Road Map 2 DR and ER Dosage Forms Flashcards
(22 cards)
Pulsatile-release systems
a type of modified-release dosage form where multiple doses of a drug are contained within the same dosage form but released at different times; first dose release immediately and second dose released hours later (e.g. Concerta)
iii. Produces a bimodal release pattern
iv. Different layers of polymers and drug can be designed to optimize release pattern
v. Can be designed to:
1. Immediately release drug followed by sustained release
2. Provide delayed release with extended release
3. Multiple bursts of drug release
Abuse deterrent
designed to discourage extraction of the active ingredient and improvised administration (e.g. injecting, chewing, snorting, smoking) to enhance euphoria
Modified-release
-a general term that refers to any formulation that releases drug other than immediately
-designed to remain intact in the stomach
-tablets do not disintegrate or erode in the stomach
-ER capsule shells may dissolve exposing slow release pellets
Delayed release
released at a time other than promptly after administration; designed to disintegrate in an area other than the stomach; once they reach the area of release, they disintegrate rapidly
Extended release
released slowly over time; aka controlled release, prolonged release, sustained release
Explain the reasons to formulate a dosage form as delayed release
a. Drug is destroyed by stomach acids
b. Drug is irritating to the stomach
c. Drug target is in the small intestine/colon
Describe the mechanism and function of enteric coatings and how release relates to GI tract pH
a. Has a coating that is designed to dissolve at a particular pH
b. Aka gastro-resistant or enteric coatings
c. Intended to move through the stomach intact and to release drug content in the intestines (small or large intestine)
d. Insoluble at low pH (i.e. the stomach…stomach pH is 1 to 3.5)
e. Soluble at higher pH specifically 5 or greater to provide release in the small intestine
Identify ways to target drug delivery to the colon
a. Drug must be formulated into enteric coated form
b. Take advantage of the bacteria in the colon to digest either a prodrug or a coating (colonic delivery)
c. Bacterially-cleaved prodrugs which allows for delivery of drugs to treat colon specific diseases with limited systemic exposure . e.g. sulfasalazine
d. Bacterially triggered drug coating
i. Insoluble coating applied to dosage form that can be digested by colon bacteria
ii. Exposure of the dosage form to bacterial enzymes generates “holes” in the coating allowing release of the drug
Advantages of ER dosage forms
i. Allow at least a two-fold reduction in dosing frequency as compared to the conventional, immediate release form
ii. ER dosage forms have lower Cmax values, resulting in fewer side effects
iii. To improve efficacy by maintaining constant plasma concentrations of the drug
iv. Increase patient compliance
Disadvantages of ER dosage forms
i. Limitations on the number of strengths available
ii. Missing a dose of an ER product is worse that missing a dose of an IR product
iii. Removal of an ER product is difficult in the event a patient has an adverse reaction
iv. Potential for dose dumping
Identify the characteristics that make a drug suitable for an ER dosage form
a. Requires multiple daily administration
b. Have short half life of less than 8 hours (drugs that have a slow elimination rate half life greater than 8 hours are generally not suitable for ER products)
c. Possess a wide safety margin
d. Relatively small doses needed for efficacy (dosage form limited to 1 gram in size)
e. Adequate water solubility and dissolution
i. Drugs with very low solubility (<0.01mg/mL) or very slow dissolution rates are not good candidates for ER dosage forms as they are dissolution rate limited
f. Uniform absorption along the entire GI tract
First order release
i. The rate of release of drug from the dosage form changes with time
1. The rate slows as the amount of drug in the dosage form decreases
ii. The rate is dependent on the concentration of drug in the dosage form
Zero order release
i. The rate of release of drug from the dosage form is constant
ii. The rate does not change as more drug is released from the dosage form
iii. The rate is independent of the concentration of drug in the dosage form
Hydrophilic matrix systems
i. Drug is dispersed in a matrix of water-swellable, hydrophilic polymer
ii. Polymer swells on contact with GI fluids form a gel-like network of polymer fibers through which the drug diffuses. Interior remains a dry core that eventually hydrates
iii. The gel layer acts as a diffusion barrier that controls the release of drug
iv. Eventually the entire dosage form turns into a gel and will gradually erode. Generally, will not appear in a patient’s stool
Insoluble matrix systems
i. Drug is embedded in a hydrophobic matrix (wax or inert polymers)… Polymers do not swell or dissolve upon exposure to GI fluid
ii. The matrix has pores that allows water to enter and drug to diffuse out of the matrix
iii. Can add pore-forming agents that create additional channels
iv. Extent of porosity of the matrix determines release rate
v. Do not disintegrate; will appear in the patient’s stool
Membrane-controlled systems
i. Contain a core reservoir of drug coated with a rate-controlling polymer membrane
ii. Membrane coating is permeable to water and the drug
iii. Water enters the dosage form and dissolves the drug. The drug then diffuses out through membrane
iv. Release rate controlled by coating material, thickness
v. Possible to use with tablets or granules
vi. Generally will not appear in the patient’s stool
vii. Can make coated beads and granules
viii. Granules coated with various insoluble polymer (some granules remain uncoated and provide immediate release)
1. The thickness of the coating and type of polymer dictates drug release
2. Can mix multiple types into one dosage form
Ion exchange resins
i. Polymeric particles that contain basic or acidic functional groups
ii. Drug complexes with an oppositely charged ionic resin
iii. Can be compressed into tablets or other solid dosage form or prepared as an oral liquid
iv. Drug is released by changes in ion concentration as the particles travel down the GI tract
v. Resins are insoluble polymers that will not be absorbed. Usually cannot be seen in stool
vi. As drug is complexed, will help to mask taste
Osmotic systems/Osmotic pumps
i. Semi-permeable membrane allows water into osmotic core containing drug
ii. Laser drilled hole is too small to allow undissolved drug to move out
iii. Osmotic pressure inside the tablet pushes the dissolved drug out of the tablet
iv. Single or double change dosage forms
v. Single = drug and osmotic agent in the same layer
vi. Double = drug and osmotic agent in separate layers…aka push-pull system
vii. Produces zero order release
viii. Tablets do not dissolve or erode. Will appear as a “ghost” in stool
Strategies used for abuse deterrent formulations
a. Physical barriers to prevent chewing, crushing, cutting
b. Chemical barriers like gelling agents to prevent extraction from common solvents
c. Aversive ingredient to make administration unpleasant is product is manipulates
d. Prodrugs that require enzymatic cleavage to produce pharmacological effect
e. Agonist/antagonist combinations (e.g. Suboxone)
Which extended-release products are non-erodible
a. Insoluble matrix systems
b. Osmotic systems
Discuss proper counseling points for modified release dosage forms
a. Take with a glass of water
b. Do not chew and crush
c. If it can be cut, it will be scored
i. Most delayed and extended-release products do not have a score and should not be split or crushed
d. Not a rapid onset form of the drug
e. Non-erodible dosage form ‘ghosts’ may appear in the stool
Types of enteric coated dosage forms
- tablets
- granules
- capsules
a. entire capsule coated or can contain coated granules - orally disintegrating tablets
a. tablet falls apart in the mouth into enteric coated microgranules. Granules remain intact until they reach the small intestine - powder for suspensions (made of enteric coated granules)
