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1. SUBJECT: PHARMACEUTICS IIIB
(Pharmaceutic Microbiology &
Immunology)
TOPIC: PREPARATION OF
GRISEOFULVIN BY
FERMENTATION
SUBMITTED BY: USMAN FAROOQ KHAN
REGISTRATION NO: FA21-PHM-089
SUBMITTED TO: DR.MUHAMMAD IKRAM

2. Griseofulvin
• Griseofulvin - antifungal antibiotic
(isolated from Penicillium sp)
• It is a secondary metabolite produced by the fungus Penicillum
griseofulvum.
• insoluble in water

3. Mode of action
• Fungistatic
• Inh fungal cell mitosis and nucleic acid
syn
• Binds to fungal microtubes  altering
fungal mitosis (metaphase)
• Active against most dermatophytes
• But not against Candida and other fungi
causing deep mycosis.

4. Biosynthetic Pathway of Fungal Cell Membrane & Site of Action
of other Antifungal Drugs

5. Pharmacokinetics
Absorption : incompletely absorbed from the GI tract, increased by
decreasing particle size and admin with fatty meals;
-peak plasma conc > 4 hours (t-max)
Distribution
Keratin precursor cells, stratum corneum
Protein-binding: 84%.
Metabolism :Hepatic
Excretion
Renal (50 %), via faeces ( 36%), via sweat; 9-24 hours (elimination half-life)
t1/2 h : 9 – 24

6. Indications
Tinea cruris: commonly referred to as jock
itch, is a fungal infection in the groin area
Tinea corporis: also known as ringworm
Treatment of following dermatophyte infections
Tinea pedis: known as Athlete's foot

7. Indications
Tinea barbae: Superficial dermatophyte
infection that is limited to the bearded
areas of the face and neck and occurs
almost exclusively in older adolescent
and adult males
Tinea capitis: Fungal infection of the scalp. It
is also called ringworm of the scalp

8. Indications
Tinea unguium when caused by one or more of the following
species of fungi:
•Epidermophyton
floccosum
•Microsporum audouinii
•Microsporum gypseum
•Trichophyton crateriform
•Trichophyton gallinae
•Trichophyton interdigitalis mentagrophytes
•schoenleini
•Trichophytum
sulphureum
•Trichophytum tonsurans
•Trichophytum verrucosum
•Trichophyton megnini
•Trichophyton
•Trichophyton rubrum
•Trichophyton

9. Dosage
• Oral: Dermatophytosis
Adult: 0.5-1 g daily in single or divided doses for
Child: 10-15 mg/kg daily.
• Food (before/after)
– Should be taken with food. (Take immediately after meals.)
Infection Dose
Tinea capitis 4 – 6 weeks
Tinea corporis 2 – 4 weeks
Tinea pedis 4 – 8 weeks
Tinea unguium
(onychomycosis)
Finger- atleast 4 mnths
Toe- atleast 6 mnths

10. • Griseofulvin is not effective in the following:
1. Superficial mycosis:
– candidiasis
– tinea versicolor
2. Deep mycosis:
- sporotrichosis
– histoplasmosis
– Chromoblastomycosis
– blastomycosis
– actinomycosis
– coccidioidomycosis
– nocardiosis

11. Contraindications
• Griseofulvin is contraindicated in
– severe hepatic disease
– Pregnancy (category C)
– porphyria
– monilial infection
– systemic lupus erythematosus

12. Adverse Effects
• Allergic reactions
• Nausea & diarrhea
• Headache
• Sleep disturbances
• Lathergy
• Photosensitivity
• Disulfirum like reaction

13. METHOD OF PREPARATION
MEDIUM PREPARATION
1. Czapek-Dox medium containing (as percentage w/v)
2. glucose 5%, sodium nitrate 0.2%
3. potassium dihydrogen phosphate 0.1%
4. magnesium sulfate 7H2 O 0.05% and potassium chloride 0.05% together with iron 200
μg./l
5. manganese 24 μg./l
6. zinc 225 μg./l
7. copper 38 μg./l
8. molybdenum 40 μg./l
9. yeast extract 1 g./l

14. PROCESS
The pH of the aqueous medium should be between 5.5 and 6.5 at the beginning
of the fermentation.
The griseofulvin produced by fermentation of an organism as specified in the
process of the invention, may be isolated from the fermentation broth by the well-
known methods for the isolation of griseofulvin. Thus, for example, the
fermentation broth may be filtered to separate the solid mycelium from the
aqueous fermentation medium, and the griseofulvin may be isolated from the
mycelium or the fermentation medium, or both, by extraction with an organic
solvent, for example chloroform, followed by recovery of the griseofulvin from
the extract.