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Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

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Open Access Full Text Article                                                       Research Article

Design, Development and Evaluation of Nimesulide-Loaded Nanosponges for Compression into Fast Dissolving Tablets to Enhance Solubility and Dissolution Rate

Sahil Ansari ¹, Pradeepa Ganesan ², Shruti A Khandke ³, Vaishnavi Vanasakrithmath ⁴, K. Sandhiya ⁵, Soham M. Naik Gaonkar ⁶, Divya Vivek Donage ⁷, Anusha C. K. ⁸*, Ganavi Maheshappa Halageri ⁹

¹ SRM Modinagar College of Pharmacy, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Delhi-NCR Campus, Delhi-Meerut Road, Modinagar, Ghaziabad, UP, India

^2,5 Shakthi Institute of Engineering and Technology, Anna University, Coimbatore, India

^3,4 KLE College of Pharmacy, Vidayanagar, Hubbli, Karnataka, India

⁶ Department of Pharmacology, KLE College of Pharmacy, Belagavi, Karnataka

⁷ Department of Pharmacy Practice, KLE college of pharmacy, Basavan Kudachi, Belagavi, Karnataka- 591124

^8* Department of Pharmacy Practice, SJM College of Pharmacy, Chitradurga, Karnataka, India

⁹ Department of Pharmacology, SJM College of Pharmacy, Chitradurga, Karnataka, India

 

 

INTRODUCTION

Poor aqueous solubility remains one of the major challenges in the development of oral drug delivery systems¹. A significant proportion of newly discovered drugs exhibit low water solubility, which leads to poor dissolution, reduced bioavailability, and variable therapeutic response. Enhancing the solubility and dissolution rate of such drugs is therefore a critical objective in pharmaceutics to ensure optimal therapeutic efficacy².

Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) widely used for its analgesic and antipyretic properties. However, it belongs to the Biopharmaceutics Classification System (BCS) Class II category, characterized by low solubility and high permeability. Due to its poor aqueous solubility, Nimesulide exhibits a slow dissolution rate, which can limit its onset of action and overall bioavailability when administered through conventional dosage forms³.

To overcome these limitations, various formulation strategies have been explored, including solid dispersions, micronization, and inclusion complexes⁴. Among these, nanotechnology-based drug delivery systems have gained significant attention due to their ability to enhance solubility and dissolution by reducing particle size and increasing surface area⁵. Nanosponges are a novel class of nanoparticulate carriers composed of porous, sponge-like structures that can encapsulate poorly soluble drugs and improve their physicochemical properties⁶.

Nanosponges offer several advantages, such as high drug loading capacity, controlled release, enhanced stability, and improved solubility of hydrophobic drugs⁷. Their porous structure allows efficient drug entrapment and gradual release, making them suitable for oral drug delivery applications⁸. Additionally, nanosponges can protect the drug from degradation and improve its therapeutic performance⁹.

Fast Dissolving Tablets (FDTs) have emerged as an innovative oral dosage form designed to disintegrate rapidly in the mouth without the need for water¹⁰. These formulations are particularly beneficial for pediatric, geriatric, and dysphagic patients, offering improved patient compliance and convenience¹¹. FDTs also provide rapid onset of action due to faster disintegration and dissolution in the oral cavity¹².

The combination of nanosponges with fast dissolving tablet technology represents a promising approach to address the solubility and dissolution limitations of poorly soluble drugs like Nimesulide. Incorporating drug-loaded nanosponges into FDTs can significantly enhance drug release, improve bioavailability, and ensure rapid therapeutic action.

Therefore, the present study aims to design, develop, and evaluate Nimesulide-loaded nanosponges and further compress them into fast dissolving tablets to enhance solubility, dissolution rate, and overall drug performance. This approach is expected to provide an effective and patient-friendly dosage form with improved pharmacokinetic and therapeutic outcomes.

MATERIALS

The materials required for this study are Nimesulide, ethyl cellulose and, polyvinyl alcohol (stabilizer), dichloromethane, mannitol, microcrystalline cellulose, crospovidone, magnesium stearate, and talc, along with distilled water and phosphate buffer solutions for evaluation studies.

Preparation of Nanosponges

Nanosponges were prepared by the emulsion solvent diffusion method. Nimesulide and ethyl cellulose were dissolved in a mixture of dichloromethane and ethanol to form the organic phase. This was added dropwise into an aqueous solution of polyvinyl alcohol (PVA) under continuous high-speed stirring. Stirring was continued until complete solvent evaporation and formation of nanosponges occurred¹³. The formed nanosponges were then collected by filtration, washed with distilled water, and dried to obtain a free-flowing powder.

 

 

Table 1: Formulation Table of Nimesulide Nanosponges

Formulation Code	Nimesulide (mg)	Ethyl Cellulose (mg)	PVA (% w/v)	Dichloromethane (mL)
F1	100	100	0.5	30
F2	100	150	0.5	30
F3	100	200	0.5	30
F4	100	250	0.5	30
F5	100	300	0.5	30

 

 

Formulation of Nimesulide Loaded Nanosponge Tablets

Nimesulide-loaded nanosponges were formulated into fast dissolving tablets by direct compression. The optimized nanosponge formulation was used as the active component. Mannitol, microcrystalline cellulose (MCC), and crospovidone were used as diluent, binder, and superdisintegrant respectively. Magnesium stearate and talc were added as lubricant and glidant. The powders were mixed uniformly and compressed into tablets using a tablet compression machine¹⁴.

 

 

 

 

Table 2: Formulation Table of Nimesulide Loaded Nanosponge Fast Dissolving Tablets

Formulation Code	Nanosponge (mg)	Mannitol (mg)	MCC (mg)	Crospovidone (mg)	Magnesium Stearate (mg)	Talc (mg)
T1	100	80	30	10	2	2
T2	100	70	40	10	2	2
T3	100	60	50	10	2	2
T4	100	50	60	10	2	2
T5	100	40	70	10	2	2

 

 

Calibration Curve of Nimesulide

The calibration curve of Nimesulide was prepared using the UV–Visible spectrophotometric method at λmax 308 nm in phosphate buffer pH 6.8. A standard stock solution was prepared and further diluted to obtain different concentrations. The absorbance of each solution was measured at 308 nm, and a calibration curve was plotted between concentration and absorbance. The curve showed linearity over the selected range and was used for quantitative analysis of Nimesulide in formulation studies¹⁵.

Particle Size Analysis and Zeta Potential

The particle size and zeta potential of Nimesulide-loaded nanosponges were determined using a dynamic light scattering (DLS) technique. The nanosponge dispersion was suitably diluted with distilled water and analyzed at room temperature. The average particle size and polydispersity index (PDI) were recorded to assess the size distribution and uniformity of the formulation. The zeta potential was measured to evaluate the surface charge and stability of the nanosponges. A higher absolute zeta potential value indicated good stability due to electrostatic repulsion between particles, preventing aggregation¹⁶.

SEM analysis

The morphology of the nanosponges was examined using Scanning Electron Microscopy (SEM). A small amount of dried sample was mounted on a carbon tape attached to an aluminum stub and sputter-coated with a thin layer of gold to ensure conductivity. The coated sample was then observed under SEM at suitable magnifications to evaluate particle shape, surface characteristics, and porosity. The micrographs obtained were used to assess the morphological features and uniformity of the formulation¹⁷.

Pre-Compression Parameters¹⁸

Bulk density (mg/mL):

Bulk density was determined by measuring the mass of powder and dividing it by the untapped volume occupied in a measuring cylinder.

Tapped density (mg/mL):

Tapped density was determined by mechanically tapping the cylinder containing powder until no further volume change was observed, and dividing mass by tapped volume.

Compressibility Index (%):

Carr’s compressibility index was calculated from bulk and tapped density values to assess flow properties of the powder blend.

Hausner’s ratio:

Hausner’s ratio was calculated as the ratio of tapped density to bulk density to evaluate powder flow behavior.

Angle of repose:

Angle of repose was determined by allowing the powder to flow through a funnel and measuring the angle formed with the horizontal plane, indicating flow properties of the blend.

Post-Compression Parameters¹⁹

Weight variation (mg/tablet):

Weight variation was determined by individually weighing 20 tablets and calculating the average weight and deviation.

Friability (%):

Friability was evaluated using a friabilator and expressed as percentage weight loss after 100 rotations.

Hardness (kg/cm²):

Tablet hardness was measured using a Monsanto hardness tester and expressed in kg/cm².

Drug content (mg):

Drug content was determined by UV spectrophotometric method at λmax 308 nm.

Wetting time (s):

Wetting time was recorded as the time required for complete wetting of the tablet surface in buffer medium.

Dissolution Test²⁰

The in vitro dissolution study of Nimesulide-loaded nanosponges fast dissolving tablets was carried out using USP Type II (paddle method) dissolution apparatus. The study was performed in 900 mL of phosphate buffer pH 6.8 maintained at 37 ± 0.5°C with a paddle speed of 50 rpm. At predetermined time intervals, samples were withdrawn and replaced with fresh dissolution medium to maintain sink conditions. The collected samples were analyzed spectrophotometrically at λmax 308 nm, and the cumulative percentage drug release was calculated.

RESULTS AND DISCUSSION

Calibration Curve of Nimesulide

The calibration curve of Nimesulide was found to be linear at λmax 308 nm in phosphate buffer pH 6.8. The drug showed good linearity over the selected concentration range, indicating compliance with Beer-Lambert’s law.

Table 3: Calibration Data of Nimesulide   

Concentration (µg/mL)	Absorbance
2	0.122
4	0.241
6	0.362
8	0.482
10	0.601

 

                    

Figure 1: Graphical Presentation of Nimesulide

Physical Appearance of Tablets

The prepared tablets were white in color, round to slightly flat in shape, and uniform in size. They exhibited a smooth surface with no visible cracks, chipping, or deformation, indicating good compressional integrity. Overall, the tablets showed consistent appearance and acceptable physical uniformity.

  

Figure 2: Physical Appearance of Nimesulide

Particle Size Analysis

The prepared nanosponges exhibited an average particle size of 180 ± 5.2 nm and PDI of 0.21, indicating a uniform nanoscale distribution. Most of the particles were found within the range of approximately 174.8 to 185.2 nm, reflecting a narrow size distribution and good homogeneity of the formulation. Such a particle size is considered optimal for nanosponge-based drug delivery systems, as it enhances surface area, leading to improved drug solubility, dissolution rate, and ultimately better bioavailability.

 

 

Figure 3: Particle Size Analysis of Nimesulide

 

 

 

 

Zeta Potential Analysis

The zeta potential of the formulation was found to be -28.6 ± 1.4 mV, indicating that the particles possess a negative surface charge. This value is close to the ideal range (±30 mV) required for stable colloidal systems, suggesting good electrostatic repulsion between particles. As a result, the formulation is expected to exhibit minimal aggregation and good physical stability over time. The low standard deviation further confirms the consistency of the surface charge among particles, indicating a stable nanosponge formulation.

Figure 4: Zeta Potential Analysis of Nimesulide

 

SEM analysis

SEM analysis showed that Nimesulide-loaded nanosponges possessed a porous, sponge-like structure with irregular to spherical morphology. The surface was rough with well-defined pores, confirming successful nanosponge formation and drug entrapment within the polymer matrix.

 

Figure 5: SEM analysis of Nimesulide

Pre-Compression Parameters

The pre-compression evaluation of the powder blend showed satisfactory flow characteristics suitable for tablet compression. The bulk density (0.42 g/mL) and tapped density (0.51 g/mL) indicate moderate packing ability of the powder particles. The compressibility index was found to be 17.65%, suggesting good to fair flow properties. Hausner’s ratio (1.21) further confirms acceptable flow behavior with minimal interparticle friction. The angle of repose (28.4°) indicates good flowability of the powder blend, which is essential for uniform die filling and consistent tablet weight during compression.

Table 4: Flow Properties of Powder Blend

 

 

 

 

Post-Compression Parameters

The prepared tablets exhibited acceptable physical and mechanical properties. The average weight variation was 152 ± 2.5 mg, indicating uniformity in tablet mass. Friability was 0.48%, which is within the acceptable limit (<1%), confirming adequate mechanical strength. The hardness of the tablets was 3.8 ± 0.4 kg/cm², suggesting sufficient integrity while maintaining fast disintegration characteristics. Drug content was 98.6 ± 1.2%, indicating uniform distribution of the drug within the formulation. The wetting time (18 ± 2 s) and dispersion time (22 ± 3 s) were low, confirming rapid tablet wetting and disintegration, which is desirable for fast dissolving tablets.

Table 5: Evaluation of Tablets

 

In-vitro Drug Release (Dissolution Study)

The in-vitro dissolution profile demonstrated a rapid and sustained release pattern of the drug from the formulation. At 5 minutes, 28% drug release was observed, which increased to 45% at 10 minutes and 63% at 15 minutes. A significant release of 78% and 92% was observed at 20 and 30 minutes, respectively. Complete drug release (98%) was achieved within 45 minutes, indicating excellent dissolution behavior. The results suggest that the formulation effectively enhances drug release, which may improve bioavailability and onset of therapeutic action.

Table 6: In-vitro Drug Release

Time (min)	% Drug Release
5	28
10	45
15	63
20	78
30	92
45	98

 

Figure 6: In-vitro Drug Release of Nimesulide

 

CONCLUSION

The study successfully developed Nimesulide-loaded nanosponges and incorporated them into fast dissolving tablets to enhance solubility and dissolution. The nanosponges showed nanosized particles (180 ± 5.2 nm), good stability (-28.6 ± 1.4 mV), and porous morphology, confirming efficient drug entrapment. The formulated tablets exhibited acceptable flow, uniform weight, low friability, adequate hardness, high drug content, and rapid disintegration.

In vitro studies showed rapid and complete drug release (98% within 45 min), indicating a significant improvement in dissolution rate. Overall, the nanosponge-based fast dissolving tablet system effectively enhanced the solubility, dissolution, and potential bioavailability of Nimesulide, making it a promising approach for improving therapeutic performance of poorly soluble drugs.

REFERENCES

1. Singla AK, Chawla M, Singh A. Review nimesulide: some pharmaceutical and pharmacological aspects-an update. Journal of pharmacy and pharmacology. 2000 May;52(5):467-86. https://doi.org/10.1211/0022357001774255 PMid:10864134

2. Bernareggi A. Clinical pharmacokinetics of nimesulide. Clinical pharmacokinetics. 1998 Oct;35(4):247-74. https://doi.org/10.2165/00003088-199835040-00001 PMid:9812177

3. Davis R, Brogden RN. Nimesulide: an update of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1994 Sep;48(3):431-54. https://doi.org/10.2165/00003495-199448030-00008 PMid:7527762

4. Rainsford KD, Consensus Report Group on Nimesulide. Nimesulide-a multifactorial approach to inflammation and pain: scientific and clinical consensus. Current medical research and opinion. 2006 Jun 1;22(6):1161-70. https://doi.org/10.1185/030079906X104849 PMid:16846549

5. Kress HG, Baltov A, Basiński A, Berghea F, Castellsague J, Codreanu C, Copaciu E, Giamberardino MA, Hakl M, Hrazdira L, Kokavec M. Acute pain: a multifaceted challenge-the role of nimesulide. Current medical research and opinion. 2016 Jan 2;32(1):23-36. https://doi.org/10.1185/03007995.2015.1100986 PMid:26414386

6. Tejashri G, Amrita B, Darshana J. Cyclodextrin based nanosponges for pharmaceutical use: A review. Acta pharmaceutica. 2013 Sep 30;63(3):335-58. https://doi.org/10.2478/acph-2013-0021 PMid:24152895

7. Trotta F, Dianzani C, Caldera F, Mognetti B, Cavalli R. The application of nanosponges to cancer drug delivery. Expert opinion on drug delivery. 2014 Jun 1;11(6):931-41. https://doi.org/10.1517/17425247.2014.911729 PMid:24811423

8. Shringirishi M, Prajapati SK, Mahor A, Alok S, Yadav P, Verma A. Nanosponges: a potential nanocarrier for novel drug delivery-a review. Asian pacific journal of tropical disease. 2014 Sep 1;4:S519-26. https://doi.org/10.1016/S2222-1808(14)60667-8

9. Gowda BJ, Ahmed MG, Almoyad MA, Wahab S, Almalki WH, Kesharwani P. Nanosponges as an emerging platform for cancer treatment and diagnosis. Advanced Functional Materials. 2024 Feb;34(7):2307074. https://doi.org/10.1002/adfm.202307074

10.    Siddiqui MN, Garg G, Sharma PK. Fast dissolving tablets: preparation, characterization and evaluation: an overview. International Journal of Pharmaceutical Sciences Review and Research. 2010 Sep;4(2):87-96.

11.    Chang RK, Guo X, Burnside BA, Couch RA. Fast-dissolving tablets. Pharmaceutical technology. 2000;24(6):52-.

12.    Gupta AK, Mittal A, Jha KK. Fast dissolving tablet-A review. The pharma innovation. 2012 Mar 1;1(1):1-8.

13. Ahmed MM, Fatima F, Anwer MK, Ansari MJ, Das SS, Alshahrani SM. Development and characterization of ethyl cellulose nanosponges for sustained release of brigatinib for the treatment of non-small cell lung cancer. Journal of Polymer Engineering. 2020 Nov 26;40(10):823-32. https://doi.org/10.1515/polyeng-2019-0365

14. Moin A, Roohi NF, Rizvi SM, Ashraf SA, Siddiqui AJ, Patel M, Ahmed SM, Gowda DV, Adnan M. Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy. RSC advances. 2020;10(57):34869-84. https://doi.org/10.1039/D0RA06611G PMid:35514416 PMCid:PMC9056836

15. Altinöz S, Dursun ÖÖ. Determination of nimesulide in pharmaceutical dosage forms by second order derivative UV spectrophotometry. Journal of pharmaceutical and biomedical analysis. 2000 Feb 1;22(1):175-82. https://doi.org/10.1016/S0731-7085(99)00264-2 PMid:10727137

16. Uppar AL, Patil CC, Namannavar S, Deshmane PA. Formulation and evaluation of Caffeine-Loaded Cubosomes hydrogel for topical delivery. Journal of Drug Delivery and Therapeutics. 2026 Apr 15;16(4):39-47. https://doi.org/10.22270/jddt.v16i4.7666

17. Ural N. The significance of scanning electron microscopy (SEM) analysis on the microstructure of improved clay: An overview. Open Geosciences. 2021 Feb 19;13(1):197-218. https://doi.org/10.1515/geo-2020-0145

18. Vreeman G, Sun CC. A strategy to optimize precompression pressure for tablet manufacturing based on in-die elastic recovery. International journal of pharmaceutics. 2024 Apr 10;654:123981. https://doi.org/10.1016/j.ijpharm.2024.123981 PMid:38460772

19. Nayak S, Rakshita AS, Kamath S. Study of post compression parameters of various marketed paracetamol tablets in India. PharmaTutor. 2019 Feb 1;7(2):35-42. https://doi.org/10.29161/PT.v7.i2.2019.35

20. Kim KH, Park JB, Kang JH, Lee KH, Kang CY. Formulation and Evaluation of Sustained Release Preparation of Ibuprofen Fast-Disintegrating Tablet (FDT). Journal of Pharmaceutical Investigation. 2011;41(1):51-7. https://doi.org/10.4333/KPS.2011.41.1.051a