PURPOSE
The purpose of the studies was to develop a formulation platform for
BCS Class IV API’s, such that the formulation will enhance the solubility and
bioavailability of the BCS Class IV API’s.
METHODS
A solid dispersion formulation was developed in which the API was
solubilized in a solid matrix in comparison to Self-Emulsifying Drug Delivery
Systems (SEDDS). Surfactant was transferred into an appropriate solvent
and the mixture was heated. After 30 minutes, polymers (PVP, Methocel®,
Soluplus®) were transferred to the mixture and heated for additional 30-60
minutes. The drug was then introduced and the solution was heated. The
formulation was split into two equal subparts. The fi rst subpart was heated
to 82ºC and the other to 180-200ºC. The API didn’t dissolve in the fi rst
subpart and the formulation was a white paste. The second subpart showed
a clear solution at 180-200ºC. When the formulation was cooled to ambient
temperature it was solid and transparent. Dissolution experiments were
performed in order to examine the formulations’ performance using 0.1 N HCl
and USP Dissolution II (paddle) at rotation speed of 100 rpm, and the volume
of the medium was 900 mL
RESULTS AND DISCUSSION
The SEDDS formula released a svery low amount of API. Solid dispersion
formulations containing PVP performed poorly on the dissolution experiments
with less than 10% of the drug being released. Formulations containing
Methocel showed similar poor performance. Formulations containing
Soluplus® and PEG 1000 gave promising results as the release of the drug
from the formulation increased signifi cantly. The level of Soluplus® in the
formulations should be 20% or greater in order to achieve a satisfactory
dissolution profi le. In addition to Soluplus®, a combination of PEG 1000 and
surfactants were used to enhance the release of API to the dissolution media.
CONCLUSION:
The incorporation of Soluplus® in the formulation in levels above
20% increased the release of the API in dissolution experiments to
satisfactory levels.
