Knipp's 1st Set Flashcards
Excipients
Coatings: control diffusion rates and modify release properties
Disintegrants: control regions of release
Lubricants: slow dissolution
Internal Excipient
- swellable matrices
- non swelling matrices
- inert plastics
Coating
- applied to outside of solid dosage forms
Goal of Coatings
- protection of agent from air or humidity
- mask taste
- special drug release
- aesthetics to eye
- prevent inadvertent contact with drug (safety)
Aqueous Film Coatings
- film forming polymer
- plasticizer for flexibility and elasticity
- colorant
- vehicle
Enteric Coatings
- added to dosage forms to prevent early release of API in metabolic regions
Goal of Enteric Coatings
- prevent acid sensitive API from gastric fluid
- prevent gastric distress from API
- target API delivery
- provide delayed/sustained release
- deliver API to higher local concentration
Sustained Release
- formulated to slow the release of the therapeutic agent so that its appearance in circulation is delayed but sustained in duration
Controlled Release
- reproducibility and predictability in the drug release kinetics
ALLOWS US TO MAINTAIN A NARROW DRUG PLASMA COCENTRATION
Examples of Controlled Release Formations
- Coated beads, granules, or microspheres
- Multitablet system
- Micro-encapsulated
- Drug Embedding in hydrophilic matrix
Steady State
rate going into the body must equal the disposition
creates safety window
Characteristics of Drugs Best Suited for Oral Controlled Release
- exhibit neither slow or fast rates of absorption/excretion
- uniformly absorbed
- administered in small doses
- good safety/therapeutic window
- chronic > acute
Physiological Factors Affecting Absorption
- absorbing surface area
- residence time
- pH
- Permeability
- dietary effects
- complexation/protein binding
- biliary uptake and clearance
Epithelia
- located on the layer of extracellular matrix proteins
- epithelial cells are polarized
- endothelial cells line the inside of body cavities, blood vessels, and lymph
- simple squamous predominantly
- endothelial cells are actually epithelial cells just in the body
Simple Squamous
thin layer of flattened cells that are relatively permeable
lines most blood vessels and placenta
Simple Columnar
usually found in GI tract
Translational
comprised of several layers with different shapes
stretch
Stratified Squamous
multiple layers of squamous cells that cover areas that wear and tear
skin is most important
Composition of Biological Membranes
- all living cells are enclosed by a membrane making it a living unit
- barrier
- cell membrane is semi-permeable permitting the rapid passage of some chemicals while rejecting others
- polarized lipid composition
Does cholesterol only have harmful effects?
NO
- too much or too little is negative
- provides fluidity at lower levels
Intestinal Transport Systems
Passive
- non saturable
- paracellular (between cells)
- transcellular (through cells)
Carrier-Mediated
- saturable
- active (energy dependent)
- facilitated diffusion (energy independent)
Drug Transporters
- membrane bound proteins found on apical and basolateral surfaces
- role is to move important molecules across membranes
- crucial determinant of the distribution of drugs
Solute Carrier Transporter
- 43 subfamilies
- generally influx
- PepT1, OAT
ABC Transporter
- 7 subfamilies
- generally efflux (multidrug resistance)
- P glycoprotein
Routes of Permeability
- influx transporter
- passive transcellular
- passive transcellular and efflux
- passive paracellular
- metabolism
- efflux
Absorptive Transporter
transfer substrates into systemic blood circulation
Secretory Transporter
transfer their substrates from blood circulation into bile, urine, lumen
GI Tract Epithelia
Buccal: stratified squamous
Sublingual: simple squamous
Esophagus: stratified squamous
Trachea: psuedostratified squamous
Stomach: columnar
Small/Large Intestine: columnar
Upper Rectum: simple columnar
Lower Rectum: stratified squamous
Role of Stomach
- digest food and control the flow of contents into intestine
acts as food reservoir
processes food into chyme
regulates food delivery
pH protects from bacteria
Role of Stomach Cont.
Fasted pH = < 3
Fed pH = 5-7
Emptying halftime = 30 min
Organization of Stomach
Fundus: contains gas and produces contractions to move contents
Body: reservoir for ingested food
Antrum: contains pyloric region and controls flow into small intestine
Intestine Facts
Mouth to Anus Time = 24-32 hours
Small Intestinal Time = 3 hours
MOST ABSORPTION OCCURS IN SMALL INTESTINE
pH = 5-6.5
Why Intestine?
LOTS MORE SURFACE AREA TO GET ABSORBED
increases in surface area in SI due to folding such as (folds of kerckring, villi, microvilli)
Characteristics of Colon
- 125 cm log from caecum to anus
- transport much slower than intestine
- varies in thickness
- illeocaecal valve limits food flow from ileum to caecum
- responsible for water and electrolyte absorption
Colon Structure
Serosa: squamous epithelium covered with adipose tissue
Muscularis Externa: inner circular muscle layer
Submucosa and muscosa
3 Layers of Colon
Muscularis mucosae
Lamina Propria
Epitheliium
Rectum
- highly folded
- stratified squamous of lower rectum allows for high drug absorption
- low residence time
Factors influencing Drug Solubility
- buffer capacity
- bile salts
- regional fluids
- other drugs
- potential issues from endogenous substrates
Challenges for Assumptions of GI Tract Physiology
- transporters and enzymes vary
- diet and chemical expose varies
- GI fluid composition varies
- pharmacogenetics and genomics are issues
- drug nutrient and drug drug interactions
ONE SIZE FORMULATIONS DO NOT FIT ALL
Disposition
comprised of distribution and elimination
Elimination
comprised of metabolism and excretion
ADMET
Absorption
Distribution
Metabolism
Excretion
Toxicity
Nature of Pharmokinetic Processes
- described by concentration time profiles
- compartments represent similar spaces
- reversible or irreversible
- linear or nonlinear
- fast and slow tend to disappear
Bioavailability
rate and extent of drug absorption
Absolute Bioavailability
AUC of a given dosage form compared with AUC of same dose injected intravenously
Relative Bioavailability
AUC of a given dosage form compare to an arbitrary reference standard
Bioequivalent
DOES NOT mean therapeutic effect of two dosage forms are equivalent
Dose
- amount of chemical in which whole organism is treated
- local concentration of chemical at response site
