What 3 factors determine whether a drug is effective, ineffective, or toxic?
- the physicochemical nature of the drug
- the drug formulation
- the route of administration
Biopharmaceutics is the study of...
...the physical and chemical properties of a drug and its dosage form, as related to the onset, duration, and intensity of drug action.
Biopharmaceutics deals with what 3 main characteristics?
1. physicochemical properties of drugs
2. drug formulation
3. drug route of administration
Biopharm is the study of the relationship of these 3 characteristics with regards to drug delivery and absorption!
What are the 4 main parameters that control the fate of a drug following administration?
The global process of metabolism and excretion is called ______________.
True or False: Pharmacokinetics is thought of as the effect of the drug on the body.
False. PK is the effect of the body on the drug.
Define pharmacokinetic calculation.
Calculations that mathematically describe the effect of the body on drug.
What is pharmacokinetics?
A quantitative and time dependent relationship between a dose of a drug and the concentration in plasma and other tissues.
Basic pharmacokinetics parameters must be ________ for a drug before ____________ statements describing those parameters can be made.
Pharmacokinetic __________ are important in a limited area of pharmacy practice, but pharmacokinetic _________ are important for most areas of pharmacy practice.
What is essential for the determination of pharmacokinetic properties of a drug?
The measurement of drug concentration in body issues.
What is TDM?
Therapeutic Drug Monitoring - when drug concentration measurements are used to monitor or change drug therapy.
Invasive TDM sites include:
Blood (serum, plasma, or whole blood)
Cerebral Spinal Fluid (CSF)
Noninvasive TDM sites include:
Hair (always making a bald guy feel left out)
True or False: The most common site of measuring drug concentration is at the site of action.
False. The SOA is theoretically the mostideal place to measure, not the most common. The most common site is the blood (serum - most common, plasma - less common, or whole blood - rare).
What is derived from centrifuged whole blood treated with an anticoagulant and contains coagulation factors and other proteins?
What is derived from centrifuged whole blood that has been allowed to coagulate, therby containing far less coag factors and other proteins?
Most clinical labs currently measure blood levels of drugs in __________.
What common graph is used to help visulatize the PK nature of a drug, as well as perform certain calculations?
Blood concentration vs. time curve
"C" = concentration
"Cp" = plasma concentration
"Cs" = serum concentration
The range of drug concentration in the blood spanning from the minimum effective concentration (MEC) to the minimum toxic concentration (MTC) is called __________.
a.k.a. Therapeutic Index or Therapeutic Window
True or False: Qualitative statements use words instead of numbers to describe pharmacokinetic parameters.
True. Qualitative : words :: Quantitative : numbers.
Drugs with a 2-fold or less difference between the MEC (minimum effective concentration) and MTC (minimum toxic concentration) are considered to have a __________________ (3 words).
Narrow therapeutic range
True or False: The therapeutic window can be considered as the difference between the MEC for an adverse response and the MEC for a desired response.
True or False: The duration of action is from the time the medication is administered to when the curve for a drug's effect falls below the MEC for a desired response.
False. The duration of action is only when the curve for a drug's effect is inside the therapeutic window. This lasts from the onset of effect until the curve falls below the MEC for a desired response.
True or False: A drug is considered to be only beneficial if it is highly potent and has an excellent adverse effect profile.
False. A drug is only beneficial to a patient if it is successfully delivered to the pharmacological site of action.
Effective drug delivery systems that ____________ adverse effects are becoming increasingly common.
True or False: Drug Elimination is synonymous with Drug Excretion.
False. Drug Elimination involves Drug Metabolism and Drug Excretion.
True or False: Biopharmaceutics deals with Drug Delivery as well as Drug Absorption.
What key factor determines if the delivery of a drug to its site of action is successful?
Drug formulation for administration to a patient.
The extent of the dose of a drug that reaches the systemic circulation intact. If 70mg of a 100mg drug reaches the systemic circulation, then bioavailability is 70%.
Think basketball scores, not golf scores: the higher the #, the better.
Drug(s) plus all other ingredients and parts of the dosage form are considered to be a ________________ (3 words).
Drug delivery system
Why are non-pharmacologically active ingredients important factors of overall drug efficacy?
They contribute to the safe delivery of the drug to its target.
What are the 3 factors that determine the clinical efficacy of a drug?
When a drug is delivered to a patient, it is administered in a _______________ via a _____________ into the systemic circulation.
specific dosage form; specific route
Name the general routes of administration for a drug and the anatomical sites (11 total).
Oral - GI tract (mostly upper intestine)
Rectal - rectum
Intravaginal - vagina
IV - veins
IM - skeletal muscle
SC - fat tissue below the dermis
Epidural - above dura mater in CNS (outermost layer of meninges)
Transdermal/Epicutaneous - skin
Opthalmic - cornea and vitreous humor (intravitrial injection)
Pulmonary - bronchial tissue
Nasal - nasal epithelium
True or False: An oral drug is absorbed by the body in the same amount with any oral dosage form (oral suspension versus capsules).
False. The percent of the drug dose that is absorbed may vary by as much as 2- to 5-fold.
List the general steps a solid oral drug dosage form takes to get into the systemic circulation.
Solid Dosage Form -> Drug Disintegration -> Drug Dissolution -> Drug in Solution - > Absorption
_________________ is mostly dependent on the formulation of the drug product rather than the chemical nature of the drug itself.
Where can the guidelines for drug disintegration of oral dosage forms be found?
USP - US Pharmacopeia
The process by which a drug goes from solid form to being dissolved into a solvent is called __________.
a. drug formulation b. drug disintegration
c. the weekend d. drug dissolution
D. Drug Dissolution.
*Although the majority of the general public may practice this recreationally on C. the weekend.
True or False: Drug dissolution occurs at the same time as drug absorption.
False. Dissolution must occur before absorption can occur.
The rate of drug dissolution is NOT dependent on which parameter? In other words, which one does not belong.
C. Drug Color does not belong.
What type of drugs are usually formulated as a salt and why?
Drugs that are poorly soluble in water (particularly weak bases) are usually formulated as a salt to improve the rate at which drug dissolution occurs. The ionization state affects the rate of dissolution for drugs with poor aqueous solubility that are weak acids/bases. When ionized, then dissolution is favored.
Factors that increase drug dissolution include:
Increase in temperature
Increase in agitation (GI peristalsis)
High aqueous (water) solubility of drug
Basic/acidic drug in an opposing environment
Decrease in particle size of disintegrated drug
Excipients in formulation that increase aqueous solubility or ionization of the drug
Factors that decrease drug dissolution include:
Decrease in temperature
Decrease in agitation (GI peristalsis)
Low aqueous (water) solubility of drug
Basic/acidic drug in a like environment
Increase in particle size of disintegrated drug
Certain solid drug excipients, such as suspending agents, tablet lubricants, and tablet coatings
Can a drug's size affect drug dissolution? Why or why not? If yes, how do you accomplish this?
Yes, if the surface area of a drug relative to the amount of drug in the disintegrated drug particle is increased, then drug dissolution will increase. This happens by making the particle size of the disintegrated drug smaller/finer during the manufacturing process. The smaller drug particle size exposes a higher percent of drug molecules to GI fluid, thereby having a larger relative drug surface area.
The manufacturing process that is used to increase the rate of dissolution of drugs that have poor aqueous solubility by increasing relative drug surface area. Products of micronization are prepared in micronized or ultramicronized formulations (eg. Estrace contains micronized estradiol).
Excipients are ___________ compounds used to formulate a drug product. Many excipients actually (encourage or impede) dissolution. Excipients that are added to increase the rate of drug disintegration are called _________.
pharmacologically inert; impede; disintegrants
How does an excipient like Alka-Seltzer increase drug dissolution?
The sodium bicarb increases the pH of the immediate environment surrounding the dissolving aspirin. Aspirin is a weak acid, so an increase in pH results in an increase in ionization, leading to an increase in dissolution.
_____________ is the most common dosage form for drug delivery that is relatively simple and inexpensive to manufacture.
Why are compressed tablets the least efficient solid oral dosage form in terms of rate and extent of drug absorption?
They disintegrate into relatively large drug particles (small surface area).
Why are some tablets sugarcoated?
Masks the poor taste of a drug formulation.
What is an advantage of film-coating tablets?
They are usually more durable than sugarcoated tabs and allow for smaller tablet size.
_______-coated tablets delay the release of a drug until the tablet passes through the stomach and reaches the upper intestines. These kinds of tablets are especially useful for drugs that are either ________ to the stomach or are susceptible to ___________ by stomach acid.
Enteric; irritating; degradation.
Sublingual tablets are designed to rapidly dissolve _______ [on top of / under] the tongue such that the drug is _________ [rapidly / slowly] absorbed into the systemic circulation from the oral cavity.
Hard gelatin capsules contain drugs in what 2 possible dosage forms?
Powder or tablet
Soft gelatin capsules contain a drug in what dosage form?
What are 4 examples of liquid dosage forms?
What are 2 reasons why liquid dosage forms are preferred?
Ideal for patients that have difficulty swallowing.
Increased efficiency of absorption since drug disintegration does not need to occur.
__________ have the slowest overall rate of absorption of the liquid oral dosage forms. Explain why.
Suspensions; solid drug particles are suspended that have to undergo dissolution prior to absorption.
All of the following liquid oral dosage forms contain drugs that have already been dissolved into the formulations, EXCEPT:
D. Suspensions contain particles suspended that MUST undergo dissolution before absorption.
What classifies a drug as being extended-release? Give 3 examples of formulations that are extended-release.
Dosage forms that allow for a 2-fold or greater reduction in dosing frequency.
What classifies a drug as being delayed-release? Give an example.
A portion of a drug is designed to release at a time other than immediately after administration. ex. enteric coated tablet.
How does food in the stomach affect transit time of a drug in the stomach?
*Drugs that are unstable to acid are more likely to be degraded when taken with food due to a longer period of time spent in a lower pH environment.
What happens to the pH of the GI tract as a drug proceeds from the stomach through to eventually the large intestines?
The pH goes from acidic to basic the closer the drug gets to the "light at the end of the tunnel." *flush
What characteristics make a drug an ideal candidate for extended-release formulation?
1. Well absorbed from small and large intestines
2. Relatively wide therapeutic range (avoids dose dumping)
3. Used for chronic rather than acute conditions
What are at least 2 advantages of extended-release formulations?
1. Sustained therapeutic blood levels of drug
2. Minimized peaks and troughs of blood levels may decrease adverse effects
3. Extended and consistent drug effect
4. Increased patient convenience and compliance
What are 2 disadvantages of extended-release formulations?
1. Takes longer to remove drug from system in case of toxicity or overdose
2. Failure of release mechanism may lead to lack of drug release or a massive drug release (dose dumping)
What is a gum matrix? What dosage form does it favor?
A material that swells when it contacts water, creating a gel-like barrier around the drug and, as a result, extending its release.
Most useful for ER formulations.
What is a polymeric matrix?
Made of plastic or ion-exchange resin that modifies oral drug release. I-E resin is either an anionic or cationic drug combined with an ionic resin of the opposite charge that is either ER or DR due to the charge attraction.
What 4 methods are used to make modified-release oral dosage forms?
1. Disperse the drug in a matrix or solid material.
2. Coat the drug onto beads or pellets.
4. Decrease the aqueous solubility of the drug.
True or False: A drug that is coated onto beads or pellets can have a many type of outer coatings that could cause rapid onset of action, pH-dependent release, or even DR until later in the GI tract.
What is a major advantage of bead-type modified-release products?
Gastric emptying has less effect on drug release since some of the beads leave the stomach each time it empties, as opposed to drugs delivered as a single dosage form that sit and wait to be emptied into the small intestine. Ex. Hydromorphone HCl ER (Exalgo)
______ technology coats a drug onto an inert bead core followed by subsequent layers of controlled release polymers. A great example is the product _______.
SODAS (Spheroidal Oral Drug Absorption System); Avinza
What is microencapsulation? What is an advantage of microencapsulating a drug?
A process in which small drug particles are coated with a substance that extends or delays their release.
Advantage: masks the bitter taste of some drugs.
True or False: Increasing aqueous solubility of the drug generally results in extended-release products, rather than delayed-release products.
False. DECREASING aqueous solubility...
What are 2 methods used to decrease aqueous solubility of a drug?
1. Formulating a drug as the free acid or base, as salt formulations generally dissolve faster than free acid/base formulations.
2. Granulate the drug with a lipophilic excipient.
What is a "core tablet"?
An inner extended/delayed-release tablet contained inside of a larger, immediate-release outer tablet.
What is an "osmotic pump"? Give 3 examples of Osmotic Pumps currently on the market.
A drug is placed inside of a tablet made of material that is semipermeable to water with a single laser-drilled hole in the top.
Water is pulled by osmotic pressure inside of the tablet which pushes drug outside thru the hole.
Ex. Procardia XL, Ditropan XL, and Concerta
True or False: The majority of drugs are not good candidates for transdermal delivery.
True. However, in some cases, transdermal delivery is preferred.
When is transdermal drug delivery appropriate?
When constant, controlled delivery of small amounts of drug is desired over a period of time.
What specific scenarios is the delivery of drugs by transdermal absorption useful?
1. When you want to avoid 1st-pass degradation by GI and hepatic metabolism.
2. Delivering small quantities of a drug.
3. Drugs that are smaller than 800 MW (400-500 is preferred).
4. Drugs with high potency.
5. Lipophilicity = good
What is a zero-order kinetic process?
A drug is delivered to the body across the skin at a constant rate regardless of the amount remaining in the patch.
What are some advantages of delivering drugs by transdermal patches?
Extended therapy with a single application
Useful for drugs with short half-lives
Avoidance of difficulties associated with GI drug delivery
An alternative to less desirable routs of administration
Increased patient compliance and convenience (easy to apply)
An increase in heat will likely __________ the rate of drug delivery.
What are some disadvantages of the transdermal drug delivery system?
Limited to drugs with specific physicochemical properties (low MW, high potency, and lipophilicity
What are the 2 major routes of pulmonary drug administration/absorption?
Why is intranasal drug delivery favorable?
The nasal mucosa have a high content of vascular tissue for absorption and easily accessible by the patient.
Bypasses 1st-pass drug degradation by GI & hepatic metabolism.
Has both local and systemic effects with the same general qualities as drugs absorbed well in the GIT.
What are 2 examples of drugs given intranasally?
How are inhalation drug products usually administered?
Powder form (less popular)
Why are drugs that are inhaled in powder form less popular?
There is an overall higher incidence of inhalation-related adverse effects (ex. bronchospasm).
True or False: Drug delivery and absorption by aerosolization (MDIs) and nebulization is nearly always used for a systemic effect.
False. MDIs and nebulization are used for a LOCAL effect on bronchial tissue, even though some systemic drug absorption does occur.
Why is drug particle size delivered by aerosolization important?
If too large, the drug can remain in the back of the mouth.
If too small, the drug will not be retained in the bronchial tissue and will be systemicall absorbed.
True or False: Drug delivery by inhaled gas is nearly always intended for systemic effects.
True that. Cheech and Chong would agree.
True or False: Volatile drugs that are highly lipophilic and have a relatively small MW are rapidly and highly absorbed systemically when administered by inhalation.
True. These conditions are highly favorable, and thus, this is the general rule.
D. local. They treat things like mydriasis, miosis, reduction of intraocular pressure, and anesthesia. Even infection when you shoot yourself in the eye with a nail gun.
What 2 factors are important in reducing adverse effects when making ophthalmic preparations?
What dosage forms can ophthalmic drugs be delivered?
A patient hands you an Rx that reads as follows:
Cipro ophthalmic soln instill 4 drops ou bid x 7 days.
What is wrong with this Rx and why?
You are wasting so much drug with 4 drops in each eye, as one drop already delivers 5-10 times more volume than the eye can already hold. Eye capacity ~5-10 microliters; most eye droppers ~50 microliters.
Why would you formulate a drug so you could "shove it"?
Rectal administration is used when oral administration is not possible or when a local effect is desired.
It also generally avoids 1st-pass GI and hepatic metabolism.
What dosage forms can drugs for rectal delivery be found?
Vaginal drug delivery is usually found in what dosage forms?
Why would a drug be formulated to be administered vaginally?
LOCAL treatment of bacterial and fungal infections
Termination of pregnancy
What are depot injections? Give an example of a drug formulated as a depot injection.
Preparations in which the drug has been formulated with an oil, such as sesame oil, and then injected into deep muscle tissue.
In some cases, the drug must be converted chemically to a lipophilic prodrug prior to formulation in oil.
Examples: Testosterone decanoate, haloperidol decanoate, Depo-Provera, etc.
What is a liposome?
Vesicles composed of an outer lipid bilayer and a hydrophilic center.
True or False: Liposomes canNOT encapsulate both hydrophilic and lipophilic drugs for drug delivery.
False. They can hold both. Hydrophilic drugs are held in the aqueous center of the lipsome. Lipophilic drugs are embedded in the lipid bilayer.
What is meant by an "amphopathic" substance? Give an example.
A substance that possess both hydrophilic and hydrophobic properties. Distearoylphosphatidylcholine (DSPC) is a common example. A DSPC molecule has a hydrophilic head and a hydrophobic tail. Heads point away while the tails associate together.
True or False: Currently, liposomal drug delivery is widely-used for many drugs.
False. Liposomal drug delivery is currently limited to parenteral infusions of a few drugs.
What are 2 main advantages over conventional IV drug solutions?
1. It is possible for some liposomes to contain the drug until it reaches the tissue at the drug's SOA, thereby avoiding unwanted adverse effects.
2. Liposomes can be used for both hydrophilic and lipophilic drugs that are difficult to formulate into a conventional IV solution.
Why is the use of the liposomal formulation of amphotericin B important to note?
AmphoB is notorious for having adverse effects, particularly nephrotoxicity and infusion-related toxicity. Using the liposomal amphoB may minimize toxicity relative to conventional amphoB.
What is one major drawback to liposomal drug delivery?
The recognition and uptake of the drug liposomes by cells in the immune system. This problem has been addressed by creating stealth liposomes.
What are sterically stabilized liposomes that are protected from the immune system by adding ligands (carbs or PEG) to the outer surface called? Give an example.
Stealth liposomes; Doxil (doxorubicin) - is an anticancer drug that is protected from destruction by monocytic phagocytes by coating the lipsomes with methoxy-polyethylene glycol.
True or False: The majority of drugs distribute freely and randomly throughout the body and may act at molecular targets regardless of whether or not the target is at the site of disease.
True. It would be best if it targeted the specific organ or the actual site of disease in the body, but this doesn't happen (e.g., cancer chemotherapy).
What are the two general ways that a drug can be targeted to a specific site of action?
Targeted Drug Therapy
Targeted Drug Delivery
_____________ is a general term for technology involving particles less than one micron in size.
What are the general methods by which a drug delivery may be enhanced by nanotechnology?
Targeted drug delivery
Improved drug solubility
Modified release properties
Most ongoing research on nanotechnology and drug delivery has been in the area of _________________.
How does receptor-mediated drug delivery work?
1. Ligand binds selectively to cell surface receptor.
2. Diseased tissue overexpresses receptor for ligand.
3. Drug is selectively delivered to and released in cells of diseased tissue.
How do thermosensitive liposomes work as a triggered-release liposomal delivery system?
Releases drug at site with temperature > 37C
How do pH-sensitive liposomes work as a triggered_release liposomal delivery system?
Releases drug at site with pH less than physiologic pH.
How do light-sensitive liposomes work as a triggered-release liposomal deliver system?
Releases drug only when exposed to certain wavelengths of light.
How does a targeted drug liposome work?
Antibody on liposome surface selectively binds to and delivers the drug liposome to tissue that expressed the antibody target.
Biopharm Exam 1
Biopharm Exam 1 - Basic Concepts and Drug Formulation & Delivery