INTRODUCTION:

Pharmaceutical research is constantly changing how medications are used by improving patient compliance, safety, and efficacy. Among these developments, the introduction of multimodal drug delivery has drawn interest and popularity from many because of its exceptional capacity to offer improved medication bioavailability, controlled release, and delivery. By encapsulating the medication in distinct particles, this method improves release kinetics and permits additional use in many clinical domains¹.

Furthermore, because it is easy to use and physical crosslinking via electrostatic interaction can help prevent the potential toxicity of unwanted influences of chemical cross linker reagents, complexation between oppositely charged macromolecules (e.g., Cs with polyanion) has demonstrated great potential in drug carrier systems such as drug-controlled release formulations².

Polyelectrolyte Complex Multiparticulate Drug Delivery System (PECMDDS):

A crucial component of drug therapy is improving the effectiveness of the medication and getting rid of the negative effects brought on by drug overdoses. Two broad principles have been applied to meet these demands: creating novel medications with greater selectivity and fewer adverse effects, as well as enhancing polymer-based controlled/sustained drug delivery systems. Three distinct methods are employed in the latter situation (polymer-based drug delivery systems) in order to accomplish the intended outcome^3,4.

a. Drug diffusion via hydrogels (films or micro/nanoparticles, for example)

b. Drug and polymer matrix erosion (micro/nanoparticles, for example)

c. Hydrolysis of the chemical bonds (drug-polymer conjugates) that bind the drug to the polymer.

When developing a drug delivery system, it is evident that the relationship between the polymeric system and the active pharmaceutical ingredient (API) is significant. A number of factors must be taken into account, such as the polymer's ability to be biocompatible, biodegradable, non-toxic, and to provide high reactivity towards the treatment under particular conditions (such as pH and temperature)⁵. Drug delivery systems have made extensive use of a number of polysaccharides, such as chitosan, alginates, pectin, cellulose, starch, dextran, agar, etc.⁶

The pharmaceutical industry has made extensive use of Cs/alginate PEC. For instance, the ionotropic gelation process was used to create Cs-alginate nanoparticles in order to investigate the potential for enclosing hydrophobic nifedipine within them and the subsequent drug release⁷. Moreover, controlled-release matrix tablet formulations for wound dressings have included alginate coated with Cs⁸.

For regulated drug delivery, a variety of drug transporter formulations made from pectin-Cs polyelectrolyte complexes are employed. These carriers come in a variety of forms, including as hydrogels, films, tablets, pellets, and beads, which are particularly useful for colonic drug delivery⁹. Because of their pH-sensitive swelling capacity and drug delivery behaviour dependent on enzyme degradation, such as beta glucosidase, Cs/pectin PECs have the potential to be used in colonic medication distributions.

The absence of endogenous digestive enzymes and the colon's lengthy residence period (10–24hours) make up for the colon's significantly reduced surface area compared to the small intestine. Colonic DDS are made to ensure that the formulation remains intact in the small intestine while also achieving the intended and efficient medication concentration in the colon. Ibuprofen is a member of the class of medications known as nonsteroidal anti-inflammatory medicines (NSAIDs), which are used to treat inflammation, fever, and pain. Ibuprofen is 99% bound to plasma proteins. Oral administration of ibuprofenis has been documented to cause gastrointestinal tract ulcers.

By lowering the frequency of dosing while maintaining a sustained therapeutic impact, the study also seeks to produce a multiparticulate preparation of ibuprofen for improved treatment of IBD with fewer side effects and improved patient compliance. Through the optimization of medication bioavailability, regulation of release patterns, and maintenance of stability under diverse physiological situations, these systems provide better treatment results with fewer adverse effects. While biocompatibility and cost-effectiveness factors help to increase accessibility and patient satisfaction, targeted delivery capabilities allow for even more personalization of treatment regimens¹⁰.

MATERIAL AND METHODS:

Chemicals and Instruments:

Ce-Chem Ltd. provided a complimentary sample of ibuprofen. Using chemika bio chemika reagents, chitosan was produced. We purchased Eudragit S-100 from Evonik Roehmpharma. In order to conduct the current investigation, a number of other polymers, chemicals, and reagents of analytical research grade were used. We buy these from authorized vendors. The instruments that are available in the institutes department will be used.

Preformulation Study:

In order to create a stable, safe, and effective dosage form, preformulation involves verifying a drug's identity based on its different physical and chemical characteristics. A medication sample's melting point was ascertained using the capillary method. UV absorption spectroscopy is among the best techniques for identifying contaminants in organic compounds. Phosphate buffer with a pH of 7.4 has been used as the solvent to create a standard solution of 100μg/ml (of the drug sample) for the spectral analysis. Using a UV spectrophotometer (UV-1800, Shimadzu, Japan), UV scanning was carried out between 200 and 400nm. Because it influences the drug's bioavailability, release rate into the dissolving medium, and ultimately the pharmaceutical product's therapeutic efficacy, the drug's solubility is a crucial physicochemical characteristic. At room temperature (25±2˚C), a solubility investigation was conducted in a few chosen aqueous and non-aqueous solvents. Identification of unknown materials, assessment of a sample's quality or consistency, and calculation of the quantity of components in a combination are all covered by FT-IR studies. Using potassium bromide (KBr) powder, an FT-IR spectra of the powdered medication was performed using an FTIR (IR Affinity-1, Shimadzu, Japan) instrument from 400 to 4000 cm^-1. To ascertain whether the drug and the polymers utilized in the formulation were physicochemically compatible, the Fourier transform infrared (FTIR) profiles of pure drug, chitosan, and physical mixes of ibuprofen with chitosan were recorded.

Preparation Polyelectrolyte Complex(PEC) hydrogels:

The ionotropic gelation approach was used to create Cs-alginate (containing HGA and LGA) and Cs-pectin (including HMP and LMP) hydrogel complexes. Separately, Cs, LMP, HMP, LGA, and HGA (2mg/mL of polymer) were dissolved in 0.05M, pH 4.3 acetate buffer. In a conical flask (total capacity 50mL), 5, 15, 25, 35, and 45mL of Cs solution were then added to 45, 35, 25, 15, and 5mL of pectin solutions, respectively, while being stirred at room temperature. Following an hour of standing, various Cs/pectin volume ratios (1:9, 3:7, 1:1, 7:3, and 9:1) are obtained. Centrifugation (centrifuge 5702) was used to separate the precipitate for 20minutes at 4400rpm. To make sure all precipitates were completely removed, the supernatant from each flask was filtered twice under vacuum using a Buchner funnel and filter paper (Whatman No. 1). After being centrifuged twice, the insoluble pellet complex (precipitate) was re-suspended in deionized water. The cleaned complex was then weighed after being freeze-dried with a freeze dryer. The precipitate and supernatant were homogenized for seven minutes to produce the homogeneous suspensions.

Characterisation PEC hydrogels:

Zeta potential, particle size, water uptake, morphology (for both the freeze-dried hydrogels and the homogeneous suspension), and gel strength were measured in order to examine the hydrogel samples that developed at the ideal ratio.

Encapsulation of API ibuprofen into PEC hydrogels:

This was accomplished by using the standardized process described in the literature to mix the API into the hydrogel mixture in a predetermined proportion. To achieve a 1:1 ratio, 5mL of ibuprofen was added drop by drop. After standing for around an hour, the mixture was centrifuged for 15 minutes at 4400rpm. To get rid of the medicine that was on the surface (not encapsulated), the precipitate (pellet) was gently rinsed with 10mL of phosphate buffer (8 pH, 50mM). To ensure the medication was fully dissolved in the buffer, the cleaned pellet was re-suspended in 100 mL of phosphate buffer and swirled for 20hours. To determine the concentration of ibuprofen, the mixture was centrifuged once more for 15minutes, and the supernatant was examined using a UV spectrophotometer to detect the absorbance at 254nm.

Characterisation of Formulation:

Determination of encapsulation efficiency:

EE of ibuprofen was calculated according to the following equation:

EE % = (Weight of ibuprofen entrapped in pellet /total weight of ibuprofen) × 100%

In-vitro drug release study and comparative release kinetics

Using pH 7.4 PBS for 60 minutes at 37^oC, ibuprofen was investigated in vitro as a model drug in drug release research from Cs-polyanion hydrogels.

The work can give a clear concept of the affects that conformation, drug release behaviour and structure polyanions exert on the structure of hydrogel created with Cs, even though the drug release behaviours of the prepared hydrogels were ineffective due to the quick drug release observed.

RESULTS AND DISCUSSION:

Preformulation Studies:

Organoleptic characteristics and Melting point:

Ibuprofen appeared a white powder which had a distinct bitter taste and smell.

Ibuprofen's observed melting point was between 76 and 78°C. The drug's observed melting points, which ranged from 75 to 77.5°C, were nearly identical to the reported peaks.

Determination of λmax of Ibuprofen:

The maximum absorbance (λmax) of ibuprofen was observed at 228nm. As a result, the analytical wavelength of 228nm was chosen (figure 1).

Figure 1: UV spectrum of Ibuprofen showing maximum absorbance (λmax) at 228nm

Table 1 and Figure 2 display the ibuprofen calibration curve that was produced by charting concentration against absorbance. Five repetitions of the entire observation were made. The concentrations were plotted against the mean absorbance value.

Table 1: Calibration data of Ibuprofen at λmax = 228.0 nm

StandardConc.(µg/ml)	Absorbance values
StandardConc.(µg/ml)	Rep-1	Rep-2	Rep-3	Rep-4	Rep-5	Mean	S.D.	%RSD
0	0	0	0	0	0	0	0	0
10	0.124	0.127	0.121	0.128	0.129	0.11	0.002	1.36
20	0.214	0.236	0.217	0.231	0.231	0.23	0.002	0.85
30	0.315	0.346	0.326	0.315	0.348	0.34	0.001	0.34
40	0.428	0.437	0.438	0.438	0.436	0.45	0.001	0.33
50	0.557	0.572	0.667	0.552	0.551	0.59	0.032	7.18

Figure 2: Standard plot of Calibration Curve of Ibuprofen

The data exhibits significant linearity, as seen by the correlation coefficient of R2 = 0.998 and the straight-line equation of Y = 0.011X - 0.002.

Solubility Outcomes:

Significant solubility was demonstrated by ibuprofen in methanol, ethanol, and chloroform solvents. Higher phosphate buffer pH values were also found to increase solubility in comparison to lower pH values. This demonstrated the pH-dependent solubility of ibuprofen.

FTIR Analysis:

Ibuprofen's carboxylic acid and para-di-substituted aromatic ring were both verified by FTIR analyses. The spectra of Ibuprofen alone and the physical mixture (figures 3 and 4) were shown to show no significant shifting or loss of functional peaks.

Figure 3: Fourier transform infrared of ibuprofen pure drug

Figure 4: FTIR spectra of Chitosan and Ibuprofen mixture

PEC hydrogels Characterisation:

Zetapotential:

The investigation of the supernatant's zeta potential revealed that, in all cases, the mixture's zeta potential was negative at less than 35% Cs content. As the Cs content increased, the mixture's zeta potential became less negative until it reached the critical ratio, which is greater than 40% for HMP and lower than this ratio for the other polyanions (table 2 and figure 5).

Table 2: Zeta potential (ζ), size distribution, water uptake (WU %) of PECs prepared

Cs: polyanion	Zeta potential (mV)	Size distribution	Water uptake (%)
Cs:HMP	-8.52±0.74	435±11	98±0.5
Cs:LMP	-29.99±0.57	408±21	91±0.7
Cs:HGA	+1.89±0.25	554±29	93±0.6
Cs:LGA	+9.99±0.0.89	180±20	95±0.8

Figure 5: Zeta potential of the supernatant of Cs /polyanion (HMP-LMP, HGA and LGA) complexes at various charge ratios at 25 ̊C (mean ± SD, n = 3)

Particle Size:

The homogeneous hydrogels' size distribution was measured and is shown in Table 2. Largest size was displayed by HGA, then by HMP, LMP, then LGA. Given that particle size increases with decreasing crosslink density and that lower crosslink densities, such HGA and LMP, show a wider particle size dispersion, this could be caused by the crosslinking density.

Water uptake (WU):

By assessing the hydrogels' swelling behavior in ultra-pure water, the water uptake (WU) capability of the materials was investigated. Table 2 displayed the WU ability results for the Cs: HGA, Cs: LGA, Cs: HMP, and Cs: LMP.

The findings showed that the samples' swelling behaviors varied very little, with HMP and LGA exhibiting the highest WU ability, followed by HGA and LMP, respectively.

Viscosity:

The measurements of the supernatants' specific viscosity show that the lowest ηsp is around zero at 35% Cs for LMP, 55% Cs for HMP, and 45% Cs for alginates (LGA and HGA). This indicates that the great majority of the polysaccharides reacted, or precipitated as a PEC, in these ratios.

As a result, the ideal ratios of 1:1 for Cs-alginates and 3:7 for Cs-pectins were selected, thoroughly described, and the drug release from these formulations was assessed over time (Figure 6).

Figure 6: Specific viscosity of the supernatant of Cs /polyanion (HMP, LMP, HGA and LGA) complexes at various charge ratio at 25ºC (mean ± SD, n = 3)

Ibuprofen Encapsulation Efficiency of PEC hydrogel:

Table 3 shows the evaluated EE for each formulation, which ranges from 36% to 56%. The LMP formulation had the highest entrapment effectiveness (56.0 ± 0.9%), followed by the two alginate formulation types (HGA = 51.0 ± 1.0 and LGA = 52.0 ± 1.3), which did not differ significantly. The EE of the HMP formulation was lower. The degree of crosslinking between the polyelectrolytes may be the cause of this difference. LMP has a higher EE since it is a tighter network.

Table 3: EE ibuprofen content (%) in PEC hydrogel prepared

Cs: polyanion	EE %
Cs:HMP	35±0.5
Cs:LMP	55±0.7
Cs:HGA	49±0.6
Cs:LGA	53±0.8

In-vitro release profile and release kinetics:

The percentage of ibuprofen that remained in the Cs hydrogel after 60 minutes was shown in Figure 7. It was shown that the hydrogels containing HMP and LGA had the largest proportion of ibuprofen that was maintained, followed by HGA and LMP. This might be explained by the pores' tiny size and fibrous appearance, which could prevent trapped molecules from moving freely.

The samples that exhibit poor swelling behavior, stronger gel, and higher adhesion ability also have a high rate of drug release, as these results are consistent with water absorption, adhesiveness, and gel strength.

Furthermore, the drug release data in Table 4 were subjected to the application of zero-order, first-order, and Higuchi mathematical drug release models. For every sample, the drug release kinetic parameters showed the strongest association with the first order (Figure 7).

Figure 7: Drug release % ibuprofen release on the membrane after 60 min at 37 ºC. Values are represented as mean ± SD (n=3)

Table 4: Release kinetics of the hydrogels (pH 4.3)

Cs: polyanion	Zero order		1st order		Higuchi
Cs: polyanion	K0 (%/min)	R2	K1(%/min)	R2	K(%/min)	R2
Cs:HMP	0.004	0.289	0.051	0.491	0.045	0.49
Cs:LMP	0.0007	0.301	0.081	0.792	0.013	0.52
Cs:HGA	0.005	0.315	0.049	0.581	0.049	0.48
Cs:LGA	0.003	0.379	0.061	0.687	0.031	0.63

Drug dissolution and absorption are described by this paradigm. The concentration of the drug in the formulation determines the rate of release, which is a sign of a porous polymer matrix.

CONCLUSION:

The ionotropic gelation method was used in the current study to successfully construct the Cs-polyanion (HGA, LGA, HMP, and LMP) hydrogel complexes at different ratios (10%, 30%, 50%, 70%, and 90% of Cs) in acetate buffer 0.05 M, 4.3 pH. The results showed that the hydrogels containing HMP and LGA had the largest proportion of ibuprofen that was retained, followed by HGA and LMP. This might be explained by the tiny pores' fibrous appearance, which could prevent trapped molecules from moving freely. Furthermore, the drug release data was subjected to Higuchi, first-order, and zero-order mathematical drug release models. For every sample, the drug release kinetic parameters showed the strongest association with the first order. Drug dissolution and absorption are described by this paradigm. The concentration of the drug in the formulation determines the rate of release, which is a sign of a porous polymer matrix.

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Received on 15.10.2025 Revised on 12.11.2025

Accepted on 04.12.2025 Published on 14.02.2026

Available online from February 18, 2026

Research J. Science and Tech. 2026; 18(1):53-60.

DOI: 10.52711/2349-2988.2026.00009

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