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J Pharmacol Ther Res 2017 Volume 1 Issue 2
November 02-03, 2017 Chicago, USA
4
th
International Congress on
International Conference and Exhibition on
Drug Discovery, Designing and Development
Biochemistry, Molecular Biology: R&D
&
Effect of manufacturing process and container closure configurations on critical quality attributes of
generic parenteral drug product: A case study of pH
Lakshmi Prasanna Kolluru
Medefil Inc., USA
Purpose/Introduction:
Product development of generic
parenteral products involves extensive studies to optimize
formulation process and manufacturing conditions such that
the developed product is like Reference Listed Drug (RLD) in
terms of all Critical Quality Attributes (CQA) over stability. CQA’s
are properties of drug product which have significant effect on
product quality. Typical CQA’s for a drug product include pH of
the formulation, assay of the chemical of interest, impurities,
visual appearance, particulate matter, color and clarity of the
solution. In this present work, we present two case studies of
generic parenteral product development to optimize pH of the
drug products under study.
Methods:
pH of a formulation is a critical quality attribute as it
significantly affects solubility and stability of the drug product.
In addition, pH of a parenteral drug product has significant
clinical effects such as electrolyte imbalances. In first case study,
we evaluated effect of container closure configurations on pH
of the drug product. We formulated the drug product and filled
it in various treated and non-treated glass vials, stoppered,
sealed and placed on stability as per International Conference
on Harmonization (ICH) guidelines. In the second case study,
we evaluated effect of nitrogen sparging during compounding
on pH of the drug product. We prepared three batches of drug
product. First batch was prepared under ambient atmospheric
conditions without nitrogen sparging, another by sparging the
water for 30 minutes before addition of Active Pharmaceutical
Ingredient (API) and blanketing the formulation with nitrogen
for rest of compounding process; and third batch with
continuous nitrogen sparging throughout compounding. pH
of all the three batches are monitored at pre-determined time
intervals throughout the manufacturing process.
Results:
Stability data of the drug product in case study 1
monitored over 6 months at 25C/65% RH and 40C/75% RH
suggest that the formulation in untreated vials showed drastic
change in pH, with the data at 3M and 6M even failing to
meet pH specifications for the finished product. However,
formulation filled in treated vials has well controlled pH and
within specifications at all conditions up to 6Mon stability. Data
analysis of various batches from case study 2 suggests better
control of pH in the second batch with sparging the water for 30
minutes before addition of nitrogen and blanketing throughout
the compounding process.
Conclusion:
Both the case studies suggest that appropriate
container closures and optimal manufacturing process have
significant effect on pH of parenteral drug products and should
be closely evaluated during product development.
Speaker Biography
Lakshmi Prasanna Kolluru is currently working as Sr. Formulation Scientist at Medefil, Inc,
a generic pharmaceutical company. She is responsible for leading product development
project teams all the way from kick-off to product approval. Prior to joining Medefil,
she has served in formulation, analytical and clinical development groups across brand
pharma, generic pharma and contract research organizations. She has graduated
with a PhD in Pharmaceutical Sciences from Mercer University, Atlanta, GA. Her
thesis research focusing on development of novel targeted drug delivery system for
tumor theragnosis has been recognized internationally by American Association of
Pharmaceutical Scientists (AAPS) for excellence in graduate research. In addition to her
active research, she serves as Editorial Board Member and Peer-Reviewer for several
international journals.
e:
prasanna.kolluru@medefilinc.com