Buccal drug delivery technologies for patient-centred treatment of radiation-induced xerostomia (dry mouth)

Abstract

Radiotherapy is a life-saving treatment for head and neck cancers, but almost 100% of patients develop dry mouth (xerostomia) because of radiation-induced damage to their salivary glands. Patients with xerostomia suffer symptoms that severely affect their health as well as physical, social and emotional aspects of their life. The current management of xerostomia is the application of saliva substitutes or systemic delivery of saliva-stimulating cholinergic agents, including pilocarpine, cevimeline or bethanechol tablets. It is almost impossible for substitutes to replicate all the functional and sensory facets of natural saliva. Salivary stimulants are a better treatment option than saliva substitutes as the former induce the secretion of natural saliva from undamaged glands; typically, these are the minor salivary glands. However, patients taking cholinergic agents systemically experience pharmacology-related side effects including sweating, excessive lacrimation and gastrointestinal tract distresses. Local delivery direct to the buccal mucosa has the potential to provide rapid onset of drug action, i.e. activation of minor salivary glands within the buccal mucosa, while sparing systemic drug exposure and off-target effects. This critical review of the technologies for the local delivery of saliva-stimulating agents includes oral disintegrating tablets (ODTs), oral disintegrating films, medicated chewing gums and implantable drug delivery devices. Our analysis makes a strong case for the development of ODTs for the buccal delivery of cholinergic agents: these must be patient-friendly delivery platforms with variable loading capacities that release the drug rapidly in fluid volumes typical of residual saliva in xerostomia (0.05-0.1 mL).

Clinical utility of hyperbaric oxygen therapy in dentistry

“…Xerostomia is defined as dry mouth resulting from reduced or absent saliva flow. Radiation therapy, such as HBOT, often damages salivary glands while also treating the diagnosed issue 31. Radiation-induced xerostomia is one of the most common morbidities of radiation therapy in patients with head and neck cancer.…”

Digital Image Disintegration Analysis: a Novel Quality Control Method for Fast Disintegrating Tablets

“…The DIDA approach is inherently flexible, so the type of disintegration medium may be changed easily, allowing the exploration of the impact of different simulants of human saliva. This study used PBS as the medium and investigated the effect of volumes, 0.05 mL and 0.7 mL, representing the disintegration environment in the mouth of patients with xerostomia at two temperatures, selected to represent temperature variation during day and night ( 9 , 12 ).…”

“…The basket-rack assembly is designed to simulate the disintegration of conventional tablets within the stomach, which is a very different environment from that found in the oral cavity of the mouth where FDTs disintegrate. In healthy individuals, the total volume of liquid available in the oral cavity is between 1 and 2 mL, typically replenished every minute, compared to the volume of the stomach of 300 to 500 mL during fasting and fed state, respectively ( 8 , 9 ). Also, fast disintegrating tablets are designed to help patients with swallowing difficulty, such as patients diagnosed with xerostomia, where a minimal volume is available for tablets to disintegrate ranging from 0.05 to 0.7 mL ( 9 ).…”

“…In healthy individuals, the total volume of liquid available in the oral cavity is between 1 and 2 mL, typically replenished every minute, compared to the volume of the stomach of 300 to 500 mL during fasting and fed state, respectively ( 8 , 9 ). Also, fast disintegrating tablets are designed to help patients with swallowing difficulty, such as patients diagnosed with xerostomia, where a minimal volume is available for tablets to disintegrate ranging from 0.05 to 0.7 mL ( 9 ). The temperature within the mouth varies depending on location, for example, the sublingual region is typically 37°C, but the buccal area can range between 33 and 37°C, so the ability to control and operate at different temperatures needs to be considered in the design of new disintegration apparatus to represent the oral cavity (&, 10 – 12 ).…”

Local Oral Pilocarpine Drops for Relieving Xerostomia (Dry Mouth) in the Elderly: A Pilot Study

“…4 Peak plasma concentrations are reached 75 minutes after ingestion of 5 mg tablets 3 times a day. Pilocarpine is eliminated mainly in the urine with an elimination half-life of about 45 minutes for 5 mg doses, 7 depending on the individual pilocarpine esterase activity. 8 However, systemic pilocarpine has frequent side effects.…”