Anuradha College of Pharmacy, Chikhili, Dist-Buldhana, M.S., India 443201.
This study focused on developing a gastroretentive drug delivery system (GRDDS) for lamotrigine, an antiepileptic drug, using floating tablets formulated with curdlan gum and hydroxypropyl methylcellulose (HPMC K100M) as matrix-forming polymers, alongside sodium bicarbonate as a gas-generating agent. The objective was to enhance gastric retention and achieve sustained drug release. Eight formulations (F1–F4 with curdlan gum, F5–F8 with HPMC K100M) were prepared via direct compression and evaluated for physicochemical properties, buoyancy, swelling, in-vitro drug release, kinetics, and stability. Formulation F4, with the highest curdlan gum concentration, exhibited a floating lag time (FLT) of 88.33±1.15 seconds, total floating time (TFT) of 12.16±0.28 hours, and zero-order release (R2=0.986) over 12 hours. Stability at 40°C/75% RH for three months confirmed its robustness. Curdlan gum outperformed HPMC K100M, suggesting its potential as a novel GRDDS polymer. This formulation could reduce dosing frequency and improve patient compliance, warranting further in-vivo studies.
Oral drug delivery remains the preferred administration route due to its convenience, costeffectiveness, and high patient compliance. However, conventional oral dosage forms often suffer from rapid gastrointestinal transit, leading to incomplete drug release and reduced bioavailability, particularly for drugs with narrow absorption windows or short half-lives1. Gastroretentive drug delivery systems (GRDDS) address these limitations by prolonging gastric residence time, enhancing absorption in the upper gastrointestinal tract2. Floating drug delivery systems, a subset of GRDDS, leverage low-density formulations to remain buoyant on gastric contents, releasing drugs in a controlled manner4.
Lamotrigine, an antiepileptic drug used for epilepsy and bipolar disorder, exhibits a short half-life (approximately 25 hours) and is primarily absorbed in the proximal gastrointestinal tract11. Its conventional immediate-release formulations require multiple daily doses, resulting in plasma level fluctuations and potential side effects. A GRDDS could sustain release, maintain therapeutic levels, and reduce dosing frequency13. Natural polymers like curdlan gum, a bacterial exopolysaccharide, offer biocompatibility and gelling properties, making them promising for sustained-release matrices10. This study compares curdlan gum with HPMC K100M, a widely used synthetic polymer, in formulating lamotrigine floating tablets.
The objectives were to design and characterize these tablets, evaluate their performance, and assess curdlan gum’s potential as a novel GRDDS polymer. Key challenges with conventional systems—such as rapid transit and variable absorption—were addressed by optimizing buoyancy and release kinetics.
MATERIALS AND METHODS
Materials:
Lamotrigine was gifted by Panacea Biotech, India. Curdlan gum (Nanjing Joyful Co. Ltd., China), HPMC K100M (Colorcon Asia Pvt. Ltd., India), sodium bicarbonate, spray-dried lactose, magnesium stearate, and talc were procured from local suppliers. All reagents were analytical grade.
Tablet Preparation:
Eight formulations (F1–F4 with increasing curdlan gum concentrations, F5–F8 with increasing HPMC K100M concentrations) were prepared by direct compression using a 12-station tablet machine (8.25 mm punches). Each 250 mg tablet contained 25 mg lamotrigine, 10% w/w sodium bicarbonate, varying polymer amounts, lactose as diluent, and magnesium stearate/talc as lubricant/glidant.
Preformulation Studies:
Lamotrigine was characterized for solubility (0.17 mg/ml in water, 4.12 mg/ml in 0.1 N HCl), melting point (215–218°C), and UV absorption (λmax=270 nm). FTIR and DSC confirmed drug-excipient compatibility. Powder blends were evaluated for micromeritic properties (angle of repose, bulk/tapped density, Carr’s index, Hausner ratio).
Tablet Evaluation:
Tablets underwent pharmacopoeial tests (weight variation, hardness, friability, drug content) per Indian Pharmacopoeia12. Buoyancy was assessed by FLT and TFT in 0.1 N HCl at 37°C. Swelling index was calculated as percentage weight increase. In-vitro dissolution used USP Apparatus II (900 ml 0.1 N HCl, 50 rpm, 37°C), with samples analyzed at 270 nm. Release kinetics were modeled (zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas). Stability of the optimized formulation (F4) was tested at 40°C/75% RH for three months.
RESULTS
Preformulation Lamotrigine exhibited a UV λmax of 270 nm, with a linear calibration curve (R2=0.997, y=0.261x+0.01). FTIR peaks (e.g., 3410 cm-1 for N-H stretching) and DSC (endotherm at 218.70°C) confirmed purity and compatibility with curdlan gum and HPMC K100M. Powder blends showed good flow (angle of repose: 22.18°–24.57°, Carr’s index: 10.81– 14.46%).
Physicochemical Properties:
Tablets met pharmacopoeial standards: diameter (8.23–8.24 mm), thickness (4.53–4.63 mm), hardness (4.33–6.00 kg/cm2), friability (0.71–0.87%), and drug content (96.4– 99.23%) (Table 1).
Table 1: Physicochemical Properties of Selected Formulations
|
Formulation |
Hardness (kg/cm2) |
Friability (%) |
Drug Content (%) |
FLT (s) |
TFT (h) |
|
F1 |
4.33±0.28 |
0.87±0.03 |
96.40±0.91 |
88.33±1.15 |
8.16±0.76 |
|
F4 |
4.83±0.57 |
0.71±0.06 |
99.23±0.85 |
163.00±1.52 |
12.16±0.28 |
|
F8 |
6.00±0.50 |
0.80±0.04 |
98.56±0.90 |
175.00±0.57 |
11.16±0.28 |
Buoyancy and Dissolution:
FLT ranged from 88.33±1.15 to 175±0.57 seconds, and TFT from 8.16±0.76 to 12.16±0.28 hours. F4 showed optimal buoyancy (FLT: 163.00±1.52 s, TFT: 12.16±0.28 h). Dissolution profiles indicated polymer concentration-dependent release, with F4 achieving zero-order release over 12 hours.
Kinetics and Stability:
F4 and F8 followed zero-order kinetics (R2=0.986 and 0.977, respectively), with non-Fickian diffusion (‘n’=0.741–0.795). F4 remained stable after three months, showing no significant changes in physicochemical properties, buoyancy, or release profile.
DISCUSSION
GRDDS enhance drug bioavailability by retaining the dosage form in the stomach, a critical factor for drugs like lamotrigine with upper gastrointestinal absorption3. F4’s superior buoyancy (short FLT, prolonged TFT) results from curdlan gum’s efficient gas entrapment and robust matrix formation10. Its zero-order release minimizes plasma fluctuations, a key advantage over conventional formulations13. Compared to HPMC K100M,
curdlan gum’s natural gelling properties offer better control over drug diffusion, aligning with studies on natural polymers in GRDDS9. Stability data suggest F4’s suitability for further development, though in-vivo validation is needed to confirm gastric retention and pharmacokinetics14.
CONCLUSION
This study developed gastroretentive floating tablets of lamotrigine, with F4 (curdlan gum) demonstrating optimal buoyancy, sustained zero-order release, and stability. Curdlan gum emerges as a promising natural polymer for GRDDS, potentially improving lamotrigine’s therapeutic efficacy. Future in-vivo studies are recommended.
ACKNOWLEDGMENTS
I thank Anuradha College of Pharmacy, Hemant Sawarkar, Aijaz Sheikh and Kailash Biyani for their support.
CONFLICTS OF INTEREST
None declared.
REFERENCES
Shubham Solanke*, Hemant Sawarkar, Aijaz Sheikh, Kailash Biyani, Design And Characterization of Gastroretentive Drug Delivery System of a Model Drug, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 734-737. https://doi.org/10.5281/zenodo.15596005
10.5281/zenodo.15596005
