DESC:4. DESCTRIPTION
Technical Field of the Invention

The present invention relates to the field of oral drug delivery. More specifically it relates to a formulation and method of preparing Sildenafil Citrate orally disintegrating strips.

Background of the Invention

Oral drug delivery is the most common route of administration that has been widely explored for systemic delivery of drugs among other dosage forms. Tablets are mostly popular and more explored route of administration owing to its low manufacturing cost and ease of transportation.

However, it carries its own set of drawbacks such as poor patient compliance especially in case of people suffering with dysphagia and also in term of poor bioavailability w.r.t certain drugs.

In such scenarios mouth dissolving strips were developed as an alternative to syrups, capsule and tablet. Sildenafil citrate is a drug which is used in the treatment of erectile dysfunction. Owing to its poor solubility, delayed on set of action is encountered. Apart from that it also undergoes extensive first pass metabolism resulting in low bioavailability.

The patent EP2575765B1 relates to formulations for delivery of sildenafil citrate to the circulatory system by administration via an oral spray formulation to treat erectile dysfunction. More specifically, an oral spray formulation for the treatment of erectile dysfunction, comprising sildenafil citrate present in an amount of 6% to 14% w/v of the formulation, wherein the pH of the formulation is from 1.5 to 2.4 and wherein the formulation is delivered transmucosally or sublingually.

The patent application CA3137260A1 discloses liquid pharmaceutical compositions comprising at least 15mg/ml of sildenafil citrate, their use in treating erectile dysfunction and their methods of manufacture.

The patent CN112826802B claims sildenafil citrate chewable tablet comprising the following components in parts by weight: 2-10 parts of sildenafil citrate, 10-50 parts of filler, 15-87.5 parts of sweetener, 1-5 parts of excipient, 0.5-5 parts of lubricant and 1.5-5 parts of compound flavoring agent; wherein the filler is one or more of mannitol, sorbitol and glucitol; the excipient is a mixture of polyvinyl acetate and xylitol; the sweetener is one or more of sucrose, aspartame and sucralose; the lubricant is one or more of magnesium stearate, stearic acid and silicon dioxide; the compound flavoring agent is a mixture of vanillin, ethyl maltol, myristic acid and phosphate ester; the mass ratio of vanillin to ethyl maltol in the mixture is 1: 2-6; the mass ratio of myristic acid to phosphate in the mixture is 1: 1-5.

Additionally, it also has the disadvantage of causing dyspepsia and burning sensation. Addressing these issues, mouth dissolving film containing solid dispersion of sildenafil citrate was prepared which has higher solubility, rapid onset of action and enhanced systemic bioavailability.

Brief Summary of the Invention

The following summary is provided to facilitate a clear understanding of the new features in the disclosed embodiment and it is not intended to be a full, detailed description. A detailed description of all the aspects of the disclosed invention can be understood by reviewing the full specification, the drawing and the claims and the abstract, as a whole.

The main objective of our system is to provide a orally disintegrating strip containing dispersion of sildenafil citrate.

The second objective of the present invention is the method of preparing orally disintegrating strip which has higher solubility, rapid onset of action and enhanced systemic bioavailability.
Our present invention relates to a method and formulation of preparing orally disintegrating strips containing dispersion of sildenafil citrate which has higher solubility, rapid onset of action and enhanced systemic bioavailability. The method comprises adding each ingredient in a stainless-steel container, after which wet slurry is prepared. The resultant mixture is subjected to vacuum degassing for 15 mins to obtain bubble free slurry. Cast the Wet slurry at process parameters of Dr. Knife thickness of 400 to 1000 microns; Temperature 95 to 100±3°C; In-direct drying for 18 min. Slit the dried casted film into 25mm x 40mm for 100mg dose. Slit the dried casted film into 25mm x 40mm for 50mg dose. Slit the dried casted film into 25mm x 20mm for 25mg dose.

BRIEF DESCRIPTION OF THE DRAWINGS
The manner in which the present invention is formulated is given a more particular description below, briefly summarized above, may be had by reference to the components, some of which is illustrated in the appended drawing It is to be noted; however, that the appended drawing illustrates only typical embodiments of this invention and are therefore should not be considered limiting of its scope, for the system may admit to other equally effective embodiments.
Throughout the drawings, the same drawing reference numerals will be understood to refer to the same elements and features.
The features and advantages of the present invention will become more apparent from the following detailed description a long with the accompanying figures, which forms a part of this application and in which:
Fig 1: Graph Diagram showing the comparative dissolution profile of the reference product Vs our present invention, in accordance with our present invention;

Detailed Description of the Invention
The principles of operation, design configurations and evaluation values in these non-limiting examples can be varied and are merely cited to illustrate at least one embodiment of the invention, without limiting the scope thereof.
The embodiments disclosed herein can be expressed in different forms and should not be considered as limited to the listed embodiments in the disclosed invention. The various embodiments outlined in the subsequent sections are constructed such that it provides a complete and a thorough understanding of the disclosed invention, by clearly describing the scope of the invention, for those skilled in the art.
Throughout this specification various indications have been given as to preferred and alternative embodiments of the invention. It should be understood that it is the appended claims, including all equivalents, which are intended to define the spirit and scope of this invention.
The present invention discloses orally disintegrating strips containing dispersion of sildenafil citrate. The sildenafil citrate was prepared in the form of orally disintegrating strips which has higher solubility, rapid onset of action and enhanced systemic bioavailability.

Here the Table 1 shows the ingredients with % values and its function for formulation 1, which is one embodiment of our present invention.
TABLE 1
* Water get evaporated during the coating prosses and traces of water content will remain product.
S. No. Ingredients Function %W/W
1 Sildenafil Citrate API 8.21 – 32.82
2 Polacrilin Potassium Taste Masking Agent 3.50 – 14.02
3 Sucralose Sweetener 0.58 – 2.34
4 Neotame Sweetener 0.12 – 0.47
5 Maltodextrin Diluent 0.84 – 3.37
6 Polyethylene oxide Film forming Agent 0.40 – 1.61
7 Monoammonium Glycyrrhizinate Sweetener 0.23 – 0.93
8 Polacrilin potassium Dissolution Enhancer 1.17 – 4.67
9 Hydroxypropyl Methylcellulose Film forming Agent 4.67 – 18.69
10 Triethyl Citrate Plasticizer 1.40 – 5.62
11 Glycerol Plasticizer 2.57 – 10.28
12 Brilliant Blue FCF Colouring Agent 0.01 – 0.04
13 Capsudex Cool 3MP Flavouring Agent 0.12 – 0.47
14 Peppermint Powder Flavouring Agent 1.17 – 4.67
15 Purified Water* Vehicle q.s.
Total 100.00%

Formulation 1 preparation method:
One embodiment of our present invention, the Sildenafil citrate orally disintegrating strips (formulation 1) preparation method comprise of the following steps:
1. Weighed quantity of purified water was taken in a ss container and kept under stirring at 350 RPM.
2. Weighed quantity of Polacrilin Potassium was added to step- 1 under stirring at 350 RPM for 2 min.
3. Weighed quantity of Sildenafil citrate was added to step- 2 under stirring at 350 RPM for 2 min.
4. Weighed quantity of sucralose was added to step- 3 under stirring at 350 RPM for 2 min.
5. Weighed quantity of Monoammonium Glycyrrhizinate was added to step- 4 under stirring at 350 RPM for 2 min.
6. Weighed quantity of Polacrilin Potassium was added to step- 5 under stirring at 350 RPM for 2 min.
7. Weighed quantity of Maltodextrin was added to step- 6 under stirring at 500rpm for 10mins.
8. Weighed quantity of Polyethylene Oxide was added to step- 7 under stirring at 500 RPM for 3 min.
9. Weighed quantity of Hydroxypropyl Methylcellulose was added to step- 8 under stirring at 500 RPM for 3 min.
10. Weighed quantity of Brilliant blue FCF was added to step- 9 under stirring at 350 RPM for 2 min.
11. Weighed quantity of neotame was added to step- 10 under stirring at 350 RPM for 2 min
12. Weighed quantity of Glycerol was added to step- 11 under stirring at 500rpm for 10mins.
13. Weighed quantity of Triethyl citrate was added to step- 12 under stirring at 500rpm for 10mins.
14. Weighed quantity of peppermint powder was added to step- 13 under stirring at 500rpm for 10mins.
15. Above step wet slurry after completion of mixing subjected to vacuum degassing for 15mins to obtain bubble free slurry.
16. Wet slurry was casted at process parameters of Dr. Knife thickness of 600 to 800 microns; Temperature 95±3°C; In-direct drying for 18 min.
17. The dried casted film was Slitted into 40mm x 30mm.

The Strips were evaluated for disintegration time, folding endurance, Assay Dissolution, and water content and the results are tabulated in table 1.1.
S. No. Test Parameters Limits Results
Initial
1 Disintegrating time NMT 60sec 58
2 Folding Endurance NLT 10 More than 150
3 Water content NMT 12% 3.27
4 Assay 90 - 110% 102.10
5 Dissolution
(0.01M Hcl Media) NLT 70% in 30 min 101.00
TABLE 1.1:
Conclusion:
Based on the data the above formulation 1 was found satisfactory in terms of chemical properties but physical adherence and texture of the film found not satisfactory.

Next the Table 2 shows the ingredients with % values and its function for formulation 2.
TABLE 2
S. No. Ingredients Function %W/W
1 Sildenafil citrate API 8.87 – 35.47
2 Polyoxyl 40 Hydrogenated Castor Oil /
Macrogol-Glycerolhydroxystearate/ Solubilising agents 0.88 – 3.54
3 Polysorbate 80 Solubilising agents 1.89 – 7.57
4 Light magnesium carbonate Taste masking Agent 1.46 – 5.86
5 Sucralose Sweetening Agent 0.76 – 3.03
6 Maltodextrin Diluent 1.02 – 4.07
7 Hydroxypropyl Methylcellulose Film Forming Agent 7.58 – 30.30
8 Propylene glycol Plasticizer 1.89 – 7.58
9 Brilliant Blue FCF Colouring Agent 0.01 – 0.05
10 Peppermint Supreme Flavouring Agent 0.63 – 2.53
11 Purified Water* Vehicle q.s.
Total 100.00%

*water get evaporated during the coating prosses and traces of water content will remain product.
Another embodiment of our present invention, the Sildenafil citrate orally disintegrating strips comprise of the following steps, given as formulation 2:
Formulation 2 preparation method
1. Weighed quantity of purified water was taken in a ss container and kept under stirring at 350 RPM.
2. Weighed quantity of Polyoxyl 40 hydrogenated castor oil was added to step- 1 under stirring at 350 RPM for 2 min.
3. Weighed quantity of Sildenafil citrate was added to step- 2 under stirring at 350 RPM for 2 min.
4. Weighed quantity of Light magnesium carbonate was added to step- 3 under stirring at 350 RPM for 2 min.
5. Weighed quantity of Sucralose was added to step- 4 under stirring at 350 RPM for 2 min.
6. Weighed quantity of Maltodextrin was added to step- 5 under stirring at 350 RPM for 2 min.
7. Weighed quantity of Polysorbate 80 was added to step- 6 under stirring at 500rpm for 10mins.
8. Weighed quantity of Propylene glycol was added to step- 7 under stirring at 500 RPM for 3 min.
9. Weighed quantity of Hydroxypropyl Methylcellulose was added to step- 8 under stirring at 500 RPM for 3 min.
10. Weighed quantity of peppermint supreme was added to step- 9 under stirring at 350 RPM for 2 min.
11. Weighed quantity of Neelicol brilliant blue FCF was added to step- 10 under stirring at 500rpm for 10mins.
12. Above step wet slurry after completion of mixing subjected to vacuum degassing for 15mins to obtain bubble free slurry.
13. Wet slurry was casted at process parameters of Dr. Knife thickness of 600 to 800 microns; Temperature 95±3°C; In-direct drying for 18 min.
14. The dried casted film was Slitted into 40mm x 30mm.

The Strips were evaluated for disintegration time, folding endurance, Assay Dissolution, and water content and the results are tabulated in table 2.1.
S. No. Test Parameters Limits Results
Initial
1 Disintegrating time NMT 60sec 51
2 Folding Endurance NLT 10 More than 150
3 Water content NMT 12% 5.86
4 Assay 90 - 110% 100.51
5 Dissolution (water Media) NLT 70% in 30 min 99.00
TABLE 2.1:
Conclusion:
Based on the experimental data the above example was found satisfactory in terms of chemical properties, but physical adherence of the film found not satisfactory.
Another embodiment of our present invention is presented as formulation 3, as given by table 3:
TABLE 3
S. No Ingredients Function %w/w
1 Sildenafil citrate API 8.28 - 33.13
2 Sucralose Sweetener 0.71 - 2.83
3 Polyoxyl 40 hydrogenated castor oil Solubilizing agent 0.83 - 3.30
4 Maltodextrin Diluent 3.38 – 13.53
5 Polacrilin potassium Taste masking 1.77 - 7.08
6 Glycerol Plasticizer 1.77 - 7.08
7 Titanium dioxide Opacifier 0.59 - 2.35
8 Natural Peppermint DM Flavour Flavour 0.59 - 2.36
9 Hypromellose (AN 15) Polymer 7.08 - 28.30
10 Neelicol Brilliant Blue FCF Colorant 0.01 - 0.04
11 Purified Water^ Vehicle Q.S
Total 100.00%
^ water get evaporated during the coating prosses and traces of water content will remain product.
Manufacturing procedure for formulation 3:
1. Weighed quantity of purified water was taken in a ss container and kept under stirring at 350 RPM.
2. Weighed quantity of Polyoxyl 40 hydrogenated castor oil was added to step- 1 under stirring at 350 RPM for 2 min.
3. Weighed quantity of Sildenafil citrate was added to step- 2 under stirring at 350 RPM for 2 min.
4. Weighed quantity of Polacrilin potassium was added to step- 3 under stirring at 350 RPM for 2 min.
5. Weighed quantity of Titanium dioxide was added to step- 4 under stirring at 350 RPM for 2 min.
6. Weighed quantity of Sucralose was added to step- 5 under stirring at 350 RPM for 2 min.
7. Weighed quantity of Maltodextrin was added to step- 6 under stirring at 500rpm for 10mins.
8. Weighed quantity of was added Hypromellose to step- 7 under stirring at 500 RPM for 3 min.
9. Weighed quantity of Natural peppermint DM flavour was added to step- 8 under stirring at 500 RPM for 3 min.
10. Weighed quantity of Glycerol was added to step- 5 under stirring at 350 RPM for 2 min.
11. Weighed quantity of Neelicol brilliant blue FCF was added to step- 6 under stirring at 500rpm for 10mins.
12. Above step wet slurry after completion of mixing subjected to vacuum degassing for 15mins to obtain bubble free slurry.
13. Wet slurry was casted at process parameters of Dr. Knife thickness of 600 to 800 microns; Temperature 95±3°C; In-direct drying for 18 min.
14. The dried casted film was Slitted into 40mm x 30mm.

The Strips were evaluated for disintegration time, folding endurance, Assay Dissolution, and water content and the results are tabulated.

S. No. Test Parameters Limits Results
Initial
1 Disintegrating time NMT 60sec 55
2 Folding Endurance NLT 10 More than 150
3 Water content NMT 12% 9.65
4 Assay 90 - 110% 99.80
5 Dissolution (water Media) NLT 70% in 30 min 98.00
Results:
Conclusion:
Based on the data the above formulation 3 found satisfactory in terms of physical and chemical properties.

Comparative Dissolution:
The formulation 3 and a reference product are compared for their dissolution properties and the results are given below
Comparative Dissolution Profile (Media – 0.01N Hcl)
Time points % Drug Release
Reference Product- Strip
(Penerect-50mg ODS)
B. No: SCB00521/B Test Product- Strip
B. No: SIL/P/ODS/0009-LSD/002
0 0 0
10 62 98
15 91 100
30 97 100
45 99 100

Referring to the formulation mentioned (formualtion-3), when substituting the glycerol in place of propylene glycol and polysorbate-80, the strip's physical and chemical properties were found to meet the desired standards. However, in comparison to formulation-1 and formulation-2, there was less adherence and physical texture also not found good. In comparison to the Reference product, formulation – 3 the dissolution results met the specification limits.
,CLAIMS:CLAIMS
I/We Claim:
1. An orally disintegrating strips containing dispersion of sildenafil citrate, wherein:
a. The ingredients and their respective function and quantity (%w/w) are taken as: Sildenafil citrate (API, 8.28 - 33.13), Sucralose (Sweetener, 0.71-2.83), Polyoxyl 40 hydrogenated castor oil (Solubilizing agent, 0.83 - 3.30), Maltodextrin (Diluent, 3.38 – 13.53), Polacrilin potassium (Taste masking, 1.77 - 7.08), Glycerol (Plasticizer, 1.77 - 7.08), Titanium dioxide (Opacifier, 0.59 - 2.35), Natural Peppermint DM Flavour (Flavour, 0.59 - 2.36), Hypromellose (AN 15) (Polymer, 7.08 - 28.30), Neelicol Brilliant Blue FCF (Colorant, 0.01 - 0.04), Purified Water(Vehicle, Q.S)
b. And the manufacturing procedure of the present invention is given as:
i. Weighed quantity of purified water was taken in a ss container and kept under stirring at 350 RPM.
ii. Weighed quantity of Polyoxyl 40 hydrogenated castor oil was added to step- i under stirring at 350 RPM for 2 min.
iii. Weighed quantity of Sildenafil citrate was added to step- ii under stirring at 350 RPM for 2 min.
iv. Weighed quantity of Polacrilin potassium was added to step- iii under stirring at 350 RPM for 2 min.
v. Weighed quantity of Titanium dioxide was added to step- iv under stirring at 350 RPM for 2 min.
vi. Weighed quantity of Sucralose was added to step- v under stirring at 350 RPM for 2 min.
vii. Weighed quantity of Maltodextrin was added to step- vi under stirring at 500rpm for 10mins.
viii. Weighed quantity of Natural peppermint DM flavour was added to step- vii under stirring at 500 RPM for 3 min.
ix. Weighed quantity of Glycerol was added to step- viii under stirring at 350 RPM for 2 min.
x. Weighed quantity of Hypromellose was added to step- xi under stirring at 500rpm for 10mins.
xi. Weighed quantity of Neelicol brilliant blue FCF was added to step- x under stirring at 500rpm for 10mins.
xii. Above step wet slurry after completion of mixing subjected to vacuum degassing for 15mins to obtain bubble free slurry.
xiii. Wet slurry was casted at process parameters of Dr. Knife thickness of 600 to 800 microns; Temperature 95±3°C; In-direct drying for 18 min.
xiv. The dried casted film was Slitted into 40mm x 30mm.
2. The orally disintegrating strips containing dispersion of sildenafil citrate, as claimed in claim 1, wherein it demonstrates the following properties: the Disintegrating time is 55 sec, the Folding Endurance is more than 150, the Water content is 9.65%, the Assay is 99.80%, Dissolution (water Media) is 98.00%