Case Study 1:

Evaluation of Polyethylene Oxide Compacts as

Gastroretentive Delivery Systems*
Background:
Objective:
• Evaluate dissolution, swelling, in vitro and in
vivo gastric retention properties of PVP-
Polyox compacts and their potential for
delivering water soluble and insoluble
compounds.
Experimental Methods:
Preparation of compacts:
• PVP K-90 (60%) and polyox WSR301 or polyox WSR303
or polyox coagulant (40%) compacts were prepared by direct
compression, using a rotary tablet press under 1.5 ton force.

• Compacts: Circular shaped / 6.5 mm in diameter and 0.9

mm in thickness / 65 mg weight.
Evaluation of Compacts:

1. Dissolution time:
The time required for complete disappearance of compact
matrix in simulated gastric fluid (SGF), maintained at 37 °C
with 100 rpm agitation.

Results:
Compacts were non-disintegrating in nature and retained their
physical integrity in simulated gastric fluid for about 6 hours.
2. Swelling:
Increase in radial dimension of compacts when immersed in a
known volume of simulated gastric fluid over 6 h’.

Results:
PVP-Polyox 301 PVP-Polyox 303 PVP-Polyox
coagulant

0.93±0.06 0.85±0.05 0.86±0.03

Swelling nature of PVP-Polyox combination is suitable for

gastroretentive formulations. It can retain the physical integrity
of dosage unit and maintain its retentive properties for a
prolonged period.
3. In vitro gastric retention:
The time required for the compact to detach from stomach
surface, under simulated conditions.

Methodology:
– Fixed 4 cm2 piece from the body region of porcine
stomach on a solid platform.
–

– The test polymeric compact was gently placed on the wet

mucosal surface and allowed to contact for 1 minute.
– It was then immersed into 250 ml of simulated gastric
fluid at 60° position.
–

– The entire set up was maintained at 37 °C and agitated at

100 rpm.
Results:
PVP-Polyox 301 PVP-Polyox 303 PVP-Polyox
coagulant

0.5 to 0.8 h 3.8 to 4.2 h 1.6 to 1.8 h

• Higher retention of PVP-Polyox 303: Higher molecular

weight of polyox 303 / possibility of forming strong bonding
with the mucosal surface.

• Inclusion of 2% MB and PAA: Increased the swelling ratio

(0.97±0.04 and 0.91±0.03, resp.). Reason: Faster dissolution
of markers (compare to compact matrix) and rapid entry of
gastric fluid into the polymer matrix.
4. In vivo Gastroretention:
Test Product: PVP-Polyox 303 compacts / 2% of Methylene blue
(MB) or phenylazoaniline (PAA) / coated with 3-4% of HPMC.
Animals: Yorkshire cross swines (n=6 to 9) / 9-10 weeks old / 47
to 53 pounds / overnight fasted.
Dosing: 75 mL of water / orogastric tubes.
Post dosing observations: animals had free access to water and
were observed for their normal behavior and/or any possible
adverse effects throughout the study.
Study Methodology: In MB compacts, three animals were
sacrificed at the end of 1 and 3 hours. The GIT was isolated and
visually examined for the location of compacts. A similar study
was repeated with PAA compacts.
Ethical approval: As per IACUC, University of the Pacific.
Results: PVP-polyox 303 compacts with MB
After 1 h: Hydrated compacts, adhering to the gastric mucosa
in the body region of stomach in all three animals.

– The force of adhesion of the swollen matrix withstood manual

flushing with water. On manual removal, the matrix deformed.

• After 3 hours: Only a mild blue stain was observed in the

body region of stomach in only one animal. In the remaining
two animals, neither blue stain nor compact fragments could
be located in stomach or intestine.
Results: PVP-polyox 303 compacts with PAA
After 1 h: Hydrated compacts retained in the body region of
stomach in all three animals.

–The force of adhesion of the hydrated compact matrix on the gastric

mucosa was not as strong as those of methylene blue compacts.
–The swollen mass of compact could be easily removed without
deformation. As observed in vitro, PAA compacts showed lower swelling
than MB compacts.

After 4 hours: Only a mild red stain of PAA was observed in the
stomach of 2 animals; No fragments of compact could be located
in any other part of GI tract; In the third animal, neither red stain
nor compact fragments could be located in stomach or intestine.
Conclusion:

PVP and Polyox compacts showed swelling and retentive

properties. Compare to liquids and disintegrating type
products, these non disintegrating compacts which reside
in the stomach for more than 1 hour are likely to
enhance bioavailability of drugs that have preferential
absorption in the upper GIT.