The Development of a Floating Drug-Delivery System for Metronidazole - Pharmaceutical Technology

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The Development of a Floating Drug-Delivery System for Metronidazole
The authors developed a metronidazole-based floating drug-delivery system to investigate the effect of rate-controlling polymers on release pattern and duration of buoyancy in matrix tablets.

Pharmaceutical Technology
pp. 41-44

Table IV: Kinetic and statistical parameters obtained from drug-release data of metronidazole floating tablets and release profiles.
The in vitro drug release was best described by the Higuchi kinetic model, and its highest linearity was R 2 = 0.903. These results confirmed that the drugs were released by a combination of diffusion and erosion (see Table IV).

Figure 1: In vitro drug-release profiles of F1, F4, and F7 drug formulations.
The floating behavior and percentage release of the metronidazole tablets also were investigated. F1 tablets had a total floating time of 4.20 h. F7 tablets had a floating time of 7 h, and F8 and F9 tablets had a floating time of 8 h. This difference may occur because NaHCO3 forms gas quickly and citric acid reduces the density of the tablet (i.e., < 1 g/cm3 ). On the other hand, F4, F5, and F6 tablets had no floating ability, perhaps because the system's density was greater than 1 g/cm3 . In addition, HPC may retard the release of carbon-dioxide gas to the system. The buoyancy of the tablets formulated with Carbomer 934P lasted for 8 h because this light and porous material helped produce a low-density system. In vitro drug-release profiles present the cumulative percent release of drug against time (see Figures 1–3). F1 tablets released about 70–93% drug. All other tablets had released about 71% drug after 8 h. No drug–drug or drug–excipient interactions were found, hence 100% release of metronidazole may be achieved with further experiments.

Figure 2: In vitro drug-release profiles of F2, F5, and F8 drug formulations.
All sustained-release formulations have rate-controlling mechanisms, such as swelling, diffusion, and erosion (13). The Higuchi kinetic model best described the drug release from these tablets, which depended on the concentration of polymers. F1 tablets, which contained only 40 mg of Methocel K15M CR, had the highest release of drug (i.e., 93.69%). Buoyancy in F1 tablets lasted 4.20 h and was decreased by increasing the amount of Methocel K15M CR. Also, the release of drug increased at first, then gradually decreased with time by the diffusion mechanism. F7, F8, and F9 tablets formulated with Carbomer 934P released approximately 71% of the drug. These conditions might have caused rapid hydration of Carbomer matrices, gel formation, swelling, and diffusion, which increased the release duration of metronidazole.

Figure 3: In vitro drug-release profiles of F3, F6, and F9 drug formulations.
F2 and F3 tablets released the drug rapidly (i.e., 1 and 2 h, respectively). A possible reason is that Methocel K15M CR increases the surface area to expose the deposited drug to the dissolution medium. The drug-release profile is important in describing bioavailability and in optimizing controlled release. The release of metronidazole from the tablets was based on non-Fickian diffusion and the concentration of the rate-controlling polymers (14). Asnaashari et al. showed that a high amount of rate-controlling polymer provided sufficient floating ability and release in formulations with two or more polymers (15). The authors' experimental results showed that drug release was almost 93.69% using 40 mg of Methocel K15M CR and 70% using Carbomer 934P. Buoyancy of F1 and F9 tablets lasted 4.20 h and 8 h, respectively, with no combinations of polymers.


These results, in combination with those of previously published reports, justify the use of rate-controlling polymers such as Methocel K15M CR, HPC, and Carbomer 934P to develop metronidazole floating-matrix tablets. The results suggest that a metronidazole-based floating drug-delivery system using a low amount of polymers could reduce the cost of pharmaceutical production and the likelihood of adverse effects. Such a formulation may maintain the specific plasma concentration and local action against H. pylori for peptic ulcer disease, and further studies could improve the formulation's clinical efficiency.


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