(693d) Continuous Manufacturing of Oral Disintegrating Films: Impact of Manufacturing Process Parameters on Product Quality

Authors: 
Mazumder, S., Office of Testing and Research, U.S. Food and Drug Administration
Krull, S. M., Office of Testing and Research, U.S. Food and Drug Administration
Yazdanpanah, N., U.S. Food and Drug Administration
Xu, X., Office of Testing and Research, U.S. Food and Drug Administration
Ashraf, M., Office of Testing and Research, U.S. Food and Drug Administration
Cruz, C. N., U.S. Food and Drug Administration
O'Connor, T., U.S. Food and Drug Administration
Pavurala, N., Office of Testing and Research, U.S. Food and Drug Administration
v\:* {behavior:url(#default#VML);} o\:* {behavior:url(#default#VML);} w\:* {behavior:url(#default#VML);} .shape {behavior:url(#default#VML);}

Pavurala, Naresh * Mazumder, Sonal 2 8 2019-04-11T15:24:00Z 2019-04-11T15:24:00Z 1 417 2383 US FDA 19 5 2795 16.00

Clean Clean false false false false EN-US X-NONE X-NONE


/* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:12.0pt; mso-para-margin-left:0in; text-indent:.25in; line-height:200%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}


text-align:center;text-indent:0in;line-height:normal"> normal">Continuous
Manufacturing of Oral Disintegrating Films: Impact of Manufacturing Process
Parameters on Product Quality

text-align:center;text-indent:0in;line-height:normal"> 12.0pt;mso-bidi-font-size:10.0pt;font-family:" times new roman color:black>

text-align:center;text-indent:0in;line-height:normal">Sonal Mazumder* 10.0pt;font-family:" times new roman bold>, Scott M. Krull, Nima YazdanPanah, Xiaoming Xu, Muhammad Ashraf, Celia
N. Cruz, Thomas F. O’Connor, Naresh Pavurala

text-align:center;text-indent:0in;line-height:normal">

 

text-align:center;text-indent:0in;line-height:normal">Office of Testing and Research, U.S.
Food and Drug Administration, Silver Spring, MD

text-align:center;text-indent:0in;line-height:normal">

text-indent:0in;line-height:normal"> font-family:" times new roman>Continuous
processing of pharmaceutical drug products has the potential to offer many
advantages over established batch process methodologies. The objective of this
work is to understand the impact of CM process variables on critical quality
attributes (CQA’s) of oral disintegrating films (ODFs). ODFs are popular dosage
forms for geriatric and pediatric patients. This can aid the understanding of
failure modes that provide the scientific foundation for systematic risk
assessment.

text-indent:0in;line-height:normal"> font-family:" times new roman>A continuous
tape caster with custom baffles was employed to manufacture Lamotrigine ODFs
using the solvent casting method. The films were characterized for drug assay,
content uniformity, disintegration, dissolution, thickness, % moisture content
and mechanical properties. Central composite (CCD) design of experiments (DoE) with
16 runs were used to obtain a comprehensive understanding of the impact of
critical process parameters (CPP) such as conduction temperature, residence
time and air flowrate on quality and performance of ODFs. Dry thickness,
tensile strength and young’s modulus were impacted by the residence time of the film inside
the dryer. The other CPP identified was air flowrate which impacted tensile
strength. Dissolution and disintegration were not significantly impacted by the
process.




Figure 1. (A)  font-family:" times new roman>3D response surface plot
showing the effect of residence time and conduction temperature on dry
thickness when Linear Air Velocity is 0.6, (B) % Model prediction error for dry
thickness

justify;text-justify:inter-ideograph;text-indent:0in;line-height:normal">Response surface models were developed to predict
the CQAs such as dry thickness (Figure 1A), tensile strength and dissolution
time. The model equation developed was tested on the DoE data and the resulting
model predictions for the CQA’s were compared to the experimental data. The
model prediction error was less than 10% for most of the DoEs
(Figure 1B).  A design space was
established and verified. font-family:" times new roman>The design space experiments revealed that
operating conditions conducive to producing ODFs with desirable CQAs are
centered around 50 ºC conduction temperature with 0.55 m/s convection air
flowrate and 24 min residence time. This work helped to elucidate the
relationships between process variables and " times new roman>CQAs for LMT ODFs which will provide insights for
designing control strategies for ODFs produced via continuous manufacturing.

justify;text-justify:inter-ideograph;line-height:normal"> normal"> font-family:" times new roman>Disclaimer " times new roman>: " times new roman> This article reflects the views of the author and
should not be construed to represent FDA’s views or policies.