DESCRIPTION
FIELD OF THE INVENTION
The present ionvention is related to the pharmaceutical formulation comprising Triazole antifungal drug with increased bioavailability. The triazole antifungal drug may be Fluconazole or Ketoconazole, more preferably fluconazole. The bio-enhancer used in the formulation is the combination of piperine, curcumin with betacyclodextrin.
PRIOR ART RELATED TO THE INVENTION
US 5616593 disclose the increase in bioavailability with the help of piperine alone. The drugs which shows increase in bioavailability are drug for treating a disease or condition of the human cardiovascular system, central nervous system, gastrointestinal tract, respiratory tract, endocrine system, genito urinary tract or haemopoietic system.
US 2004/0121028 relates to the isolation and preparation of an active fraction from plant Cuminum cyminum, its further purification and standardization as chemically defined entity (ies) with their intended use as drug bioavailability enhancer for the drugs belonging to therapeutic categories such as antimicrobial, antifungal, anti-viral, antitubercular, antileprosy, anti-inflammatory, antiarthritic, cardiovascular, antihistaminics, respiratory distress relieving drugs, immunosuppressants, anti-ulcerogenic, anti-cancer, CNS drugs, corticosteroids, nutraceuticals in compositions to be administered orally/parenterally, topically, inhalations (including nebulizers), rectally, vaginally in human beings and/or veterinary conditions.
US 2007/0082870 relates to methods of increasing the aqueous solubility of an antifungal azole using hydroxybutenyl cyclodextrins. This invention also relates to method of increasing the bioavailability of an antifungal azole compounds administered to subjects.
US 2003/0170326 relates to a bio enhancing composition containing extract and/or bioactive fraction/isolate from the plant Zingiber officinale in combinations combination with drugs, nutrients, nutraceuticals, micronutrients and herbal drugs/products and optionally containing piperine as a extract/active fraction obtained from piper nigrum, piper longum or its oleoresin as a

bioavailability enhancer and its process for producing the extract or fractions
from the plant source.
Thus, none of the above prior art discloses the combination of piperine,
curcumin and betacyclodextrin. Keeping in mind the increase in microbial
resistance at a faster rate towards antimicrobials, there is a urgent need for a
formulation which increases the bioavailability and the effectiveness of the
antimicrobials to kill the microbes.
OBJECTIVES OF THE INVENTION
The object of the present invention is to provide a formulation that effective to
treat the fungal infection.
Yet another object of the present invention is to provide a formulation which is
relatively higher bioavailable as compared to the conventional formulation.
Yet another object of the present invention is to lower the resistance towards
the antifungal drug.
Yet another object of the present invention is to provide the formulation having
lesser therapeutic dose as compared to the conventional formulation.
Yet another object of the present invention is to provide a formulation having
fewer side effects.
SUMMARY OF THE INVENTION
The present pharmaceutical formulation provides the antifungal agent having
high bioavailability as well as will decrease the fungal resistance. The antifungal
agent may be from triazole antifungal drugs, preferably fluconazole or
ketoconazole more preferably fluconazole. The bioenhancers used is the
combination of piperine, curcumin and betacyclodextrin.
DETAILED DESCRIPTION OF THE INVENTION
A study on fluconazole resistance states that "We report on the mechanism of
fluconazole resistance in Candida glabrata from a case of infection in which
pre- and posttreatment isolates were available for comparison. The resistant,
posttreatment isolate was cross-resistant to ketoconazole and itraconazole, in
common with other azole-resistant yeasts. Resistance was due to reduced
levels of accumulation of [3H] fluconazole rather than to changes at the level of
ergosterol biosynthesis. Studies with metabolic or respiratory inhibitors showed
that this phenomenon was a consequence of energy-dependent drug efflux, as
opposed to a barrier to influx. Since energy-dependent efflux is a characteristic

CLAIMS
1. A pharmaceutical formulation comprising 100 mg to 400 mg of
Fluconazole, preferably 200 mg, and bioavailability enhancers, along
with pharmaceutically acceptable excipients.
2. The bioavailability enhancers as claimed in claim 1 are piperine, present
in the range of 17 mg to 30 mg, preferably 20 mg, curcumin, present in
the range of 20 mg to 35 mg, preferably 25 mg and beta cyclodextrin
present in the range 100 mg to 300 mg, preferably 150 mg.
3. The pharmaceutically acceptable excipients claimed in 1 are selected
from diluents, binding agents, disintegrants, and lubricants.
4. The diluents as claimed in claim 3 can be selected from lactose, sucrose,
glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.
5. The binding agents as claimed in claim 3 can be selected from
polyvinylpyrrolidone (PVP), Hydroxy propyl cellulose, polyethylene glycol
(PEG), xylitol, sorbitol and maltitol which are mixed with the appropriate
solvent.
6. The solvent as claimed in claim 5 can be selected from purified water or
isopropyl alcohol or the mixture of both.
7. The disintegrants as claimed in claim 3 can be selected from polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) and sodium starch glycolate.
8. The lubricants as claimed in claim 3 can be selected from talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid.
9. The formulation as claimed in claim 1 can be coated with Hydroxypropyl
Methyl Cellulose, along with suitable plasticizer, opacifier, coloring agent and the solvent.