Title:pH-Dependent Behavior of Novel Gellan Beads Loaded with Naproxen
Volume: 15
Issue: 1
Author(s): Tomasz Osmalek*, Anna Froelich, Bartlomiej Milanowski, Magdalena Bialas, Kinga Hyla and Miroslaw Szybowicz
Affiliation:
- Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan,Poland
Keywords:
Beads, drug release, gellan gum, ionotropic gelation, naproxen, swelling.
Abstract: Background: Oral administration of non-selective COX inhibitors involves the risk of serious
side-effects. In the case of naproxen (NPX), the most frequent are those related to malfunctioning of
the gastric mucosa. On the other hand, NPX and other NSAIDs are extensively studied in terms of colorectal
cancer (CRC) prevention and inhibition, since it has been evidenced that COX-2 corresponds with
the risk of the tumor occurrence and growth. Both side-effects in the stomach and possible antitumor activity
of NPX justify the attempts to search for novel carriers for NPX with the site specific release in the
colon. Thus, the aim of the work was to design, formulate and characterize low-acyl gellan gum (GG)
macro beads as potential carriers for the delivery of NPX to the distal parts of the gastrointestinal tract.
Methods: The beads were obtained by the ionotropic gelation technique. CaCl2 solution was used as a
cross-linking medium. After production, the beads were dried and used for further experiments. First,
pure NPX and the beads were evaluated by Raman spectroscopy and DSC studies. The surface and morphology
of the beads were analyzed by SEM. Next, the drug encapsulation efficiency and content in the
beads were determined. The swelling and degradation behavior of the beads were evaluated in four simulated
gastrointestinal fluids at different pH (1.2; 4.5; 6.8 and 7.4). The NPX in vitro release studies were
conducted on USP I apparatus (rotating basket) at pH=7.4 and compared to the commercial enteric tablet.
Results: The polymer content of 0.5 % was considered as too low to obtain spherical beads in the dried
form. Raman spectra confirmed that NPX did not undergo structural changes during production process.
DSC studies showed that thermal decomposition at lower temperatures was observed for formulations
with the lowest amount of GG. It turned out that the most important factor which determined the morphology
of the beads was the amount of gellan gum in the initial mixture. The beads revealed 13.9-
39.9% of drug loading and 75.3-99.7% drug encapsulation efficiency. Swelling of the beads was pHdependent
as the beads remained stable in the acidic environment but started to absorb water. In pH=7.4
after 3 hours, the beginning of the physical decomposition of the polymer matrix was observed. The drug
release studies showed that in pH=7.4 the commercial tablets released 90% of the drug after 45 minutes
while the amount of NPX released from pellets after the same time was 40-80%.
Conclusion: In general, it can be stated that gellan macro beads may be regarded as suitable for site
specific delivery of NPX to the colon. However, these simple to obtain beads can be potentially used
as carriers for many different drugs whenever it is necessary to omit the stomach.
