Pharmaceutical Research

, 36:36 | Cite as

Ocular Pharmacokinetics of a Topical Ophthalmic Nanomicellar Solution of Cyclosporine (Cequa®) for Dry Eye Disease

  • Abhirup Mandal
  • Vrinda Gote
  • Dhananjay Pal
  • Abayomi Ogundele
  • Ashim K. MitraEmail author
Expert Review
Part of the following topical collections:
  1. Ophthalmic Drug Discovery and Development


Cequa®, a unique and first-in-class preservative free cyclosporine-A (CsA) nanomicellar topical formulation was recently approved by US FDA for treatment of dry eye disease or keratoconjuntivitis sicca (KCS). Being highly hydrophobic, CsA is currently available as an oil based emulsion, which has its own shortcomings. Developing an aqueous and clear formulation of CsA is imperative yet a challenging need in the quest for a safe and better drug product. In this regard, a novel, clear, aqueous nanomicellar solution of CsA was developed which has the potential to deliver therapeutic concentrations of CsA with minimal discomfort to patients. Highly promising pre-clinical results of Cequa® (OTX-101), has led to its advancement to the clinical trials. Phase III clinical trials have demonstrated that OTX-101 is highly effective, safe, and has a rapid onset of action in treating KCS. This review presents a comprehensive insight on formulation development, preclinical and clinical pharmacokinetic results of Cequa®. Additionally, the translational development of Cequa® from the laboratory benchtop to patient bedside has been discussed.

Key words

tear micelles OTX-101 formulation keratoconjunctivits sicca (KCS) non-ionic ocular drug delivery 



Antigen presenting cells


Area under curve


Balanced salt solution




Circulation, accumulation, penetration, internalization and release


Critical micelle concentration




Filamentary keratitis


Intercellular adhesion molecule 1


Impression cytology


Interleukin 2


Intraocular pressure


Keratoconjunctivitis sicca


Lacrimal functional unit


Meibomian gland dysfunction


Matrix metallopeptidase 9


Mitochondrial permeability transition pore


Cytoplasmic component of nuclear factor of activated T cells


Nuclear component of nuclear factor of activated T cells


Polyethylene glycol




Vascular cell adhesion molecule-1


Acknowledgements and Disclosures

The authors would like to acknowledge the contributions of Dr. Kishore Cholkar and Dr. Brian C. Gilger for the pharmacokinetic portions of the pre-clinical studies. The authors also acknowledge Joseph Tauber (Tauber Eye Centre), Sidney L. Weiss (Auven Therapeutics), William Kramer (Kramer consulting LLC) and Poonam Velagaleti (I-novion, Inc.) for their contributions in the various phases of the clinical studies. Authors also acknowledge Ocular Technologies Sarl (now wholly owned subsidiary of Sun Pharmaceutical Industries) and Sun Pharmaceutical Industries for sponsoring, conducting, monitoring and analyzing the clinical studies.

Supplementary material

11095_2018_2556_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 21 kb)


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Authors and Affiliations

  1. 1.Division of Pharmacology and Pharmaceutical Sciences, School of PharmacyUniversity of MissouriKansas CityUSA
  2. 2.Sun Pharmaceutical Industries Ltd.Sun Ophthalmics Inc.PrincetonUSA
  3. 3.Department of Ophthalmology, School of MedicineUniversity of MissouriKansas CityUSA

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