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