Suppository, Inserts, and Sticks Flashcards
Suppository
Solid DF
One or more API dispersed in suitable base
Molded formed into shape for insertion
Insertion in orificies for systemic or local effects
Inserts
Solid DF
insert naturally occurring body cavity other than rectum (w/ mouth or rectum)
Medication Sticks
convenient form of administration
Reasons for choosing rectal route:
- Patient cannot make use of the oral route
- The drug is not well suited for oral administration
- For localized treatment
Reasons for not using route
- Cultural acceptance
- Slow and incomplete absorbance of drug
- Inter- and intra- drug level variations
- Difficult for large- scale production
Why is water attracted with a resulting unpleassnt sensation ofor the patiens?
Due to osmotic effects
Enzyme not present in rectum resulting to greater stability of peptide-like drugs
Esterase or Peptidase
T/F. Penetration enhancers may be used in improve the absorption profile of the drugs
True.
How is drug from the rectum absorbed?
Through passive diffusion
Is the rate and extent of drug absorption in the rectum lower or higher than the oral route? Why?
Lower than oral Route due to small surface area of absorption
What vein in the hepatic system causes the first-pass effect?
Superior Hemorrhoidal Vein
What is the limitation of the use of surfactants in rectal drug delivery?
Surfactants may lead to irritation to the rectal mucosa
This delivery contains low amount of fluid and has limited buffer capacity
Rectal Drug Delivery
At what mL do rectally instilled preparations tend to be confined in the rectum or sigmoid colon? Then where does it travel after this?
About 50 mL, to the ascending colon if more mL
T/F. Drugs in rectal drug delivery are erratically absorbed.
True. They are unpredictable or incompletely absorbed.
Advantages of Rectal Administration
▶ First-pass effect
▶ Drug stability
▶ Large dose drugs
▶ Irritating drugs
▶ Unpleasant tasting or smelling drugs
▶ Pediatric use
▶ Unconscious, n/v
▶ Upper GIT disease
▶ Rapid drug effect system
Disadvantages of Rectal Administration
▶ Lack of flexibility of the dosage
▶ Expensive (high demand)
▶ Exhibit variable effectiveness
▶ Erratic absorption
▶ Dose of drug may be greater than or less than the dose of the same drug given orally
▶ Factors affecting dosing (anatomic and physiologic factor and physicochemical factors)
▶ Physiologic Factors and Drug effect (i.e. Circulation route and pH and lack of buffering capacity of rectal fluids, colonic content)
What factors affect the greater absorption in the rectum?
▶ fecal matter
▶ enema
▶ diarrhea
▶ colonic obstruction d/t tumor,
▶ tissue DHN
In Lipid - Water Partition Coeffcient of the drug, the base consideration is an important decision. What base is suitable for a lipophilic drug?
Fatty base
Physicochemical factors of the drug and base that affect rectal absorption
▶ lipid water solubility
▶ particle size
▶ lipid water partition coefficient in relation to suppository base
What base is suitable for a water soluble or oil soluble drugs?
Water - soluble drugs
Why are rectal suppositories have a thicker end?
To prevent expulsion when the sphincter contracts
How should the rectal drug be inserted in the rectum?
Inserted base or blunt end up
Absorption of rectum, a lipoidal system, is through the?
Superior vena cavaa
Where is rectal drug delivery dependent?
Physicochemical properties of Drug
Composition of Base
What is a useful measure for drug absorption?
Partition between suppository base and rectal fluid
How does uptake in rectal drug delivery occur?
Trancellular absorption via pH parition hypotheses
Use of Surfactants in Rectal Drug Delivery
Modify membrane permeability
enhance wetting and spreading of base
dissolution of the drug
What animal of choice is used in evaluation of rectal drug availability?
Dogs
In the treatment of local conditions like hemorrhoids, what base is widely used for rectal drug delivery?
Fatty ointments
What delivery forms are employed in the administration of drugs for systemic effects?
Tablets, capsules, microenemas
Characteristics of rectal suppositories in adults include:
tapered at one or both ends
weighing 2 g
bullter torpedo or little finger
32 mm (1.5 in.) long
What is the weight of pediatric rectal suppositories? What is its shape?
half the wt and size of adult
pencil shape
The 2 g weight for rectal adult suppositories is based on what suppository base?
Cocoa butter base
What indications of drug have systemic effect and administred rectally?
Sedatives, Tranquilizers, Analgesics
the largest OTC rectal suppositories
Hemorrhoidal treatment
classification of rectal suppository bases
fatty, water soluble, and water miscible
Shell suppositories similar to soft - gel capsules
Rectal capsules
They are of elongated shape and have a smooth external appearance that may be lubricated.
Rectal Capsules
For capsules, to achieve a systemic effect, how is it usually filled with?
Solution of suspension of the durg in vegetable oil or liquid paraffin
Why do rectal tablets have difficulty in disintegrating?
Due to low amount of water present in the rectum
Have difficulty disintegrating due to low amount of water present in the rectum
Rectal Tablets
Used to stimulate defecation
Effervescent rectal tablet preparations
Substances in liquid form designed for rectal administration
Enemas
Component of Enemas
Vehicle or
One or more active substance dispered in sutiable solvents
Solvents used in enemas for active substances
Water
Glycerol
Macrogols (PEGs)
Stabilizers and excipients help enemas through?
Improvement of dissolution rate
Contains small volume (approx. 3mL) rectal DF which can release drug immediately without melting and dissolution if the vehicle is water
Microenemas
Rectal Powders are used for
Solutions
Why are rectal powders lyophilized?
To have a porous product that has a large surface area and dissolves rapidly
These are inserted in the lower part of the rectum for a limited time and removed.
Rectal tampons
What is the dose of vaginal administration if local action is only intended?
smaller doses with reduced absorptionand systemic distribution toxicity
Antifungals used mentioned that can be applied in?
Clotrimazole, Miconazole, Clindamycin
Miconazole can treat
vaginal infection
What influences passive drug absorption?
Absorption site physiology
Absorption site pH
solubility and partitioning characterisitcs of he drug
Why is vaginal fluid in the women’s body acidic?
Due to the presence microflora consisting lactobacilus
What size of the particles in VDD can cause irritation in the human body
Insoluble, 50 micrometer
T/F. Vaginal pH increases with menstrual, cervical, and uterine secretions
True
Important charac of an ideal vaginal
should be long acting, reducing the frequency of administration
* should be stable in a range of climatic conditions
* should not lead to any irritation, burning or itching
* should not cause any leakage
* should not cause staining or discolouring of under garments
* the formulation should be colourless and odourless
* the formulation should not adversely affect sexual activity
* women should be able to use it without the knowledge of a male partner
* should be easy to insert and/or apply, without the need for an applicat
DDS that is usually oviform and may weigh 1 to 5 grams
Vaginalsupp. or pessaries
What base is usually used in preparing pessaries
glycerol - gelatin bases
vaginal semisolids can cause
problems of drugs that are prone to hydrolysis
Thin layers of polymeric
material for single- dose
Vaginal film
Bioadhesives utilized to minimize leakage and improve retention in vagina
Xanthan gum
Carbapol
Solid, single- dose preparations
*Ovoid (other shapes are available)
tablets that may or may not be coated
*Preferred for drugs that are prone to
hydrolysis, and in countries that are
tropica
Vaginal Tablet
controlled release, and prolonged delivery
Vaginal ring
What entraps the polymer network present in flexible and vainal renig ?
flexible, circular netowrk eg. estring
General Specifications of Supposiroty Bases
base is nontoxic and nonirritating to mucous membranes.
*The base is compatible with a variety of drugs and should be pharmacologically inert.
*The base melts or dissolves in rectal fluids.
*The base should be stable on storage; it should not bind or otherwise interfere with release or
absorption of drug substances.
Bases used in suppository bases
Cocoa butter
Cocoa butter substiute
glycerinated gelatin
halogenated vegtableoil
mixtures of PEg
fatty acid esters of PEG
What is the rate of spreading and transportation based n?
partially based viscous
Glycerinated gelatin
slow dissolution
What type of emulsions suppository that increases the propbabiity of drug transfer to the inner phase?
o/w emulsions
What can be used for insufficient air displacement and agglomeration that can affect dissolution of drug particles and increase producing a w/o emulsions system?
Surfactants
Increasing viscosity causes agglomeration, name viscosity enhancing additives that can slow down the release of drugs?
colloidal silicon dioxide
aluminum monostearte
lecithin addition causes what to high amount solid drugs?
decreases the attraction between the drug particles, enhancing the flow properties of the dispersion
reasons why cocoa butter is not used as a base?
*polymorphic behaviour,
*insufficient contraction during cooling,
*low softening point,
*chemical instability,
*poor water-absorptive power, and its price`
parameter that refers directly to the amount of mono- and di-glycerides present in the fatty base
hydroxyl number of these bases
advantage of high OH bases
larger melting capacity and solidifying ranges
Other name for cocoa butter
theobroma oil
content of unsaturated FA in theobroma oil
40%
Cocoa butter melts at
body temperature, temperature dependent
What should be added to avoid eutexia when adding theobroma oil and another substnace?
addition of higher melting wax i.e. white ewax and synthetic spermaceti
Examples of CB substitutes
Palm Kernel Oil
Cottonseed Oil
Stearic Acid
Palmitic Acid
Glycerol Monopalmitate
Glycerol MonostearteAdva
Advantages of CB substie over CB
decrease potential for rancidity and phase transition behavior
Why must glycerinated gelatin be moistened prior to insertion?
It absorbs mositure as a results of hygroscopic properties of glycerin. It can have dehydrating effect and irritate tissue skin.
Examples of water soluble bases
Glycerinated gelatin a
Polyethylene glycol (macrogol)
Purpose of glycerol-gelatin base
laxative
What is prepared easily from
unlubricated molding, but not so from handrolling
PEG suppositories
What does cooling to near the melting point prevent?
Prevent fissuring caused by crystallization
Components of glycerinated gelatin
Glycerin - 70%
Gelatin - 20%
Drug 10%
What does a higher proportion of gelatin indicate in the glycerinated gelatin based?
The base will be rigid and more long acting
What base is usually used for vaginal supp instead of rectal?
Glycerinated gelatin, it can cause osmotic laxative effect in rectal supp.
How to decrease induced irritation of the rectum for PEG?
addition of at least 20% water and moistening before insertion
Why should PEG bases be stored in tightly packed containers?
To avoid the development of peroxides in the base
How are suppositories produced?
Hand molding
Molding (fusion)
Cold Compression
It is the oldest and simplest method, by rolling the suppository into the desired shape. The mass is then rolled into a cylindrical rod of desire length and diameter.
Hand molding
Elegant suppository can be made by compression the cold-grated mass into the desired shape .
It is simple and more elegant appearance than hand molding.
It avoids the possibility of sedimentation of the insoluble solids in the suppository base.
Compression Molding
Most commonly used method for production of suppository on both small & large scale.
First, the base is melted on water bath, and then the drugs are either emulsified or suspended in it. Then, the mass is pour into cooled metal molds, which are usually chrome or nickel plated.
Pour Molding
The molding operation (pouring,
cooling & removal) can be
performed by machine .
The output of a typical rotary
machine, range from 3500 to
6000 suppositories per hour
Automatic Molding Machine
PEG bases are incompatible with
Silver salts
Tannic Acids
Aminopyrine
Quinine
Icthammol
Aspirin
Benzocaine
Sulphonamides
Softerns PEG
high concentration of salicylic acid
What is added to improve consistency of suppositories?
Stearyl, cetyl, myristyl alcohols, stearic acid
What makes syntheic fat bases more brittle?
high degree hydrogenation
high stearate content
higher solid contents
contraction facilitate the removal of
the suppository from the mold , eliminating the need for mold release agents
Good mold release
Mold Releasing agents
mineral oil aq soln of sls
alcohols
silicones
soap
It results from the autoxidation and
subsequent decomposition of unsaturated fats into low & medium molecular weight saturated & unsaturated aldehydes, ketones and acids, which have strong unpleasant odor
Rancidity
