Formulation and Evaluation of Sustained Release Floating Microspheres of Doxofylline

Gastroretentive drug delivery systems (GRDDS) are designed to prolong gastric residence time and improve bioavailability of drugs absorbed mainly in the stomach or upper gastrointestinal tract. Floating microspheres represent an important multiparticulate gastroretentive system due to their low density and prolonged gastric retention.  Doxofylline is a xanthine derivative used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Because of its short biological half-life, sustained release formulations are required to reduce dosing frequency and improve patient compliance. The objective of the present work was to formulate and evaluate sustained release floating microspheres of Doxofylline using hydrophilic polymers.

MATERIALS AND METHODS

2.1 MATERIALS

• Drug: Doxofylline
• Polymers: HPMC K100LV, HPMC K4M, HPMC K15M, Ethylcellulose
• Solvents: Ethanol and Dichloromethane
• Stabilizer: Polyvinyl alcohol (PVA)

2.2 Preparation of Floating Microspheres

Floating microspheres were prepared by emulsion solvent diffusion technique using ethanol and dichloromethane (1:1) as solvent system. The polymer-drug solution was added to aqueous PVA solution under stirring at controlled temperature (30–40°C). Microspheres formed were filtered, washed, and dried.

2.3 Evaluation Parameters

The prepared microspheres were evaluated for:

• Particle size
• Bulk density
• Tapped density
• Carr’s index
• Hausner ratio
• Angle of repose
• Percentage yield
• Buoyancy
• Drug entrapment efficiency
• In-vitro drug release
• Release kinetics
• Stability studies

RESULTS AND DISCUSSION

3.1 Physical Characterization of Doxofylline

Table 1: Physical Properties of Doxofylline

The drug sample complied with standard physicochemical characteristics and showed purity of 99.65%.

3.2 Calibration Curve

The calibration curve of Doxofylline in 0.1 N HCl obeyed Beer-Lambert’s law at 271 nm.

Y=0.0735x+0.0054Y = 0.0735x + 0.0054Y=0.0735x+0.0054

Correlation coefficient:

R=0.9998R = 0.9998R=0.9998  

3.3 Micromeritic Properties

Table 2: Micromeritic Evaluation of Microspheres

All formulations showed good flow properties suitable for capsule filling.

3.4 Percentage Yield

Table 3: Percentage Yield

Batch A5 showed maximum percentage yield.

3.5 Buoyancy Studies

Table 4: Percentage Buoyancy

The optimized formulation remained buoyant for more than 12 hours due to hollow internal structure.

3.6 Drug Entrapment Efficiency

Table 5: Drug Entrapment Efficiency

Higher polymer concentration improved drug retention.

3.7 In-vitro Drug Release

Table 6: Drug Release Profile of Optimized Batch A5

The formulation exhibited sustained release over 12 hours with initial burst release followed by controlled release.

3.8 Release Kinetics

The optimized formulation followed Higuchi diffusion kinetics and Korsmeyer-Peppas non-Fickian diffusion mechanism.

Higuchi Model

Q=Kt0.5Q = Kt^{0.5}Q=Kt0.5

Korsmeyer-Peppas Equation

MtM∞=Ktn\frac{M_t}{M_\infty}=Kt^nM∞​Mt​​=Ktn

The diffusion exponent value indicated anomalous transport.

Table 7: Stability Study of Optimized Batch A5

The optimized formulation remained stable under accelerated conditions.

Estimated shelf life:

T0.9=0.1054K25T_{0.9}=\frac{0.1054}{K_{25}}T0.9​=K25​0.1054​

Shelf life was found to be approximately 1.9 years.

3.10 SEM Studies

SEM studies revealed:

• Smooth outer surface
• Hollow internal cavity
• Porous structure
• Spherical morphology

These characteristics were responsible for floating behavior and sustained release.

3.11 FTIR and XRD Studies

FTIR studies confirmed absence of drug-polymer interaction. XRD studies indicated the crystalline nature of Doxofylline remained intact in the optimized formulation.