Science of dosage forms & physical pharmacy Flashcards
defrine drug, drug product and dosage form
drug = agent intended for use in diagnosis, mitigation, treatment, cure of prevention of disease
dosage form = types of preparation drug can be presented
*dosae form can also bs called drug delivery system, but DDS is more specific
drug product = specific preparation or formulation of a drug (active ingredite, excipients, dosage form, method of preparation)
dosage form vs drug delivery system
dosage form is the type of prepatation of the drug presented to the patient ie vaccine
drug delivery system is more specific ie lipid nanoparticle encapsulates Rna endocing for target protein
what is the scope of pharamceutics
physical pharmacy
dosage form design
compounding and manufacturing
biopharmaceutics
pharmaceutical microbiology
*concerned w/ formuilation, manufacture, stability and effectiveness
*pharmaceutics converts a drug into a medicine
classification of dosage forms
solid: powders, capsules and tablets
liquid: solutions and some dispersions
semisoldiL creams ointments and suppositores
brand vs generic
brand:
- innovator product from company that disovered and developed
- is a new active ingredient
generic
- copy of brand w/ same actives, strength and dosage form
explain the rationale for the need for dosage forms
- want safe and convient means to get small dose of drug
* some drugs bigger dose like 325 and some v small like digoin 0.25
- protect drug against chemical decomposition from external and internal (gastic acid) env
- conceal odor and taste
- ensure or control the release of drug into the body to achieve a predicatable therapetuic response to drug formulation
what are the 3 important consideration in drug formulation
drug factors: both physical and chemcial properties of the substance
therapeutic considerations: both disease and patient factors
biopharmaceutic considerations: factors affecting abs of drug from diff admin routes
what are some drug factors to consider in dosage form design
- structural properties
crstalline form polymorphism, polarity, degree of ionizatoin)
- dissolution of porperties
- stability
- mechanisms of decomposition
- consider interaction of drug w/ other components of formulation
- organoleptic properties of the formulation
therapeutic factors in dosage form design
*nature of illness, disease defines these
- systemic or local admin
- targeted deliver
- reuqired duration of action
- dose: amount administered
- dose regimin: dose, interval between doses, duration of therapy
- fast relase vs sutained release
- patient characteristics
- age, emergency condiiotns
what biopharmaceutical factors influencer dosage form design
- ADME
- mechansism: passive diffusion where diff in conc drives abs or specialized transport mech
- how route of admin influences biopharmaceutical properties
- doseage forms that avoid first pass metabolism may allow for dec dosages & faster onset of action
- physical form also influences rate of abs and onset of action
what are the types of solid dosage forms
- tablets (coated or uncoated)
- capsules - ER
- powders
- troches and lozenges
what are the types of liquid dosage forms
solutions: (aq, non aq, syrups, elixirs)
- dispersions: emulsions, suspensions, magmas)
- sterile products (aq or non aq solutions, suspensions or emulsions)
- infusions (large volve parenterals like IV bags)
types of semi solid dosage forms
ointment, cream, lotion, paste, gels, suppositories
other types of dosage forms
aerosols
transdermal patches
inserts
sponges
how do excipients indluence final product
form, texture, stability, taste, appearance
what are all the systemic routes of administeration?
(enteral)
Oral: mouth (to GI tract)
sublingual: under tongue
buccal: mount cavity
rectal: rectum
what are the systemic routes of administration
(parenteral)
* these must be sterile
intravenous IV: vein
intramuscular: muscle
intrathecal: spine
intraosseous: bone
intra-articular: joint
instasynovial: joint-fluid area
intradermal: skin
sub-cutaneous (SC): beneath skin
intracardiac: heart
what are local routes of administration
topical (epicutaneous: skin surface
transdermal (+ systemic): skin surface
ophthalmic/intraocular: eye *must be sterile
conjunctival: conjunctiva *must eb sterile
otic (aural): ear
nasal: nasal cavity
inhalation: lung
rectal: rectum
vaginal: vagina
urethral: urethra
how do you chose a dosage form for a patient?
- consider disease
- local vs systemic effect (lotion vs tablet)
- rapid or systained release (local vs genral anesthesia
- Condition of patient
- willingness/ abiltiy to take medicatoin
- young kid may be uncoorperative, consider nausea/vomiting, comatose vs conscious pat
- Age of patient
* v young or v old: may be diff to swallow tab -> convert to liq dose - physical and chemcial drug properties
* consider stablilty issues, abs may be too slow in some routes
stages of innovator drug development processes from drug discovery to phase IV studies
- drug discovery and pre clinical R&D (1-3 years)
- animal models usually 2 species
- Company can then apply for an IND to proceed to phase 1 clinical trials
*Goal= make sure safe for human consumption & some promise for efficacy
- iND submitted to FDA, molecule is now called “ new drug” there is a 30 day safety review before clinical trials can start
- this step is just to let it go to clincial trail
- During phase 1 studies
- info about pharmacokinetics and pharmacologial effects, MOA in humans
- 20-80 subjects studied
- Phase 1 studies in healthy subjects to establish the safety aspect
- Phase 2
- are early controlled clinical studies
- Looking at short term side efects and any risks
- well controlled closely monitored in small umber of patients (several hundred people)
- Looking at safety and efficacy
- Phase 3:
- expanded controlled and unconrolled studied
- Overall benefit and risk analysis
- Several hundred to several thousand
*Both phase 2 and 3 FDA can implement a cliical hold
if phase 3 is satisfactory -> submit a doctumer including what happened during clincial test, animal studies results, manufacturing, how it behaves in body, ingedients etc.
Once NDA is approved drug can be marketed and copmanies keep cllecting safety info in phase 4 studies (post marketing surveys)
Also has a long term animal testing
At end of phase 3 clinical trails NDA/NDS (in canada) is sumitted (new drug applciation)
FDA then determines if it is safe and efifcacious enough for marketing
what are the preclincial phases in drug development
- drug discovery:
* botanicals and natural substances; synthetic chemistry; biotechnology and gene manipulation [new discoveries are patented] - Potential candidate identified for pharmacological studies in animals :
- efficacy and toxicity data obtained
- At this stage thousands of compounds may be candidates but only a few compounds are selected for further study
- Lead candidate(s) identified for development
- Biopharmaceutical and pharmaceutical experiments are conducted
- Preformulation studies
- ADME: absorption, distribution, metabolism, and excretion
- Mechanisms of action
- Dosage form, route of administration, formulation composition, stability
- In vitro and in vivo (acute and chronic studies in animals) toxicity
- Scale-up and manufacturing process development
what are the main diff in the innovator vs generic drug developemnt process?
*3-6 years and 4M rather than 10-15 years and 1.4B
- APT is sourced and tested
- reverse engineer the brand name to find the active
- test the generic formuatoin in manufacturing setting
- do bioequivilance studies, must have same characteristics as brand name
- generic manufacturerse are reuqires to serve a notice of allegation to brand name manufacturer *say you arent infiging on patents
- once has HC approval, can be sold
criteria fo generic drug
contain same API as innovator drug
- identical strength, doseage and route of admin
- have same use indications
- be bioequivalent
- meet same batch requirements for identity, strength, purity and quality
- be manufactured under same strict FDA GMP reg req for innovator products
time frame and cost for brand vs generic
brand: 10-15 years and 1.4B
generic: 3-6 years and 4M
role of biopharmaceutics and pharmaceutics in drug development
used in pre clinical phase experiments
preformulation studies
ADME: absorption, distribution, metabolism, and excretion
Mechanisms of action
Dosage form, route of administration, formulation composition, stability
In vitro and in vivo (acute and chronic studies in animals) toxicity
purpose of the Hatch-Waxmann act?
- generic drug ocmpany does not hae to discover a new drug entity or do any pre clinical reserach and devleopment
- does not have to releat $ animal and clinical reserach on ingredients or dosage forms that already approved for safety and effectiveness
- whyg enric drugs are cheaper
what is bioavailability
measure of the rate and extent of abs of a drug
ie max conc of drug in blood Cmax and conc of drug in blood over time (calc frm AUC in plasma conc vs time curve)
define bioequivalence
two diff product of the same drug provide the same bioavailability
how are bioequivalence studies used in generic drug developemnt
need to make sure the generic has same bioavailability of the brand
- acceptability criteria is 80-125%
*two medicines are equiv is no more than 20% difference between the AUC and Cman
-study types: two period, two sequence, two treatment, single dose, crossover study design, single dose parallel study design or replicate study design
what is purpose of a patent and how long does it protect an invention
- gives company sole right to sell drug
- active for 20 years
