Gastroretentive Floating Drug Delivery: A novel Approach for Ondansetron release Enhancement

Oral administration is the most widely accepted route for delivering therapeutic agents because of its simplicity, non-invasiveness, and cost-effectiveness. Despite these advantages, a key limitation of this route lies in the relatively short gastric residence time of conventional dosage forms, which may hinder the absorption and overall bioavailability of drugs that are absorbed primarily in the upper gastrointestinal tract (GIT). To overcome this drawback, Gastroretentive Drug Delivery Systems (GRDDS) have been developed as an advanced strategy in controlled drug delivery. These systems are designed to extend the retention of dosage forms within the stomach, thereby improving drug absorption, reducing dosing frequency, and enhancing therapeutic efficacy.

Among the different approaches to gastroretention, Floating Drug Delivery Systems (FDDS) are considered highly effective. By maintaining a bulk density lower than that of gastric fluids, FDDS remain buoyant in the stomach for prolonged periods, allowing sustained and site-specific drug release. The success of such systems depends on both physiological parameters (such as gastric motility, pH variation, and fed/fasted state) and formulation factors (such as polymer type, dosage form size, and excipient selection). FDDS are particularly advantageous for drugs that degrade in the intestinal environment, exhibit poor solubility at alkaline pH, or are intended for localized stomach action.

In this context, the present study focuses on the formulation and evaluation of a floating gastroretentive system for Ondansetron, a selective 5-HT? receptor antagonist commonly prescribed for the management of nausea and vomiting. By incorporating a floating mechanism, the system aims to increase gastric residence, provide controlled release, and ultimately improve the therapeutic performance and patient compliance associated with Ondansetron therapy.

These systems are especially advantageous for drugs that are absorbed mainly in the stomach or the upper small intestine, as well as those that undergo degradation in the alkaline environment of the distal intestine. Ondansetron, a selective 5-HT? receptor antagonist, is frequently prescribed for the prevention of nausea and vomiting induced by chemotherapy, radiotherapy, and surgical procedures. Although highly effective, its clinical utility is restricted by a short elimination half-life of about 3–4 hours and moderate oral bioavailability of nearly 60%. To overcome these drawbacks, designing a gastroretentive floating drug delivery system (FDDS) offers a promising strategy to extend gastric residence, provide controlled release, and enhance drug absorption. The present work is directed towards the formulation and evaluation of a floating system for Ondansetron, with the goal of improving its pharmacokinetic behavior, sustaining gastric retention, and ultimately enhancing both therapeutic effectiveness and patient adherence.

MATERIALS AND METHODS

Materials

Ondansetron was obtained from Zeel Pharma (Mumbai, India). Hydroxypropyl Methylcellulose (HPMC K4M), Eudragit RL-100, and Hydroxypropyl Cellulose (HPC) were procured from Colorcon Pvt. Ltd. (Goa, India). Ethyl Cellulose, Microcrystalline Cellulose (MCC), Polyvinylpyrrolidone (PVP), Sodium Bicarbonate, Citric Acid, Isopropyl Alcohol, Magnesium Stearate, and Lactose were supplied by SD Fines (Mumbai, India). All reagents and excipients used were of analytical or pharmaceutical grade.

Preparation of Floating Tablets

Floating tablets of Ondansetron (250 mg per tablet) were prepared using the wet granulation method. Sodium bicarbonate and citric acid were incorporated as effervescent agents to generate buoyancy, while different polymers were employed in varying ratios to achieve controlled release (Table 6.3).

Method of Granule Preparation

1. Ondansetron and selected hydrophilic polymers were sieved through mesh #40 and blended for 10 minutes.
2. The gas-generating agents (sodium bicarbonate and citric acid) were sieved through mesh #60 and added to the mixture.
3. A binding solution of PVP in isopropyl alcohol was prepared separately.
4. The powder blend was granulated using the binding solution.
5. The resulting wet mass was dried at room temperature and passed through mesh #40.
6. Magnesium stearate was sieved through mesh #60 and incorporated into the dried granules.
7. The granules were blended thoroughly for 15 minutes to ensure uniform distribution of excipients.
8. Finally, the granules were compressed into tablets using a single-punch tablet compression machine.

Table 1.1: Composition of different Ondansetron floating tablet formulations

Preformulation Studies

Characterization of Ondansetron

A. Organoleptic Properties

Ondansetron was observed as a crystalline powder with a color ranging from off-white to pale yellow. It exhibited a characteristic odor and a distinctly bitter taste.

B. Melting Point

The melting point of Ondansetron was determined to be within the range of 218–225 °C, which is consistent with reported literature values, confirming its identity and purity.

C. FTIR Spectroscopy

Figure 1.2: FTIR Spectrum of Ondansetron generate graph

D. UV spectroscopy (Determination of amax)

Figure 1.3: UV spectrum of Ondansetron.

Evaluation of Granules

The prepared granules of different formulations (F1–F7) were evaluated for bulk density, tapped density, Carr’s compressibility index, Hausner’s ratio, and angle of repose. The results are summarized in Table 1.2.

Table 1.2: Physicochemical evaluation of granules