rectal and vaginal dosage forms

Question 1

suppositories definition

Answer 1

dosage form adapted for application into the rectum

-melt, soften or dissolve at body temperature

Question 2

inserts definition

Answer 2

solid dosage from inserted into naturally occuring body cavity other than mouth or rectum

Question 3

suppositories definition round 2

Answer 3

semi-solid or solid dosage form

intended to be inserted into body orfices

• rectum
• vagina (inserts or pessaries)
• urethra (inserts or bougies)

Question 4

advantages (6(

Answer 4

patients cannot swallow
-(children, elderly, nausea, and vomiting)

GI tract irritant drugs

treatment of diseases of lower parts of GI

once daily use

local and systemic effect

avoid hepatic first pass metabolism (if administered correctly

Question 5

disadvantages

Answer 5

poor compliance

discomfort and leakage

variation of absorption
- shit first

irritation of mucous membranes caused by some drugs or bases

upward movement of suppository from local site can inc first pass metabolism

Question 6

classification of suppositories

Answer 6

rectal
vaginal (inserts or pessaries)
urethral (inserts or bougies)

Question 7

rectal suppositories shape

Answer 7

bullet and torpedo shape

Question 8

rectal suppositories weight

• baby
• adult
• rectal rocket

Answer 8

baby: 1g
adult: 2g

rectal rocket 4-5g

Question 9

rectal suppositories local action

Answer 9

hemorrhoids
itching
infections

Question 10

rectal suppositories systemic action

Answer 10

antinauseants
analgesics
hormones

Question 11

rectal suppositories drug content

Answer 11

0. 1% up to 30-40% (from blank weight

- variable

Question 12

other rectal preparations (8)

Answer 12

rectal capsules
rectal tablets
solutions (enemas)
suspension
emulsions
ointments
foams
tampons

Question 13

benefit of rectal rocket

Answer 13

internal and external treatment

Question 14

vaginal inserts shape

Answer 14

usually globular, oval or cone shaped

Question 15

vaginal inserts weight

Answer 15

3-5g each

Question 16

vaginal inserts bases

Answer 16

water soluble or water miscible vehicles

PEG or glycerinated gelatin

Question 17

vaginal inserts uses

Answer 17

contraceptives
gynecological ailments
antiseptics

Question 18

other dosage forms for vaginal application

Answer 18

solutions
ointments
creams
gels
foams
implants
tablets

Question 19

urethral inserts shape

Answer 19

cylindrical
-vary in length according to gender

females
50mm length

males
12.5mm in length

Question 20

urethral inserts diameter

Answer 20

3-6mm

Question 21

urethral inserts weight

• female
• male

Answer 21

~2g female

~4g male

Question 22

urethral inserts uses (3)

Answer 22

severe ED
-alprostadil

antibacterial

local anesthetic preparative for urethral exam

Question 23

composition of suppositories (3)

Answer 23

1) API
2) additives
3) suppository bases

Question 24

Other types of suppositories

Answer 24

hollow type
-drug in sol’n/suspension in hollow cavity

multilayered
-good for sep incompatible reagents/excipients

sustained release
-viscosity inducing ingredient to modify release

thermo-reversible liquid

• forms gel when warm
• mucoadhesive properties

effervescent

• foams and froths in contact with body fluid
• aids in dispersion of drug

Question 25

rectal cavity physiological factors - mucus fluid - pH - surface area - fecal matter

Answer 25

small mucus fluid volume (1-3mL) -problem for drugs that are poorly water sol pH = 6.8 - 7.4 and lower buffer capacity -excipients and API can change pH of fluids small surface area relative to GI presence of fecal matter -council evacuate b4 insert

Question 26

blood supply to rectal area

Answer 26

inferior rectal vein | superior rectal vein

Question 27

inferior rectal vein

Answer 27

transports drugs into IVC and bypass iver

Question 28

superior rectal vein

Answer 28

transports drugs to upper part of rectal cavity to the liver

Question 29

why is it hard to predict if drug will avoid liver metabolism

Answer 29

depends on if abs by IRV or SRV

Question 30

Cocoa butter and fatty base, drug release and absorption

Answer 30

oleaginous (fatty base) melts and spreads, drug partitions from molten base, dissolves in mucus, diffuses across membrane

Question 31

PEG base, drug release and absorption

Answer 31

hydrophilic base absorbs water and dissolves in fluids drug dissolves in mucus and diffuses across membrane

Question 32

formulation and drug properties factors: melting or dissolution of base (2)

Answer 32

1) melting point - melt at body T or few below - fatty bases melt 2) aqueous solubility and dissolution - water sol bases need dissolve to release drug, slower release than fatty bases

Question 33

formulation and drug properties factors: release and diffusion of drug (4)

Answer 33

1) solubility of drug in vehicle and in rectal fluids' 2) drug particle size 3) spreading capacity 4) base viscosity at rectal temperature

Question 34

formulation and drug properties factors: rectal mucosa

Answer 34

1) pKa of drug 2) pH induced in rectal fluids 3) presence of buffers 4) partition coefficient of drug

Question 35

solubility of drug in vehicle | -what mixes

Answer 35

if put liophilic drug in fatty base - low tendency drug escape from base into rectal cavity SO FB use hydrophillic drug

Question 36

solubility of drug in rectal fluids considerations

Answer 36

small vol rectal fluids -difficult for poorly water sol drugs dissolve +add wetting agents or surfactants to increase solubility of drug

Question 37

drug particle size consideration

Answer 37

smaller particle size = more dissolution = more absorption = prevents sedimentation ALSO remains longer in vehicle and eliminates some mechanical irritation

Question 38

spreading capacity considerations

Answer 38

increase area for absorption | -add surfactant to increase spreading capacity

Question 39

viscosity of base at rectal temperature considerations

Answer 39

higher viscosity = diffuse slowly = helps disperse drug uniformely throughout melted base

Question 40

pKa of drug considerations

Answer 40

unionized cross membrane easier

Question 41

pH induced in rectal fluids considerations

Answer 41

recal fluids dont have high buffer capacity supp base/ presence of buffer affect drug ionization

Question 42

partition coefficient considerations

Answer 42

drug needs some lipophillic properties to permeate through rectal mucosa

Question 43

drug release from oleaginous base

Answer 43

hydrophillic drugs - good release resulting in abs lipophilic drugs - tend to remain in base, slow release, little abs - if possible use ionized salt form of drug or fatty acid base with surfactant

Question 44

drug release from water soluble suppository

Answer 44

hydrophillic drugs - moderate release (dpnds on disoolution of base and diffusion of drug) lipophilic drugs -good to moderate release resulting in absorption

Question 45

higher molecular weight PEGs result in what

Answer 45

longer dissolution time

Question 46

Preparation of suppositiories (3) | -what is the most common

Answer 46

hand rolling and shaping -traditional - not really used now compression - no heat (good for heat labile drugs) - not very popular - requires specialized machine and limited shapes made - base and drug mixed then compressed into mold fusion molding (most common) - base melted in controlled water bath - drug disoolved/dispersed into base - pured into molds (metal, plastic)

Question 47

Hand rolling and shaping: specialized equipment?

Answer 47

no specialized equipment

Question 48

Hand rolling and shaping: role

Answer 48

historic

Question 49

Hand rolling and shaping: difficult?

Answer 49

requires lot of skill

Question 50

Hand rolling and shaping: what base

Answer 50

generally cocoa butter bc easy manipulate

Question 51

Hand rolling and shaping: steps (5)

Answer 51

1) triturate fine powder/extracts making paste with cocoa butter 2) add grated cocoa butter and triturate to incorporate 3) knead mass until pliable 4) roll out cylinder pipe using both hands and cut into pieces 5) roll to suppository shape

Question 52

Compression molding: process

Answer 52

base and ingredients combined by mixing into paste-like consistency mixed mass forced into special molds

Question 53

Compression molding: advantages

Answer 53

suitible for heat labile substances good for substances that are insoluble in base

Question 54

Compression molding: disadvantages

Answer 54

requires special suppository machine limited shapes can be made

Question 55

fusion molding: preparation

Answer 55

melting supp base and dispersing/dissolving drug into melted base

Question 56

fusion molding: steps (7)

Answer 56

1) calbration of mold 2) melt base in water bath at low heat 3) incorporate API and additives into melted base 4) pour melt base into molds ctsly to prevent layering 5) allow suppositories to cool 6) trim excess with spatula 7) remove formed suppositories from mold and wrap individually (if metal mold used) or dispense in disposable plastic mold

Question 57

packaging suppositories (3)

Answer 57

lined with grease proof paper or wrapped in foil and placed in partitioned rigid paper boxes in compounding more commoly dispensed in disposable plastic molds inside paper box or disposable plastic shells ``` hygroscopic products (glycerol suppositories) -dispensed in tightly closed glass or plastic containers ```

Question 58

quality control tests: visual examination (3)

Answer 58

color: intensity, nature, homogeneity texture-surface: smoothness of the surface appearance: dry or oily?moist

Question 59

quality control tests: weight uniformity

Answer 59

yes this is one eeeeee

Question 60

quality control tests: more industrial tests not done in pharmacy

Answer 60

uniformity of APIs mechanical str disintegration tests melting behaviour drug release from suppositories

Question 61

determination of amount of base required (4)

Answer 61

density factor calculation estimation ratio 0.7 estimated DF double casting method

Question 62

what does a DF of 1.2 mean

Answer 62

1.2g of API will displace 1g of base

Question 63

when do we need density factors

Answer 63

when quant of drug is more than 100mg in a 2g mold (5%)

Question 64

estimation by ratio

Answer 64

used to calc DF of a drug using the ratio of blank supp of an unknown base to a blank of cocoa butter

Question 65

0.7 estimated DF

Answer 65

powders have an estimated average displacement of 0.7g of suppository base for each gram of drug INVERSE OF DF

Question 66

DOUBLE CASTING TECHNIQUE: when to use (3)

Answer 66

when the quantity of drug is greater than 100mg drug is used for systemic effect DFs are not known

Question 67

double casting technique: steps (4)

Answer 67

1) first cast - mix all of drug with a portion of the base - fill partially each of the cavities 2) overfill cavities with plain base - if needed for DF determination, calibrate at least 3 cavities with plain base 3) let coool, removed excess from top, remove suppositories and re-melt 4) second cast to distribute evenly the drug

Question 68

why do we overfill in double casting technique

Answer 68

because pores form, if overfill pore form on overfill that is removed

Question 69

how do you calculate the DF from the double casting method

Answer 69

paddock method