingual dose.
Data from: Assinder et al. J Pharm Sci 66:775, 1977.
Effect of buffer pH on the buccal absorption of nicotine
Adapted from: Svensson CK. Clin Pharmacokinet 12:30, 1987.
Rectal Route of Administration
aspirin, dipyrone, paracetamol, theophylline, chlorpromazine and some barbiturates
Advantages: By-pass liver - Some of the veins draining the rectum lead directly to general circulation - by-passing the liver. Useful for patients unable to take drugs orally or with younger children. Disadvantages: Erratic absorption - incomplete and erratic. Not well accepted.Availability (%) of lidocaine after IV, oral and rectal administration
Data from: de Boer et al. Clin Pharmacol Ther 26:701-709, 1979.
SubjectIV
1100
2100
3100
4100
5100
6100
100
Oral
17
49
53
13
35
37
34
Rectal
59
87
80
31
100
59
71
Intravenous
Route of Administration
Intravenous
Route of Administration
Advantages:
Rapid - A quick response is possible Total dose - The whole dose is delivered to the blood stream. Large doses can be given by extending the time of infusion. Veins relatively insensitive - to irritation by irritant drugs at high concentration in dosage forms.Intravenous
Route of Administration
Disadvantages:
It may be difficult to find a suitable vein. May be toxic - Because of the rapid response, toxicity can be a problem with rapid drug administrations, could then be given as an infusion while monitoring for toxicity. Requires trained personnel - Trained personnel are required to give intravenous injections. Expensive - Sterility, pyrogen testing and larger volume of solvent means greater cost for preparation, transport and storage. Risk of infection.Intravenous
Route of Administration
There are some preparations that, due to poor solubility of the drug, contain solvents that may produce rate-related toxicity. For example, diazepam injection USP contains 40% propylene glycol, among other solvents. Injected rapidly, diazepam may induce hypotension or arrhythmias. For this reason, it is recommended that IV injections of diazepam be given no more rapidly than 1 mL/min.
While it is generally viewed that 100% of drug administered
intravenously is bioavailable, prodrug administration via this
route may result in less than 100% bioavailability.
Drug Bioavailability
Chloramphenicol succinate~70%
Dexamethasone phosphate~90%
Dexamethasone sulfate~40%
Prednisolone phosphate~90%
Prednisolone phthalate~50%
Comparative bioavailability of IV chloramphenicol succinate and oral chloramphencol palmitate
IV PO
Mean C90-min (mg/L)22.627.5
Mean AUC (mg/hr/L) 78110
Subcutaneous Route of Administration
This involves administration of the drug dose just under the skin.Advantages:
Can be given by patient, e.g. in the case of insulin Absorption slow but usually complete. Absorption rate can be improved by massage or heat. Vasoconstrictor may be added to reduce the absorption of a local anesthetic agent, thereby prolonging its effect at the site of interest.Subcutaneous Route of Administration
Disadvantages:
Can be painful Irritant drugs can cause local tissue damage Maximum of 2 ml injection thus often small doses limit use.D. Subcutaneous
Advantages:
prompt absorption from aqueous solnslittle training necessaryavoid harsh GI tract environmentcan be used for suspensionsDisadvantages:
cannot be used for large volumespotential pain and tissue damagevariability in absorption from various sitesSubcutaneous Route of Administration
Methods of increasing the rate of absorption
Enhancing blood flow to the site of injectionBy massaging, application of heat, co-administration of vasodilators locally or by exercise.
Increasing the drug-tissue contact area:By co-administering the enzyme hyaluronidase that breaks down the connective tissue - permits the drug to spread
Subcutaneous Route of Administration
Methods of decreasing the rate of absorption
VasoconstrictionBy local cooling
Co-injection of a vasoconstrictor such as adrenaline
Immobilization of limb
Sites for SC injection
Disappearance of I125-insulin from subcutaneous injection
at different sites. Data from Koivisto & Felig, Ann Intern Med 92:59, 1980.
Disappearance of I125-insulin from subcutaneous injection
at different sites. Data from Koivisto & Felig, Ann Intern Med 92:59, 1980.
Intramuscular Route of Administration
Intramuscular
Injection is administered into the gluteal muscle of the buttock or the deltoid muscle of the upper arm and the vastus lateralis muscle of the thigh.Larger volume than SC can be given by IM A depot or sustained release effect is possible with IM injections, e.g. procaine penicillin The site of injection will influence the absorption, generally the deltoid muscle is the best site Absorption is sometimes erratic, especially for poorly soluble drugs, e.g. diazepam, phenytoin. The solvent may be absorbed faster than the drug causing precipitation of the drug at the site of injection.Advantages:
less skill necessary for administrationcan be used to administer oily vehiclesprompt absorption from aqueous solnDisadvantages:
painfulcannot be used in presence of abnormal clotting timedrug may ppt at the site of administrationvariability in bioavailabilityZ-track method for IM injections
Injection site
deltoid
vastus lateralis
gluteus maximus
Males
11.7
9.8
11.1
Females
10.2
9.4
4.3
Data from: Vukovich et al. Clin Pharmacol Ther 18:215, 1975.
Peak plasma cephradine concentrations (mcg/mL) after IM
administration to different sites in male and female
subjects
Inhalation
Route of Administration
C. Nasal
Historically utilized only for local effectsGrowing number of compounds administered intranasally that are intended for systemic effectsFor drugs that are destroyed in the GI environment (or first-pass effect)As an alternative to intravenous administration better safety and patient acceptanceDrugs include anticonvulsants (midazolam), narcotic antagonists (naloxone), peptides (calcitonin, insulin), and smoking cessation agents (nicotine)
Mucosal Atomizer Device
From: www.ofmaa.org
Intranasal naloxone administration in the field by paramedics
Factors that influence absorption from the nasal mucosa
pHConcentrationMolecular weightFormulationCondition of nasal mucosaFigure from: http://www.drugdeliverytech.com/cgi-bin/articles.cgi?idArticle=61
Nasal to brain delivery of drugs
Topical
Route of Administration
40
50
60
70
80
90
100
110
0306090120
Time (minutes)
% of initial counts
Abdomen
Arm
Leg
Oral
Sublingual
0
2
4
6
8
10
12
14
51530456090120
Time (min)
Isosorbide Conc (ng/ml)
0
5
10
15
20
25
30
35
55.566.577.589
Buffer pH
% Absorbed