Drug Dosage Forms for

Reproductive Organs Infection

&
How to PRESCRIBE IT
 PRESCRIBING
Pathophysiology/Pathogenesis
Diagnosis, Therapeutic objective

Drug of Choice
Mechanism of action, Indication, Contraindication,
side effect, interaction

Route of administration
Dosage form

Dose, frequency, length of therapy,

time of administration, how to use
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 outline
Reproductive Organs Infection
Intravaginal drug delivery
Mechanism
Advantages and limitations
Dosage Forms
Prescription

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Reproductive Organs Infection

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 STANDAR KOMPETENSI
DOKTER INDONESIA (2012)

No. Disease (LEVEL 4A)

1 Sindrom duh (discharge) genital (gonore dan nongonore)
2 Infeksi saluran kemih bagian bawah
3 Vulvitis
4 Vaginitis
5 Vaginosis bakterialis
6 Salpingitis
7 Abses folikel rambut atau kelenjar sebasea

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 Treatment of
Reproductive Organs Infection

Systemic Local
(Oral, Parenteral) (Topical)
Affected by the Affected by the local
systemic condition condition
Late onset of action Faster onset of action
Higher dose Bypass the 1st pass
Bioavailability? metabolism in liver
Girls Shorter duration of the
treatment

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 vaginal drug delivery

mechanism, advantages,
limitations, DOSAGE FORMS

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 MECHANISM (1/2)

Intravaginally to the vaginal epithelium

Transvaginally through the vaginal mucosa

uterus & systemic circulation

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 Mechanism (2/2)
1. Diffusion through the cell due to a
concentration gradient (trans cellular route),
2. Vesicular or receptor-mediated transport
mechanism, or
3. Diffusion between cells through the tight
junctions (intercellular route)

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Factors influencing the absorption -
Vaginal Drug Delivery (1/4)

Anatomy and
Physicochemical
Physiology

Administration
Device

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 Factors influencing the absorption anatomy &
physiology FACTORS (2/4)

Anatomy:
Fibromuscular tube, rugae and microridges on the epithelial cell
vagina can expand (placement of the drug, increase the
surface area)
Arteries and veins form a dense network rich blood suppply
Physiology
Vaginal secretions
Enzyme activity (lower)
Vaginal pH (3.5 to 4.9)
Maintained by bacterial conversion of glycogen from exfoliated
epithelial cells to lactic acid
All affected by age (hormone levels), stage in the menstrual cycle,
infections, estrogen levels and variations in the level of cervical
mucus

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Factors influencing the absorption
PHYSICO-CHEMICAL
FACTORS (3/4)
Physicochemical characteristics of the active
ingredients;
pH and mucosal irritancy;
osmolarity;
Viscosity (solution, gels) and
density (powder, tablet) to the formulation;
concentration and volume administration

Type of the dosage forms;

The particle size of the molecule of drug,
Hydrophilicity or lipophilicity of drug molecule,
Molecular weight of the drug molecule,
The chemical nature,
The ionization surface charge

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 Factors influencing the absorption
ADMINISTRATION DEVICE (4/4)

The viscosity of the semi solid

dosage forms (creams, gel, etc)
Size of the solid dosage forms
(vaginal tablet, et)

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 THE Advantages of
THE intravaginal drug delivery systems (1/2)

Alternative route in certain cases of therapeutic

importance
In cases of nausea and vomiting, the act of taking
medication orally may induce emesis
Irritation to the stomach and small intestine associated
with certain drugs
Hepatic first pass elimination of high clearance drugs may
be avoided
Contact with digestive fluid is avoided
Drug delivery can be stopped by removing the dosage
form e.g. vaginal rings

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 The Advantages of
intravaginal drug delivery systems (2/2)

Rapid drug absorption and quick onset

of action can be achieved
Convenient for the patients, especially
for those on long term therapy, when
compared with parenteral medication
The vaginal bioavailability of smaller
drug molecules is good
Self medication is possible 16
 Limitations
Some of the drugs are sensitive at the
vaginal pH
Local irritation of some drugs
Influence of sexual intercourses
Gender specificity
Personal hygiene
Sometimes there is a leakage of the
drugs from the vagina and the under
garments becomes wet 17
Intravaginal drug delivery

DOSAGE FORMS

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 DOSAGE FORMS
Vaginal rings
Vaginal gel and creams
Vaginal tablets
Suppositories (ovula)
Other (ex. Foams, solutions, etc)
Bioadhesive micro-particulated drug
delivery devices or systems

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 DOSAGE FORMS
vaginal tablet and vaginal suppository
Both melt in vaginal cavity
Release the active constituent over prolong period of
time
Vaginal tablet contain similar component as like
conventional oral tab, easier to manufacture and
insertion
Vaginal gel and vaginal cream
Messy to use
Uncomfortable
May not provide an exact dose
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 Vaginal tablet

O Nystatin Clotrimazole
(Canesten)

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Applicator

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 Metronidazole DOSAGE FORMS
an antibiotic effective against anaerobic
bacteria and certain parasites

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 Metronidazole DOSE
Bacterial Vaginosis:
Tab 500 mg orally twice daily for 7 days
Tab 750 mg (extended release tablets)
once daily for 7 days
One applicator-full of 0.75% vaginal gel,
once or twice daily for 5 days.

Trichomoniasis:
2 g single dose or 1 g twice
alternative 500 mg twice daily for 5 25
days.
 Combination
Antibiotic Metronidazole anti fungi
Nystatin
Vaginal suppository = ovule

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clindamycin

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Intravaginal drug delivery

The Prescription

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Bacterial vaginosis

Current Diagnosis and Treatment in Family Medicine. 2nd edition.

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 dr. Vina
SIP. No 1234567
Jl. Salemba 6, Jakarta
_______________________________________________
Jakarta, 10 November 2012

R/ Clindamisin cream intravaginal tube No. I

S 1 dd per vag a.n
-------------------------------------------------------------------- initial

Pro : Mrs. A
Age : 30 yrs

Dalacin V Cream

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 dr. Vina
SIP. No 1234567
Jl. Salemba 6, Jakarta
_______________________________________________
Jakarta, 10 November 2012

R/ Clindamisin ovule No. III

S 1 dd ovule I per vag a.n
-------------------------------------------------------------------- initial

Pro : Mrs. A
Age : 30 yrs

Cleocin

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 dr. Vina
SIP. No 1234567
Jl. Salemba 6, Jakarta
_______________________________________________
Jakarta, 10 November 2012

R/ Clindamisin 300 mg Capsule No. XIV

S 2 dd Caps I
-------------------------------------------------------------------- initial

Pro : Mrs. A
Age : 30 yrs

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 dr. Vina
SIP. No 1234567
Jl. Salemba 6, Jakarta
_______________________________________________
Jakarta, 10 November 2012

R/ Metronidazol vaginal gel tube No. I

S 2 dd per vag
-------------------------------------------------------------------- initial

Pro : Mrs. A
Age : 30 yrs

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Vulvovaginal candidiasis

Recommended Dose/route Alternative

regimens regimens
Clotrimazole cream 1% 5 g intravaginally Fluconazole 150 mg
x 7d po once
Clotrimazole vaginal 100 mg
tablet intravaginally x 7 d
200 mg
intravaginally x 3 d
Nystatin vaginal 100.000 units
tablet intravaginal x 14 d

Current Diagnosis and Treatment in Family Medicine. 2nd edition.

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 dr. Vina
SIP. No 1234567
Jl. Salemba 6, Jakarta
_______________________________________________
Jakarta, 10 November 2013

R/ Canesten vag tab 100 mg No. VII

S 1 dd tab I per vag a.n
-------------------------------------------------------------------- initial

Pro : Mrs. A
Age : 30 yrs

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 dr. Vina
SIP. No 1234567
Jl. Salemba 6, Jakarta
_______________________________________________
Jakarta, 10 November 2013

R/ Nistatin vag tab No. XIV

S 1 dd tab I per vag a.n
-------------------------------------------------------------------- initial

Pro : Mrs. A
Age : 30 yrs

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 dr. Vina
SIP. No 1234567
Jl. Salemba 6, Jakarta
_______________________________________________
Jakarta, 10 November 2013

R/ Flagystatin ovule No. X

S 1 dd ovule I per vag a.n
-------------------------------------------------------------------- initial

Pro : Mrs. A
Age : 30 yrs
( or R/ Flagystatin ovule No. X )

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 Trichomoniasis
Recommended regimens Dose/route

Metronidazole tablet 2 g po single dose or

500 mg po bid x 7d
Tinidazole tablet 2 g po single dose

Metronidazole gel is not recommended because it is less efficacious (<50%)

Management of genital ulcers and discharge. www.guidelines.gov

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 POTENTIAL HARMS
DRUGS Route POTENTIAL HARMS
Azoles Topical Usually no systemic side effects.
Local burning might occur.
Creams and suppositories are oil based and might
weaken latex condoms and diaphragms.
Oral Nausea, abdominal pain, headache.
Elevations of liver enzymes (rare)
Clindamycin Topical Oil based and might weaken latex condoms and
(Cream) diaphragms.
Associated with low birth weight and neonatal
infection if used in the latter half of the pregnancy
Metronidazole Oral Lactating women should withholding breastfeeding
during treatment and 12-24 hours after the last dose
(3 d for tinidazole)
consuming alcohol should be avoided during
treatment and 24 hours thereafter
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Disease chracterized by vaginal discharge. In: STDtreatment guidelines. 2010
APPLYING THE VAGINAL
DOSAGE FORMS

WITH WITHOUT
APPLICATO APPLICATO
R R

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 Applying the vaginal creams,
ointments and gels
(most of these drugs come with an applicator)
1. Wash your hands.
2. Remove the cap from the tube containing the drug.
3. Screw the applicator to the tube.
4. Squeeze the tube until the required amount is in the applicator.
5. Remove the applicator from the tube (hold the cylinder).
6. Apply a small amount of cream to the outside of the applicator.
7. Lie on your back, draw your knees up and spread them apart.
8. Gently insert the applicator into the vagina as far as possible, do NOT use force.
9. Hold the cylinder and with the other hand push the plunger down thus inserting
the drug into the vagina.
10. Withdraw the applicator from the vagina.
11. Discard the applicator if disposable or clean thoroughly (boiled water) if not.
12. Wash your hands.
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APPLYING THE vaginal gel

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Applying THE vaginal creams,
ointments, and gel

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 applying THE vaginal tablet
WITH applicator
1. Wash your hands.
2 Remove the wrapper from the tablet.
3. Place the tablet into the open end of the applicator.
4. Lie on your back, draw your knees up a little and spread them
apart.
5. Gently insert the applicator with the tablet in front into the
vagina as far as possible, do NOT use force!
6. Depress the plunger so that the tablet is released.
7. Withdraw the applicator.
8. Discard the applicator (if disposable).
9. Clean both parts of the applicator thoroughly with soap and
boiled, lukewarm water (if not disposable).
10. Wash your hands.

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Applying the vaginal tablet with
applicator

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 APPLYING THE Vaginal tablet
without applicator
1. Wash your hands
2. Remove the wrapper from the tablet.
3. Dip the tablet in lukewarm water just to moisten it.
4. Lie on your back, draw your knees up and spread them apart.
5. Gently insert the tablet into the vagina as high as possible, do
NOT use force!
6. Wash your hands.

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 References
Kumar L, Verma R. IJPRD/2010/PUB/ARTI/VOV-2/ISSUE-6/AUG/003
De Vries TPGM, Henning RH, Hogerzeil. Presle DA. Guide to good
prescribing. WHO. 1994.
Choudhury A, Das S, Kar M. A review on novelty and potentiality of vaginal
drug delivery. International Journal of PharmTech Research. Vol. 3 No. 2
p1033-1044. 2011.
Dobaria N, Mashru R, Vadia NH. Vaginal drug delivery systems: a revies of
current status. East and Central African Journal of Pharmaceutical
Sciences. Vol. 10 (2007). P3-13.
Centers for Disease Control and Prevention (CDC). Diseases characterized
by vaginal discharge. In: Sexually transmitted disease treatment guidelines,
2013 [Erratum appears in MMWR Recomm Rep. 2011 Jan 12;60(1):18].
MMWR Recomm Rep. 2010 Dec 17;59(RR-12):56-63.

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THANK YOU

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