10 min - جامعة نزوى · 2015-02-24 · a suppository is a drug delivery system that is...

10 min

SUPPOSITORY

Chapter Content

Suppository

1. Suppositories and Factors Affecting Drug Absorption

2. Ideal Suppository and Different Types of Bases

3. Methods of Suppository Manufacturing

Suppository

Learning Outcome

1. Apply the concept of suppository administration

2. Perform calculations for suppositories using different

bases

Late 14th Century

Suppositorium

"To place under"

What ?

Suppository

Suppository

Solid Dosage Form

A suppository is a drug delivery system that is

inserted into the rectum (rectal suppository),

vagina (vaginal suppository) or urethra (urethral

suppository), where it dissolves or melts and is

absorbed into the blood stream.

A suppository is a drug delivery system that is

inserted into the rectum (rectal suppository),

vagina (vaginal suppository) or urethra (urethral

suppository), where it dissolves or melts and is

absorbed into the blood stream.

BASE

Growth in Suppository

Sales WORLDWIDE

DRUG

PATIENT

NOT VERY

COMMON

DOSAGE FORMS

(SUPPOSITORY)

BASE

BASE MELTS

DRUG RECTAL FLUID SOLUTION

ABSORPTION

DRUG

PATIENT

NOT VERY

COMMON

DOSAGE FORMS

(SUPPOSITORY)

BASE

BASE MELTS

DRUG RECTAL FLUID SOLUTION

ABSORPTION

Zoom Shape 1

MUCOSA

RECTUM

RECTAL FLUID

MUCOSA

DRUG

SINK

CONDITION

ALLOWS

CONTINOUS

PASSIVE

DIFFUSION

SINK

CONDITION

ALLOWS

CONTINOUS

PASSIVE

DIFFUSION

CLASSIFICATION

APPLICATION USE

RECTAL

URETHRAL

VAGINAL

LOCAL

SYSTEMIC

Glycerin Suppository

LOCAL EFFECT

CONSTIPATION

Irritates the RECTAL MUCOSA

Peristalsis Movement of contents in GI

INDICATIONS

EASY to

ADMINISTER

Reasons for choosingRectal Route

Patient not able to use Oral route

Drug not suitable for Oral administration

Patient not able to use Oral route

Unconscious

Gastrointestinal Problem

Indigestion

Mentally disturbed

Very Young and Old Patients

Drug not suitable for Oral administration

Gastro Intestinal Side effects

Zoom Shape 1

ULCER

BLEEDING

Drug not suitable for Oral administration

Gastro Intestinal Side effects

Drug not suitable for Oral administration

Unstable in stomach pH

High FIRST PASS METABOLISM

High FIRST PASS METABOLISM

High FIRST PASS METABOLISM

High FIRST PASS METABOLISM

High FIRST PASS METABOLISM

RECTAL

IRRITATION

&

SENSATION

RECTAL IRRITATION

Rectal Fluid

DRUGZoom

Shape 1

IRR

ITA

TIO

N

IRRITATIONBODY

NATURALLY

COUNTERS THIS

WATER

MOLECULES

SENSATION

RECTAL IRRITATION

Rectal Fluid

DRUG

& SENSATION

Factors

Quantity of rectal fluid

Properties of Rectal Fluid

Particle Size of the drug

The suppository is expelled or not

Dissolution of slightly soluble

substance

The presences of surface active

agents

Physicochemical characteristics of

drug

Factors

Quantity of rectal fluid

Properties of Rectal Fluid

Particle Size of the drug

The suppository is expelled or not

Dissolution of slightly soluble

substance

The presences of surface active

agents

Physicochemical characteristics of

drug

Factors

Quantity of rectal fluid

Properties of Rectal Fluid

Particle Size of the drug

The suppository is expelled or not

Dissolution of slightly soluble

substance

The presences of surface active

agents

Physicochemical characteristics of

drug

Factors

Quantity of rectal fluid

Properties of Rectal Fluid

Particle Size of the drug

The suppository is expelled or not

Dissolution of slightly soluble

substance

The presences of surface active

agents

Physicochemical characteristics of

drug

Factors

Quantity of rectal fluid

Properties of Rectal Fluid

Particle Size of the drug

The suppository is expelled or not

Dissolution of slightly soluble

substance

The presences of surface active

agents

Physicochemical characteristics of

drug

Factors

Quantity of rectal fluid

Properties of Rectal Fluid

Particle Size of the drug

The suppository is expelled or not

Dissolution of slightly soluble

substance

The presences of surface active

agents

Physicochemical characteristics of

drug

Factors

Quantity of rectal fluid

Properties of Rectal Fluid

Particle Size of the drug

The suppository is expelled or not

Dissolution of slightly soluble

substance

The presences of surface active

agents

Physicochemical characteristics of

drug

Factors

Quantity of rectal fluid

Properties of Rectal Fluid

Particle Size of the drug

The suppository is expelled or not

Dissolution of slightly soluble

substance

The presences of surface active

agents

Physicochemical characteristics of

drug

Quantity of Rectal

Fluid

Irritation

Sensation

Zoom Shape 1

2-3 mLDRUG particles do not dissolve

Quantity of Rectal

Fluid

Irritation

Sensation

Dissolution of Slightly Soluble Substance

DRUG (Hydrophilic)

PROCESS

OF

ABSORPTION

ABSORPTION

DISSOLUTION

Crossing the RECTAL

MEMBRANE

Dissolution of Slightly Soluble Substance

DRUG (Hydrophilic)

PROCESS

OF

ABSORPTION

ABSORPTION

DISSOLUTION

Crossing the RECTAL

MEMBRANE

Dissolution of Slightly Soluble Substance

DRUG (Hydrophobic)

PROCESS

OF

ABSORPTION

ABSORPTION

DISSOLUTION

Crossing the RECTAL

MEMBRANE

DISSOLUTION

Crossing the RECTAL

MEMBRANE

DISSOLUTION

Crossing the RECTAL

MEMBRANE

RATE LIMITING STEP

Combinations

DRUG BASE

HYDROPHILIC

HYDROPHOBIC

4

It is the DRUG

that undergoes

ABSORPTION

and NOT the

BASE

MAKE THE FOUR

COMBINATIONS AND TELL THE RATE LIMITING

STEPS

DRUG

RECTAL MEMBRANE

RECTAL FLUID

BASE

COMBINATIONS

NATURE SAME MEANS NO RLS

HYDROPHILIC (Hp)

HYDROPHOBIC (Hb)

DRUG

RECTAL MEMBRANE

RECTAL FLUID

Hp

Hb

Hp

BASE

Drug (Hydrophilic) Base (Hydrophobic)

SLOWEST =RLS

ABSORPTION

Drug (Hydrophilic) Base (Hydrophobic)

SLOWEST =RLS

Drug (Hydrophilic) Base (Hydrophobic)

SLOWEST =RLSRLS

Properties of Rectal Fluid

Viscosity Surface Tension

Zoom Shape 1 Zoom Shape 1

Zoom Shape 1

VISCOSITY > ABSORPTION

Properties of Rectal Fluid

Viscosity Surface Tension

ST > Ab

Properties of Rectal Fluid

Viscosity Surface Tension

Particle Size of the drug

Absolute Surface Area

Effective Surface Area

ESTERASE

PEPTIDASE

Stability of Peptide-like Drugs

STABILITY

Physicochemical Characteristics of Drug that

Affect its Absorption

Lipid – Water Partition Coefficient

DRUGOIL

AQUEOUS

HYDROPHILIC

Ko/w

Important Points

Rancidity in fats increases the iodine value

Water number can be increased by the

addition of surfactants

Good suppository base has low acid value or

no acids

Decomposition with Acid,

moisture or oxygen

Characteristics of

Ideal Suppository

Bases

Suppository bases are agents into

which the drug is incorporated

when in a molten state and then

solidified to form the suppository.

Suppository Bases

IDEAL SUPPOSITORY BASES

Melts at 37.5o C (rectal temp) or dissolve in

body fluids

Non toxic, Non sensitizing, or Non irritating to

sensitive or inflamed tissues

Compatible with a broad variety of drugs

No meta stable forms

No meta stable forms

Solidify quickly after melting

Easily molded & easily removed from the mold

Release the active ingredient readily

High water no.- Increase % of water or

solutions that can be incorporated

Chemically stable

Easy to handle

For fatty bases,

Acid value is below 0.2

Saponification value ranges from 200 to 245

Iodine value is less than 7

Low interval between “melting point” and

“solidification point”

Function of Suppository Bases

Dilute the drug to non irritating level

Control the rate of drug release

Represent the drug in an acceptable,

usable form

Types of Suppository Bases

Cocoa Butter Substitues

Identified by the USP

Cocoa Butter

Glycerinated gelatin bases

Polyethylene glycol bases

Surfactant or water-dispersible bases

Tableted suppositories or inserts

Advantages of Suppository

Accurate dosage forms

Good, when oral dosage forms cannot be taken

Drugs sensitive to the gastric pH and gastric enzymes

Drugs irritating to the stomach

Useful in Nausea and vomiting

conditions

LOCAL EFFECT

Faster Onset of Action

May Bypass First Pass Hepatic Metabolism

Disadvantages of Suppository

Patient acceptability

Not suitable for patients suffering from diarrhea

Dose can be big and can cause irritation

Incomplete absorption as suppository promotes bowel evacuation

Different Types of Bases

Cocoa Butter (Theobroma oil)

Naturally

occurring

Polymorphism is the ability of a solid material to exist in more

than one form or crystal structure

Crystalline

Heated

above 35

°C or

solidify at

< 15 °C

Alpha, Beta, Beta prime & Gamma

Forms are recognized

It is a lower melting point polymorph and will convert to

more stable form over time

Non reactive & Non irritating

Advantages of Cocca Butter

At room temperature has a amorphous solid form

Melts at 30-35 °C to a non irritating oil

Rapidly solidifies when cooled

Miscible with many ingredients

Disadvantages of Cocca Butter

Rancidity due to oxidation of unsaturated glycerides

Melt at hot climates

Overcome by

adding beeswax -

10%

Liquefy with certain drug

Liquefy with certain drug

Overheating leads to isomerization

Insufficient contraction at cooling

Low softening point, chemical instability

Poor water-absorptive power

Expensive

Susceptible to oxidation

(need a something more hydrophilic)

Adhesion or sticking to the mold