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Drug Dosage Form Design & Drug Delivery System Design - Coggle Diagram
Drug Dosage Form Design & Drug Delivery System Design
Biopharmaceutics
Definition: The study of the
relation
of the
physical and chemical properties
of a drug to its
bioavailability, pharmacokinetics, and pharmacodynamic and toxicological effects
Considerations in the design and manufacture of a drug product
API
: Stability, Solubility, pH and pKa, Crystalline form, excipient interaction & compatibility, Impurities, Salt form, Particle size, Complexation
Drug product
: dosage form, Immediate or modified release, dosage strength, bioavailability, stability, excipients, manufacturing variables
Physiological factors
: route of administration, absorption (permeation of drug across cell membranes), protein binding, blood flow, surface area, biotransformation
PK/PD
: Bioavailability, therapeutic objective/index, adverse reactions/toxic effects, pharmacokinetics, dose
Manufacturing considerations
: production method/technologies, QA/QC, specifications of raw materials, cost, stability testing
Patient considerations
: compliance, labelling, product appearance, cost
Drug Absorption
Gastric Emptying Rate influenced by
Presence of food
Big meals = slow down rate of gastric emptying
Meals that contain large fragments of food or are nutrient-dense will take longer to empty and hence will delay the passage of dosage forms to the small intestine
Food Content
High fat content = slow down rate of gastric emptying
Digested fat has a marked inhibitory effect on gastric emptying, retardation will occur to varying
degrees. The delaying effect of lipid on gastric emptying is increased in the elderly.
Strong alcohols = slow down rate of gastric emptying,
beer/white wine = speed up rate of gastric emptying
Smoking delays the gastric emptying of alcohol.
Low pH (more acidic) = faster rate of gastric emptying
pH of content of the food affects gastric emptying rate. Pure carbohydrate meals do not affect acidity as much as a high protein meal (peptides and amino acids are potent stimulators of stomach acid secretion, thereby lowering pH).
Posture
Lying down = slow down rate of gastric emptying
Upright positions = speed up rate of gastric emptying
When patients lie on their left side,
floating formulations (alginates) are presented to the pylorus ahead of the food and emptied first.
Gender
Women = slower rate of gastric emptying than men
Pregnancy can drastically alter transit of drugs in certain regions of the GIT; pregnant women have decreased oesophageal sphincter pressure and impaired colonic motility which can lead to heartburn and constipation.
Various diseases
Certain disease states can alter gastric emptying rates.
Rate-limiting steps
Disintegration
of the drug product and subsequent release of the drug:
Disintegration = breaking down of drug/component into fragments or granules to improve its solubility
Dissolution
of the drug in an aqueous environment
Increased solubility of drug = Increased dissolution rate of drug = Better absorption
Dissolution rate (of solution of solids) is measured by the Noyes Whitney Equation:
dM/dt = k(cs-c)
Where
k = DA/delta
dM/dt = mass rate of dissolution (mass/time)
k = the rate constant of dissolution (time^-1)
cs = the saturation solubility of the solvate in bulk
c = concentration of solute in bulk solution at time t
D = diffusion coefficient of the dissolved solute
A = area of the solvate particles exposed to the solvent
delta = thickness of the diffusion layer
Absorption across cell membranes
into the systemic circulation
Passive diffusion
: movement of molecules from a region of higher concentration to lower concentration (down the concentration gradient).
Passive diffusion is measured by Fick's Law of Diffusion:
dQ/dt ={DAK/h}(CGI – CP)
dQ/dt = rate of diffusion
D = diffusion coefficient
K = partition coefficient;
A = surface area of membrane
h = membrane thickness
CGI - CP = difference between the concentrations of drug in the GI tract and plasma
Carrier-mediated transport
: transport of drugs against concentration gradient. Requires energy expenditure.
Vesicular transport
: process of pinocytosis or phagocytosis where drug is surrounded and engulfed into a cell, forming a vacuole or vesicle.
Drug Bioavailability
Bioequivalent drug products:
pharmaceutical equivalents whose bioavailability does not show a significant difference when administered at same dose under similar experimental conditions, either single or multiple dose.
Generic drug product
= a drug product
bioequivalent
to the reference listed drug product
What are drug delivery systems?
They are formulations or devices that enable the introduction of a therapeutic substance into the body and improves its efficacy and safety by controlling the rate, time, and place of release of drugs in the body in a safe, efficient, reproducible and convenient manner.
What are excipeints?
Pharmacodynamically inactive substances added to formulations to provide certain functional properties to the drug and/or its dosage form. Inappropriate excipient choice may alter bioavailabilty, stability and properties of drug/dosage form.
Many different types of excipients with a whole array of functions.
Refer to table of excipients.
