Introduction of Dosage form Design

NCE

'New chemical entity'. A newly discovered drug, in the early stages of testing

what factors need to be considered during pre-formulation of drug?

1. particle size and distribution 2. polymorphism 3. solubility 4. dissolution rate 5. membrane permeability 6. pKa/dissociation constants 7. stability 8. partition coefficient

which BCS class has high solubility and high permeability?

BCS 1

excipients

inactive substances used as a carrier for the active ingredients of a medication

how does a sublingual administration vs intravenous work on time and course of drug in the body?

sublingual= quick immediate effect but short duration (think a small peak graph) intravenous= constant amount of drug adminstered in body for longer period of time (think of a flat line graph)

what does it mean when equivalent doses of drug in different formulations provide different AUC values?

-it means that they have different extent of absorption -A different AUC means that the total amount of drug absorbed into the bloodstream over time differs between the two formulations

active transport

-moving from low to high concentration -requires both energy and a carrier protein

Why use dosage forms?

1) provide correct dose 2) protect the API during storage 3) protect the API from gastric acid (stomach) 4) conceal bad taste or odor of API 5) provide rate-controlled drug action 6) provide optimal drug action from topical sites 7) provide insertion into body cavity 8) provide inhalation therapy

what makes up a drug product?

API and excipients

ADME

Absorption Distribution Metabolism Elimination

API

Active pharmaceutical ingredient (exerts pharmacological effect)

which BCS class is least preferred?

BCS 4 low solubility low permeability

biopharmaceutics

Biopharmaceutics is the study of how the physical and chemical properties of a drug, the formulation of that drug (like tablets, capsules, or liquids), and the way it is delivered (like orally, injected, or inhaled) affect the drug's absorption, distribution, metabolism, and excretion in the body.

when rate of absorption is decreased, the Cmax is ________ and Tmax_________

Cmax is lowered and Tmax occurs at a later time

Concentration time curve graph features

Cmax= peak heaight concentrtion Tmax= time of peak concentration AUC= area under the curve= entire amount of drug in the blood MEC= maximum effectiveness concentration MTC= maximum toxic concentration

oral bioavailability equation

F oral= fa x fG x fH fa= fraction of dose released from formulation and pass thru gut wall fG= fraction escaped metabolism in intestine) fH= fraction escaped metabolism in liver

what administration route gives 100% bioavailability?

IV intravenous route

facilitated diffusion

Movement of specific molecules across cell membranes through protein channels -move from high to low concentration -NO energy needed

pharmacokinetics vs pharmacodynamics

Pharmacokinetics: What the BODY does on the drug (ADME) Pharmacodynamics: What the DRUG does on the body (biological and physiological effects of drug)

what is pharmaceutics?

The science of preparing and dispensing drugs, including dosage form design.

define dosage form

a preparation devised to make possible the administration of medication in measured or prescribed amount

bioequivalence

bioequivalent drugs are similar in both rate and extent of bioavailability -AUC and Cmax are similar

BCS

biopharmaceutical classification system The Biopharmaceutical Classification System (BCS) is a scientific framework that categorizes drugs based on their solubility and intestinal permeability.

example of drug that uses facilitated diffusion

cephalosporin -from high --> low con. gradient

the process of absorption in passive diffusion is driven by the ______ _______

concentration gradient -going from high --> low

why does bioavailability generally decrease via other routes (oral, etc) ?

due to incomplete absorption and first-pass metabolism (liver)

what is absolute bioavailability?

fraction of the drug absorbed through non IV compared to IV admin of same drug

pre-formulation studies of drug substance

involves characterization of drug's physical, chemical, and mechanical properties in order to choose what other excipients should be used

BCS 2

low solubility, high permeability

what is relative bioavailability?

measures the bioavailability (AUC) of a certain drug when compared with another formulation of the same drug, usually an established standard

can an ionized form or non-ionized form of a drug pass through a cell membrane?

only NON-IONIZED form of a drug

a drug which is a weak acid with pka=3, can it be absorbed at ph 2?

pH = pKa + log [A-]/[HA] 2= 3 + log [A-]/[HA] -1= log [A-]/[HA] 10^-1 = [A-]/[HA] 1/10 = [A-]/[HA] so only 1 molecule of ionized vs 9 molecules ionized -so more uncharged molecules -yes then it can be absorbed!!!!

Henderson-Hasselbalch equation

pH = pKa + log [A-]/[HA] base over acid

what happens if MEC is not reached?

patient will not exhibit adequate response

amphetamine weak base with pka=10, can it be absorbed at ph 8?

ph = pka + log [B]/[BH+] 8= 10 + log [B]/[BH+] -2= log [B]/[BH+] 10^-2 = [B]/[BH+] 1/100= [B]/[BH+] so here we have 1 molecule of unionized molecule and 100 ionized charged molecules SO NOT CANNOT ABSORB

why wouldnt you give a pure drug to a patient?

small doses, unstable, and patient compliance

Fick's first law of diffusion

states that the diffusion flux of a substance is proportional to the concentration gradient.

bioavailability

the fraction of an administered dose of unchanged drug that reaches the systemic circulation -basically is how much drug is available in the body

passive diffusion

the movement of drugs from an area of higher concentration to lower concentration -NO energy needed

drugs are made with disease in mind while pharmaceutics have the _______ in mind?

the patient!

what kind of transport does 5-fluoracil use?

uses active transport to go against concentration gradient -low --> high -an anti-cancer drug

endocytosis

whole molecules are engulfed by the cell membrane

can 2 cruves with different C max and Tmax have similar AUC?

yess This reflects differences in absorption rates but not necessarily in the total amount of drug absorbed.