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Ph.D.
(Pharmacy)
FORMULATION, OPTIMIZATION, AND CHARACTERIZATION OF
CASPOFUNGIN NANOFORMULATIONS

Ph.D. Scholar : Mercy Macwan Anil
Research Supervisor : Dr. B. G. Prajapati

Regi. No.: 18276011005
Abstract :
Delivering drugs to the ocular region has always been a daunting task, the reason lies
with the existing anatomical and physiological structure of the eye thus, Scientists and
Researchers continue to expand their knowledge in this area and strive to present drug
delivery science that can circumvent problems related to the conventional approaches.
This dissertation is presented with a similar aim, the presented study outlines Nano-
formulation based Approaches for ocular drug delivery which shows the potential to
enhance the ocular permeability of an anti-fungal agent, Caspofungin.

The quality-based design was employed to prepare the formulations, the prepared
formulations are Nano-emulsions, Solid-Lipid Nanoparticles, and Liposomes, for all the
formulations Critical Quality Attributes and Critical Product Attributes were studied, the
broad knowledge space constituted of literature, guidance from the supervisors and
experience. The first formulation made was nano-emulsion, The nanoemulsion was
prepared in two steps: (1) Preparation of primary emulsion (2) Preparation of secondary
emulsion using CSPF, Oleic acid (5% w/v), and Tween 80 (5% w/v) and was further
optimized by Box-Behnken mathematical model. The optimized batch of NE showed a
globule size of 111.5±2.35 nm and PDI of 0.179, there was no irritation observed to the
HET membrane and there was no change in the physical appearance of nano-emulsion or
phase separation observed in both 40°C and 25°C conditions after Stability studies. The
second formulation prepared was Liposomes for ocular delivery of Caspofungin as a
therapeutic agent; it was prepared with one or more phospholipids with cholesterol for
better penetration through the cornea. The quality by Design (QbD) approach has been
used to identify the critical and non-critical elements based on the intensity of impact on
the final product or formulation which is liposomal Caspofungin. The aqueous dispersion
of liposomes was obtained by the thin film hydration method which was further taken for
size reduction using various methods. Further Extrusion was considered as it showed
minimum vesicle size and PDI and further size reduction can be carried out using multiple
passes of extrusion. The results of the formulation showed that after the optimization the
desired vesicle size i.e. 113 and PDI 0.100 was achieved. The third formulation prepared
was Solid Lipid Nanoparticles, prepared by the solvent evaporation method followed by
the ultra-sonication method. Taguchi design was used to screen the excipients and 32
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