Formulation Development And Evaluation Of Floating Tablet Containing Domperidone Maleate

Domperidone Maleate is a dopamine D₂ receptor antagonist widely used for the treatment of nausea, vomiting, and gastrointestinal disorders. It has a short biological half-life and is mainly absorbed in the upper gastrointestinal tract, which limits its oral bioavailability. Gastroretentive floating drug delivery systems are designed to prolong gastric residence time, thereby improving drug absorption and providing sustained drug release. Floating tablets remain buoyant in gastric fluid for an extended period, resulting in enhanced therapeutic efficacy and reduced dosing frequency. Therefore, the present study focuses on the formulation and evaluation of floating tablets containing Domperidone Maleate using suitable polymers and gas-generating agents to achieve prolonged gastric retention and controlled drug release.

2. Pre-formulation Studies Preformulation

studies are critical to understand the physical and chemical characteristics of the drug and excipients, ensuring stability and compatibility prior to formulation development.

2.1.Organoleptic Properties:

The physical appearance of Domperidone Maleate was observed visually for color, texture, and odor.

2.2 Melting Point Determination:

Melting point was determined using a digital melting point apparatus by the capillary tube method. The observed value was compared with standard reference.

2.3 Solubility Studies:

Solubility was tested in various solvents including distilled water, ethanol, methanol, 0.1N HCl, and phosphate buffer (pH 6.8). Approximately 1–2 mg of drug was added to 5 mL of solvent in a test tube, shaken, and observed for solubility.

2.4 Calibration Curve:

A stock solution of Domperidone Maleate (1000 µg/mL) was prepared in Methanol. Serial dilutions (5, 10, 15, 20, 25 µg/mL) were scanned in UV spectrophotometer at λmax = 284 nm to generate a standard curve.

 3. Formulation Development

Floating tablets were formulated using the direct compression method. A total of eight formulations (F1to F8) were prepared using varying concentrations of HPMC K4M, and TSP

3.1 Role of Key Ingredients:

 • HPMC K4M : Serve as matrix-forming agents to control drug release.

• TSP : Natural polymer added for additional swelling and gel-forming capacity.

• Sodium Bicarbonate + Citric Acid: Gas-generating agents to achieve buoyancy

 • Lactose: Used as a diluent to maintain tablet weight and compressibility.

• Magnesium Stearate and Talc: Used as lubricant and glidant respectively.

3.2 Method:

1. All excipients and the API were passed through a 40mesh sieve.

2. The weighed quantities were transferred into a polyethylene bag and mixed thoroughly.

3. Magnesium stearate and talc were added last to ensure uniform distribution.

4. The blend was compressed into tablets using a rotary tablet press with 8 mm flat-faced punches

3.3 Formulation Composition:

Each tablet contained 10 mg Domperidone Maleate with varying polymer ratios (see table in Results section for full composition)

 

 

Fig. 1: Floating Lag Time F1- F8 Batch

 

   

 

Fig 2 Swelling Index of F1-F4                       Fig 3 Swelling Index of F5-F8

 

 

 

 

Fig 5 Drug Release Batch F5 to F8

 

 

Fig 6 Drug Release Batch F5 to F8

 

       

 

             Figure No.7: Contour plot for Y1 (% CDR)    Fig NO 8 3D surface plot for Y1

 

   

 

FIG NO 9 Contour plot for Y2 Fig NO 10 3D surface plot for Y2

 

  

 

FIG NO 11 Contour plot for Y3          Fig NO 12 3D surface plot for Y3

DISCUSSION

The present investigation focused on the formulation and optimization of Gastroretentive floating tablets of Domperidone Maleate, a BCS Class II drug with limited bioavailability due to extensive first-pass metabolism and low aqueous solubility. Developing a floating drug delivery system allowed for prolonged gastric retention, facilitating localized drug release in the upper gastrointestinal tract (GIT) — a region where Domperidone Maleate demonstrates optimal absorption.

5.1 Pre-compression and Blend Properties

The pre-compression parameters of all formulations (F1–F8) were within acceptable limits, indicating good flowability and compressibility of the powder blend. Carr's Index, Hausner's ratio, and angle of repose confirmed satisfactory flow properties suitable for direct compression. Among all formulations, F7 showed the best flow characteristics with the lowest Carr's Index (9.69%), Hausner's ratio (1.10), and angle of repose (24.8°).

5.2 Physicochemical Evaluation

The post-compression evaluation of all formulations (F1–F8) complied with the acceptable pharmacopeial limits for weight variation, hardness, thickness, friability, and assay, indicating satisfactory tablet quality. Among all formulations, F7 showed the best performance with the lowest friability (0.22%) and the highest assay (99.76%).

5.3 In Vitro Buoyancy Study

The in vitro buoyancy study showed that all formulations floated for more than 12 hours, indicating excellent floating ability. Among all formulations, F7 exhibited the shortest floating lag time (74 sec), demonstrating rapid buoyancy and better gastroretentive performance.

5.4 Swelling Index

The swelling index of all formulations increased progressively with time, indicating effective hydration and swelling of the polymer matrix. Among all formulations, F7 exhibited the highest swelling index (62.45 ± 0.33% at 10 h), suggesting superior swelling behavior and sustained drug release potential.

5.6 Drug content

The drug content of all formulations (F1–F8) was within the acceptable pharmacopeial limit, indicating uniform drug distribution in the tablets. Among all formulations, F7 showed the highest drug content (99.76%), demonstrating excellent content uniformity and formulation accuracy.

5.7 IN- VITRO DRUG RELEASE

The in vitro drug release study showed a sustained release pattern for all formulations over 12 hours, confirming the effectiveness of the gastroretentive matrix system. Among all formulations, F7 exhibited the highest cumulative drug release (103.46%), indicating optimum polymer concentration and superior drug release performance.

5.8 Design Of Experiment

The Box–Behnken design and regression analysis demonstrated that HPMC K4M, Tamarind Seed Polysaccharide (TSP), and Sodium Bicarbonate significantly influenced % drug release, floating lag time, and total floating time (p < 0.05). The quadratic models showed good agreement between experimental and predicted responses, confirming the suitability of the optimization model.

5.9 MATHEMATICAL MODELING OF DISSOLUTION PROFILES

The drug release data showed a good fit to the Higuchi and Korsmeyer–Peppas kinetic models, indicating diffusion-controlled drug release from the floating matrix tablets. The n values (0.502–0.763) suggested that the drug release followed non-Fickian (anomalous) diffusion, involving both diffusion and polymer relaxation mechanisms.

5.10 STABILITY STUDY OF DOMPERIDONE MALEATE TABLET

The stability study demonstrated that the optimized Domperidone Maleate floating tablets remained physically and chemically stable under both storage conditions, with no significant changes in tablet properties after one month. The results confirmed that the formulation maintained acceptable weight variation, hardness, friability, floating behavior, and drug release, indicating good stability.

CONCLUSION

The present study successfully formulated and evaluated gastroretentive floating tablets of Domperidone Maleate using HPMC K4M, Tamarind Seed Polysaccharide (TSP), and Sodium Bicarbonate by the direct compression method. All formulations exhibited satisfactory pre-compression and post-compression characteristics within acceptable pharmacopeial limits. Among the prepared formulations, F7 was identified as the optimized formulation, showing excellent floating behavior with a floating lag time of 74 seconds and a total floating time of more than 12 hours. It also demonstrated the highest swelling index, uniform drug content (99.76%), and sustained drug release (103.46%) over 12 hours.

The Box–Behnken Design confirmed that the selected formulation variables significantly influenced the critical quality attributes, while kinetic modeling indicated that drug release followed the Higuchi and Korsmeyer–Peppas models with a non-Fickian diffusion mechanism. Furthermore, the optimized formulation remained stable under accelerated stability conditions without significant changes in its physicochemical properties. Therefore, the developed floating tablet of Domperidone Maleate has the potential to improve gastric retention, provide sustained drug release, and enhance therapeutic efficacy and patient compliance.

Acknowledgements: The authors gratefully acknowledge Loknete Dr. J.D Pawar College of Pharmacy, Manur, for providing necessary research facilities and infrastructure support. We also extend our appreciation to the laboratory staff for their technical assistance during the formulation and evaluation processes.

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16. Streubel A, Siepmann J, Bodmeier R. Floating matrix tablets based on low density foam powder: Effects of formulation and processing parameters on drug release. Eur J Pharm Sci. 2003;18:37-45.
17. Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gastroretentive dosage forms: Overview and special case of Helicobacter pylori. J Control Release. 2006;111:1-18.
18. Whitehead L, Fell JT, Collett JH. Development of a gastroretentive dosage form. Eur J Pharm Sci. 1996;4:182.
19. Y, Niwa T, Takeuchi H, Hino T, Itoh Y. Hollow microspheres for use as a floating controlled drug delivery system in the stomach. J Pharm Sci. 1992;81:135-140.
20. Moes AJ. Gastroretentive dosage forms. Crit Rev Ther Drug Carrier Syst. 1993;10:143-195.
21. Hughes Medical Institute. Fast dissolving tablets [Internet]. Available from:http://www.hughes-medical.com/products/fast dissolvingtablets2.htm
22. Eurand Technologies. Dosage form technology [Internet]. Available from: http://www.eurand.com/Technologies/Dosage-Form-Technology/
23. Stomach diagram [Internet]. Available http://unmasadalha.blogspot.in/2016/01/stomach-diagram.html