June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A novel BAK free, room temperature stable, swollen micelle microemulsion formulation of latanoprost
Author Affiliations & Notes
  • Ajay Khopade
    Formulation R& D, Sun Pharma Advanced Research Company Ltd, Baroda, India
  • Arindam Halder
    Formulation R& D, Sun Pharma Advanced Research Company Ltd, Baroda, India
  • Malay Shah
    Formulation R& D, Sun Pharma Advanced Research Company Ltd, Baroda, India
  • Vinod Burade
    Pharmcology, Sun PharmaAdvanced Research Co. Ltd, Vadodara, India
  • Harry Ruan
    Toxicology, Sun Pharma Advanced Research Co. Ltd, Vadodara, India
  • prashant pansare
    Toxicology, Sun Pharma Advanced Research Co. Ltd, Vadodara, India
  • Dipali Desai
    Systems Biology, Sun Pharma Advanced Research Co. Ltd, Vadodara, India
  • Footnotes
    Commercial Relationships   Ajay Khopade, Sun Pharma Advanced Research Co. Ltd (E); Arindam Halder, Sun Pharma Advanced Research Co. Ltd (E); Malay Shah, Sun Pharma Advanced Research Co. Ltd (E); Vinod Burade, Sun Pharma Advanced Research Co. Ltd (E); Harry Ruan, Sun Pharma Advanced Research Co. Ltd (E); prashant pansare, Sun Pharma Advanced Research Co. Ltd. (E); Dipali Desai, Sun Pharma Advanced Research Co. Ltd (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4117. doi:
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      Ajay Khopade, Arindam Halder, Malay Shah, Vinod Burade, Harry Ruan, prashant pansare, Dipali Desai; A novel BAK free, room temperature stable, swollen micelle microemulsion formulation of latanoprost. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4117.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Benzalkonium chloride (BAK) containing latanoprost formulation restricts its chronic usage owing to its ocular surface toxicity and cannot be stored at room temperature (RT) over shelf life. The developed proprietary technology, swollen micelle microemulsion (SMM) allows adequate latanoprost stability at RT without using BAK in the formulation.It minimizes any adverse preservative effect, providing an improved ocular surface tolerance.

Methods : Latanoprost-loaded SMM technology was developed and optimized for stability at RT, safety and efficacy. SMM system is a unique combination of oil and non-ionic surface active system. This was characterized in-vitro by measuring droplet size, zeta potential, optical clarity, long term stability and cytotoxicity tests in Statens Serum institut Rabbit Cornea (SIRC) cells. Exploratory In vivo studies were performed in New Zealand White rabbits and beagle dogs to compare the toxicity and efficacy profile at 30 μl dose (0.05% latanoprost). Ocular lesions in rabbits were evaluated with hand held ophthalmoscope (Alcon - Heine Mini 2000) while Intraocular pressure (IOP) in beagle dogs was measured using a pneumatonometer.

Results : Latanoprost SMM was almost clear emulsion. The droplet size was less than 100nm and did not posses any charge. It was stable for 36 months at 25°C and 6 months at 40°C meeting ICH stability requirement of the formulation suggesting that it does not require refrigeration for storage or transport. Formulation was shown to be less toxic than the BAK-containing formulation in SIRC cells. In New Zealand white rabbits, improved tolerability is achieved under multiple-dose (10 times/day) administration up to 14 days on ocular surface against BAK control. Significant level of IOP reduction was obtained upon multiple dose instillations in beagle dogs over 10 days.

Conclusions : SMM system is a unique approach for the delivery of latanoprost to the ocular surface. Latanoprost SMM can be effectively stored in natural polyethylene bottle without loss of drug potency at 40°C. Absence of BAK resulted in improved ocular safety without loss of pharmaceutical activity. This new technology has been developed for the treatment of patients with glaucoma suffering from dry eye and can also be used for the efficient delivery of other prostaglandin analogues.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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