INTRODUCTION:

Oral medication is the most common and convenient form of drug delivery, offering easy administration, low cost, and effectiveness in treating a wide range of conditions, including serious illnesses like cancer and gastrointestinal disorders¹.

While oral preparations offer many advantages, they also face several limitations, mainly due to the physical and chemical properties of certain drugs, such as low aqueous solubility and poor cell membrane permeability. Drug absorption through oral routes can also be limited due to factors such as low chemical stability, biological integrity, and other physiological factors, including efflux transporters, pH barriers, and metabolic enzymes. On top of that, some drugs may create local irritation or nausea after an oral administration route. A new era in drug discovery has emerged, where many newly developed drugs, especially those with low water solubility, fail to be adequately absorbed. This can lead to toxic effects and reduce their chances of gaining approval. Poor solubility is one of the major challenges faced by formulation scientists in modern drug development ^{2, 3}. Researchers are now exploring various advanced techniques to enhance the dissolution of poorly soluble drugs, including methods such as salt formation, nanotechnology, and co-crystallization. Among these, solid dispersion stands out as one of the simplest and most effective approaches to enhance solubility, dissolution rate and bioavailability of the drugs^4-8.

Naproxen, a weak acidic NSAID (pKa 4.15) with poor water solubility and classified as a BCS Class II drug, poses gastrointestinal risks due to its low dissolution. Formulators address this issue using safe and cost-effective solid dispersion techniques to enhance its solubility ^{9. 10}. The poor solubility of naproxen can lead to uneven plasma drug distribution, causing potential harm to patients, including liver injury, hepatotoxicity, and severe gastrointestinal side effects such as upper GI tract bleeding. The method of solid dispersion is a convenient, economical, safe, and effective way of improving the solubility rate of Naproxen. In this research study, an attempt was made to enhance the solubility of the drug naproxen using a cost-effective and straightforward technique of solid dispersion, and to determine the effect of various carriers on the dissolution rate of a poorly soluble drug in water^11,12.

β-Cyclodextrin is essential for improving the solubility, dissolution rate, and bioavailability of sparingly soluble drugs. Solid dispersions are a system where a drug is uniformly dispersed in a solid matrix, which can be a polymer or a carrier material. β-Cyclodextrin is utilized as a carrier material in solid dispersions because it can form inclusion complexes with guest molecules, such as hydrophobic drugs^13-15.

The Pluronic surfactants are amphiphilic, possessing both hydrophobic and hydrophilic units in their structure, and can enhance the solubility of poorly soluble drugs. To begin with, the reduction in surface tension will result in a fine change in the wetting properties of the drug particles, thereby increasing their solubility in water-based systems¹⁶.

The synergistic use of Pluronic and β-Cyclodextrin in a solid dispersion system enhances the solubility, dissolution rate, and overall bioavailability of highly insoluble medications, such as Naproxen¹⁷. A non-ionic surfactant, such as Pluronic, promotes the wetting and dispersibility of the drug and facilitates micelle formation, which solubilizes the hydrophobic molecules of the drug. On the other hand, β-cyclodextrin forms a stable inclusion complex with the drug, engulfing it in its hydrophobic cavity, thereby increasing its solubility in water¹⁸. Combined, Pluronic prevents the crystallization of drugs and enhances the dispersion process. At the same time, β-Cyclodextrin facilitates injection possibilities and intensifies the level of molecular solubilization and stabilization ¹⁹. This two-fold vehicle maintains the drug in amorphous or molecularly dispersed form, which leads to faster and broader dissolution. The concentration system enhances the physical stability and may even mask the bitter aftertaste of the medication. In general, the oral delivery of poorly soluble drugs and their therapeutic activities are significantly enhanced in a solid dispersion system containing Pluronic and β-cyclodextrin.

MATERIALS AND METHODS:

Materials:

Naproxen was collected as a gift sample from Dr. Reddy’s Laboratories, Hyderabad, India. β-Cyclodextrin was obtained from Wacker Metroark Chemicals Pvt. Ltd., Chandni, West Bengal. Pluronic was supplied by Loba Chemie Pvt. Ltd., Mumbai, Maharashtra, along with other excipients including Magnesium Stearate, Microcrystalline Cellulose, Hydroxy Propyl Methyl Cellulose (HPMC) E 50 LV, Talc, and Lactose. Hydrochloric Acid was purchased from Merck Life Science Pvt. Ltd., Mumbai, India, and Ethanol was sourced from Changshu Hongsheng Fine Chemical Co. Ltd. All reagents and chemicals used were of analytical grade and were used as received without further purification.

Methods:

Drug-excipient compatibility study:

Physical compatibility study:

The physical compatibility of naproxen with the selected excipients (β-cyclodextrin and Pluronic) was evaluated through visual inspection. Accurately weighed amounts of naproxen were mixed with each excipient in 1:1 ratios and stored in clean, dry, and tightly closed glass vials. The prepared drug-excipient mixtures were stored under different environmental conditions to assess their physical compatibility. These conditions included room temperature (25 ± 2 °C), elevated temperature (40 ± 2 °C), and high humidity (75% relative humidity) maintained in a stability chamber.

Chemical compatibility study:

FTIR study²⁰:

Fourier Transform Infrared (FTIR) spectroscopy was performed to investigate possible chemical interactions between naproxen and the excipients (β-cyclodextrin and Pluronic). The analysis was performed using a Shimadzu FT-IR 8300 Spectrophotometer (Shimadzu, Tokyo, Japan), employing the potassium bromide (KBr) pellet technique. Each sample was mixed with KBr in a 1:6 (sample: KBr) ratio and then finely ground to ensure uniformity. The mixture was then compressed into transparent pellets using a hydraulic press at a pressure of five tons for five minutes. The prepared pellets were placed in the light path, and spectra were recorded over a wavelength range of 4000 to 400 cm⁻¹. The resulting FTIR spectra were analyzed to detect any shifts, disappearance, or formation of new peaks, which could indicate potential interactions or incompatibility between the drug and the excipients.

X-ray Diffraction (XRD) analysis ²¹:

X-ray diffraction (XRD) analysis was conducted to determine the crystalline or amorphous nature of naproxen and its solid dispersion formulations. The study was performed using a D8 Advanced X-ray diffractometer equipped with a copper-targeted graphite monochromator. The instrument operated at a voltage of 40 kV and a current of 30 mA. The scanning parameters were set with a chart speed of 5°/min and a scanning range of 6°/min, covering a 2θ angle range from 5° to 70°. The diffraction patterns obtained were used to identify the physical state of the drug in the formulations, where the reduction or absence of sharp crystalline peaks indicated the conversion of naproxen into an amorphous form.

Preparation of solid dispersion with β-cyclodextrin:

Accurate amount of naproxen and β-cyclodextrin were mixed in weight ratios of 1:2, 1:4, and 1:6 (w/w) and dissolved in a solvent mixture of ethanol and water (70:30 v/v). The mixture was stirred vigorously using a magnetic stirrer until a clear solution was formed. Ethanol was removed by heating the solution at 50 °C with continuous stirring, followed by removal of water under vacuum at 51 °C using a lyophilization process. The resulting solid mass was thoroughly dried, pulverized using a mortar, passed through a #60 mesh sieve, and stored in a desiccator for further evaluation.

Preparation of ternary solid dispersions:

Naproxen, β-cyclodextrin, and pluronic were mixed in weight ratios of 1:4:1, 1:4:2, and 1:4:3 (w/w/w) and dissolved in a solvent mixture of ethanol and water (70:30 v/v). The mixture was stirred continuously on a magnetic stirrer until a clear solution was obtained. Ethanol was removed by heating the solution to 50 °C under constant stirring, followed by vacuum drying at 51 °C to remove water. The resulting mass was further dried in a hot air oven at 60 °C to ensure complete dryness. The dried material was then powdered using a mortar, passed through a #60 mesh sieve, and stored in a desiccator for further analysis. The different solid dispersion formulations are listed in Table 1.

Table 1. Formulations of solid dispersions

Sl. No.	Formulation code	Naproxen: β-cyclodextrin (w/w)	Naproxen: β-cyclodextrin: pluronic (w/w/w)
1	SDN1	1:2	-
2	SDN2	1:4	-
3	SDN3	1:6	-
4	SDN4	-	1:4:1
5	SDN5	-	1:4:2
6	SDN6	-	1:4:3

Preparation of tablets using pure naproxen and ternary solid dispersion:

Tablets were prepared using both pure naproxen and the optimized ternary solid dispersion to compare their performance. All ingredients were accurately weighed for the preparation of 10 tablets. The formulation consisted of naproxen (or its ternary solid dispersion) as the active pharmaceutical ingredient, microcrystalline cellulose (MCC) as a diluent, hydroxypropyl methylcellulose (HPMC) as a binder, and talc, along with magnesium stearate as a glidant and lubricant, respectively. Initially, naproxen (or its solid dispersion), MCC, and HPMC were blended thoroughly to ensure uniform mixing. Just before compression, talc and magnesium stearate were added and gently mixed to avoid over-lubrication. The prepared blend was then compressed into tablets using a single-station tablet compression machine. The resulting tablets were stored in tightly closed containers under suitable conditions for subsequent evaluation and comparison.

Characterizations of solid dispersion:

Solubility study²²:

The solubility of ternary solid dispersions was evaluated to assess the enhancement in naproxen solubility. An accurately weighed quantity of each formulation, equivalent to 10 mg of naproxen, was added to 100 mL of distilled water and stirred for 24 hours at room temperature using a magnetic stirrer. The resulting suspensions were filtered through Whatman filter paper, and the filtrates were analyzed using a UV-Visible spectrophotometer (Shimadzu UV-Vis 1900i) at the maximum absorbance wavelength (λmax) of naproxen. The concentration of dissolved naproxen was calculated using a pre-established calibration curve and compared with the solubility of pure naproxen to determine the extent of solubility enhancement.

In vitro dissolution study of tablets containing pure naproxen and ternary solid dispersion^23,24:

In vitro dissolution studies were conducted to compare the drug release profiles of tablets formulated with pure naproxen and those containing the ternary solid dispersion. Dissolution testing was performed using a USP Type II (paddle) dissolution apparatus (LABINDIA DS 8000) operated at a rotation speed of 50 rpm and maintained at a temperature of 37 ± 0.5 °C. The test medium consisted of 900 mL of simulated gastric fluid (pH 1.2) to simulate stomach conditions. Tablets containing pure naproxen and ternary solid dispersion were placed in the dissolution medium, and 5 mL samples were withdrawn at predetermined time intervals—2, 5, 10, 20, 30, 40, 50, and 60 minutes. After each withdrawal, the same volume of fresh dissolution medium was immediately added to maintain sink conditions. The collected samples were filtered through Whatman filter paper using a 0.45 μm membrane filter to remove any undissolved particles. The filtrates were then analyzed using a UV-Visible spectrophotometer (JASCO V-550) at a wavelength of 210 nm, corresponding to the maximum absorbance (λmax) of naproxen. Each test was performed in triplicate, and the results were expressed as mean ± standard deviation. The comparative dissolution profiles provided insight into the improved drug release behavior of the ternary solid dispersion tablets over the pure drug formulation.

RESULT AND DISCUSSION:

Drug excipient compatibility study:

Physical compatibility study:

Stability study was carried out over 90 days to evaluate the physical compatibility of naproxen with various excipients. The drug was mixed individually with β-cyclodextrin, MCC, HPMC, magnesium stearate, and with a combination of β-cyclodextrin and Pluronic. All formulations remained white with no visible change in color throughout the study period. This indicated no signs of physical or chemical interaction between naproxen and the excipients. Hence, the excipients were found to be stable and suitable for use in naproxen tablet formulation.

Chemical compatibility study:

FTIR Study:

Table 2.: Infrared spectral assignments for naproxen

Functional Group	Wave Number (cm-1)
- COOH (Carboxyl group)	1726.29
C — O	1176.58
C = C (aromatic stretch)	1604.77
- CH3	1452.38
O – H (carboxylic acid)	2973.16

Figure 1: FTIR spectrum of Drug, physical mixture and solid dispersion

The FTIR spectrum of pure naproxen displayed characteristic peaks at 1726.29 cm⁻¹ (carboxyl group), 1176.58 cm⁻¹ (C–O stretching), 1604.77 cm⁻¹ (aromatic C=C stretching), 1452.38 cm⁻¹ (–CH₃ bending), and 2973.16 cm⁻¹ (O–H stretching of the carboxylic acid group). These peaks represent the functional groups present in the naproxen molecule. When the FTIR spectrum of the pure drug was compared with that of the drug-excipient mixtures, no significant shifts, disappearance, or formation of new peaks were observed. This confirms the absence of any chemical interaction between naproxen and the selected excipients, indicating their compatibility for formulation development.

XRD studies:

Figure 2: XRD analysis of Naproxen, physical mixture, solid dispersion with carriers

The X-ray diffraction (XRD) pattern of pure naproxen exhibited distinct and sharp peaks at 2θ angles of 6.85°, 12.2°, 17.72°, 18.9°, 19.94°, 22.24°, 23.52°, and 28.28°, indicating its highly crystalline nature. In contrast, the XRD patterns of the physical mixture and solid dispersion formulations showed a noticeable reduction in peak intensity and broadening or disappearance of characteristic peaks. This significant change in the diffraction pattern suggests a loss of crystallinity and transformation of naproxen into an amorphous or partially amorphous state within the solid dispersion. The reduced crystallinity contributes to enhanced solubility and dissolution, supporting the effectiveness of the solid dispersion technique.

Solubility study:

Table 3: Solubility study of Naproxen and solid dispersion formulation (Mean ± SD, n = 3).

Formulation code	Solubility (mg/mL)	Increased in solubility (No of folds)
Naproxen	0.585 ± 0.01	-
SD1	4.80 ± 0.03	8.21
SD2	8.57 ± 0.04	14.65
SD3	7.03 ± 0.03	12.02
SD4	8.74 ± 0.02	14.94
SD5	9.82 ± 0.05	16.78
SD6	10.58 ± 0.04	18.09

The solubility data of pure naproxen and its various solid dispersion (SD) formulations (SD1–SD6) show a marked improvement in aqueous solubility through solid dispersion techniques. Pure naproxen, serving as the baseline, exhibited a solubility of 0.585 ± 0.01 mg/mL. All SD formulations demonstrated significant enhancement in solubility, with the SD6 formulation showing the highest solubility at 10.58 ± 0.04 mg/mL, representing an 18.09-fold increase. SD5 followed closely with 9.82 ± 0.05 mg/mL (16.78-fold), while SD4 and SD2 exhibited solubilities of 8.74 ± 0.02 mg/mL and 8.57 ± 0.04 mg/mL, corresponding to 14.94 and 14.65-fold increases, respectively. SD3 and SD1 showed solubility values of 7.03 ± 0.03 mg/mL (12.02-fold) and 4.80 ± 0.03 mg/mL (8.21-fold). These findings clearly indicate that solid dispersion, especially in the ternary system (SD6), is highly effective in enhancing the aqueous solubility of naproxen.

In vitro dissolution study:

Figure 3: Graph of cumulative percentage drug release vs time.

The figure illustrates the cumulative percentage of drug release over time for pure naproxen (NPX) and its three solid dispersion formulations (SD1, SD2, and SD3). As shown in the graph, NPX exhibits the lowest drug release throughout the 120-minute period, indicating its limited solubility and slower dissolution rate. In contrast, all solid dispersion formulations show enhanced drug release profiles, with SD2 demonstrating the highest cumulative drug release, reaching nearly 80% at 120 minutes. SD3 and SD1 follow in descending order of release performance. The enhanced release in SD formulations can be attributed to improved solubility and wettability of Naproxen in the dispersion matrix.

Figure 4: Graph of cumulative percentage drug release vs time

The figure presents the cumulative drug release data for NPX and additional solid dispersion formulations: SD4, SD5, and SD6. Again, NPX demonstrates the lowest release, reaching just above 50% at 120 minutes, reinforcing its inherent solubility limitations. In contrast, all SD formulations display markedly enhanced release rates. SD6 achieves the highest release (~90%) at the final time point, followed by SD5 and SD4. This progressive improvement indicates that formulation variables significantly influence the performance of solid dispersions. The results demonstrated that all solid dispersion formulations exhibited significantly higher release rates compared to pure Naproxen, indicating improved dissolution behavior. Among the formulations, the optimized solid dispersion (SD6) showed the highest cumulative drug release, reaching 94.89% within 120 minutes. This enhancement can be attributed to the synergistic effect of β-CD and pluronic in improving solubility, wettability, and dispersibility of Naproxen.

CONCLUSION:

The study demonstrates that incorporating pluronic along with β-cyclodextrin (β-CD) as hydrophilic carriers in the solid dispersion system significantly enhances the solubility and dissolution rate of Naproxen compared to its pure form. An increase in pluronic concentration was found to positively influence drug release, with the optimized formulation (SD6) showing the highest solubilization and dissolution efficiency. Characterization through FTIR and XRD confirmed the successful formation of solid dispersions, indicating that naproxen was molecularly dispersed within the carrier matrix and underwent a transformation from crystalline to amorphous state, contributing to improved drug release. These findings suggest that the concentration of pluronic plays a crucial role in optimizing the performance of β-CD-based solid dispersions, offering a promising strategy for enhancing the bioavailability of poorly water-soluble drugs, such as naproxen.

ACKNOWLEDGEMENT:

We are sincerely thankful to the Department of Pharmaceutical Technology, Maulana Abul Kalam Azad University of Technology, West Bengal for providing the necessary facilities and support required to carry out this research work.

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Received on 16.07.2025 Revised on 05.12.2025

Accepted on 19.02.2026 Published on 01.07.2026

Available online from July 04, 2026

Research J. Pharmacy and Technology. 2026;19(7):3233-3238.

DOI: 10.52711/0974-360X.2026.00460

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