Lecture 6

Intra l Drug Delivery

Advantages

Easiness of administration,

Possibility of auto-administration,

Bypassing hepatic first pass-effect,

Used for both systemic and local drug delivery,

Low enzymatic activity.

The possibility of preferential transfer of absorbed drugs to the

uterus (referred as the first-uterine-pass effect)

Disadvantages

Use of the as a preferential route of drug delivery does not

seem to be feasible for most drugs,

Gender-specificity is a strong barrier to the use and development of

l drug delivery,

Menstrual cycle associated l changes,

Genital hygiene issues,

Local side effects,

Variable drug permeability.

Factors affecting drug absorption from the

Condition of the epithelial membrane.

Nature of the delivery system.

Physicochemical factors of the drug including molecular weight

and size, lipophilicity, ionization state,..etc.

Thickness of the l wall and factors influencing it e.g. ovarian

cycle, pregnancy and post menopausal changes.
 Presence of cervical mucous.

Rate limiting step for systemic drug absorption via the

Drugs with high l membrane permeability coefficient.

Permeability across the layer formed by l fluid Sandwiched

between the l epithelial membrane and the delivery device.

Drugs with low l membrane permeability coefficient.

Permeability across the l epithelium.

Therefore,

For systemic drug absorption to occur from the l route; the drug
must have:

Sufficient lipophilicity to diffuse through the lipid structure of

the membrane.

Some degree of aqueous solubility to ensure dissolution in l

fluid.

Types of intra l drug delivery systems

Gels/Hydrogels

Adv : rapid drug release from conventional gels, suitable for relatively
polar drugs, viscoelastic properties may enhance intra l residence time.

Disadv : messy in use, prone to leakage and do not offer sustained release
over long periods.

Ointments and creams

Disadv : messy in use, prone to leakage and do not offer sustained release
over long periods.
Tablets

Adv : may be formulated with mucoadhesive polymers.

Disadv : unlike oral solid dosage form, it has limited applications for
controlled release. Mostly suitable for immediate release application.

Pessaries/Suppositories

Adv : rapid drug release, can accommodate drug in solution or

suspension.

Particulate systems (nanoparticles, microspheres,..etc)

Adv :

-Controlled release possible via reservoir, erodible and swelling

mechanisms.

-Use of polyadhesive polymers for a sustained effect.

-Enhance intra l distribution.

-May offer protection for labile drugs.

-May be combined with other systems e.g. gels where the gel act as a
drug carrier.

Intra l ring

Design

The l ring is a flexible ring about 2 inches in diameter that is

inserted into the .

The ring contains solid drug homogenously dispersed throughout a

polymeric matrix. It is mainly used to release progestin and
estrogen into the body to avoid pregnancy.

The drug release rate is proportional to both the drug loading and
the surface area of the device.
 Drug release from these systems is via matrix permeation
mechanism, involving dissolution of the well dispersed drug
particles into the surrounding polymer network. Drug molecules
near the surface of a matrix ring are released first, creating a drug
depleted layer, which other solubilized molecules in the inner
layers of the ring must diffuse through in order to be released.

Partition into and diffusion across the l fluid then take place;

Penetration through the l epithelium to the blood is the last

step.

Advantages

Permits self insertion and removal.

Provides constant controlled drug release with minimal plasma

level fluctuation.

Disdvantages

Increased frequency of l discharge among ring users which

could contribute to its discontinuation.

Rectal Drug Delivery

Physiology of the rectum

The length of the human rectum is approximately 10-15 cm.

Rectal fluid content is about 3ml and has a pH of 7-8.

No villi are present in the rectum so the area of drug absorption

from the rectal route is very small compared to that of the small
intestine.
 The rectum is drained by three veins ; superior, middle and inferior
rectal veins. The superior and middle rectal veins drains to the
portal circulation whereas, the inferior vein bypasses the portal
circulation and goes directly to the general circulation.

Advantages

Used for both local and systemic effects;

Objectionable drug taste can be avoided (particularly in children);

The rate of drug absorption is not influenced by the ingestion of

food or the rate of gastric emptying;

First pass effect partially avoided.

Contact with the digestive fluids of the upper GIT is avoided,

thereby preventing the breakdown of some drugs.

Disadvantages

Patients acceptability of rectal administration is poor.

Drug absorption from the rectal mucosa may be interrupted by

defecation (particularly with irritant drugs).

The surface area available for drug absorption is considered small.

The small volume of rectal fluid may produce problems with

dissolution of some drugs.

Some drugs are subjected to degradation by the microorganisms of

the rectum.

Factors affecting drug absorption from the rectal mucosa

Nature of the formulation

 Mucoadhesive liquid suppositories

These drug delivery systems combine bioadhesive properties with

thermal gelling polymers.

Bioadhesive polymers: Hydroxypropylcellulose, carbopol;

Thermal gelling polymers: Poloxamer 407 and Poloxamer 188.

Gellation temperatures falls between 30 and 36C.

These dosage forms increases bioavailability because they offer

reduced formulation migration as a function of mucoadhesive
potential.

They offer sustained and controlled release drug formulations.

Lecture 7

Transdermal Drug Delivery

Advantages

Provides controlled continuous delivery of drugs via the skin to

the systemic circulation.

Provides non-painful delivery of the drugs, therefore, increases

pts compliance.

Avoids first pass effect.

Avoids various GIT conditions including digestive fluids of the

upper GIT, variability in drug absorption rates due to drug and
food ingestion and gastric emptying rate.

Allows removal of dose if any side effect starts to appear.

Ease of application.

Disadvantages

Possibility of local irritation at the site of application (especially

with long term application)
 Erythema, itching, and local edema can be caused by the drug, the
adhesive, or other excipients in case of patch formulation

Factors affecting transdermal bioavailability