Extemporaneously compounded buccal pilocarpine preparations, acceptability and pilot testing for the treatment of xerostomia (dry mouth) in Australia

Abstract

Xerostomia, the subjective feeling of dry mouth, is characterised by hypofunctioning salivary glands in which either the quantity or quality of saliva is reduced. It is a common symptom for a variety of diseases such as rheumatic and dysmetabolic diseases, and is the primary symptom associated with Sjögren's syndrome. Xerostomia is also caused by treatments such as radiotherapy to the head and neck region and is a side effect of a range of medications. People with xerostomia usually experience dryness of mouth, lips and throat. They are more susceptible to dental caries, oral mucositis and enhanced tooth decay. They have problems with moistening, chewing and swallowing foods and taste alterations associated with reduction in salivary flow can affect their ability to taste food. These consequences can lead to decreased food consumption, which can cause malnutrition and further suppression of their immune defence mechanisms with increased risk of morbidity and reduced quality of life. Some approaches to managing xerostomia include sipping fluids such as water more frequently to moisten the oral mucosa, chewing sugar free gum to stimulate more saliva secretion, and using saliva replacement gels or drops. However, these strategies often do not provide sufficient relief due to the short-term effect they produce. Thus, a strong rationale exists for the development and evaluation of a medication to help treat dry mouth symptoms. Pilocarpine oral tablets (Salagen) are available in at least 24 countries including the USA, Canada and the UK, and a wide range of countries across Europe, South America and Asia, for the treatment of radiation-induced xerostomia and xerostomia as a result of Sjögren's syndrome. Pilocarpine is a non-selective muscarinic agonist that stimulates the muscarinic cholinergic receptors on the surface of exocrine glands, including salivary glands and sweat glands, resulting in increased salivation and sweating. An oral dose of 5 mg pilocarpine in the form of tablets or capsules to be taken three times daily produces the most effective therapeutic response in terms of subjective relief of dry mouth according to many clinical studies. An oral dosage form of pilocarpine is not commercially available in Australia. Pilocarpine is only commercially available as 1% and 2% eye drops, which are registered on the Australian Register of Therapeutic Goods (ARTG) for the treatment of glaucoma. When these eye drops were given by mouth for the treatment of dry mouth as part of a previous clinical trial, which was done in an inpatient palliative population within a hospital setting, they tasted unpleasant to most of the patients and were not acceptable as a dosage form for dry mouth treatment for that reason. This thesis investigates the potential to use pilocarpine dosage forms that can be compounded in pharmacies for delivering 5 mg

Systemic versus local injection of bone marrow mesenchymal stem cells on 5-fluorouracil treated parotid glands of albino rats

“…And in recent years, it was administrated as the only standard cytostatic drug in the treatment of colorectal carcinoma [18]. The PG is the most significant SG in terms of the amount of saliva it produces during stimulated salivary flow, reaching more than half of the total volume of salivary secretions [19].…”