Preparation and In Vitro Evaluation of Levofloxacin-Loaded Floating Tables Using Various Rate-Controlling Agents

Abstract

Floating tablets are a new approach to extending the time a drug is in the stomach to improve therapy outcomes. Floating tablets were formulated with the drug, the polymers hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), and starch, fillers, and lubricants. The tablets were prepared using the direction compression method. The tablets’ physical quality control tests were found to be within acceptable limits. The tablets extended drug release up to 12 h and were uniform in their drug contents. The swelling index of the tablets ranged from 60 ± 0.11 to 66 ± 0.14%, and the tablets were less dense than water. The floating lag time (10 ± 0.23 to 16 ± 0.09 s) and total floating time (>12 h) showed good floating behaviors. The kinetic modeling showed that the drug was released from the tablets by pseudo-diffusion, swelling, erosion, or anomalous non-Fickian diffusion. F6 (starch and CMC) showed higher n values (0.994 ± 0.04), exhibiting pseudo-zero-order drug release kinetics compared to those of other tablets. The dissolution data of the test and reference tables were not similar (P > 0.05). In terms of antimicrobial activity, the zones of inhibition of the test F6 tablet powders (5.3 ± 0.08 mm) and the reference tablet powders (5.9 ± 0.13 mm) were found to be significantly similar (P > 0.05). The study concluded that these floating tablets can improve the gastric residence time and therapeutic outcomes.

Introduction

Helicobacter pylorus is known to be widespread throughout the world. H. pylorus is the cause of chronic active gastritis, duodenal ulcers, and stomach cancer.¹ Although the bacteria are resistant to many drugs in vitro, they are difficult to eliminate from the human body.² Effective eradication of H. pylorus requires a longer residence time of drugs in the stomach and the floating system;³ this is a novel approach to gastric retention. The system⁴ floats longer on gastric fluid because its density is lower than that of gastric fluid. Floating systems⁴ are divided into effervescent and noneffervescent types. Effervescent floating systems⁴ have a gas-generating agent and release the drug over a longer period of time, which was used in the current study. Polymers⁵ that form gel easily are highly swellable and can be added to floating systems. The white powder HPMC⁶ is a nonionic cellulose ether that has high tensile strength, biodegradability, and remarkable biocompatibility. It is used as a filler and polymer in drug delivery systems. CMC^7,8 is used for various drug delivery applications as matrix-forming agents and diluents because of their affordability, nontoxicity, biodegradability, and compatibility.⁹⁻¹¹ These polymers were included in the current study in the floating tablets of levofloxacin due to their hydrophilic nature.

Levofloxacin¹² is a fluoroquinolone antibiotic, and ofloxacin has levorotatory isomers. Oral bioavailability is 100% and is only slightly affected by food. It is widely distributed in the body; the average volume of distribution is 1.1 L/kg; 24–38% binds to serum plasma proteins (mainly albumin), which does not depend on the concentration of the drug in the serum.¹³ The plasma elimination half-life is 6–8 h with normal renal function. About 80% of the drug is excreted unchanged in the urine. Levofloxacin¹⁴ is effective against both Gram-positive and Gram-negative bacteria, including Helicobacter pylori. Being a water-soluble drug, it was selected for this study because of its short half-life and its activity against H. pylori. It was selected as an addition to floating tablets for site-specific delivery in the stomach.

The levofloxacin floating tablets were prepared using direct compression methods. They were evaluated for various characteristics and aimed to attain a total floating time of 12 h.

Materials and Methods

Materials

Levofloxacin was purchased along with Avicel 102, HPMC, starch, CMC, lubricants, and sodium bicarbonate from BDH, England. Hydrochloric acid (HCl) 35% and buffer tablets were purchased from Sigma-Aldrich, USA. The instruments used for the experiments are as follows: Fourier transform infrared spectrophotometer (L1600300 spectrum, Two Lita, Llantrisant, UK), vernier caliper (Erweka, Germany), UV–visible spectrophotometer (UV-1800, Hitachi, Italy), hardness tester, single punch tableting machine, friabilator (Erweka, Germany), and digital electronic balance (ATX224, Shimadzu, Philippines).

Tablet Formulations

Levofloxacin’s (drug API) amount (250 mg) was kept constant in the floating tablets of levofloxacin. Different polymers (HPMC, CMC, and starch) were incorporated into the tablets either alone or in combinations, and lubricants (magnesium stearate and talc) and fillers were also added. About 140 tablets were prepared for each type of formulation as pilot lots. Table 1 shows the formulations.

Table 1. Floating Tablet Formulations.

ingredients	F1 [mg]	F2 [mg]	F3 [mg]	F4 [mg]	F5 [mg]	F6 [mg]
levofloxacin	250	250	250	250	250	250
HPMC	195			97.5	97.5
starch		195		97.5		97.5
CMC			195		97.5	97.5
magnesium stearate	9.8	9.8	9.8	9.8	9.8	9.8
talc	11.8	11.8	11.8	11.8	11.8	11.8
sodium bicarbonate	74.2	74.2	74.2	74.2	74.2	74.2
spray-dried lactose	71.2	71.2	71.2	71.2	71.2	7.2
total weight (mg)	612	612	612	612	612	612

Flow Properties of Formulation Powder Mixtures

The formulation powder mixture’s flow properties, such as Hausner’s ratios, compressibility indices, and angles of repose, were determined using USP29-NF24¹⁵ standard methods. Angle of repose: funnel and cone assemblies were used to determine the angle of repose. The funnel was fixed with a stand above the Petri dish. The formulation powder mixtures (50 g) were passed through the funnel into a Petri dish to get the heap of powders. The heap height (h) and diameter (d) were determined by a clean ruler. From the diameter, the radius “r” was calculated. The angle of repose (θ) was calculated from eq 1.¹⁵ In order to determine the compressibility index and Hausner’s ratio, 16 bulk and tapped densities were to be determined. The formulation powder mixtures (50 g) were individually added to a graduated cylinder (50 mL). Their surfaces were leveled and tapped once to obtain the bulk volume. Then, the cylinder was tapped 100 times to obtain the tapped volume. The values of these volumes were added to eq 2(15) to calculate the bulk density and the tapped density.

1

2

where “v” refers to the bulk or tapped volume and “m” stands for powder mass. The values of bulk (ρ_bulk) and tapped densities (ρ_tapped) were used in the equations to calculate the compressibility index and Hausner’s ratio.¹⁶ Experiments were carried out in triplicate.

3

4

FTIR Analysis

In accordance with standard guidelines,¹⁷ FTIR analysis was performed using the FTIR spectrophotometer (LI600300 spectrum, Two Lita, Llantrisant, UK) to ascertain any potential interactions between the drug and excipients. The samples were separately added to the inlet chamber of the spectrophotometer, and the instrument was run at room temperature, measuring wavenumber 4000–400 cm^–1.

Preparation of Tablets

The direct compression method¹⁸ was used for preparing the tablets. The formulation mixtures were passed twice through sieve no. 60 to ensure proper mixing. The mixtures were tableted by using a single punch machine (Erweka, Germany). About 130 tablets were produced in each batch. The hardness was maintained at 5–10 kg/cm².

Physical Quality Control Tests

Shape and general appearance:¹⁹ with naked eyes, the tablet’s appearance was checked. The shapes of the tablets were examined with a magnifying lens. Diameter and thickness: 10 tablets were randomly picked from each batch of tablets. Their diameter and thickness²⁰ were measured using clean vernier calipers (Erweka, Germany). Hardness test: for the hardness test, 10 tablets were chosen at random from each batch of tablets. Their hardness was determined by using a hardness tester (Erweka Model TB, Germany). Friability test: to determine their friability, 20 tablets were selected, weighed (W₁), and placed in the friabilator (Erweka, Germany) for 4 min at a speed of 25 rpm. The ultimate weight, W₂, was measured after 100 revolutions. Friability²¹ was calculated in percent (%) using eq 5. Weight variation test:²² for the weight variation test, 20 tablets were selected randomly from each batch of tablets. Each tablet was individually weighed by using a digital electronic balance (Shimadzu, Philippines). The average weight of 20 tablets was calculated. The value of the tests was expressed as the mean ± SD.

5

Tablet Density

The tablets were weighed using a digital electronic balance (ATX224, Shimadzu, Philippines), and their volumes were determined from the die cavity. Eq 6 was used to calculate density.²³

6

Swelling and Floating Behaviors

Each type of tablet was randomly chosen and weighed (W_o) using a digital balance. The tablet was added to 25 mL of a 0.1 N HCl solution in a vessel and agitated at 25 rpm at 37 ± 0.5 °C. The tablet was taken from the vessel; water was removed from the surface using filter paper, and it was weighed (W_t). Then the values of the weights were added to eq 7.²⁴ The USP paddle method²⁵ was employed to study floating behaviors for 24 h using 0.1 N HCl solutions (900 mL) in a flask of the apparatus. The temperature of the medium was maintained at 37 ± 2 °C with a rotational speed of 50 rpm. The floating lag time of the tablet was noted, and the total floating time was also noted by using a stopwatch.

7

Tablet’s Content Uniformity

In each batch, 20 tablets were randomly taken and crushed into powder, and the equivalent weight of 250 mg of the drug was added to a 100-mL flask with 0.1 N HCl solutions. About 5 mL was taken from this solution and diluted to 100 mL with the same solution. In a similar way, it was diluted several times and filtered. The 5 mL samples were taken with a filter syringe and examined at 293 nm using a spectrophotometer, and the absorbance (abs) was added in eq 8. For reference tablets, a similar process was used. This method was used with slight changes by Samanthula et al.²⁶

8

Dissolution Study

In the vessel of USP apparatus type-II,^26,27 900 mL of a 0.1 N HCl solution was added. The paddle rotation was kept at 100 rpm and a constant temperature of 37 ± 0.5 °C. The tablet was added, and the experiment was continued for 10 h. At regular intervals, 5 mL of samples was taken, and the same amount of medium was added to the flask as the solution. The samples were filtered and examined using a UV–visible spectrophotometer to measure the absorbances of the drug at 294 nm. The drug amount was determined by using the drug standard calibration curve.

Drug Release Kinetics

To determine the drug release mechanisms, drug release data were fitted into the following various kinetic models:

• 1.
  Zero-order kinetic model²⁷

  9

  where K₁ is the rate constant, and the time is shown by t but the unit is concentration/time.
• 2.
  1st-order kinetic model²⁷

  10

  where Ln 100 is the initial concentration, while K₂ is the 1st-order constant.
• 3.
  Hixon Crowell’s erosion model²⁷

  11

  where (100 – W) ^1/3 is the initial amount, while K₃ is the model constant and 100 1/3 indicates the level at time t.²⁷
• 4.
  Higuchi’s diffusion model²⁷

  12

  where K₄ is the model constant.
• 5.
  Power law kinetic model²⁷

  13

Dissolution Profile Comparison

For comparison of the drug release profile of the test tablets with reference tablets (Levoflox 250 mg tablets), dissolution data were fitted in the two models: difference factor f₁ and similarity factor f₂ below.²⁸

14

15

Antimicrobial Activity

The antimicrobial activity²⁹ was determined by the disc diffusion method. Mueller–Hinton (beef extract, casein’s acid hydrolysate, starch, and agar) and Sabouraud (40 g/L dextrose, 10 g/L peptone, and 20 g/L agar) agar media solutions were added into Petri dishes of 90 mm and inoculated with the H. pylori strains 39 and solidified. After that, 6 mm cuts were made in the center of the medium and filled with standard powder (ciprofloxacin) and tablet powder. The Petri dishes were incubated for a period of 24 h; zone of inhibition diameters was measured, and experiments were completed in triplicate.

Statistical Tools

One-way of variance (SPPS version 27.0.1) was applied to compare the dissolution profiles of test tablets with reference. The rest of the data were calculated as the mean ± SD in Microsoft Excel.

Results and Discussion

Flow Properties

The flow properties of all formulation powder mixtures were performed using USP29-NF24 standard methods. The all formulation powder mixtures’ Hausner’s ratio ranged from 1.11 ± 0.05 to 1.16 ± 0.16. Their angle of repose of the mixtures ranged from 23.7 ± 0.16 to 26.6 ± 0.08°. The compressibility index of all mixtures ranged from 10.2 ± 0.16 to 12.5 ± 0.18%. These flow properties of the mixtures were found within the USP29-NF24’s limits³⁰ of good to excellent flow for angle of repose (25–35°), Hausner’s ratio (1.01 ± 0.87 to 1.18 ± 0.01), and compressibility index (1.56 ± 0.14). The different formulation powder mixtures had insignificant variations (P > 0.05), which might be due to the presence of lubricants. These results are consistent with the findings of Qin et al.,³¹ who evaluated drug (API) powder and various formulations’ flow properties and found that their powder mixtures were free-flowing and facilitated the tableting process.³⁰ These results are given in Table 2.

Table 2. Formulation Powder Mixture Flow Properties.

formulations	compressibility index [%]	Hausner’s ratio	angle of repose [°]
F1	10.2 ± 0.16	1.16 ± 0.16	26.6 ± 0.08
F2	12.4 ± 0.14	1.15 ± 0.12	23.8 ± 0.19
F3	10.6 ± 0.14	1.12 ± 0.05	25.4 ± 0.18
F4	12.5 ± 0.18	1.11 ± 0.09	24.9 ± 0.05
F5	10.5 ± 0.13	1.13 ± 0.01	23.7 ± 0.16
F6	11.8 ± 0.14	1.11 ± 0.05	25.4 ± 0.02

FTIR Analysis

The drug (API) powder and formulation powder mixtures were analyzed through FTIR analysis to check for any potential interactions between the drug and excipients in the formulation powder mixtures. The drug (API) powder functional groups were OH/NH (3681.45 cm^–1), C–H stretching asymmetric (2974.43 cm^–1), C=O (1724.54 cm^–1), C=C stretching (1619.32 cm^–1), and C–H bend (1458.37 cm^–1). The same functional groups were found in the powder formulation mixtures shown in Table 3, which showed negligible changes. Khatri et al. conducted an FTIR study to check the compatibility of the drug and excipients, and they found that there were slight variations in the functional groups of the drug and formulation mixtures, which exhibited negligible interactions, and these confirm the current study results.³²

Table 3. Interpretations of the FTIR Analysis.

functional groups	drug (API) powder (cm–1)	F1 formulation powder mixture (cm–1)	F2 formulation powder mixture (cm–1)	F3 formulation powder mixture (cm–1)
OH/NH group	3681.45	3679.22	3674.26	3675.36
C–H stretching asymmetric	2974.43	2974.12	2974.31	2973.43
C=O stretching	1724.54	1720.21	1722.46	1723.31
C=C stretching	1619.32	1619.29	1619.62	1619.54
C–H bending	1458.37	1456.48	1440.43	1449.36

Tablet’s Swelling Index

In the swelling study, the tablets swelled by 60 ± 0.11 to 66 ± 0.14% of their original size. F1 swelled 60 ± 0.11, F2 62 ± 0.06, F3 63 ± 0.15, F4 64 ± 0.21, F5 65 ± 0.08, and F6 66 ± 0.14% of the original size. The possible reason for swelling might be the hydrophilic nature of polymers; they swell due to the penetration of the solution. Tablets’ swelling was also observed by Anusha et al.,³³ who developed tablets using hydrophilic polymers, which swell when the medium penetrates inside the tablets. Results are presented in Figure 1.

Figure 1.

Percent swelling of the tablets.

Floating Behaviors and Densities of Tablets

In the floating behavior study, the floating lag time and total floating time were determined. The floating lag time of the tablets ranged from 10 ± 0.23 to 16 ± 0.09 s, and the total floating time of the tablets was found to be greater than 12 h, indicating good flow behaviors. The densities of all the tablets were calculated and ranged from 0.46 ± 0.12 g/cm³ to 0.78 ± 0.25 g/cm³. F1 had significantly (P < 0.05) less floating lag time (10 ± 0.23 s) and density (0.46 ± 0.12 g/cm³) than those of other tablets. The floating tablet’s density was less than that of water (1.004 g/cm³)³⁴ and showed excellent floating behaviors, which might be due to the addition of a gas-generating material, sodium bicarbonate, and hydrophilic polymers, which might cause its floating to the surface of the medium. These results were similar to the findings of Rabani et al.,³⁵ who also found floating behaviors of their tablets and suggested that it was due to the addition of gas-generating agents (citric acid and sodium bicarbonate) in the tablets, which could bring the tablets to the surface of the solution. Table 4 presents the results.

Table 4. Floating Parameters of the Floating Tablets.

formulations	density of tablets [g/cm3]	floating lag time [s]	total floating time [h]
F1	0.46 ± 0.12	10 ± 0.23	>12 ± 0.21
F2	0.58 ± 0.05	14 ± 0.16	>12 ± 0.10
F3	0.64 ± 0.02	12 ± 0.08	>12 ± 0.24
F4	0.76 ± 0.19	15 ± 0.06	>12 ± 0.18
F5	0.78 ± 0.25	16 ± 0.09	>12 ± 0.14
F6	0.70 ± 0.08	13 ± 0.05	>12 ± 0.12

Physical Quality Control Tests

The surfaces of the tablets were level, clean, smooth, and elegant in their appearance. The tablet thicknesses ranged from 3.1 ± 0.02 to 3.1 ± 0.09 mm, which was found within the USP limits (2–4 mm).³⁰ The tablet diameters ranged from 9.0 ± 0.02 to 9.0 ± 0.03 mm, which fell within the USP’s limits (4–13 mm).³⁰ The tablet hardnesses ranged from 8.6 ± 0.06 to 9.3 ± 0.04 kg/cm², which was found within the limits of USP (5–10 kg/cm²).³⁰ The tablet friabilities ranged from 0.01 ± 0.14 to 0.07 ± 0.18%, which was within USP limits (<1%).³⁰ The tablet weights ranged from 612.0 ± 0.01 to 612.3 ± 0.06 mg, which was within USP’s limits (weight ≥ 324 with 5% variations).³⁰ These results were found within the USP’s limits,³⁰ indicating that tablets were prepared with constant processing variables. The physical quality of tablets might affect the drug release in the tablet dissolution study. These findings were consistent with the findings of Huang et al.,³⁶ who prepared tablets, and their tablets’ physical quality control tests met the compendial limits, which was due to constant tablet processing parameters. These findings are given in Table 5.

Table 5. Tablets of Physical Test Quality Control Tests.

formulations	thickness (mm)	diameter (mm)	crushing strength (kg/cm2)	friability (%)	weight (mg)
F1	3.1 ± 0.02	9.0 ± 0.02	9.2 ± 0.01	0.06 ± 0.16	612.0 ± 0.01
F2	3.1 ± 0.08	9.0 ± 0.03	8.9 ± 0.02	0.05 ± 0.03	612.2 ± 0.10
F3	3.1 ± 0.06	9.0 ± 0.02	9.1 ± 0.04	0.06 ± 0.08	612.1 ± 0.02
F4	3.1 ± 0.09	9.0 ± 0.03	8.8 ± 0.07	0.07 ± 0.18	612.3 ± 0.06
F5	3.1 ± 0.05	9.0 ± 0.01	8.6 ± 0.06	0.04 ± 0.17	612.1 ± 0.01
F6	3.1 ± 0.04	9.0 ± 0.05	9.3 ± 0.04	0.02 ± 0.12	612.0 ± 0.03
F7	3.1 ± 0.08	9.0 ± 0.05	8.9 ± 0.01	0.01 ± 0.14	612.1 ± 0.05

In Vitro Dissolution

The in vitro dissolution studies were performed according to standard procedures^26,27 for 24 h; it was found that the floating tablet extended the drug release rates up to 12 h. It was noted that formulation F1 released 100 ± 0.01% of the drug in 12 h and formulation F2 released 99 ± 0.03% of the drug in 12 h. F3 released 98.0 2 ± 0.26% and F4 released 97.80 ± 0.10% of the drug in 12 h. F5 released 95.81 ± 0.21% and F6 released 93.68 ± 0.14% of the drug in 12 h. F6 (93.68 ± 0.02%) had longer drug release rates than those of other tablets. The reference tablets released 100 ± 0.02% of the drug in 2 h. These tablets extended the drug release rates, which might be due to the presence of hydrophilic polymers. Tablets swell as the medium penetrates inside, and their micropores decrease in size, causing retardation of drug release. These results confirm the findings of Emami et al.,³⁷ who also used hydrophilic polymers in the tablets, and drug release rates were extended due to swelling of the polymeric network when the medium penetrated into the tablets, which reduced the micropores and extended the drug release rates. Khan et al.³⁸ found that their floating tablets with hydrophilic polymers (HPMC K100 M and xanthan gum) extended their drug release rates for a longer period of time. These results are displayed in Figure 2.

Figure 2.

Drug release profiles of floating tablets and reference tablets.

Content Uniformity

The content uniformity test for each batch of tablets was performed. The content of levofloxacin ranged from 99.96 ± 0.13 to 101.3 ± 0.18% in the tablets and was found within the USP29-24³⁰ limits (90–110%). F1 and F5 showed that the content was significantly (P < 0.05) uniformly distributed in the tablet formulations. This might be due to the proper mixing of the drug with excipients, which might distribute the drug throughout the formulation mixtures. Gangane et al.³⁹ also found that their drug was uniformly dispersed in their tablets, which could be the result of proper mixing of drugs with excipients in their formulations, which confirms the finding of the present study. Table 6 indicates these results.

Table 6. Content Uniformity of the Levofloxacin Tablets.

formulations	content uniformity [%]
F1	100.0 ± 0.02
F2	99.98 ± 0.12
F3	99.99 ± 0.14
F4	101.3 ± 0.18
F5	100.6 ± 0.16
F6	99.96 ± 0.13

Drug Release Kinetics

The drug release data of the tablets followed the zero-order kinetic model, as the r² values ranged from 0.988 ± 0.41 to 0.997 ± 0.14, indicating that the drug was released by pseudo-zero-order kinetics, which might be due to the addition of polymers in the tablets. These results are similar to those of Shanmugam et al.,⁴⁰ who found that their tablets might release the drug with zero-order kinetics. The resultant r² values of the 1st-order kinetic model ranged from 0.186 ± 0.06 to 0.432 ± 0.21, showing that the drug was not released from the tablets by 1st-order kinetics, which might be due to the polymeric nature of the tablets, which might extend drug release rates rather than burst release of the drug. These findings confirm the results of Khan et al.,⁴¹ who found that their drug release data of the floating tablets did not follow the 1st-order models. The Higuchi model’s r²-values ranged from 0.987 ± 0.06 to 0.994 ± 0.19, showing pseudo-diffusion release mechanisms. These results are similar to those of Shanmugam et al. and Khan et al.,^40,41 who also found that their drug could be released by pseudo-diffusion. The r²-values of Hixon Crowell’s kinetic model ranged from 0.985 ± 0.28 to 0.995 ± 0.18, showing that the drug was released by pseudo-swelling and erosion mechanisms. It might be due to the addition of the polymers in tablets, which might control the drug release with swelling or erosion release mechanisms. Shanmugam et al.⁴⁰ applied Hixon Crowell’s model to their drug release data and found that their drug might be released by pseudo-swelling and erosion mechanisms, which support the findings of the current study. The r²-values of the power law kinetic model ranged from 0.989 ± 0.02 to 0.995 ± 0.25, showing linearity in the drug release from tablets, and the n-values (exponential amount of drug) ranged from 0.865 ± 0.18 to 0.994 ± 0.04, showing that the drug was released by pseudo-anomalous non-Fickian diffusion. F6 was found to have a higher n-value of 0.994 ± 0.04, which is near 1.0 (the maximum value of n), showing pseudo-zero-order release kinetics. This might be due to the fact that the reference tablets were immediate-release tablets without the addition of rate-controlling polymers. These findings of drug release kinetics or mechanisms are similar to those of Shanmugam et al.,⁴⁰⁻⁴² who found that their tablets released the drugs by pseudoanomalous non-Fickian diffusion. The reference tablets only followed the ester-order kinetic model with r²-values of 0.986 ± 0.14 but did not follow the other kinetic models with lower r²-values shown in Table 7.

Table 7. Release Mechanism of the Floating Tablets^a.

formulations	1st-order kinetic model (r2)	zero-order kinetic model (r2)	Higuchi’s kinetic model (r2)	Hixon Crowell’s kinetic model (r2)	power law kinetic model (r2)	n-values	release mechanism
F1	0.321 ± 0.31	0.990 ± 0.28	0.987 ± 0.06	0.985 ± 0.28	0.989 ± 0.08	0.869 ± 0.11	ANFD
F2	0.265 ± 0.18	0.988 ± 0.41	0.989 ± 0.31	0.988 ± 0.10	0.989 ± 0.02	0.865 ± 0.18	ANFD
F3	0.186 ± 0.06	0.989 ± 0.48	0.990 ± 0.11	0.989 ± 0.06	0.990 ± 0.06	0.901 ± 0.26	ANFD
F4	0.432 ± 0.21	0.993 ± 0.16	0.991 ± 0.32	0.992 ± 0.12	0.992 ± 0.18	0.866 ± 0.13	ANFD
F5	0.268 ± 0.12	0.996 ± 0.04	0.992 ± 0.26	0.993 ± 0.26	0.993 ± 0.04	0.993 ± 0.09	ANFD
F6	0.324 ± 0.08	0.997 ± 0.14	0.994 ± 0.19	0.995 ± 0.18	0.995 ± 0.25	0.994 ± 0.04	ANFD
Reference tablets	0.986 ± 0.14	0.123 ± 0.41	0.432 ± 0.07	0.489 ± 0.03	0.436 ± 0.13	0.348 ± 0.02	does not follow

^aNDFD = anomalous non-Fickian diffusion.

Difference and Similarity Factors

The difference factor f₁ values ranged from 18.6 ± 0.31 to 26.8 ± 0.16 and f₂ values ranged from 26.9 ± 0.21 to 40.4 ± 0.02, which was not found within the acceptable⁴³ limits of f₁ (1–15) and f₂ (50–100). These indicated that the drug release data of the test tablets did not match the reference dissolution profile as the obtained values of f₁ and f₂ were not within the acceptable limits. These results are listed in Table 8. These findings confirm those of Somasundaram and Azab et al.,^44,45 who found that the drug release profiles of the test tablets did not match those of the reference tablets when applied to f₁ and f₂. One-way analysis was also applied for comparison of test tablet dissolution profiles, and P-values were found to be greater than 0.05, indicating differences in dissolution profiles. F6 is different than the other formulations as the P-value was 0.198.

Table 8. Values of Difference and Similarity Factors.

test vs reference	f1	f2
F1 vs reference tablets	22.6 ± 0.18	40.4 ± 0.02
F2 vs reference tablets	24.1 ± 0.24	38.2 ± 0.15
F3 vs reference tablets	18.6 ± 0.31	35.4 ± 0.08
F4 vs reference tablets	19.2 ± 0.11	30.2 ± 0.05
F5 vs reference tablets	25.4 ± 0.28	28.1 ± 0.12
F6 vs reference tablets	26.8 ± 0.16	26.9 ± 0.21

Antimicrobial Activity

The antimicrobial activity of the test F6 tablet powders (5.3 ± 0.08 mm) and the reference tablet powders (5.9 ± 0.13 mm) was found to have insignificant variations (P > 0.05). The current study’s findings support the finding of Somasundaram,⁴⁴ who found that levofloxacin-based therapy (74.5 ± 0.01%) was connected with a significant (P < 0.04) higher rate of eradication against H. pylori than that of clarithromycin-based therapy (62%) in 14 days.

Conclusions

The levofloxacin floating tablets were prepared by direct compression using the polymers HPMC, CMC, and starch. Physical quality control tests were found within USP29-NF24 official compendial limits. Tablets swelled 60 ± 0.11 to 66 ± 0.14% of their original size, indicating good swelling behavior. The tablets’ floating lag time (10 ± 0.23 to 16 ± 0.09 s) and total floating time (>12 h) showed good floating behaviors. The tablets extended the drug release rates up to 12 h. The drug content (99.96 ± 0.13 to 101.3 ± 0.18%) was uniformly found in the tablets. The tablets released the drug by pseudo-diffusion, swelling, erosion, or anomalous non-Fickian diffusion, and F6 exhibited higher n-values (0.994 ± 0.04) indicating pseudo-zero-order kinetics than those of the rest of the tablets. The dissolution patterns of the test and reference tablets were not similar using similarity and difference factors and one-way analysis of variance (P > 0.05). The antimicrobial activity of the test F6 tablet powders (5.3 ± 0.08 mm) and the reference tablet powders (5.9 ± 0.13 mm) was found to have insignificant variations (P > 0.05). It is concluded from the study that the floating tablets could improve the gastric residence time and patient compliance.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.3c05419.

• Standard calibration curve of levofloxacin (PDF)

Author Contributions

F.Y.S. and K.A.K. designed the work, carried out the experimental work, and evaluated and inferred the data. A.Y.S., A.A., M.A.B., A.A.F., and O.A.M. performed the experiments and analyzed and interpreted the data using software.

The authors declare no competing financial interest.