Formulation and Evaluation of Dendrimer-Loaded Naproxen Sodium Tablets for Enhanced Controlled Release

Yash S. Bachhav, Pallavi S. Bachhav, Dipika H. Gosavi, Nikhil M. Kadam, Ritesh R. Karmarkar, Pratiksha S. Shewale, Radhika V. Kharote, Bhagyashri S. Suryawanshi,

doi:10.5281/zenodo.14003588

Research Paper | Open Access
Volume 02 | Issue 10 | Article Id IJPS/240210198

Formulation and Evaluation of Dendrimer-Loaded Naproxen Sodium Tablets for Enhanced Controlled Release
Yash S. Bachhav* Pallavi S. Bachhav Dipika H. Gosavi Nikhil M. Kadam Ritesh R. Karmarkar Pratiksha S. Shewale Radhika V. Kharote Bhagyashri S. Suryawanshi
^1*,2,3,4,5,6Department of Pharmaceutics, MGV’s S. P. H. College of Pharmacy, Malegaon- 423105 Dist. Nashik, Maharashtra, India.
¹Department of Pharmaceutics, Divine College of Pharmacy, Satana- 423301 Dist. Nashik, Maharashtra, India.
⁷Department of Pharmacognosy, MGV’s S. P. H. College of Pharmacy, Malegaon- 423105 Dist. Nashik, Maharashtra, India.

Abstract

Naproxen sodium, a nonsteroidal anti-inflammatory drug (NSAID), is widely used for treating pain and inflammation but is associated with gastrointestinal (GI) side effects such as ulcers and bleeding, especially with prolonged use. This study aimed to develop dendrimer-loaded naproxen sodium tablets to enhance solubility and provide controlled release, thereby reducing GI irritation. Poly(amidoamine) (PAMAM) dendrimers were used as carriers to encapsulate naproxen sodium via the solvent evaporation technique. The dendrimer-drug complex was formulated into tablets using both direct compression and wet granulation methods. The formulations were evaluated for pre- and post-compression properties, including bulk density, hardness, friability, and in vitro dissolution profiles. Results indicated that the dendrimer-loaded formulations achieved sustained release over 12 hours, with the F2 and F3 formulations showing significant improvements in drug release profiles compared to conventional naproxen sodium tablets. These findings suggest that dendrimer-based delivery systems can reduce peak plasma concentrations, improve therapeutic efficacy, and potentially minimize GI side effects. Further clinical studies are needed to validate these in vitro results and confirm the safety and effectiveness of this novel drug delivery system.

Keywords

Naproxen sodium, PAMAM dendrimers, controlled release, NSAIDs, gastrointestinal side effects, drug delivery system.

Introduction

Naproxen sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) known for its efficacy in treating pain, inflammation, and various arthritic conditions [1]. Despite its therapeutic advantages, its use is often limited by gastrointestinal (GI) side effects, including ulcers and bleeding, particularly with prolonged administration [2]. Conventional formulations lead to rapid absorption and high peak plasma concentrations, increasing the likelihood of adverse effects [3]. To overcome these limitations, controlled-release formulations are essential [4]. Dendrimers, which are highly branched macromolecules, have emerged as promising carriers for drug delivery [5]. Poly(amidoamine) (PAMAM) dendrimers, in particular, offer significant potential due to their biocompatibility, ability to encapsulate hydrophobic drugs, and controlled release properties [6].

This study focuses on developing dendrimer-loaded naproxen sodium tablets that aim to enhance the drug’s solubility and achieve sustained release, thereby reducing peak plasma concentration and minimizing GI irritation [7]. The research involves synthesizing dendrimer-drug complexes, formulating them into tablets, and evaluating their physical and mechanical properties, as well as their in vitro release profiles [8]. The ultimate goal is to establish a new delivery system that improves the therapeutic efficacy of naproxen sodium while enhancing patient compliance [9].

MATERIALS AND METHOD

Materials

Material	Source	Role in Formulation
Naproxen Sodium	Sigma-Aldrich	Active pharmaceutical ingredient (NSAID for pain and inflammation)
PAMAM Dendrimers (G4)	Dendritech Inc.	Drug carrier for encapsulating naproxen sodium, enhancing solubility and controlling release
Microcrystalline Cellulose	FMC Biopolymer	Diluent and binder, providing bulk to the formulation
Polyvinylpyrrolidone (PVP)	BASF	Binder, enhancing tablet strength
Magnesium Stearate	Sigma-Aldrich	Lubricant, preventing tablet sticking during compression
Talc	Sigma-Aldrich	Glidant, improving powder flowability
Lactose	BASF	Diluent, increasing tablet bulk and aiding compressibility
Distilled Water	Lab Use	Granulating agent, used in wet granulation process

Method

Synthesis of Dendrimer-Loaded Naproxen Sodium Complex
Naproxen sodium was encapsulated within PAMAM dendrimers using the solvent evaporation technique [10]. The complex was characterized for drug loading efficiency and particle size [11].
Tablet Formulation
Direct Compression: The dendrimer-drug complex was mixed with excipients and compressed into tablets [12].
Wet Granulation: The complex was granulated with distilled water, dried, and compressed into tablets [13]. Pre-compression and post-compression parameters were evaluated [14].

FORMULATION TABLE

Formulation Components	F1	F2	F3
Dendrimer-Naproxen Sodium Complex	50 mg	100 mg	150 mg
Microcrystalline Cellulose	100 mg	100 mg	100 mg
Lactose	50 mg	50 mg	50 mg
PVP	10 mg	10 mg	10 mg
Magnesium Stearate	5 mg	5 mg	5 mg
Talc	2 mg	2 mg	2 mg
Total Weight	217 mg	267 mg	317 mg

EVALUATION

Pre-Compression Parameters:
1. Bulk Density: Determined using a graduated cylinder [15].
2. Tapped Density: Measured after tapping the cylinder [16].
3. Compressibility Index: Calculated to assess flowability [17].
4. Angle of Repose: Evaluated to determine powder flow properties [18].
Post-Compression Parameters:
1. Hardness: Measured using a hardness tester [19].
2. Friability: Evaluated using a friabilator [20].
3. Disintegration Time: Assessed in a disintegration tester [21].
4. Weight Variation: Calculated by weighing 20 tablets individually [22].
5. In Vitro Dissolution Studies: Conducted in a USP Type II apparatus using simulated gastric and intestinal fluids [23].

RESULTS AND DISCUSSION

Evaluation Parameter	F1	F2	F3
Pre-Compression Parameters
Bulk Density (g/mL)	0.43	0.45	0.47
Tapped Density (g/mL)	0.50	0.52	0.54
Compressibility Index (%)	14.0	13.5	13.0
Angle of Repose (°)	28.5	27.8	27.2
Post-Compression Parameters
Hardness (kg/cm?2;)	5.5	5.8	6.2
Friability (%)	0.80	0.75	0.70
Disintegration Time (min)	7	9	12
Weight Variation (mg)	215-219	265-270	315-320

In Vitro Drug Release Data

Time (Hours)	F1 Release (%)	F2 Release (%)	F3 Release (%)
1	10	8	6
2	20	15	12
4	40	30	25
6	60	50	45
8	75	70	65
10	85	80	75
12	95	90	85

The dendrimer-loaded naproxen sodium tablets demonstrated good encapsulation efficiency, achieving around 90%. Pre-compression evaluations indicated optimal flow properties. The post-compression tests showed sufficient hardness (5.5–6.2 kg/cm?2;) and low friability (<1>

CONCLUSION

The development of dendrimer-loaded naproxen sodium tablets shows promise for enhancing controlled drug release while minimizing gastrointestinal side effects. The favorable in vitro results suggest that dendrimers can be effectively used as a drug delivery system for NSAIDs, improving therapeutic efficacy and patient compliance. Future work will focus on clinical trials to further validate these findings.

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