PHRX 3031 Ceutics - FINAL cumulative section theoretical concepts

define pharmaceutics

the disipline of pharmacy that deals with the science of dosage form design and the process of turning a new chemical entity (NCE) into a medication that can be used bith safely and effectively

what is a chemical?

a substance composed of chemical elements

what is a drug?

a substance intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease

what is a drug product?

the finnished dosage form that contains a drug substance, generally in association with other active or inactive ingredients

what is a dosage form?

the physical form in which a drug is produced and dispenses (tablet, capsule etc)

compare active and inactive ingredients

active ingredient: the chemical that actually causes the medications desired effect

inactive ingredient: any component of a drug product other than the active ingredient

give an example of active and inactive ingredients in the case of Advil

active = ibuprofen

inactive = methylparaben

compare brand and generic drugs

brand: when a drug is approved by the FDA for the first time, there is only one manufacturer that will sell the drug under a patent. the drug will be considered as only the brand name until the patent expires

generic: drug produced after the brand name pateint expires

compare OTC and prescription drugs

OTC drugs can be dispensed without a prescription and prescription drugs can only be dispensed with a prescription

what are 9 examples of dosage forms?

- tablets

- capsules

- powders

- implants

- suppositories

- injections

- ointment

- lotion

- granules

explain how the conjugated estrogens differ in an estrogen dosage form

estradiol: hydroxyl, more OH groups allow for more H bonding and will be more soluble

estrone: ketone that will be less soluble

what are 3 dosage forms of estrogen and how do they meet different needs?

tablets: estrodial will dissolve easier but has high first pass effect

transdermal: estrone used often and will bypass first pass memtabolism

vaginal ring: topical application for local symptoms

state 11 examples of why different dosage forms are necessary

- for safe and convient dosage delivery

- protect drug from chemical degradation

- make oral preparations

- provide injectable forms

- provide slow or targeted release of drug

- provide topical administration

- can be used for insertion of drug into body orfice

- can make a drug an inhalent for direct delivery to lungs

how can drugs be damaged by oxygen? what can be done to protect?

when some drug products are exposed to oxygen, they can give rise to free radical reactions which will decrease the stability of the drug, leadting to degradation. drugs can be protected from this by amber colored vials

in what 4 ways can dosage forms be categoriezed based on physcial properties?

- gaseous

- liquid

- semisolid

- solid

what are 2 gaseous dosage forms?

- medicinal gasses

- aerodispersions

what are medicinal gasses?

inhalation anestetics that are vaporized before administration by inhilation

what are aerodispersions?

solid/liquid particles that are inhaled

what are 3 liquid dosage forms?

- solutions

- emulsions

- suspensions

what are solutions?

prepared by dissolving one or more solutes in a solvent

what are emulsions?

a dispersion system consisting of 2 immiscible liquids. either oin in water (o/w) or water in oil (w/o)

what are suspensions?

a dispersion system where solid particles are dispersed in a liquid phase

what considerations should be made with suspensions?

if they are not mixed well dosed will vary, so they should not be used for drugs with high potency

what are 6 semi-solid dosage forms?

- gels

- creams

- ointments

- pastes

- suppositories

- pressaries

what are gels?

semisolid system in which a liquid phase is constained within a 3D cross linked matrix

what are creams?

semisolid emulsion systems containing more than 10% water

compare o/w and w/o creams

o/w: more comfortable, less greasy and more water washable

w/o: more greasy and moisturizing, better to realease lipophillic API

what are ointments?

semisolid doage forms with oleaginous (oil), water soluble (PEG) or emulsifying base

what are pastes?

semisolid dispersion system where solid particles are more than 25% of mixture and are dispersed in ointments

what are suppositories?

shaped semisolid form for rectal administration that will melt/dissolve at body temperature

what are pessaries?

shaped semisolid form of vaginal suppositoeies that melt/dissolve at body temperature

what is an example of an unshaped solid dosage form?

powders for external or internal use

what are 4 examples of shaped solid dosage forms?

- tablets

- capsules

- implants

- transdermal patches

what are the overall ideas of each generation of dosage forms?

1st = immediate release of API

2nd = controlled release of API

3rd = targeted distribution of drug delivery systems

what concepts are defined by 1st generation dosage forms?

disintegration of the dosage form and dissolution of API is a spontaneous process, drug abdorption and distribution is based ONLY on the phisiochemical properties of API

define 2nd generation dosage forms

the release of API is under control of the drug delivrey system (temporal control)

what are 3 advantages of 2nd generation dosage forms?

- avoids flutuations of plasma drug concentrations (safety)

- decreased adminsitration frequency (better complience)

- can be more cost effective

what are 3 examples of 2nd generation dosage forms?

- sustained release (SR)

- controlled release (CR)

- pulsatile release

compare sustained and controlled release dosage forms

sustained: release of initial API dose and then prolonged release after; slows release but may not keep constant drug levels

controlled: releases drug at a constant, controlled rate to maintain drug levels

define the concepts of 3rd generation dosage forms

invlve targeted ditribution of drug to a particular organ/tissue rather than the entire body

compare passive and active targeting

passive: drug delivery based on natural properties of the body like leaky vasculature

active: drug delivery with a specific ligand that will bring the drug to specific targets in body

compare thermodynamics and kinetics

thermodynamics: describes the changes in the form of energy when a rxn occurs, determines if rxn happens or not, will depend on the initial and final state NOT the path to get there

kinetics: describes how quickly or slowly a rxn occurs, based on the activation energy, will consider the PATH to get from initial to dinal state

what is the 1st law of thermodynamics?

energy is conserved, it can not be created or destroyed

what is the 2nd law of thermodynamics?

in an isolated system, natural processes are spontaneous when they lead to an increase in disorder (entropy) (S)

what is the 3rd law of thermodynamics?

the entropy of a perfect crystal is 0 when the temperatire of the crystal is equal to absolute 0 (0K)

what is steady state?

a state in which one specific component does not change with time

what is equilibrium?

a state in which the concentrations of reactants and products do not change with time (entire reaction)

what 5 things are considered in pharmaceutical equilibrium?

- solubility equilibria

- pH equilibria

- complexation equilibria

- protein binding

- partitioning

when is a specific time where solubility equilibria is important?

★ suspensions

- in a suspension, there will be an equilibrium between soluble and insoluble states

when should pH equilibria be especially considered?

- drugs you need to eat with food

- optometria formulations

when should complexation equilibria be especially considered?

- inorganic compounds like cisplatin and drugs that contain platinum

- important for intercalation

define phase in terms of thermodynamics

a distinct region within a system

define component in terms of thermodynamics

one independent constituent of a system

define homogenous system in terms of thermodynamics

all components belong to the same phase

define heterogenous system in terms of thermodynamics

not all components are in the same phase (ex. some may be liquid and some may be solid)

define system in terms of thermodynamics

a specific region of the universe that is being studied, has a boundary from its surroundings so it can be studied

define surrounding in terms of thermodynamics

everything outside the system being studied, can exchange energy or have influence on the system itself

define universe in terms of thermodynamics

an isolated system that cannot exchange energy with anything outside itself

what 4 thermodynamic variables are considered for a system?

- composition

- temperature (most variable)

- pressure

- volume (directly related to temperature)

what is the equation of state?

the reationship between P, V and T

define open system

a system in which both energy and matter can enter and leave

define closed system

a system in which matter is NOT exchanged with surroundings (energy can move)

define isolated system

a system in which neither matter or energy is exchanged with the surroundings

what is an isothermal process?

a process that occurs at a constant temperature

what is an adiabatic process?

a process that occurs with no exchange of heat

what is an intensive property?

a property of a system that does NOT depend on the size of the system

what is an extensive property?

a property of a system that does depend on the size of the system

what is internal energy?

★ E

the sum of the kinetic and potential enregy

for ideal gasses, what is the relationship between internal energy and temperature?

increase internal energy = increase temperature of gas

what does it mean if work (w) is negative?

negative w = work is being done on the system

define enthalpy

∆ H

- heat gained by the system during a process

what does positive enthalpy mean?

endothermic, heat is absorbed from the surrounding

what does negative enthalpy mean?

exothermic, heat is released to surrounding

what is entropy?

S

mesasure of disorder of a system

what is the coorelation between entropy and spontaneity?

natural processes are considered spontaneous when they lead to an increase in disorder (entropy)

describe entropy change with phase change

solid = lowest entropy

liquid = middle

gas = highest enropy (most disorder)

what does it mean when entropy (S) is negative?

the process leads to a more ordered system

how can entropy tell you the direction of a reaction?

in an isolated system, chemical reactions will occur in the direction that leads to an increase of disorder (entropy)

what does ∆G and ∆G* tell us?

∆G: free energy of reaction at any condition

∆G*: standard state free energy of reaction

what does a larger ∆G* value indicate?

the reaction will have to go further to get from standard state conditions to equilibrium

what are 3 consequenses of thermodynamics on drug formulations?

- drug turns cloudy in fridge

- pH can change with temperature

- we use sweeteners in solutions with positive enthalpy values to give refreshing sensation

what are 3 examples of pharmaceutical solvents?

- syrups

- tinctures

- elixirs

describe syrup NF

example is syrup NF which is 85% w/v sucrose so there is 85g sucrose in 100 ml water

describe tinctures

alcohol and water solvent used to extract natural products, has a higher alcoholic content than elixirs

describe elixirs

sweetened alcohol and water solvent used for making medicated syrups, less alcoholic content than tinctures

what is the symbol for moles?

n

how do we calculate # of moles?

mass/molar mass

what is the symbol for molarity?

M

how do we calculate molarity?

# moles / liter of solution

what is the symbol for molality?

m

how do we calculate molarity?

# moles / kg solvent

what is the symbol for normality?

N

how do we calculate normality?

# equivilents / liter of solution

what is the symbol for mole fraction?

X

how do we calculate mole fraction?

# moles of solute / total # moles

define solubility

ability of solute to homologously mix into solvent at a standard temperature

define polar protic solvents

contain a proton (H) which helps with H bonding

define polar aportive solvents

polar but does NOT contain a proton (H)

describe nonpolar solvents

oil substances

what are the 2 most common solvents?

most common is water followed by ethanol