Self preserved aqueous pharmaceutical compositions
View Patent ↗The use of a borate/polyol and zinc system to enhance the antimicrobial activity of multi-dose pharmaceutical compositions is described. The compositions do not require a conventional anti-microbial preservative and therefore are referred to as being ‘self-preserved’. The compositions possess sufficient antimicrobial activity to satisfy the preservative efficacy requirements of the USP for aqueous ophthalmic compositions.
1. A multi-dose, self-preserved ophthalmic composition, said composition comprising:
a therapeutically effective amount of an ophthalmic therapeutic agent selected from the group consisting of beta-blockers, carbonic anhydrase inhibitors, prostaglandin analogs, neuroprotectants, anti-angiogenesis agents, quinolones, anti-inflammatory agents, growth factors, immunosuppressant agents and anti-allergic agents; and
a preservative system consisting essentially of:
i. borate at a concentration in the composition of 0.3 to 1.5 w/v % wherein the borate comprises one or more borates;
ii. polyol at a concentration in the composition of 0.6 to 2.0 w/v % wherein the polyol comprises sorbitol and propylene glycol; and
iii. zinc ions, wherein the zinc ions are provided by zinc chloride at a concentration in the composition of 0.0005 to 0.005 w/v %;
wherein the preservative system has sufficient antimicrobial activity to allow the composition to satisfy USP 26 preservative efficacy requirements.
2. A composition as in claim 1 wherein the therapeutic agent is a prostaglandin analog.
3. A composition as in claim 1 wherein the therapeutic agent is travoprost.
4. A method of enhancing the antimicrobial activity of an aqueous ophthalmic pharmaceutical composition, which comprises including a preservative system in the composition, the preservative system consisting essentially of:
i. borate at a concentration in the composition of 0.3 to 1.5 w/v % wherein the borate comprises one or more borates;
ii. polyol at a concentration in the composition of 0.6 to 2.0 w/v % wherein the polyol comprises sorbitol and propylene glycol; and
iii. zinc ions, wherein the zinc ions are provided by zinc chloride at a concentration in the composition of 0.0005 to 0.005 w/v %; wherein:
i. the preservative system has sufficient antimicrobial activity to allow the composition to satisfy USP 26 preservative efficacy requirements; and
ii. the composition includes a therapeutically effective amount of an ophthalmic therapeutic agent selected from the group consisting of beta-blockers, carbonic anhydrase inhibitors, prostaglandin analogs, neuroprotectants, anti-angiogenesis agents, quinolones, anti-inflammatory agents, growth factors, immunosuppressant agents and anti-allergic agents.
5. A method as in claim 4 wherein the therapeutic agent is a prostaglandin analog.
6. A method as in claim 4 wherein the therapeutic agent is travoprost.
7. A composition as in claim 1 wherein the concentration of borate in the composition is 0.5-1.2 w/v %.
8. A composition as in claim 3 wherein the concentration of borate in the composition is 0.5-1.2 w/v %.
9. A method as in claim 4 wherein the concentration of borate in the composition is 0.5-1.2 w/v %.
10. A method as in claim 6 wherein the concentration of borate in the composition is 0.5-1.2 w/v %.