Mouth Dissolving Tablets as an Effective Drug Delivery Approach for Chemotherapy-Induced Nausea and Vomiting (CINV)

Chemotherapy remains one of the most effective therapeutic approaches for the treatment and management of various malignancies; however, its clinical usefulness is often limited by a range of adverse effects, among which chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing and debilitating. CINV not only affects the physical well-being of patients but also significantly compromises their psychological health, nutritional status, and overall quality of life. In severe cases, uncontrolled nausea and vomiting may lead to dehydration, electrolyte imbalance, weight loss, and may even result in discontinuation or refusal of further chemotherapy cycles. Despite significant advances in antiemetic pharmacotherapy, CINV continues to pose a major clinical challenge. The incidence and severity of CINV depend on multiple factors, including the emetogenic potential of chemotherapeutic agents, dosage, treatment regimen, and patient-specific variables such as age, gender, and previous experience with chemotherapy. Although modern antiemetic guidelines recommend the use of serotonin (5-HT?) receptor antagonists, neurokinin-1 (NK1) receptor antagonists, and corticosteroids, optimal control of CINV is not always achieved in clinical practice. Conventional oral dosage forms such as tablets and capsules are widely used for the administration of antiemetic drugs. However, these dosage forms may not be suitable for patients experiencing acute nausea, vomiting, dysphagia, or oral mucositis following chemotherapy. Difficulty in swallowing, fear of vomiting after ingestion, and the need for water intake further reduce patient compliance with conventional oral formulations. Parenteral routes, although effective, are invasive, costly, and less convenient for long-term or outpatient use. Therefore, there is a growing need for patient-friendly, non-invasive drug delivery systems that can provide rapid onset of action and improve adherence to antiemetic therapy. Mouth dissolving tablets (MDTs), also known as orally disintegrating tablets (ODTs), have emerged as a promising alternative to conventional oral dosage forms. MDTs are solid dosage forms designed to disintegrate rapidly in the oral cavity, usually within a few seconds, without the need for water. Upon contact with saliva, the tablet breaks down and releases the drug, which is subsequently swallowed or partially absorbed through the oral mucosa. This unique characteristic makes MDTs particularly suitable for patients who have difficulty swallowing or who experience nausea and vomiting, such as those undergoing chemotherapy. The advantages of MDTs include ease of administration, rapid disintegration, faster onset of therapeutic action, and improved patient compliance. Additionally, MDTs may allow partial pregastric absorption of the drug, potentially reducing first-pass metabolism and enhancing bioavailability. From a patient-centric perspective, MDTs offer greater convenience and acceptability, especially in vulnerable populations such as pediatric, geriatric, and oncology patients. These benefits have led to increasing interest in the development of MDT formulations for a variety of therapeutic agents, including antiemetics. Several antiemetic drugs commonly used in the management of CINV, such as ondansetron, granisetron, and other 5-HT? receptor antagonists, possess physicochemical properties that make them suitable candidates for formulation as mouth dissolving tablets. Clinical studies have demonstrated that orally disintegrating formulations of these agents provide efficacy comparable to conventional oral tablets while offering superior patient convenience and compliance. Furthermore, advancements in formulation technologies, including the use of super-disintegrants, taste-masking techniques, and optimized excipient combinations, have enhanced the performance and stability of MDTs. In this context, the present review aims to provide a comprehensive overview of mouth dissolving tablets as an effective drug delivery approach for the management of chemotherapy-induced nausea and vomiting. The review discusses the pathophysiology of CINV, the rationale for selecting MDTs as a suitable dosage form, formulation strategies, and available clinical evidence supporting their use. Additionally, the challenges and limitations associated with MDT development, as well as future perspectives in the field of antiemetic drug delivery, are highlighted to emphasize the potential of MDTs in improving supportive care for cancer patients. Cancer chemotherapy has transformed the prognosis of many malignant diseases; however, its therapeutic success is frequently accompanied by undesirable adverse effects that compromise patient comfort and treatment continuity. Among these, chemotherapy-induced nausea and vomiting (CINV) remains one of the most feared complications, despite significant progress in antiemetic therapy. CINV not only causes physical discomfort but also contributes to anxiety, nutritional deficiencies, dehydration, and a substantial decline in overall quality of life. Inadequate control of nausea and vomiting may result in dose reduction, treatment delays, or complete discontinuation of chemotherapy, thereby negatively affecting clinical outcomes.

The development of CINV Is complex and multifactorial, involving both central and peripheral mechanisms. Chemotherapeutic agents stimulate the release of neurotransmitters such as serotonin from enterochromaffin cells in the gastrointestinal tract, which in turn activate vagal afferents and the chemoreceptor trigger zone, leading to stimulation of the vomiting center in the brain. Based on the time of onset, CINV is categorized into acute, delayed, anticipatory, breakthrough, and refractory types, each presenting unique management challenges. Although current antiemetic guidelines have improved symptom control, a significant proportion of patients continue to experience nausea, particularly in delayed and breakthrough phases. Oral administration remains the most preferred route for antiemetic therapy due to its convenience and non-invasiveness. However, the effectiveness of conventional oral dosage forms such as tablets and capsules is often limited in patients receiving chemotherapy. Severe nausea, repeated vomiting, oral mucositis, xerostomia, and dysphagia can make swallowing difficult and unpleasant. Additionally, the requirement of water intake for conventional tablets may further aggravate nausea, leading to poor adherence and suboptimal therapeutic outcomes. These limitations highlight the need for innovative oral drug delivery systems that can be administered easily and provide rapid symptomatic relief. Mouth dissolving tablets (MDTs) have gained considerable attention as a novel oral drug delivery system designed to overcome the shortcomings of traditional solid dosage forms. MDTs are formulated to disintegrate or dissolve rapidly in the saliva when placed on the tongue, eliminating the need for water and active swallowing. This feature is particularly advantageous for oncology patients experiencing nausea, gag reflex sensitivity, or difficulty in swallowing. Furthermore, rapid disintegration may facilitate faster drug availability, which is critical in the prompt management of acute nausea and vomiting. From a formulation perspective, MDTs combine the advantages of solid dosage forms with the convenience of liquid formulations. Advances in pharmaceutical technology, including the use of super-disintegrants, porous matrices, and taste-masking techniques, have enabled the development of MDTs with acceptable mechanical strength, palatability, and stability. Several antiemetic agents, especially 5-HT? receptor antagonists such as ondansetron and granisetron, are well suited for MDT formulation due to their low dose requirements and favorable pharmacokinetic profiles. Given the growing emphasis on patient-centric drug delivery and supportive cancer care, mouth dissolving tablets represent a promising strategy for improving the management of chemotherapy-induced nausea and vomiting. This review aims to critically examine the relevance of MDTs in CINV therapy, highlighting their formulation aspects, clinical potential, advantages, limitations, and future prospects. By addressing both pharmaceutical and clinical considerations, this review seeks to provide a comprehensive understanding of MDTs as an effective and patient-friendly antiemetic drug delivery approach.

Chemotherapy-Induced Nausea and Vomiting: Pathophysiology and Clinical Challenges

Pathophysiology of Chemotherapy-Induced Nausea and Vomiting: Chemotherapy-induced nausea and vomiting (CINV) is a complex physiological process involving both peripheral and central nervous system pathways. It occurs due to the stimulation of specific neurotransmitters and receptors following the administration of chemotherapeutic agents. The severity and onset of CINV depend on the emetogenic potential of the chemotherapy regimen, dose, schedule, and patient-related factors. At the peripheral level, chemotherapeutic drugs cause damage to the gastrointestinal mucosa, particularly the enterochromaffin cells of the small intestine. This damage leads to the excessive release of serotonin (5-hydroxytryptamine, 5-HT). The released serotonin activates 5-HT? receptors located on vagal afferent nerves, which transmit signals to the vomiting center in the brainstem. At the central level, the emetic signals are processed in the chemoreceptor trigger zone (CTZ), located in the area postrema of the medulla oblongata. The CTZ lacks a complete blood–brain barrier, making it highly sensitive to circulating emetogenic substances such as chemotherapeutic agents and their metabolites. Neurotransmitters including serotonin, dopamine, substance P, and neurokinin-1 (NK1) play a crucial role in stimulating the CTZ and vomiting center. Based on the timing and mechanism, CINV is classified into different types:

• Acute CINV, occurring within the first 24 hours of chemotherapy, mainly mediated by serotonin release.
• Delayed CINV, occurring after 24 hours and lasting several days, predominantly associated with substance P and NK1 receptor activation.
• Anticipatory CINV, a conditioned response triggered by prior negative chemotherapy experiences.
• Breakthrough CINV, occurring despite prophylactic antiemetic therapy.
• Refractory CINV, persisting even after aggressive antiemetic treatment.

The involvement of multiple neurotransmitter pathways explains why CINV is difficult to control using a single pharmacological agent and often requires combination therapy.

Clinical Challenges in the Management of CINV

Despite advancements in antiemetic therapy and evidence-based clinical guidelines, effective management of CINV remains challenging. One of the major clinical issues is incomplete symptom control, particularly nausea, which is often more difficult to manage than vomiting. While vomiting episodes may be reduced, persistent nausea continues to significantly affect patient comfort and quality of life. Another major challenge is patient non-compliance with oral antiemetic therapy. Patients undergoing chemotherapy often experience severe nausea, repeated vomiting, oral mucositis, dysphagia, xerostomia, and gag reflex sensitivity. These conditions make swallowing conventional oral tablets difficult and unpleasant. Additionally, the requirement of water intake for tablet administration may worsen nausea, leading to skipped doses and reduced therapeutic effectiveness.