Secondary Manufacturing Flashcards
(44 cards)
What are primary pharmaceutical processes
The Reactions and separations involved in the manufacturing of the pure API
What are secondary pharmaceutical prcesses
The blending and formulation steps required to formulate the dosage form of the product
Why are tablets not jsut pure API?
Need the tablet to be large enough to be taken by a person so even if only a very small amount of API is required, bulking agents etc are required
Differentiate between sustained release and immediate release
Immediate release is ensuring the API reaches the desired area asap
Sustained release is attempting to maintain as constant as possible levels of the API over a long period
These are influenced more by the formulation of the drug than the API itself
6 drug Administration routes
- Oral
- Pulmonary (e.g. inhaler)
- Transdermal (e.g. cream)
- Intravenous
- “Direct Application” (e.g. eye drops)
- Implantable controlled-release devices
Define Pharmacokinetics
The rate at which the API is released from dosage form, absorbed into the system ciruclation, metabolised and excreted
Define the minimum toxic concentration (MTC)
The [API] that once exceeded will begin to result in undesirable side effects and (potentially irreversible) toxicity (e.g. liver damage) being observed
Define minimum effective concentration (MEC)
[API]min that has a measureable pharmaceutical effect on a statistically representative group of patients
Define Therapeutic Index (TI)
The [API] window rhar we want to maintain for the duration of the treatment
TI = MTC - MEC
Define the LADME model
- Liberation
- Absorption
- Distribution
- Elimination
4a. Metabolism
4b. Excretion
Define Bioavailability (F)
The fraction of the administered dose that reaches the systemic circulation as the parent drug (not as metabolites)
- Tells us to what extent API was dissolved and already metabolised absorption
- If low either need to change the route of administration or the physical/chemical properties of the API
Bioavailability Equation
F = AUC/Dose
AUC = Area Under Curve
F = Value between 0 & 1
The lower it is the more waste there is
Define Apparent Volume Distribution
V = Total Amount of drug in the body/ Plasma Concentration
Partition Coefficient Equation
P = [Octanol]/[Water]
Uses of the Partition Coefficient
- Gives the ability of the API to be liberated, absorbed and distributed
- if substance is lipophilic conc in plasma wil be low but amount in body will be high as it will have accumulated in lipophilic tissues
Biopharmaceuticals Classification System
I) High solubility & High Permeability
II) Low Solubility & High Permeability
III) High Solubility & Low Permability
IV) Low Solubility & Low Permeability
Methods of improving solubility
- Milling the API it so it is well distributed in the tablet
- Change the form of the API to amorphous or metastable crystal
Dissolution rate of particles equation
dm/dt = D/delta x A(c* - c_bulk)
Delta = thickness of the boundary layer
c* dependent on pH, Temperature & solid phase form
Typical Components of a tablet
- API
- Filler (bulking agent)
- Binder
- Disintergrant or Matrix-forming polymer
- Lubricant/glidant
- Coating Polymer + Pigment
Role of a filler/bulking agent
- No active role
- Usually for low dose APIs
- Usually sugars
Must be:
- Tolerated by population
- Soluble
- Easy to handle, compress, blend etc
- Be of a specific grade (differing properties)
Role of a binder
Increase adhesion between particles
Role of Disintergrant or Matrix forming polymer
Disintergrant - Swells in contact with liquid to help break up the tablet
Matrix forming polymer - Forms gel upon contact with liquid; helping tablet keep together to slow dissolution
Roe of lubricant/glidant
Reduce friction between tablet particle and walls of the process equipment
Role of Coating polymer or pigment
- Increase shelf life
- May prevent acid hydrolysis so that tablet is absorbed in intestine not stomach
- May add a visual appeal
