DESCRIPTION
FIELD OF THE INVENTION
The present invention is related to an effervescent pharmaceutical composition
having sildenafil as an active constituent wherein the route of administration of
the said formulation is vaginal. The said invention is used for increasing
chances of pregnancy during in-vitro fertilization (IVF) technique and for
improving female sexual dysfunctioning (FSD).
BACKGROUND OF THE INVENTION
Using transvaginal ultrasound, endometrial thickness was noted to improve
when sildenafil citrate was administered. It is suspected that this medication
causes selective vasodilatation, resulting in improved endometrial development.
(Zinger M, Liu JH, Thomas MA, J Womens Health (Larchmt). 2006 May; 15
(4):442-4.)
Vaginal administration of sildenafil enhanced endometrial development in 70%
of patients studied. High implantation and ongoing pregnancy rates were
achieved in a cohort with a poor prognosis for success. (By Geoffrey Sher,
Jeffrey D Fisch, Fertility and Sterility (2002) Volume: 78, Issue: 5, Pages: 1073-
1076)
Sildenafil is a type 5-specific PDE inhibitor that augments the vasodilator/
effects of NO on vascular smooth muscle by preventing the degradation of
cGMP. Vaginal sildenafil (suppositories) may be effective for improving uterine
artery blood flow and endometrial development in IVF patients with prior poor
endometrial response.( Geoffrey Sher and Jeffrey D. Fisch, Oxford Journals
Medicine Human Reproduction Volume15, Issue 4 Pp. 806-809.)
OBJECTIVES OF THE INVENTION
The object of the present invention is to provide a pharmaceutical formulation of
sildenafil which bypasses the first pass metabolism.
Another object of the present invention is to improve the patient's compliance.
Yet another object of the present invention is to provide a formulation which is
effective in increasing endometrial thickness.
Yet another object of the present invention is to provide a formulation which
effectively releases the drug in a very short span of time.

Another object of the present invention is to provide a formulation which treats
some of the underlying causes of the failure of in-vitro fertilization.
Yet another object of the invention is to provide a formulation having fast onset
of action with high peak plasma concentration.
Another object of the present invention is to provide a pharmaceutical
formulation having fewer side effects.
Yet another object of the present invention is to provide a method for the
preparation of the said invention.
DETAILED DESCRIPTION OF THE INVENTION
Adequate growth of the endometrium is indispensable for successful
pregnancy. We often see patients with a thin endometrium, which may be
caused by impairment of the normal process of endometrial growth. Low
pregnancy rates are noted in patients with a thin endometrium. Very recently,
pathophysiological features of thin endometrium has been showed and
suggested that a it may be due to high blood flow impedance of uterine radial
arteries, which are in the lower extremity of uterine arteries. Uterine blood flow
is an important factor for endometrial growth. Interestingly, it is found that blood
flow impedance of uterine radial arteries remains high throughout the menstrual
cycle in patients with a thin endometrium, suggesting that reduced blood supply
to uterus is associated with poor endometrial growth in patients with a thin
endometrium. In a recent report, thin endometrium could be a trigger, impairing
the growth of the glandular epithelium and resulting in a decrease in vascular
endothelial growth factor (VEGF) expression, which is a key factor for regulating
angiogenesis in the human endometrium. Low VEGF levels cause poor
vascular development, which in turn decreases blood flow in the endometrium.
The vicious circle leads to a thin endometrium. Thus, it is likely that high blood
flow impedance of uterine radial arteries is involved in the etiology of a thin
endometrium. (Fertility Sterility 2010;93:1851-8)
The present invention is related to vaginal effervescent tablets of Sildenafil,
used for increasing chances of pregnancy during in-vitro fertilization (IVF)
technique and for improving female sexual dysfunctioning (FSD).
In the present invention, sildenafil is present as a free base or its
pharmaceutically acceptable salt in the range 20 mg to 80 7ng, preferably 25 mg
with other pharmaceutically acceptable excipients.

The present formulation is prepared by using the suitable pharmaceutical
excipients, along with the said quantity of Active Pharmaceutical Ingredients.
The excipients used may be selected from the group of diluents, binding
agents, disintegrants, and lubricants.
The diluents can be selected from lactose, sucrose, glucose, mannitol, sorbitol,
calcium carbonate, and magnesium stearate.
The binding agents can be selected from polyvinylpyrrolidone (PVP),
polyethylene glycol (PEG), xylitol, sorbitol and maltitol which are mixed with the
appropriate solvent.
The solvent can be selected from purified water or isopropyl alcohol or the
mixture of both.
For imparting the effervescent property to the formulation sodium bicarbonate is
preferably used.
The disintegrants can be selected from polyvinylpyrrolidone (crospovidone),
crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) and
sodium starch glycolate.
The lubricants can be selected from talc or silica, and fats, e.g. vegetable
stearin, magnesium stearate or stearic acid.
The formulation can be prepared, but not limited to, in the following manner-1) Weigh all the ingredients as follows:
(Table Removed)
2) Sift the following ingredients-
(Table Removed)
3) Dry Mixing- Take the sifted material of step 2 and transfer to RMG. Run the RMG for 10 minutes.
4) Dissolve Povidone 120 gm in 750 ml purified water.
5) Pour the solution obtained in step 4 over the sifted and mixed material obtained in step 3.
6) Switch on the RMG. Start impeller initially at low speed 5 minutes and add 1850 ml purified water.
7) Pass the wet mass through sieve # 8.
8) Dry the wet mass on Fluidised bed drier at a temperature 50-55°C for the time 50-75 minutes to get moisture content 2-3.5%.
9) Sift the dried granules through sieve #18.
10) Lubrication- Pass the following ingredients through sieve and mixed in rototube.
(Table Removed)
11)The granules obtained in step 9 and step 10 were mixed and compressed to form tablets.

We Claim-
1. An effervescent pharmaceutical formulation comprising sildenafil as a
free base or its pharmaceutically acceptable salt in the range 20 mg to
80 mg, preferably 25 mg along with pharmaceutically acceptable
excipients.
2. The pharmaceutically acceptable excipients are selected from diluents,
binding agents, disintegrants, and lubricants.
3. The diluents as claimed in claim 2 can be selected from lactose, sucrose,
glucose, mannitol, sorbitol, calcium carbonate, Sodium bicarbonate and
magnesium stearate.
4. The binding agents as claimed in claim 2 can be selected from
polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), xylitol, sorbitol
and maltitol which are mixed with the appropriate solvent.
5. The solvent as claimed in claim 4 can be selected from purified water or
isopropyl alcohol or the mixture of both.
6. The disintegrants as claimed in claim 2 can be selected from
polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl
cellulose (croscarmellose sodium) and sodium starch glycolate.
7. The lubricants as claimed in claim 2 can be selected from talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid.