Formulation and Evaluation of Lansoprazole Nanosuspension: A Novel Pediatric Oral Drug-Delivery System

TABLE 1: FORMULATION TABLE FOR LANSOPRAZOLE NANOSUSPENSION

FORMULATION OF NANOSUSPENSION WITH HIGH SHEAR HOMOGENIZATION

The lansoprazole loaded nanosuspension were prepared by high shear homogenization using tween 80 as a stabilizer and xanthan gum as a viscosifying agent. Five formulations (LSN 1- LSN 5) was prepared by varying the concentration of avicel RC while keeping the amounts of lansoprazole, tween 80 and xanthan gum constant, as shown in above Table 1.

PHASE 1 Preparation of organic phase:

Dissolve lansoprazole in 10- 15ml ethanol and add tween 80 and xanthan gum. In a foil covered beaker (as lansoprazole is light sensitive) and stir until a clear solution obtain.

PHASE 2 Preparation of aqueous phase:

Dissolve avicel RC in 50ml purified water in separate beakers and stir for 30 minutes

PHASE 3 nanoprecipitation

Under high-speed homogenization add organic phase dropwise into aqueous phase for about 10 to 15 mins with the help of tissue homogenizer.

PHASE 4 Solvent evaporation

Allow the ethanol to evaporate at room temperature.

PHASE 5 Addition of Additives

Dissolve methyl paraben in water and add sorbitol, raspberry syrup and erythrosine to improve its appearance finally add this mixture into homogenized portion

PHASE 6 PH adjustment

Prepare the sodium bicarbonate solution and add dropwise by checking PH (up to 8.5).

FINAL PREPARATION

After the formulation, make up the volume up to 100 ml.

PREFORMULATION STUDIES:

The appearance, melting point, calibration curve and compatibility studies (FTIR) are undergone for ensuring there is no chemical interaction and acceptable physiochemical properties for future development of formulation.

EVALUATION STUDIES:

Determination of Ph:

The pH of the prepared lansoprazole syrup was determined using a calibrated digital pH meter. The meter was calibrated with standard buffer solutions, and the electrode was immersed in the formulation. After the reading stabilized, the pH was recorded in triplicate and the mean value was calculated. pH is an important parameter for the stability of lansoprazole formulations^.[15][16]

Particle Size and Polydispersity Index (PDI)

The particle size and PDI of the prepared lansoprazole nanosuspension were determined using Dynamic Light Scattering (DLS). The sample was suitably diluted and analyzed to measure the average particle size and size distribution. A lower PDI indicates a more uniform particle-size distribution^.[17][18]

Zeta Potential

The zeta potential of the prepared lansoprazole nanosuspension was determined using a zeta-potential analyzer based on electrophoretic mobility. The suitably diluted sample was analyzed, and the zeta-potential value was recorded in mV. It indicates the surface charge and physical stability of the nanosuspension; a higher absolute zeta-potential value generally indicates better electrostatic stability^{.[19][20][21]}

Sedimentation Volume:

The sedimentation volume of the prepared lansoprazole nanosuspension was determined to evaluate its physical stability and settling behavior. A known volume of the formulation was kept undisturbed, and the final sediment volume (Vu) was measured at specified intervals. The sedimentation volume was calculated as F = Vu/Vo, where Vo is the original volume of the suspension^{.[22][23][24]}

Viscosity:

The viscosity of the prepared lansoprazole nanosuspension was determined using an Ostwald viscometer by measuring the time required for the sample to flow between two calibration marks. The measurement was performed in triplicate, and the average viscosity was calculated. Viscosity is an important parameter affecting the flow properties, sedimentation, and physical stability of the nanosuspension^.[25][26]

Surface Tension:

The surface tension of the prepared lansoprazole nanosuspension was determined using a stalagmometer by the drop-count method. The number of drops formed by the nanosuspension was compared with that of distilled water under identical conditions. Surface tension is an important property affecting the wetting and dispersion of drug particles in the formulation^.[27]

Redispersibility:

The redispersibility of the prepared lansoprazole nanosuspension was evaluated by allowing it to stand and then gently shaking the container to redisperse the settled particles. The formulation was observed for the ease of redispersion, uniformity, and absence of lumps or aggregates. Good redispersibility indicates good physical stability and minimal caking.^[28][29]

Scanning Electron Microscopy (SEM)

Scanning Electron Microscopy (SEM) was used to examine the surface morphology, shape, and approximate particle size of the prepared lansoprazole nanosuspension. The dried sample was mounted on an SEM stub, coated if required, and scanned using an electron beam to obtain high-resolution images. The images were examined for particle shape, surface characteristics, uniformity, and aggregation^.[30]

3. RESULT AND DISSCUSSION:

PHYSICAL CHARACTERISTICS:

The physical characteristics of lansoprazole was observed and tabulated

TABLE 2: Physical characteristics of lansoprazole

MELTING POINT:

The melting point of lansoprazole was observed and tabulated:

TABLE 3: MELTING POINT OF LANSOPRAZOLE

Thus, the melting point of lansoprazole was found to be 180.0 ± 1.0 °C, with decomposition. (lansoprazole undergoes color changes before it attains its melting point)

SOLUBILITY TEST:

The solubility test was conducted with different solvents

TABLE 4:SOLUBILITY STUDY OF LANSOPRAZOLE WITH DIFFERENT SOLVENTS

λmax of lansoprazole:

FIGURE 1: λmax of lansoprazole

Calibration graph of lansoprazole:

FIGURE 2: CALIBRATION CURVE OF LANSOPRAZOLE

Determination of pH:

The observed pH value of lansoprazole nanosuspension is tabulated below;

TABLE 5: pH RESULTS OF LANSOPRAZOLE NANOSUSPENSION

The pH of the prepared lansoprazole nanosuspensions was found to be satisfactory, with LNS4 (pH 8.50) selected as the best formulation with respect to pH stability.

Viscosity:

The viscosity of the nanosuspension determined by Brookfield viscometer was tabulated below

TABLE 6: OBSERVED VISCOSITY OF LANSOPRAZOLE NANOSUSPENSION FORMULATIONS

On the above observed values the LNS 3 & 2 exhibits low viscosity among all batches facilitates easier pouring which increases high risk of rapid sedimentation. Thus LNS 4 exhibits highest viscosity & highly stable.

Particle size determination:

TABLE 7: PARTICLE SIZE VALUES OF 5 FORMULATIONS

FIGURE 3: REPORT OF PARTICLE SIZE ANALYSIS

The hydrodynamic diameter of the formulations varied between 178nm and 672nm, with PDI values ranging from 0.212 to 0.351. Formulations LNS1, LNS2, and LNS3 generated hydrodynamic diameters exceeding 500nm (505 nm,620 nm, and 672, respectively) coupled with high PDI values (≥ 0.342). PDI values exceeding 0.300 reflect polydisperse populations where particles of unequal dimensions coexist, predisposing the system to Ostwald ripening and physical instability over storage. A low PDI (0.212) prevents particle size drift and sediment compaction over extended shelf life. Based on these combined physicochemical metrics, LNS4 is identified as the optimal formulation batch for subsequent solid-state characterization, stability testing, and in vitro dissolution studies.

Zeta potential:

TABLE 8 : ZETA POTENTIAL REPORT OF LNS FORMULATIONS

FIGURE 4:ZETA POTENTIAL REPORT

The surface charge and physical stability of the prepared Lansoprazole nanosuspension formulations (LNS1–LNS5) were evaluated using dynamic light scattering on a Malvern Zetasizer (v2.3). The measured zeta potential values, summarized in Table 23, ranged from -23.5 mV to -35.0mV, providing clear insights into the electrostatic repulsion governing particle interaction within the suspension.

Among all five formulations, LNS4 exhibited the highest negative zeta potential magnitude of -35.0 mV, indicating an optimal electrokinetic potential and superior colloidal stability.

({LNS4} > {LNS5} > {LNS1} > {LNS2} > {LNS3}),

Formulation LNS4 was selected as the optimized batch for further solid-state characterization and long-term stability testing due to its robust resistance against particle coalescence.

MORPHOLOGY:

The morphology of the LNS formulations was performed using OPTICAL MICROSCOPY and  SCANNING ELECTRON MICROSCOPY the reports are given below:

FIGURE 5: MICROSCOPICAL IMAGE OF LNS FORMULATION

FIGURE 6: SEM IMAGE OF LNS 2                       FIGURE 7: SEM IMAGE OF LNS4

The surface morphology of lansoprazole nanosuspension (LNS1 – LNS5) was evaluated using optical microscopy and scanning electron microscopy and the photomicrographs are presented in above figures The SEM images confirmed the successful formation of nanoparticles, as all batches exhibited discrete, well-dispersed particles without marked aggregation. The majority of particles appeared spherical to oval with smooth surfaces, which is a desirable characteristic for nano formulation systems. LNS 4 shows smooth, well dispersed even sized particles.

Surface Tension:

The surface tension by drop count method was calculated with the help of stalagmometer for 5 formulations of prepared lansoprazole nanosuspension

TABLE 9: SURFACE TENSION OF LNS FORMULATIONS

On the above observed formulations the LNS1 and LNS2 is with lower surface tension which leads to particle aggregation. Here LNS 4 has higher surface tension and its is considered as an optimal formulaation.

SEDIMENTATION VOLUME:

TABLE 10:SEDIMENTATION VOLUME OF LNS FORMULATIONS

Based on the sedimentation volume analysis, Formulation LNS4 is identified as the optimized formulation. It provides maximum physical stability, minimum particle settling rate, and the most favourable suspended character essential for long-term shelf life.

REDISPERSIBILITY:

TABLE 11: REDISPERSIBILITY OF 5 LANSOPRAZOLE FORMULATIONS

Formulation LNS4 exhibits optimal redispersibility characteristics requiring only 5 inversion strokes after 24 hours. Combined with its superior sedimentation volume, LNS4 is confirmed as the best formulation for Lansoprazole suspension.

IN-VITR0 DRUG RELEASE STUDIES:

FIGURE 8: INVITRO DRUG RELEASE OF LNS FORMULATION

From the above fig it is evident that the drug release of LNS 1, 2, 3 and 5found to be low and it was assumed to be because of the high amount of avicel RC and low amounts of xanthan gum and tween 80. Whereas the formulations. LNS  4  shows better drug release which was due to the optimization of ratios of Avicel RC, xanthan gum and tween 80 which exhibited a release of 94% respectively.

DRUG RELEASE KINETICS STUDIES:

ZERO ORDER KINETICS:

FIGURE 9: ZERO ORDER KINETICS OF LNS FORMULATION

The drug release curves for all five formulations are linear over time. This indicates a constant rate of release, which is a hallmark of zero-order kinetics. An R² value of 0.9999 indicates a good linear fit. This confirms that all LNS follows zero-order kinetics almost perfectly. The slope represents the release rate (K₀) in % per hour. So, LNS 4 releases approximately 16.33% of drug per hour, consistently.

Higuchis plot:

FIGURE :10 HIGUCHIS PLOT OF LNS FORMULATION

The cumulative % drug release of LNS1–LNS 5 plotted against the square root of time showed a near-linear relationship (y = 18.58x – 16.48, R² = 0.9216), indicating diffusion-controlled release. The slope (18.58) represents the Higuchi release constant, while the negative intercept suggests a short lag phase before steady diffusion. Among the formulations, LNS 4 exhibited the highest release rate, reflecting faster drug diffusion through its matrix.

KORSEMEYER PEPPAS PLOT:

Figure:11 KORSEMEYER PEPPAS PLOT