Oral pharmaceutical composition comprising Zonisamide and process of preparation thereof
The present invention relates to the pharmaceutical composition comprising Zonisamide and one or more pharmaceutically acceptable excipients and also relates to the process for the preparation of the pharmaceutical composition comprising Zonisamide.
1. A method of treating seizures in a subject in need thereof, comprising administering to the subject a liquid oral pharmaceutical suspension comprising:
zonisamide in an amount of about 20 mg/mL;
a suspending agent comprising about 2 mg/mL to about 3.5 mg/mL xanthan gum and about 20 mg/mL of a combination of microcrystalline cellulose and sodium carboxymethylcellulose;
one or more buffering agents; and
one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients comprise a preservative;
wherein the liquid oral pharmaceutical suspension has a pH of 3.5 to 5.0;
wherein the liquid oral pharmaceutical suspension is stable for at least 6 months when stored at 40° C. and 25% relative humidity.
2. The method of claim 1 , wherein the one or more buffering agents are selected from the group consisting of sodium acetate, sodium citrate, ammonium sulfate, sodium phosphate, disodium hydrogen phosphate, potassium citrate, citric acid monohydrate, trisodium citrate dihydrate, and combinations thereof.
3. The method of claim 1 , wherein the one or more buffering agents comprise citric acid monohydrate and tri-sodium citrate dihydrate.
4. The method of claim 3 , wherein the citric acid monohydrate is present at about 3.7 mg/mL and the tri-sodium citrate dihydrate is present at about 3.6 mg/mL.
5. The method of claim 1 , wherein the preservative is selected from the group consisting of benzyl alcohol, chloro-butanol, chloro-cresol, alkyl esters of paraben, phenol, phenyl ethanol, propylene glycol, chloroform, benzoic acid, potassium sorbate, sodium benzoate, and combinations thereof.
6. The method of claim 5 , wherein the preservative comprises sodium benzoate, wherein the sodium benzoate is present at about 1 mg/mL or about 2 mg/mL.
7. The method of claim 1 , further comprising one or more sweetening agents, one or more flavoring agents, one or more vehicles, or combinations thereof.
8. The method of claim 7 , wherein the one or more sweetening agents are selected from the group consisting of sucralose, sucrose, glycerol, liquid glucose, sorbitol, maltitol, saccharin sodium, aspartame, and combinations thereof.
9. The method of claim 8 , wherein the one or more sweetening agents comprises sucralose, wherein sucralose is present at about 2 mg/mL.
10. The method of claim 7 , wherein the one or more flavoring agents are selected from the group consisting of essential oils, fruit flavors, and combinations thereof.
11. The method of claim 10 , wherein the essential oil is selected from the group consisting of peppermint oil, orange oil, lemon oil, and combinations thereof.
12. The method of claim 10 , wherein the fruit flavour is selected from the group consisting of peppermint flavour, raspberry flavour, strawberry flavour, tutti-fruit flavour, and combinations thereof.
13. The method of claim 7 , wherein the one or more vehicles are aqueous vehicles selected from the group consisting of purified water, hydro-alcoholic, a polyhydric alcohol, and combinations thereof.
14. The method of claim 1 , wherein the pH is 4.2, 4.3, 4.4, or 4.5.
15. The method of claim 1 , wherein the liquid oral pharmaceutical suspension is stable for at least 6 months when stored at 40° C. and 25% relative humidity and has a single max impurity of 0.06% or less and total impurities of 0.10% or less.
16. The method of claim 1 , wherein the liquid oral pharmaceutical suspension is stable for at least 6 months when stored at 40° C. and 25% relative humidity and exhibits less than 0.05% of impurity A and less than 0.25% of total impurity.
17. The method of claim 1 , the liquid oral pharmaceutical suspension comprising:
zonisamide in an amount of about 20 mg/mL;
xanthan gum in an amount of about 3.5 mg/mL;
a combination of microcrystalline cellulose and sodium carboxymethylcellulose in an amount of about 20 mg/mL;
sodium benzoate in an amount of about 1.0 mg/mL;
one or more buffering agents comprising citric acid monohydrate and tri-sodium citrate dihydrate;
one or more sweetening agents;
one or more flavoring agents; and
purified water.
18. The method of claim 1 , wherein the seizure is a partial seizure or an epileptic seizure.
19. The method of claim 1 , wherein the subject is an adult or a child, and wherein the subject has trouble swallowing a solid oral dosage form.
20. The method of claim 18 , wherein the liquid oral pharmaceutical suspension is used as an adjunctive therapy in the treatment of partial seizures in adults with epilepsy.