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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

Gastroretentive Floating Microspheres of Metaxalone: A Novel Drug Delivery Approach for Muscle Relaxation

Brijesh Shukla ¹, Akash Sharma ²*

¹ Department of Pharmacy, Seiko College of Pharmacy, Harauni, Lucknow-226008, Uttar Pradesh, India

² Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow-226025, Uttar Pradesh, India

 

 

INTRODUCTION

Floating Drug Delivery Systems (FDDS) were first described by Davis in 1968 as an innovative strategy to prolong the residence time of dosage forms in the upper gastrointestinal tract (GIT). ¹ These systems are designed to remain buoyant on gastric fluids due to their low density, allowing the drug to be released gradually over an extended period. ² By maintaining prolonged gastric residence time (GRT), FDDS ensure sustained drug release, minimize plasma concentration fluctuations, and enhance therapeutic efficacy. ³ This approach is particularly beneficial for drugs with a narrow absorption window in the upper GIT, drugs unstable or poorly soluble in alkaline environments, and drugs with better solubility in acidic pH. ⁴

FDDS are broadly classified into effervescent and non-effervescent systems. Effervescent systems contain gas-generating agents, such as sodium bicarbonate or citric acid, which release carbon dioxide upon contact with gastric fluid. The generated gas reduces the density of the dosage form, thereby promoting buoyancy. ⁵ Non-effervescent systems, including hydrodynamically balanced systems (HBS), employ gel-forming polymers such as hydroxypropyl methylcellulose (HPMC), polyacrylates, or sodium alginate. These polymers swell upon hydration, entrapping air within the matrix to maintain flotation. ⁶ Other strategies include raft-forming systems, where viscous gels entrap gas to create a floating barrier, and low-density or microballoon systems composed of hollow microspheres with intrinsic buoyancy. ⁷

Microspheres, a key application of FDDS, are discrete spherical particles with a size range of 1-1000 μm. They may be biodegradable, synthetic, magnetic, radioactive, or bioadhesive. ⁸ Floating microspheres, generally prepared using polymers such as ethylcellulose, Eudragit, or chitosan, are preferred due to their large surface area, uniform drug distribution, and ability to sustain drug release while remaining buoyant. ⁹ The floating ability is attributed to air-filled cavities or hollow cores within the polymer matrix, produced via solvent evaporation, diffusion, or gas-forming methods. ¹⁰ Magnetic microspheres can be directed to targeted sites using external magnetic fields, whereas bioadhesive microspheres improve gastric retention by adhering to the mucosal lining. ¹¹

The major advantages of FDDS include improved bioavailability of drugs absorbed in the upper GIT, reduced dosing frequency, better patient compliance, and applicability for both local and systemic delivery. However, patients with gastrointestinal motility disorders, rapid gastric emptying, or variable gastric pH conditions may experience limited effectiveness. ¹³ FDDS have been widely explored for delivering antibiotics (e.g., amoxicillin for Helicobacter pylori eradication), antacids, cardiovascular drugs, and anticancer agents. ¹⁴

Preparation techniques for floating microspheres include single and double emulsion solvent evaporation for hydrophobic and hydrophilic drugs, respectively. ¹⁵ Other approaches involve coacervation phase separation for heat-sensitive drugs, spray drying for uniform particle size, solvent diffusion evaporation for hollow structures, and ionotropic gelation for polyelectrolyte-based systems. ¹⁶ The choice of method depends on drug solubility, polymer compatibility, and desired release profile. ¹⁷

FDDS, particularly floating microspheres, offer a promising approach to enhance therapeutic efficacy for drugs exhibiting site-specific absorption in the stomach and upper intestine. ¹⁷ Their ability to combine controlled drug release with prolonged gastric retention underscores their relevance in modern pharmaceutical formulation. Recent research continues to optimize buoyancy, drug loading, and release kinetics to improve clinical utility. ¹⁸ Similar strategies have enhanced solubility and bioavailability for poorly soluble drugs like curcumin through non-aqueous self-emulsifying nanoemulsions¹⁹, supporting the development of gastroretentive microspheres for metaxalone to improve therapeutic performance. ²⁰

Aim and Objective

Oral administration continues to be the most convenient and widely preferred route for delivering drugs to conscious patients, despite the advancement of numerous modern dosage forms. Among the innovative approaches, floating drug delivery systems offer distinct advantages by prolonging gastric residence time and ensuring sustained drug release in the stomach. The present investigation focuses on improving the bioavailability of metaxalone, a centrally acting skeletal muscle relaxant, through the formulation and evaluation of floating microspheres designed for extended gastric retention. Metaxalone has a short elimination half-life of approximately 5–6 hours and a low oral bioavailability of about 25%, which necessitates multiple daily doses to sustain therapeutic plasma concentrations. Its rapid absorption from the stomach, coupled with quick systemic clearance, makes it a suitable candidate for a gastro-retentive floating system. In this formulation, ethyl cellulose serves as a low-density polymer to confer buoyancy, hydroxypropyl methylcellulose (HPMC) is incorporated to achieve controlled release, and sodium alginate is employed as a natural biopolymeric matrix for efficient drug entrapment. Sodium bicarbonate functions as the effervescent agent generating CO₂ to facilitate floating, while calcium chloride is utilized as a cross-linking agent. Clinically, metaxalone is indicated for relieving pain and discomfort in rheumatologic, orthopedic, and traumatic musculoskeletal conditions, usually in combination with analgesics and rest. Although its exact mechanism remains uncertain, it is postulated to act via central nervous system (CNS) depression rather than direct skeletal muscle effects. The drug is generally well tolerated, with mild CNS-related adverse reactions such as dizziness, drowsiness, headache, irritability, nausea, and vomiting.

DRUGS, POLYMERS, AND METHODS

Drugs and Chemicals

Metaxalone, a skeletal muscle relaxant, was obtained from Solitaire Pharmacia Pvt. Ltd., Chandigarh, India. Analytical-grade excipients were procured from various suppliers: sodium alginate from SD Fine Chem Ltd., sodium bicarbonate from SRIT Datia, ethanol from Merck, calcium chloride from Qualigens, hydroxyethyl cellulose (HEC) from Loba Chemie, glacial acetic acid from Fisher Scientific, and sodium carboxymethyl cellulose (NaCMC) from Himedia.

Instruments and Apparatus:

The following equipment was employed:

• 26G syringe needle, 10 cm long, from Hindustan Syringes and Medical Devices Ltd.
• Magnetic stirrer (Simco Microscope)
• UV–Visible Double Beam Spectrophotometer (2201 Systronics)
• Electronic balance (Contech)
• Whatman filter paper (Pall–Gelman Science)
• USP Standard dissolution apparatus (Veego)
• Melting point apparatus (Rolex)

Methods

Determination of Melting Point

The melting point of metaxalone was determined using the capillary method. The powdered drug was filled into a capillary tube, sealed at one end, and placed in the melting point apparatus. The temperature at which the first signs of melting appeared was recorded.

UV Spectrophotometric Analysis

A stock solution (1 mg/mL) of Metaxalone was prepared using phosphate buffer (pH 7.4) and 0.1 N HCl (pH 1.2). Serial dilutions (5–30 µg/mL) were made from the stock. The absorbance was measured between 200 and 400 nm to determine λmax for each medium.

The spectrophotometric method used in this study was developed and validated in accordance with standard analytical quality-by-design (AQbD) principles to ensure precision and reproducibility, as previously demonstrated by Srujani et al. in related RP-HPLC and UV analytical method developments for Duvelisib, Pemigatinib, and Tenofovir determination (Srujani et al., 2020; Srujani et al., 2021b).

Fourier Transform Infrared (FTIR) Spectroscopy

FTIR spectra were recorded using the KBr pellet method in the range of 400–600 cm⁻¹. The drug was mixed with potassium bromide and compressed into pellets using a hydraulic press. The spectra of the sample were compared with those of pure metaxalone for confirmation.

Solubility Studies

One milligram of metaxalone was dissolved in 1 mL of various solvents and buffer systems to assess solubility characteristics.

Calibration Curve Preparation

A standard solution of metaxalone (10 mg in 100 mL) was prepared separately in phosphate buffer (pH 7.4) and 0.1 N HCl. Serial dilutions were made, and absorbance was measured at λmax: 259 nm (water), 375 nm (phosphate buffer pH 7.4), and 265 nm (0.1 N HCl).

Polymer Identification

The chemical compatibility of sodium alginate with metaxalone was checked using FTIR spectroscopy in the 400-600 cm⁻¹ range.

Drug Excipient Compatibility Studies

The drug and each excipient were blended in a 1:1 ratio and stored in glass vials under accelerated stability conditions (25°C/75% RH and 60°C/75% RH) for two months. Both open and sealed vials were used. Physical changes were noted at weekly intervals. FTIR analysis was conducted to detect any chemical interactions.

 

 

Formulation Table

Table 1: Metaxalone alginate microspheres were prepared via ionotropic gelation using varying polymer ratios.

Formulation Code	Metaxalone (mg)	NaCMC (mg)	HEC (mg)	NaHCO₃ (mg)	Na-Alg (mg)	CaCl₂ (%)
F1	500	0.75	0.5	250	1.5	4
F2	500	0.75	100	250	1.5	4
F3	500	100	0.75	50	1.5	4
F4	500	150	0.5	125	1.5	4
F5	500	100	1.5	50	1.5	4
F6	500	225	0.75	100	1.5	4
F7	500	0.75	0.5	250	1.5	4
F8	500	0.75	0.5	250	1.5	4
F9	500	0.75	100	250	1.5	4
F10	500	100	0.75	50	1.5	4

 

 

 

Evaluation of Prepared Microspheres

Micromeritic Properties

Bulk density, tapped density, angle of repose, Hausner’s ratio, and Carr’s compressibility index were measured to determine flow properties.

Particle Size Distribution

Microspheres (1 g) were passed through a series of sieves of different mesh sizes. The fraction retained on each sieve was weighed, and the mean particle size was calculated.

Density Measurements

Loose bulk density (LBD) and tapped bulk density (TBD) were calculated using a graduated cylinder. To determine the tapped bulk density (TBD), the graduated cylinder was tapped 100 times.

Formulas:

LBD = Mass of microspheres / Volume before tapping

TBD = Mass of microspheres / Volume after tapping

Angle of Repose

The funnel method was used to determine the angle of repose (θ):

θ = tan⁻¹(h / r)

Carr’s Index and Hausner’s Ratio

Carr’s Index = [(TBD – LBD) / TBD] × 100

Hausner’s Ratio = TBD / LBD

Percentage Yield

% Yield = (Practical weight / Theoretical weight) × 100

Drug Entrapment Efficiency

The percentage of entrapment is calculated as (Actual drug content / Theoretical drug content) × 100.

Buoyancy Test

Microspheres (500 mg) were dispersed in simulated gastric fluid (pH 1.2) containing 0.02% Tween 20 and stirred at 100 rpm for 4 h. Floating and settled fractions were separated, dried, and weighed.

% Buoyancy = [Wf / (Wf + Ws)] × 100

Differential Scanning Calorimetry (DSC)

Samples (2 mg) were heated from 25°C to 200°C under nitrogen flow (30 mL/min) to assess thermal behavior.

In Vitro Drug Release

Dissolution testing was conducted using USP basket apparatus at 50 rpm in 900 mL of medium maintained at 37 ± 1°C. Samples (5 mL) were withdrawn at predetermined intervals, filtered (0.25 µm), and analyzed spectrophotometrically.

Stability Studies

Optimized microsphere formulations were stored in sealed glass vials at 25 ± 5°C / 75% RH and 40 ± 5°C / 75% RH for three months. Poststorage, buoyancy and drug release profiles were re-evaluated to assess stability.

RESULTS AND DISCUSSION

Identification Test for Drugs

Melting Point Determination

Metaxalone's melting point was 122°C, indicating purity, according to the literature and pharmacological profile. The Digital Melting Point Apparatus measured the drug's melting point.

Solubility

Table 2: Solubility of Metaxalone

S.No.	Solvents	Result
1	Water	Freely Soluble
2	Alcohol	Partially Soluble: after half an hour, residue remained in the test tube.
3	Ether	Not Soluble
4	Acetone	Not Soluble

 

UV-Spectrophotometry

Research using ultraviolet spectroscopy was conducted in three distinct mediums ranging from 220 nm to 440 nm: water, where the highest value observed was 259.2 nm in water, while the highest value in the other medium was 375 nm.

 

 

 

Figure 1: λmax Scan for Metaxalone at 259.2 nm in Water

Figure 2: λmax Scan for Metaxalone at 265 nm in 0.1 N HCl pH 1.2

Figure 3: λmax Scan for Metaxalone at 375 nm in Phosphate Buffer pH 7.4

FTIR Spectra of Pure Drug

Below the figure is a comparison of the FTIR spectra obtained from a pure metaxalone sample and a standard functional group.

Figure 4 FTIR Spectra of Metaxalone

Table 3: IR Frequencies for Metaxalone

Functional Group	Observed frequencies (cm⁻¹)
NH Stretching	3516.35
OH Stretching	3045.7
C=O Stretching	1678.13
C=C Stretching	1599.04

 

The process involves the preparation of a calibration curve for the purpose of estimating the drug concentration.

The drug is diluted in different solvents at a concentration of 10 g/ml, and when using the spectrophotometer for the λmax run, the maximum wavelength is found to be 259 nm with an absorbance of 0.459.

Calibration curve in water

Table 4: Calibration Curve Readings

S.No.	Concentration (μg/ml)	l max (nm)	Absorbance
1	2	259	0.072
2	4	259	0.165
3	6	259	0.252
4	8	259	0.338
5	10	259	0.459

Figure 5: Calibration Curve of Metaxalone in Water

Calibration curve in buffer 7.4

Table 5: Calibration Curve Readings

S.No.	Concentration (μg/ml)	l max (nm)	Absorbance
1	2	375	0.091
2	4	375	0.168
3	6	375	0.245
4	8	375	0.324
5	10	375	0.411

 

Figure 6: Calibration Curve of Metaxalone in Buffer 7.4

 

 

Calibration curve in 0.1 N HCl

Table 6: Calibration Curve Readings

S.No.	Concentration (μg/ml)	l max (nm)	Absorbance
1	2	265	0.104
2	4	265	0.178
3	6	265	0.275
4	8	265	0.419
5	10	265	0.511

 

 

Figure 7: Calibration Curve of Metaxalone in 0.1 N HCl

 

Table 7: Loss on drying reading

S.No.	Time interval	Wt. of Drug	Wt. of Petri dish	Total Wt.
1	0 min	500 mg	48.310 gm	48.81 gm
2	30 min	480 mg	48.310 gm	48.79 gm
3	60 min	475 mg	48.310 gm	58.78 gm
4	90 min	470 mg	48.310 gm	48.71 gm
5	150 min	470 mg	48.310 gm	m

 

 

Loss on drying

The loss on the drying method involves weighing a 500 mg medication dosage into a Petri dish and heating it in a hot air oven at 105°C until weight loss ceases after a predetermined time.

 

 

Figure 8: Loss on Drying Curve of Metaxalone

 

Identification of polymer used

The obtained sample was determined to be pure ethyl cellulose and sodium alginate because the FTIR spectrometer recorded their IR spectra, as shown in the figure, and compared them to the standard functional group frequencies of the two substances. The results showed that both ethyl cellulose and sodium alginate fell within the reported range of frequencies.

 

 

Figure 9: FT-IR spectra of sodium alginate

Table 8: FT-IR frequencies of Sodium Alginate

S.No.	Functional Group	Observed Frequencies (cm⁻¹)
1	Oh, stretching.	3428
2	CH stretching	2980
3	-CH₂	1613

 

Compatibility studies between drug and excipient

The drug-excipient compatibility tests involved taking samples that had been stored under different accelerated circumstances and analyzing their physical properties, such as how their color changed at different intervals.

Infrared spectroscopy was used to conduct the investigation of the drug-polymer interaction. We used an FTIR spectrophotometer (PERKIN ELIMER BX) to acquire the infrared spectra of the drug and different polymers that would be employed in the formulation. We then compared these spectra to the individual spectra.

 

 

Figure 10: FTIR of Drug and Excipient

Table 9: IR Frequencies of Drug and Excipient

S.No.	Functional Groups	Observed frequencies (cm⁻¹)
1	NH- stretching	3360.5
2	OH-stretching	2950.8
3	CH-stretching	2809.8
4	C=O stretching	1513.8
5	-COO- stretching vibration	1411.2
6	C-C stretch	1112.5
7	C-H roking	840

 

Table 10: Physical Compatibility Studies

Temperature and humidity		0 Days	15 Days	30 Days	60 Days
25°C ±2°C/75% RH ± 5%	A1	No change	No change	No change	No change
	B1	No change	No change	No change	No change
	C1	No change	No change	No change	No change
60°C ±2°C/75% RH ± 5%	A2	No change	No change	No change	No change
	B2	No change	No change	No change	No change
	C2	No change	No change	No change	No change

 

 

Take a sample that has been in storage for at least 60 days and run it through an FTIR analyzer to find out whether the chemicals are compatible. Based on the data in the table, it seems that both the pure drug and combination spectra have comparable peaks; hence, drug-polymer interaction is not present.

The Metaxalone FTIR spectrum was obtained using the Potassium Bromide Disc Method with a Fourier transform infrared spectrophotometer (PERKIN ELMER BX). The identification and purity of the medicine were validated upon comparison of the discovered major peaks with the reference FTIR spectra of Metaxalone. Neither the pure drug nor the combination spectra demonstrate drug-polymer interaction due to identical peaks.

 

 

 

Evaluation of Prepared Microspheres

Micromeritics characterization

Table 11: Micromeritics study of formulated microspheres

Formulation Code	Angle of Repose ± SD	Tapped SD	Bulk Density ± SD	Carr’s Index ± SD	Hausner’s Ratio ± SD
F1	21.241±0.010	0.641±0.012	0.410±0.022	9.345±0.120	1.031±0.024
F2	22.431±0.031	0.662±0.004	0.482±0.002	10.121±0.216	1.118±0.014
F3	25.840±0.012	0.542±0.010	0.498±0.008	11.328±1.421	1.106±0.032
F4	24.620±0.110	0.492±0.011	0.532±0.018	11.524±1.598	1.132±0.034
F5	22.324±0.012	0.521±0.060	0.598±0.163	10.369±0.436	1.210±0.124
F6	26.012±0.019	0.612±0.010	0.564±0.019	11.324±1.457	1.160±0.063
F7	23.160±0.022	0.542±0.022	0.498±0.026	11.587±0.254	1.131±0.120
F8	27.113±0.115	0.513±0.024	0.641±0.036	12.342±0.254	1.140±0.082
F9	19.118±0.014	0.523±0.018	0.602±0.021	7.185±0.651	1.006±0.026
F10	22.124±0.016	0.512±0.014	0.501±0.012	7.233±1.341	1.032±0.061

 

Table 12: Drug entrapment efficiency, percent yield, % buoyancy, and drug content of microspheres.

Formulation Code	% Drug entrapment efficiency	% Yield	% Buoyancy	Theoretical drug content (gm)	Actual drug content (gm)
F1	68.48	61.45	68.4	0.5	0.3642
F2	60.34	60.32	68.6	0.5	0.362
F3	68.34	63.21	76.3	0.5	0.3562
F4	57.34	58.32	70.25	0.5	0.3642
F5	58.43	61.32	81.32	0.5	0.3732
F6	59.38	58.36	70.25	0.5	0.3754
F7	66.38	62.38	70.32	0.5	0.3553
F8	69.29	70.34	72.65	0.5	0.3653
F9	67.95	66.32	74.21	0.5	0.3685
F10	60.35	59.34	78.12	0.5	0.3102

 

 

Morphological characteristics of the microspheres:

The ionotropic gelation process produced floating microspheres of metaxalone that were characterized by being of the monolithic matrix type, discrete, spherical, and free-flowing. Consistently, the microcapsules' sizes varied from 300 μm. Microcapsules were found to be completely spherical and covered by the coat polymer in their scanning electron microscope photos.

 

 

Figure 11: Small spheres, measuring around 300 to 900 μm in diameter.

Figure 12: Size of an Individual Microsphere

Figure 13: Texture of individual microspheres

 

Differential Scanning Calorimetry (DSC)

For checking the melting point of the pure metaxalone drug, DSC is taken and is observed near about 194°C.

Figure 14: Pure medication differential scanning calorimetry

 

 

There was a single endothermic peak at 194°C on the DSC curve of Metaxalone. At around 165°C, the improved formulation shows a low-intensity peak in the DSC profile. That the formulation's crystallinity is decreased and that the drug and polymer do not interact is shown conclusively by this.

 

 

Figure 15: An Analysis of Thiocolchicoside Microspheres by Differential Scanning Calorimetry (DSC)

 

In vitro dissolution studies

In vitro drug release testing was performed on the prepared microspheres in 900 mL of hydrobromic acid (HBr) buffer at a pH of 1.2. An eight-stage basket-type dissolving rate equipment (Veego) that is typical for the USP was used to perform the investigation. All through the experiment, the dissolving media was kept at a steady 37 ± 0.5°C while the baskets were spun at a rate of 50 revolutions per minute (rpm) to mimic circumstances in the gastrointestinal tract.

Accelerated Stability Studies

One way to gauge the quality of dosage forms is by looking at their stability in preparation. As a result, the stability of microspheres loaded with metaxalone was the subject of expedited testing. When compared to the microspheres loaded with metaxalone before storage in the stability chamber, physical characteristics, including color, surface shape, and particle movement, showed little change, according to the data. The floating ratio and medication loading also changed very little.

 

 

Table 13: Profile of in vitro release of microspheres containing metaxalone

Time	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10
(hr)	% Drug Release F1	% Drug Release F2	% Drug Release F3	% Drug Release F4	% Drug Release F5	% Drug Release F6	% Drug Release F7	% Drug Release F8	% Drug Release F9	% Drug Release F10
0	0	0	0	0	0	0	0	0	0	0
1.5	18.24	17.21	26.21	20.2	23.91	17.23	22.12	25.31	18.35	17.21
3	24.32	25.31	30.29	29.41	31.32	25.31	30.12	32.31	27.42	27.35
4.5	35.32	38.22	39.32	37.31	39.65	34.45	39.34	39.34	36.62	35.25
6	43.39	49.35	49.24	45.37	50.42	41.32	52.15	47.56	47.52	45.96
7.5	51.27	54.85	60.21	57.48	54.95	48.35	60.32	56.25	52.52	52.45
9	68.24	66.65	65.31	62.35	65.45	58.52	64.45	64.87	60.24	60.42
11	72.34	70.21	71.1	70.14	73.34	67.32	68.14	73.21	67.81	67.45
12	78.37	76.02	80.32	80.21	82.34	75.98	77.85	80.32	77.41	77.68

 

Figure 16: Shows the drug release percentage of the optimized formulation, which is 16 %

Figure 17: Drug release versus time graphs for each formulation

Table 14: Accelerated optimized formulation stability study

Temperature & percentage relative humidity	Items		Days
			0	30	60	Color
25±5°C & 75% RH	% Buoyancy	F5	74.6	70.4	64.20	Brownish yellow in color
	%Drug release	F5	82.4	80.4	80.09	Brownish yellow in color
40±5°C & 75% RH	% Buoyancy	F5	72.4	71.3	67.43	Brownish yellow in color
	%Drug release	F5	81.2	81.3	80.54	Brownish yellow in color

 

 

DISCUSSION

This study aimed to manufacture gastroretentive floating microspheres of metaxalone to address its restricted oral bioavailability and brief half-life. The formulated products exhibited satisfactory micromeritic properties, indicating favorable flow characteristics and suitability for large-scale production. Entrapment effectiveness varied from 57% to 69%, with the optimal formulation (F5) achieving 58.43%. The entrapment effectiveness of alginate-based floating microspheres typically ranges from 50% to 70%, contingent upon the polymer ratio and drug solubility, as corroborated by previous studies (Pawar et al., 2011; Virmani and Gupta, 2017). Buoyancy is a crucial factor for stomach retention. The optimized microspheres in this study exhibited over 80% buoyancy for 12 hours, consistent with previous research employing sodium bicarbonate and ethylcellulose as gas-generating and low-density agents, respectively (Singh and Kim, 2000; Shah et al., 2009). The hollow internal structure identified using SEM further corroborated the buoyancy process. In vitro release studies indicated a sustained release of 82.34% over 12 hours for the improved batch. The delayed release profile can be ascribed to the synergistic use of sodium alginate and HPMC, which create a gel matrix that modulates drug transport, while ethylcellulose contributes hydrophobicity to further hinder release. Comparable biphasic release patterns have been seen for several muscle relaxants and centrally acting pharmaceuticals encapsulated in gastroretentive microspheres (Deshpande et al., 1996; Vrettos et al., 2021). DSC and FTIR analyses indicated a lack of significant drug–polymer interactions, while stability tests showed little change in buoyancy and release kinetics under accelerated conditions, affirming the formulation's robustness. The findings suggest that ionotropic gelation is an effective method for encapsulating metaxalone, preserving structural integrity, and ensuring predictable release performance. The produced floating microspheres exhibited prolonged gastric retention, sustained drug release, and enhanced entrapment efficiency. These qualities aim to enhance the bioavailability of metaxalone, decrease dosing frequency, and ultimately increase patient adherence. The findings align with previous research indicating that floating microspheres may serve as a viable approach for drugs characterized by a limited absorption window or brief half-life (Kotreka & Adeyeye, 2011; Ishak, 2015) The absence of significant drug–polymer interaction in the present work is consistent with our earlier findings on sulfamethoxazole derivatives, where compatibility and stability played a pivotal role in ensuring reproducible drug delivery outcomes (Sharma et al., 2025).”

The analytical estimation of metaxalone using spectrophotometric techniques followed a systematic validation approach, comparable to earlier AQbD-guided analytical methods established by Srujani et al. for various active pharmaceutical ingredients (Duvelisib, Fedratinib, and Pemigatinib). These studies highlight the importance of design of experiments (DoE)-based optimization in achieving reproducible analytical precision and method robustness.

CONCLUSION

The findings of this study indicate that the floating microsphere drug delivery system significantly enhances the gastrointestinal bioavailability of metaxalone. The formulation maintained buoyancy in gastric fluid, allowing the drug to dissolve gradually in the acidic environment and enter the systemic circulation in a controlled manner. This sustained release profile prolonged gastric residence time, resulting in more stable plasma drug concentrations compared to conventional oral dosage forms. Consequently, the approach offers the potential for reduced dosing frequency, improved therapeutic efficacy, and better patient compliance.

List of Symbols and Abbreviations

Abbreviation	Full Form
API	Active Pharmaceutical Ingredient
DMSO	Dimethyl Sulfoxide
FTIR	Fourier Transform Infrared Spectroscopy
GC	Gas Chromatography
HPLC	High-Performance Liquid Chromatography
IR	Infrared Spectroscopy
LC-MS	Liquid Chromatography–Mass Spectrometry
LOD	Limit of Detection
LOQ	Limit of Quantification
MS	Mass Spectrometry
NMR	Nuclear Magnetic Resonance
pKa	Acid Dissociation Constant
RP-HPLC	Reverse Phase High-Performance Liquid Chromatography
SEM	Scanning Electron Microscopy
TLC	Thin Layer Chromatography
UV	Ultraviolet
UV-Vis	Ultraviolet–Visible Spectroscopy
XRD	X-ray Diffraction

 

Acknowledgements: The authors gratefully acknowledge the support of their respective institutions and research laboratories for providing the necessary facilities and infrastructure to carry out this work.

Author Contributions: Conceptualization: Brijesh Shukla; Methodology: Brijesh Shukla, Akash Sharma; Investigation: Brijesh Shukla; Writing Original Draft: Brijesh Shukla, Akash Sharma Writing Review & Editing: Brijesh Shukla, Akash Sharma; Supervision: Akash Sharma*.

Funding Source: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of Interest: The authors declare that there are no conflicts of interest regarding the publication of this manuscript.

Ethical Approval: Not applicable. This study does not involve any human or animal testing.

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