Biomedical Engineering Reference
In-Depth Information
Chemistry, Manufacturing, and Control of Ophthalmic
Formulations
Malay Ghosh and Imran Ahmed
Abstract
A road map to develop ophthalmic formulations for topical ocular applications is provided in this chapter.
This includes design of appropriate studies, development of formulations matching target product profile,
selection of suitable packaging, stability assessment, and critical aspects of manufacturing. Uniqueness and
challenges associated with ophthalmic formulation development are also described. The chapter further
outlines the regulatory requirements necessary to file IND and NDA.
Key words
Preformulation, Drug substance, Drug product, Pharmaceutical development, Dosage
form, Impurities, Tests and specifications, Container closure system, Manufacturing, Sterilization,
Stability, ICH, FDA, Regulatory submission
1
Introduction
Ophthalmic preparations are sterile products that may be adminis-
tered topically to the eye or injected into ocular tissue compartments
in the anterior or the posterior segments of the eye (Fig.
1
)[
1
,
2
].
Dosage forms for the eye include, but are not restricted to, solutions,
suspensions, emulsions, gels, ointments, implants, and inserts [
3
].
Ophthalmic formulations, like dosage forms used for other routes of
delivery, must fulfill the essential requirements of safety, stability,
manufacturability, and bioavailability. In addition to fulfilling these
common requirements ophthalmic dosage forms must be designed
with special attention to formulation factors that may affect ocular
tolerability and safety, such as the pH, buffer type, buffer capacity,
excipient type and levels, osmolarity, sterility, endotoxin content,
preservatives, and particulate matter. As such, the chemistry,
manufacturing, and controls (CMC) of ophthalmic formulations is
especially constrained by issues related to patient safety and tolera-
bility, compendia requirement, and regulatory guidelines [
1
].
This chapter provides CMC guidance for the design and devel-
opment of ophthalmic formulations with emphasis on topical ocu-
lar drug delivery. The development scientist may utilize the
information presented herein to help design and carry out the
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