L5: Drug formulation Flashcards
(30 cards)
What is pharmaceutical availability and what affects it in oral dosing?
It refers to the extent a drug becomes available in systemic circulation. In oral dosing, it is affected by the rate of tablet disintegration and the dissolution of drug particles in intestinal fluid
What physical formulation factors affect pharmaceutical availability?
Tablet compression and excipients (affect disintegration), interaction with GI fluids (via excipients), drug form (crystalline/salt and counter-ion effects), and particle size (smaller dissolves faster)
What is an excipient and give an example of its function?
An excipient is an inactive ingredient added to aid formulation
Example function: emulsifying agents that help combine immiscible components and improve drug stability
Define bioequivalence.
Two drug formulations are bioequivalent if they have comparable bioavailability, Cmax, Tmax, and overall exposure (AUC)
When are drugs considered bioinequivalent?
When two formulations show significant differences in bioavailability, such as absorption rate or plasma concentration profile
What are the key parameters on a plasma concentration–time curve?
Cmax (peak plasma concentration), Tmax (time to peak), AUC (total exposure), onset time (when MEC is reached), therapeutic range (between MEC and MTC), and duration of action
What is therapeutic equivalence?
When two drugs produce the same clinical effect and safety profile, regardless of dose form or formulation
How can a change in formulation lead to bioinequivalence?
Altering excipients or salt forms can increase dissolution rate, altering Cmax and Tmax, potentially leading to toxicity or reduced efficacy
How is the route of administration determined?
Based on therapeutic objectives (fast vs slow onset) and drug properties (e.g. solubility, stability, molecular size)
What formulation factors affect insulin absorption?
Physical state (crystalline vs amorphous), zinc/protein content (which prolongs release), and pH/buffer nature (which affects solubility and dispersion)
How do different insulin formulations vary in absorption?
Soluble/amorphous forms act rapidly with short duration. Crystalline forms with zinc and buffers act slowly with prolonged action
How does the drug suspension medium affect diffusion rate?
Thick, oil-based suspensions reduce diffusion and slow absorption at the injection site
How can diffusion rate impact long-acting formulations?
Oil-based suspensions slow drug movement, allowing sustained release over days or weeks after IM injection
How can administration route alter drug dosing for the same compound?
Different routes affect absorption rate and plasma concentrations—e.g., IM may have lower Cmax than oral or vice versa
What is the mechanism of diabetes insipidus?
Caused by low ADH (vasopressin), reducing water reabsorption in renal collecting ducts, leading to excessive Na⁺ and water loss
How do local anaesthetic formulations differ to prolong effect?
Some include vasoconstrictors (e.g., adrenaline) to reduce local blood flow, slowing drug clearance and prolonging effect
Why is avoiding first-pass metabolism useful?
It increases the fraction of active drug reaching systemic circulation, allowing for lower doses and faster therapeutic onset
What are routes that bypass first-pass metabolism?
Sublingual, buccal, rectal, and transdermal routes avoid hepatic first-pass effect and often provide faster or more consistent drug delivery.
How can oral formulations be modified to control drug release?
Through delayed or slow-release designs, such as enteric coating (dissolves in intestine) or matrix tablets (sustain release)
What are benefits of controlled-release oral formulations?
Prolongs duration
reduces dosing frequency
minimizes side effects
may reduce gastric irritation
Why might some slow-release designs be ineffective?
If conventional formulations already provide a long effect, slow-release may be redundant or introduce risks (e.g., neutropenia)
What two criteria must be met for combination oral therapies to be acceptable?
Both drugs must require the same dosing frequency, and fixed doses must be therapeutically effective without frequent dose adjustment
What are the advantages of combination oral formulations?
Improved compliance
reduced pill burden
simplified treatment regimens
What are potential formulation goals when combining two drugs in one product?
To create synergy or additive effects
ease of administration
minimize side effects through complementary mechanisms
