DDS LEC - L1: Suppositories and Transdermal Drug Delivery Systems

Suppositories

• Solid dosage form in which one or more active pharmaceutical ingredient are dispersed in a suitable base and molded into a suitable shape for insertion into body orifices

• Intended for insertion into body orifices where they melt, soften, or dissolve and exert local or systemic effects

Reasons Suppositories Have Been Employed

• Promote defacation

  • laxative

  • by irritating mucus membrane in rectum

• Introduce drug into the body

  • absorption: rectum → systemic effect

• Treat anorectal disease

  • local effect

Advantages of Suppositories

• Avoid first-pass effect

  • won’t pass through digestive system

  • no hepatic

  • won’t be degraded by acid

• Drug stability

• Large-dose drugs

  • easier to administer

  • can make large bullets up to 5 grams

• Irritating drugs

  • pwede ilagay and it won’t irritate the digestive system

• Unpleasant tasting or smelling drugs

• Achievement of rapid systemic drug effect

  • directly absorbed

  • wala nang ibang dadaanan

Disadvantages of Suppositories

• Perceived lack of flexibility

  • social stigma

  • uncomfortable

• Expensive if made on demand

  • because there are only few formulations here

  • pinapagawa pa sa ibang bansa

• Defacation may interrupt absorption process

• Absorption surface area is smaller

  • only rectal

• Possibility of degradation (possibly from different local environment)

Local Action

• Affects only where you apply it

  • Rectal Suppositories

  • Vaginal Suppositories

  • Urethral Suppositories

Rectal Suppositories

• Tapered at one or both ends

• Bullet shape

• Size

  • Adult - 32 mm

  • Child - 1 g

• Weight

  • Adult - 2 g

  • Child - 1 g

• Frequently used to relieve constipation or the pain, irritation, itching, and inflammation associated with hemorrhoids

  • Ex. Glycerin Suppositories - has dehydrating effect used to defacate

32 mm; 2 g

Size and Weight of Rectal Suppository for Adults

16 mm; 1 g

Size and Weight of Rectal Suppository for Children

Vaginal Suppositories

• Pessary (other name)

  • US - medical device to avoid hip bending

  • British Pharmacopoeia - vaginal suppository

• Globular, conical, or oviform in shape

• Weight:

  • 5 g

• Employed mainly as contraceptives, antiseptics, and specific agents for invasive pathogens

  • Ex. Nonoxynol 9 - spermicidal agent that breaks lining to not reach the egg cell

  • Ex. Trichomonacides - Candida albicans

5 g

Weight of Vaginal Suppositories

Urethral Suppositories

• No longer used because it is invasive

• Bougies (other name)

• Thinner and tapered, slender, pencil-shaped

• Size:

  • Male - 140 mm

  • Female - 70 mm

• Weight:

  • Male - 4 g

  • Female - 2 g

• Used for antibacterial or local anesthetic

• Smaller in size

140 mm; 4 g

Size and Weight of Urethral Suppository in Males

70 mm; 2 g

Size and Weight of Urethral Suppository in Females

Systemic Action

• Whole body effect

• The mucous membrane of the rectum permits absorption of many soluble drugs

  • Ex:

    • Chlorpromazine

    • Morphine - opioid analgesic

    • Ergotamine - migraine

    • Ondansetron - nausea and vomiting

Bases

• Plays an important role in the release of the medication

• Requirement:

  • _____ should remain solid at room temperature, but soften, melt, or dissolve readily at body temperature.

Types of Bases

1. Fatty or Oleaginous Bases

2. Water-Soluble and Water-Miscible Bases

3. Miscellaneous Bases

Fatty or Oleaginous Bases

• Most frequently employed suppository base

• Examples:

  • Palm Oil

  • Kernel Oil

  • Cottonseed Oil

  • Cocoa Butter, NF

Cocoa Butter, NF

• From the roasted seed of Theobroma cacao

• Yellowish-white solid with agreeable chocolate-like odor at room temperature

• Melting point range: 30°C to 36°C

Form VI (β’1)

Most stable and preferred polymorph form

Water-Soluble and Water-Miscible Bases

• Must be placed in a container that is impervious to liquids or vapors

• Examples:

  • Glycerinated gelatin

  • Polyethylene glycols

  • glycol-surfactant combinations

• Downside: If it is oil-loving, it will stay sa rectum lang

Miscellaneous Bases

• Mixtures of oleaginous and water-soluble or water-miscible materials

• More stable than water-soluble

• Polyoxyl 40 stearate - mixture of monostearate and distearate esters of mixed polyxyethylene diols and free glycols

Polyoxyl 40 stearate

Mixture of monostearate and distearate esters of mixed polyoxyethylene diols and free glycols

Methods of Preparation

• Fusion or Melt Molding

• Compression Molding

• Hand Rolling and Shaping

Fusion or Melt Molding

• Most common method

• Molds

  • Made from stainless steel, aluminum, brass, and plastic

  • Capacity: 6, 12 to 50 g

• Pouring is done excessively because it shrinks when cooled

Compression Molding

• Forcing the suppository mixture into special molds using suppository-making machines.

• For drugs that are thermolabile and for drugs that are insoluble in the base.

• Mix and then put to machine

Hand Rolling and Shaping

• Traditional method

• Uses grated cocoa butter

  • Triturate with other ingredients

  • Roll them into a ball

  • Turn to cylinder in preferred size

  • Use fingertips to make it bullet-shaped 

    • Use glassine so that it’s not sticky

Vaginal Inserts

• Compressed tablets accompanied with a plastic inserter

  • Intended to be administered and inserted in the vagina

• Disintegrates in the vagina after administration

• Easy to manufacture, stable, and less messy than suppositories

Medication Sticks

• Convenient form for administering topical medication

• Prepared similar to suppositories, except the the melt is poured into the administering device

Transdermal

• Deliver drug through the skin to the general circulation with the skin not being the target organ.

• Occlusive

• Works best in less keratinized (hindi makapal) and less hairy skin

Richard Stoughton

First conceived of the percutaneous absorption of drug substances in 1965.

Scopolamine

• Drug for motion sickness, nausea and vomiting

• Administered at the back of the ear

Skin

Provides a reasonable site to administer therapeutic agents for both local and systemic effects.

Factors Affecting Percutaneous Absorption

• Drug Concentration - the higher the drug concentration, the higher chance of absorption (mas nag-effect)

• Area of Application - less keratinized and less hairy area

• Physicochemical Attraction - should be sa oil-based ilalagay

• Molecular Weight - higher mw, mas gusto ang lipid layer and vise versa

• Hydration - works best on hydrated skin; doesn’t like dry parts of the skin

• Contact Time - the longer it is on the skin, higher absorption and more effective

• Vehicle Selection - should be soluble

Drug Concentration

The higher the drug concentration, the higher chance of absorption (mas nag-effect).

Area of Application

Should be applied on less keratinized and less hairy area

Physicochemical Attraction

• Lipid-Lipid

• Lipophilic - sebum prone / oil-based

  • Should be sa oil-based ilalagay

• Ionized - better penetration

Molecular Weight

Higher MW, mas gusto ang lipid layer and vise versa

Hydration

• Works best on hydrated skin

• Doesn’t like dry parts of the skin

Contact Time

The longer it is on the skin → higher absorption and more effective

Vehicle Selection

• Vehicle should be soluble

• Soluble API

Transdermal Parts

• Occlusive Backing

• Drug Reservoir

• Release Liner

• Adhesive Layer

Occlusive Backing

Protect the system from environmental entry and from loss of drug from the system.

Drug Reservoir

• Store and release the drug at the skin site

  • API is stored here

• Protected by Occlusive Backing

Release Liner

Removed before application and enables drug release.

Adhesive Layer

• Maintain contact with the skin after application.

• Sticky part

Design Features

• Monolithic Systems

• Membrane-Controlled Systems

Monolithic Systems

• No Drug Reservoir

• Drug is incorporated in a drug matrix layer that controls the rate at which the drug is released for absorption.

  • API is directly here

• Matrix may either be with or without excess of drug.

• Example:

  • Nicotine Patch

Membrane-Controlled Systems

• Has Rate-Controlling Membrane

• Has Drug Reservoir/pouch

• Has the backing, adhesive, and protecting layers

• Release-Rate is controlled by the membrane

  • Dahan-dahan i-ddump ang API

Advantages of Transdermal Delivery Systems

• Avoid first-pass effect

• Substitute for oral administration

• Noninvasive (compared to suppositories), avoiding inconvenience of parenteral therapy

• Provide extensive therapy (can add potency) with single application

• Activity of drugs with short half-life is extended

• Drug therapy may be terminated rapidly (can just take it off)

Disadvantages of Transdermal Delivery Systems

• Only relatively potent drugs are suitable candidates

• Patients can develop contact dermatitis at the site of application