Dosage Forms Flashcards
What is the aim of dosage form design?
To achieve a predictable therapeutic response to a drug included in a formulation which is capable of a large scale manufacture with reproducible product quality
Am what are the eight functions of additives?
Solubilise Suspend Thicken Preserve Emulsify Modify dissolution Improve the compressibility Improve the flavor of drug substances
What are the requirement for product quality?
Chemical and physical stability Preservation against microbial contamination Uniformity of dose of drug Acceptability to users Suitable packaging and labelling
Give examples of oral dosage forms (DF)
Solutions, tablets, capsules , powders ect.
Give an example of rectal DF
Ointments, crams , powders ect.
Give examples of topical DF?
Ointments, creams , lotions, gels, solutions
Give examples of parenteral DF
Injections , implants ect.
Give examples of respiratory DF?
Aerosols , sprays , inhalations ect.
Give an example of nasal DF
Solutions, inhalations
Give an example of eye DF
Solutions , ointments , creams
Give examples of ear DF
Solutions, creams , ointments and suspensions
What are three factors to be considered before the formulation of a dosage form?
Factors affecting drug absorption from different administration routes
Drug factors such as solubility
Clinical indication and Patient factors such as age , body weight other illnesses
What issues are important to design dosage forms?
Drug absorption
Drug distribution
Metabolism
Excretion
What form must a drug be in to be absorbed via the membranes and epithelial of the skin, gastrointestinal tract and lungs into the body fluids?
Drug must be in solution form
What is the rate of diffusion influenced by?
Lipid solubility and ionisation degree of the drug
Give an example of a specialised transport mechanism
Glucose transport to the brain via the glucose receptor located on the blood brain barrier
Or
P-go protein which is an ATP-dependent efflux pump capable of transporting many drugs across cell membranes
What is first pass metabolism?
Where the concentration of s drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall
Where does a drug enter once it is swallowed?
Absorbed by the digestive system and enters the hepatic portal system
Where is the drug carried after the hepatic portal system?
Through the portal vein into the liver before it reaches the rest of the body
What does the liver do in regard to drug metabolism?
It metabolizes many drugs sometimes to the extent that only a small amount of the active drug emerges from the liver to the rest of the circulatory system
What is the problem of first pass metabolism?
It greatly reduces the bioavailability of the drug
What is the bioavailable fraction determined by?
The fraction of drug that is absorbed from the GI tract and the fraction that escapes metabolism during its first pass through the liver
How may the first-pass effect be avoided?
By considering other administration for example, intravenous, intramuscular, or sublingual that avoid the first-pass effect
What must be adjusted if a different administration route is used?
The dosage
What is needed if the metabolite is inactive?
A larger oral dose is required to attain the desired therapeutic effect than with a lower dosage in a route with no first-pass effect.
Give an example of a drug with a high first pass metabolism
propranolol
What is needed if the metabolite is active?
Oral dosage must be carefully tailored to the desired therapeutic effect. First-pass metabolism in this case will result in a quicker therapeutic response than that achieved by a rout with no first-pass effect
What is the fastest to slowest in terms of onset of action?
- intra muscular injections
- buccal tablets
- capsules
- intra venous injections
- depot injections
4>1~3>2>5
How long to intra venous injections take till onset of action?
seconds
How long does intra muscular, buccal tablets, aerosols and gases take till onset of action?
minutes
How long do short- term depot injections, capsules ect. Take till onset of action?
Minutes to hours
How long do enteric-coated formulation take till onset of action?
Several hours
How long do depot-injection and implants take till onset of action?
Depot injections, implants
What are the routes of drug administration?
Oral/buccal/sublingual Respiratory route Nasal Topical route Ocular parenteral route Rectal route vaginal
What route of drug administration is the safest?
Oral route
What is absorbed by in the oral route?
Mucosa and various epithelia of GI
What is the problem with the oral route?
Slow onset of action
Risk of irregular absorption
Destruction of drugs by enzymes and secretions of the GI tract (e.g. insulin)
Where are weak acids better absorbed?
Stomach pH 1
Where are weak bases better absorbed?
In the intestine 7-8pH of the large intestine
What are the most popular oral dosage forms?
Tablets Capsules Suspensions Solutions Emulsions
What is sublingual route?
When dosage is put under the tongue
What is buccal route?
In the pouch of the cheek
Why is sublingual mucosa more permeable to the buccal mucosa?
Due to higher vascularisation and thinner epithelium (rapid onset of action)
What are problems of sublingual route?
Cannot be used for systemic transmucosal drug administration due to the wash of the area by saliva, thus there is little time for the drug to be retained at the site of action
Give an example of sublingual administrated drug?
nitriglycerin for patients with heart disease
What are general advantages of oral route of drug administration?
Non- invasive , well-accepted ,convient ,accessible
First-pass metabolism by the liver is avoided
Drugs can be given to unconscious patients
What are the advantages of sublingual routes?
Fast onset if drug action due to higher permeability
Local action of drugs
What are advantages of buccal routes?
Local and systemic effects (oral transmucosal delivery)
Suitable for proteins and peptides due to immobile mucosa and extended smooth muscle area so longer retention to the region
What are disadvantages of buccal route?
Low drug bioavailability due to low flux of the drug through the buccal mucosa due to low permeability
Why are anti-nausea medicines used via the buccal route? the dosage forms of respiratory
The nausea itself can cause swallowed tablets to be vomited and therefore rendered ineffective
What dosage forms are used for sublingual and buccal use?
Tablets
Soft gelatine capsules filled with liquid drug
What are the dosage forms of respiratory route?
aerosol, gas, inhalation to the lungs
What is the aim of the respiratory route?
For treatment od airways diseases (bronchial asthma, cystic fibrosis)
What do lungs provide?
A large surface area for drug absorption
Is first pass metabolism avoided using respiratory route?
Yes
What is aerosol?
A two-phase system of solid particles/liquid droplets dispersed in air/other gaseous phase, having small size to enable stability as a suspension.
What is the deposition of a drug/aerosol in the airway dependent on?
Physicochemical properties of the drug
The formulation
The delivery/liberating device
The patient (breathing pattern and clinical status)
What are the particle size that reaches the peripheral regions (bronchioles and alveolar regions)?
5 or 6 micrometres
What is the particle sizes that reach the alveolar sacs?
0.5-1 micrometers
What can happen to large particles or droplets deposited on the upper respiratory tract ?
They can be cleared from the lung by the mucocilliary action, so the drug becomes available for systemic absorption and causes side-effects
What is a nebulizer?
When the drug solution/suspension is contained in the nebulised is converted to a fine mist which is inhaled through a mouthpiece or face-mask
What is a metered dose inhaler?
Pressurized canisters fitted with a metering valve. A predetermined dose is released as a spray every time that the metring value is activated.
What are advantages of nasal drug delivery?
Large surface area (160 cm squared) and a rich blood supply
Avoids first-pass metabolism
Absorption levels reach some levels similar to those as if the drug was administrated intra-venous.
What are the disadvantages of the nasal drug delivery?
Metabolism and degradation of drug due to high enzymatic action of the nasal mucosa. Although esterases can be useful for prodrugs
Mucous flow and biliary movement will remove some of the drug towards the orifice of the noise which lead to drug lost
Swallowing can lead to systemic effect
What is topical-transdermal route?
Application of the drug onto the skin with aim to treat, protect, restore locally (more common) or to achieve systemic administration via delivery across the skin (transdermal) for conditions such as angina, pain, motion sickness
What are dosage forms of topical-transdermal route?
Cream, ointment, gels
Location, solution, aerosols
Transdermal patches
What is drug penetration via the transdermal route controlled by?
Stratum corneum hydration (this Si the outermost layer of the epidermis, consisting of dead cells that lack nulcei and organelles)
Temperature
pH
Drug concentration
Molecular characteristics of the drug
The vehicle that the drug is solubilised/dispersed in
What are advantages of transdermal route?
First-pass metabolism is avoided
Irritation to the GI tract is eliminated
Non- invasive and can be self-administrated
Can provide release for long period of time
Inexpensive
What are disadvantages of transdermal route?
Limited number of drugs are amenable to administration by this route
Only small molecules quite hydrophilic can pass freely across the skin without taking into account passing through stratum corneum (drug partition coefficient is very important)
Excess drug cannot be removed from the blood circulation
What is the ocular route?
Drugs are administrated for local effects (mydriasis,miosis), anaesthesia or to reduce intraocular pressure
Where is the drug delivered via the ocular route?
On the eye, into the eye or onto the conjunctiva
What fraction of drug dose penetrates the eye?
1/10
What does the conjunctiva?
Helps lubricate the eye by producing mucus and tears, although a smaller volume of tears than lacrimal gland
It also helps prevent the entrance if microbes into the eye
What is the cornea?
Is the transparent front of the eye that covers the iris, pupil, and anterior chamber.
What is the pre-corneal tear film?
A thin layer of lubricating substance
What is the pH of the eye?
7-7.4
What are factors affecting drug permeation?
Ionization and pH
protein binding
Drug distribution in the eye:
Rate of drug loss from the precorneal area
Rate of drug uptake by cones
Drug penetration through the sclera (white of the eye):
Through perivascular spaces
Through the aqueous media of gel-like mucopolysaccharides
Across the scleral collagen fibrils
What are factors influencing drug retention?
Proper placement of eye drops
Influence of instilled volume
Preservatives
Effect of systemically admistrated drugs
What do topically applied timolol and antihistamines do?
Reduce tear flow
What drug stimulates tear flow?
Topically applied pilocarpine
What do general anaesthetics inhibit?
Lid movement
What are dosage forms for ocular delivery?
Aqueous solutions ad suspensions
Ointments (longer drug contact with the eye)
Inserts (oculosert: pilocarpine)
What are requirements of drugs for ocular delivery?
Sterility Free of any small particles PH 7.4 Toncity Viscosity
What are the three main parenteral routes?
Intravenous
Intramuscular
Subcutaneous
What is the parenteral route?
A drug is injected via a hollow needle into the body at various sites and depth
What are some less frequently used parenteral routes of administration?
intraarteial
intraperitineal
intracardiac
intrathecal
What is intravenous injection?
Provides the most rapid drug onset of action-no barrier to absorption
e.g. chemotherapeutic agents
What is intramuscular?
Less hazardous, easier to use but more painful and with longer onset of drug action then the i.v. injection
What is the difference between i.v. and i.m injections?
Drugs levels in the blood of i.mare lower to those achieved with i.v because the drug has to be absorbed by the tissue. The absorption is depended on various factors such as depth of injection, muscle exercise, local blood flow supply, ect.
How can depot be formulated?
Suspension of the drug in aqueous or oily vehicles, emulsions
What is the order of onset of action of injections?
s.c slower than i.m (due to lower blood supply ),slower than i.v
Give example of sc. drugs?
Heparin and insulin
When/why would you take parenteral route?
Rapid absorption is essential
Emergency situations or patient is unable to take oral medication
Drug is either destroyed, or inactivated or poorly absorbed in case of oral administration
What are advantages of parenteral route?
Fast drug absorption and drug action
Blood levels are more predictable than those achieved by oral dosage forms
What are disadvantages of parenteral route?
Expensive
Must be sterile
Trained personnel is required
Difficulty with removing the drug from circulation in case of adverse effect or overdose
When is rectal route used?
When drugs are inactivated in GI tract
Patient unable to take oral medication due to unconscious, vomiting, postoperative
Drugs are used for local action
What are dosage forms for the rectal route?
Cleansing solutions
semisolids preparation
Solid preparations
What are the 3 heamorrohodial veins that supply the rectum?
Middle and lower vein that drain directly into the general circulation , upper one drains into portal vein leading to the liver
What are the disadvantages of the rectal route?
Drug metabolism in the liver do the bioavailability will be less than 100%
Irregular and unpredictable drug absorption depended on the part of the rectum the drug is absorbed
What are advantages of vaginal route?
Higher bioavailability than oral route
First-pass metabolism in liver avoided
What are disadvantages of vaginal route?
The thickness of the vaginal epithelium and blood circulation of this region changes with menstrual cycle and age, thus drug absorption is altered
What are dosage forms for vaginal administration?
Tablets, capsules, solutions, creams ect.
Name the types of dosage forms?
Liquid
Semi-solid
Solid
Give examples of liquid dosage forms?
Aerosols, ear and eye drops,lotions ect.
Give examples of semi-solid?
Creams, gels,ointments
Give examples solids?
Capsules, powders,pasteilles
What are solutions of liquid dosage forms?
Homogenous mixtures of two or more salutes dissolved in one or more solvents
Name some oral solutions
Syrups-aqueous solutions that contain sugar
Elixirs- clear flavoured liquids contain a high proportion of sucrose or a suitable polyhydric alcohol and sometimes alcohol
linctuses- viscous liquids used in the treatment of cough
Mixtures- oral and suspensions
Oral drops
Mouthwashes
gargles
What is the isotonic and pH of nasal solutions?
0.9% & pH 5.5-6.5
What does overuse of topical decongestants result in?
Oedema of nasal muscosa
What are enemas?
Oily or aqueous solutions administrated rectally used to treat constipation or ulcerative colitis or X-ray examination of the lower bowl
What are suspensions?
Liquid dosage forms where the active ingredient/s are isoluble in an aqueous or oily vehicle
What are emulsions?
Mixtures of two immiscible liquids, usually oil and water to form small droplets
What are applications?
Solutions, suspensions or emulsions used for topical use.
What are lotions?
Solutions ,suspensions or emulsions door external use
What are liniments?
Liquids for external uses to alleviate the discomfort of muscle strains and injuries
What are collodions?
Liquids for external use used to seal minor cuts and wounds that have partially healed.
What are aerosols?
Drug in solution/suspension in pressurized pack in presence of suitable propellant. Used for asthma or topically for muscle sprains and injuries
What are inhalation?
Volatile substances for use on the upper respiratory tract disorders like nasal congestion
What are irrigation?
Sterile solutions used for treatment off infected bladders
What are paints?
Solutions for application to the skin or mucous membrane. For skin paints are formulated with a volatile vehicle. When used for the throat and mucous surfaces a viscous vehicle is included normally, so to retain the preparation on the infected area
What are eye drops?
Sterile preparations used to administer drugs to the eye
What are injections?
Sterile, progeny-free preparations for parenteral administration
What are pyrogens?
Fever producing organic substances due to microbial contamination
What vehicles are used for injections?
Aqueous- sterile water for injection, bacteriostatic
nonaqueous- fixed vegetable oils, glycerine, alcohols
What are oleaginous injections mostly used?
Intra muscular
What are some semi-solid dosage forms?
Gels
Creams
Ointments
Pastes
What are gels?
Transparent or translucent dosage forms for local use, for eczema, psoriasis ect.
What are creams used for?
Emulsions for external use. Microbial contamination is possible due to the water consent so preservatives are added or short shelf life
What are ointments?
Oily semisolids for topical use as emollient or drug delivery to the surface or for deeper penetration into the skin
What are pastes?
Vehicles with high concentration of solid material (like starch)
Name solid dosage forms?
Tablets Capsules Dusting powders Powders(oral) Granules Lozenges Pastilles Implants insufflations Suppositories Pessaries Transdermal delivery systems
What are tablets?
Prepared by compression and contain drugs and excipients for specific functions
What are capsules?
Drugs and appropriate fillers are enclosed in a hard or soft gelatin shell, content can be liquid or powder or small pellets with different coatings
What are dusting powders?
Finely divided powders for external use. Used as disinfection and antisepsis in minor wounds lubricants to prevent friction between skin surfaces
What are powders (oral)?
They can be packed as bulk e.g. antacids or divided powders e.g. sachet
What are granules?
Small particles of irregular shape
What are lozenges?
Large tablets designed to be sucked and remain in the mouth for 15 min. For mouth and throat infections
What are pastilles?
Used as lozenges. They contain antiseptic as active substances and are jelly like and basic component is acacia or gelatin. used to treat mouth and throat infections
What are implants?
Placed under the skin by a small surgical incision. They are used as hormone replacement therapy or contraceptive. They are long term therapy due to slow drug release (3yrs). They must be sterile.
What are insufflations?
Drugs in dry powder form in a capsule. Administration involves a device where the capsule is broken and the powder is inhaled by the patient. It is used to treat asthma.
What are suppositories?
Are inserted into the rectum for local or systemic action
What are pessaries?
Are inserted into the vagina for both, local and systemic action
What are transdermal delivery systems?
Adhesive patches, which release the drug in a controlled manner for a specified time to produce a systemic affect.
