Self preserved aqueous pharmaceutical compositions

A technology of composition and ophthalmic composition, applied in the field of actic, can solve problems such as blindness and loss of visual function

Active Publication Date: 2012-12-19
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This is also a serious problem because eye infections caused by Pseudomonas aeruginosa or other virulent microorganisms can lead to loss of visual function or even blindness

Method used

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  • Self preserved aqueous pharmaceutical compositions
  • Self preserved aqueous pharmaceutical compositions
  • Self preserved aqueous pharmaceutical compositions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment A-E

[0091] The formulations of Examples A-E were evaluated to determine the effect of buffer anions on preservative effectiveness. As detailed below, the formulations of Examples A and B do not contain buffers. Although these formulations meet the USP preservative effectiveness requirements, there is still a great need for a buffer system in order to prevent pH deviations within the shelf life of the commodity (ie, up to two years or more). The formulation of Example C contains a borate / polyol buffer system, but this system has the smallest buffer capacity. Like the formulations of Examples A and B, the formulation of Example C meets USP requirements. The formulations of Examples D and E contain a significantly higher concentration of buffer, and therefore have a greater buffer capacity. However, the presence of a relatively large amount of buffer anion causes the formulation to fail to meet the requirements for preservative efficacy. Therefore, the comparison of Examples A-E sh...

Embodiment F-J

[0099] In these examples, the amount of sorbitol was reduced to 1% while maintaining the concentration of boric acid at 1% to reduce the concentration of buffer anions. In addition, Examples G, I and J contained 0.75% propylene glycol. The anion buffer concentration in all 5 examples was about 19 mM.

[0100] The compositions of Examples F and G contained 0.18 mM zinc. It has much higher activity against Staphylococcus aureus than the preparations of Examples D and E above. In particular, the compositions of Examples F and G meet the USP preservative standards for Staphylococcus aureus. However, although the antibacterial activity against E. coli is improved when the zinc ion concentration is 0.18 mM (Examples F and G) and 0.36 mM (Examples H and I) compared with Examples D and E, it is in the first 14 days is not enough to continuously meet the USP anti-corrosion standards. Increasing the zinc concentration to 1.8 mM (Example J) improved the antibacterial activity of the sol...

Embodiment K-N

[0106] In these examples, the content of sorbitol was reduced to 0.25% while maintaining the concentration of boric acid at 1% to reduce the concentration of buffer anions. In addition, the compositions of Examples L-N contained 0.75% of propylene glycol. The anion buffer concentration of the formulations of Examples K and L is about 4 mM, which is in the preferred range below 5 mM as described herein. Compared with the formulations of Examples F-J, the anti-E. coli activity of these compositions was significantly improved when the zinc concentration was 0.18 mM (0.0025 w / v%), and the compositions met the USP preservative standards. In Examples M and N, the pH was adjusted to 5.5 and 6.5, respectively, while maintaining the preservative effect of USP. The results obtained for the representative composition of the present invention, namely the formulations of Examples K-N, further demonstrate the importance of limiting the buffer anion concentration to meet the requirements for...

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PUM

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Abstract

The present invention is directed to the provision of multi-dose, self-preserved ophthalmic compositions. The compositions possess sufficient antimicrobial activity to satisfy USP preservative efficacy requirements, as well as similar preservative standards (e.g., EP and JP), without requiring the presence of conventional anti-microbial preservative agents, such as benzalkonium chloride. The compositions are effectively preserved by a balanced ionic buffer system containing zinc ions at a concentration of 0.04 to 0.9 mM, preferably 0.04 to 0.4 mM. One aspect of the balanced buffer system is limitation of the amount of buffering anions present to a concentration of 15 mM or less, preferably 5 mM or less. In a preferred embodiment, the compositions also contain borate or, most preferably, one or more borate / polyol complexes. The use of propylene glycol as the polyol in such complexes is strongly preferred. Limiting the amount of divalent metals other than zinc and the amount of ionized salts present has also been determined to be important to maximize the antimicrobial activity of the balanced buffer systems.

Description

[0001] Cross-participants for related applications [0002] This application claims the priority of U.S. provisional patent application serial numbers 60 / 827,411 and 60 / 826,529 filed on September 28, 2006 and September 21, 2006, respectively. Background of the invention [0003] The present invention relates to a self-preserved pharmaceutical composition. More particularly, the present invention relates to an aqueous multi-dose pharmaceutical composition which is formulated to have sufficient antibacterial activity to meet the requirements of the United States Pharmacopoeia (USP) and others. According to the preservative efficacy requirements of similar national guidelines, the pharmaceutical composition does not require conventional antibacterial preservatives, such as benzalkonium chloride, polyquaternium-1, hydrogen peroxide (such as sodium perborate), or chlorine-containing agents. This self-preservation ability is based on the unique combination and standard of formulation ing...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/02A61K47/10A61K47/26A61K9/00
Inventor B・P・卡布拉M・A・乔罕L・W・施内德尔韩维新
Owner NOVARTIS AG
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