dosage fr finals

what is hard gelatin made out of ?

gelatin + water + sugar

hard gelatin moisture content

10-15%

hard gelatin

2 parts

large narrow - body

wider smaller - cap

what are soft gelatin capsules made out of?

gelatin + glycerin or sorbitol + preservatives + water

hermetically sealed

difficult to compound

types of gelatin

type A : pork skin

type B: animal bones

gelatin alternatives

• polysaccharide (pullulan)

  • plant caps

  • water soluble

  • non-hydroscropic

• cellulose derivatives (hypromellose)

  • Vcaps

coni-snap

tapered rims

indentations / dimples

locking grooves

coni-snap supro

smaller

makes seperating 2 parts more difficult

weight variation (gross weight)

± 10%

content uniformity (API strength)

± 5%

QA compendial requirements

content uniformity : 9/10 should have drug strength 85-115%

stability testing

moisture permeation test

disintegration test

dissolution test

tablet advantages

temper resistant

convenient to use

how to make tabs?

1. tab manufacture

2. compression

3. wet granulation

4. dry granulation

5. direct compression

wet granulation

drugs with low compressibility / weak physical strength

dry granulation

drugs unstable in water / heat

direct compression

drugs with high compressibility / flowability

no need for granules

microcrystalline cellulose

dibasic sodium calcium phosphate

compression aid

sodium starch glycolate

disintegrant

magnesium stearate

tableting lubricant

tablet defects

capping

lamination

chipping

cracking

mottling

sticking

picking

capping

upper or lower part of the tablet separates from the main body

• not enough binder

• didnt dry well

lamination

seperation of tab into 2 or more distinct layers

• air entrapment

• too oily

chipping

breaking of tablet edges while tablet leaves press

• too dry

cracking

small fine cracks

• granules too big/dry

mottlings

unequal distribution of tablet color

sticking

tablet material adhering to dye wall

sticks to other tabs

picking

adheres to the surface of the punches

letter may be too big

effervescent tablets

release CO2

rapdily dissolving tabs storage

very hydroscopic

• if you leave outside = start dissolving

friability is an issue

• if shake = break

individually packed

multiple compressed tabs

seperate incompatible drugs

deliver drugs @ different rates

film coated tabs IR

coat dissolves in stomach fluid

film coated tabs MR

coat does not dissolve in GI tract

dissolve in stomach

eudragit E

dissolve in small intestine

eudragit L or S

neutral in charge, insoluble in water, swll to release

eudragit NE or NM

insoluble in water, swell to release, high Tg

eudragit RS or RL

enteric coated tabs

polymors used

cellulose acetate phthalate

HPMC succinate

methcrylic acid co-polymers

shellac

types of ER release

gum-type

slow-release pellets, beads or granules

core tabs

microencapsulation

osmotically controlled release oral delivery system (OROS)

composition

trilayer surronded by semi-permeable membrane

2 drug layers → push compartment q

OROS

how does it work?

passes through semi-permeable membrane

control rate of passage into tablet membrane core

OROS

benefit

reduced fluctuation between drug peak and serum concentrations

binders

acacia

alginic acid

polyvinylpyrrolidone

microcrystalline cellulose

common excipients

binders

diluents

disintegrants

lubricants

glidants

antioxidants

when are lubricants usually added?

at the last step

glidants

tac

colloidal silicon dioxide

antioxidants

ascorbic acid

sodium ascorbate

sodium bisulfite

sodium metabisulfite

lubricants

metallic stearate

stearic acid

talc

4Ds

disintegration

deaggregation

dissolution

diffusion

which forms should not disintegrate slowly?

buccal

vaginal

sublingual

some film coated tabs

what does delay disintegration must occur with?

enteric coated tablets

diluents

fillers added to bulk up tab

hydroscopic

coming in contact with liquid → disintegrates

advantages of suppositories

avoids 1st past effect

how is drug absorbed in the rectum?

lining of rectum ampule and passes into circulation via hemorrhoidal veins

rectal circulation route

lower hemorrhodial veins

lymphatic circulation

rectal colonic contents

enema administered and allowed to at before suppository of a drug to be abs

rectal pHand lower buffer capacity

6.8-7.4 negligible buffer capacity

too alkaline will irritate the rectal area

rectal like dissolves like

lipo drug distributed in fatty suppository base in low concentrations = less tendency to escape to surrounding aqueous fluids

suppository bases

melt or dissolve

stable during storage

contact slightly on cooling to release from mold

do not melt at ambient temp

fatty base

melt to release 3-7 mins

1-4 days to return to stable form

stable fatty base temp

34.5C

examples of fatty base

beeswax

cetyl ester wax

fatty base

hydrogenated vegetable oils with emulsifers

fattibase

wecobee

witespol

fatty base advatages

innocuous

non-reactive

melt at body temp

fatty base disadvantage

melt in warm weather

leakage

water soluble/miscible bases

glycerinated gelatin

dissolve 30-40 mins

vaginal application

hydroscopic nature of gelatin

promotes laxation

water soluble/miscible bases

PEG

dissolve 30-50 mins

hydroscopic → irritating to body cavity tissues

drug release

• from slow to rapid

1. lipophilic: fatty base

2. lipophilic: water base / water-miscible drug

3. hydrophilic drug: fatty base

vaginal pH

4-5

preparation of suppositories

hand molding

compression molding

fusion

intra-nasal drug delivery

epithelial lining

• goblet cells

mucus layer

advantages of nasal delivery

targeted treatment

fast onset of action

minimize side effects

intranasal absorption

paracellular

• tight junction

• slow and passive

transcellular absorption

• partitioning coefficient

physiochemical properties of intranasal

solubility

• rapid dissolution of drug solids

ionization

• non-ionized better

intranasal delivery

by pass BBB

delivery of large drug molecules

peptide drugs

across nasal endothlium

avoid degradation in GI

nasal vaccines

stimulate mocusal-nasal associated lymphoid tissue to produce secretory IgA / IgM and IgG

how are drugs intranasally?

nasal

spray

powders

• > 10 um

nasal drops

solution formulation

deposit as film

disperse as drug

nasal spray

solution or susp

nebulized or aero

< 10um

droplets or larger particles

deposit in front part of nasal cavity

• limited abs

• variable bioavailability

nasal spray

squeeze bottle

solution → mist

metered-spray

spray pumped used

no propellent

accurate

atomization spray

more accurate

nasal solution enhanced by solvents

propylene gycol

alcohol

medium chain glycerides

nasal solution pH

4.5-6.5

intranasal

osmolarity/tonicity

isotonic solution PREFFERED

intranasal preservatives

benzalkonium chloride

enhancement of nasal absorption

increase viscosity

use of muco-adhesives

permeability enhancers

pulmonary drug delivery

systemic

anesthesisa

parkinson

diabetes

pulmonary advantages

avoid 1st pass

less amount of drug to treat therapeutic effect

reduce systemic side effects

pulmonary disadvantages

small portion of the dose can reach the lungs due to particle deposition in respiratory tract

complicated devices are needed

gas

can easily reach alveoli

penetration of droplets/particles depends on ?

delivery system

conditions of airways

particle size

aerodynamic particle size

diameter of spherical particle of standard denity → same terminal settling into velocity in air

factors affecting aerodynamic particles size

physiochemical properties

humidity and tonicity

surface active agents

effect of particle size

depth of particle penetration depends on aerodynamic particle size

smaller particles can pen deeper

mode of particle deposition

inertial impacting

blocked by airways : large particles

mode of particle deposition

sedimentation particles

fall out of air flow, epithelium of airways