Table 2.

Published studies evaluating the clinical efficacy of topical pilocarpine delivery formulations in improving salivary gland flow and relieving symptoms of xerostomia. The studies are presented in chronological order.

Reference	Year of Publishment	Volunteers	Drug Formulation for Topical Administration	Reference/Outcome
Rhodus et al. [78]	1992	18	Pilocarpine ophthalmic solution	Both whole unstimulated salivary flow and parotid stimulated salivary flow presented a significant improvement in the pilocarpine group, compared to those of the placebo group.
Davies et al. [79]	1994	20	Mouthwash	The increased pilocarpine mouthwash effectiveness, compared to that of the artificial saliva in relieving the patients’ symptoms was noted by patients.
Hamlar et al. [86]	1996	40	Candy-like pastilles	The alleviation of subjective xerostomia’s symptoms was reported by 74% of patients. Moreover, the topical pilocarpine administration approached the same level of efficacy compared to previous delivery methods for radiation-induced xerostomia yet presenting the comparative advantage of a significantly improved patient tolerance.
Bernardi et al. [80]	2002	40	Mouthwash	The results of pilocarpine mouthwash solutions in increasing salivary flow in healthy participants was proved, with no adverse effects.
Frydrych et al. [38]	2002	23	Mouth spray	All patients treated with pilocarpine demonstrated improvement in stimulated and unstimulated salivary flow rates. Candida counts decreased among the cases.
Taweechaisupapong et al. [59]	2006	33	Lozenges	Salivary production in pilocarpine treatment group, as compared to that of the placebo group, appeared a statistically significant improvement. The 5 mg pilocarpine lozenge claims the top spot, as far as the clinical results are concerned.
Gibson et al. [91]	2007	8	Hydrogel buccal inserts	Better oral and ocular scores, along with a generally ameliorated saliva production were noted, while all patients, with the exception of one who wore dentures, agreed on the decent tolerance of the inserts.
Kim et al. [81]	2014	60	Mouthwash	The unstimulated whole salivary flow rate was increased.
Tanigawa et al. [82]	2015	40	Mouthwash	47% of patients treated with pilocarpine reported an overall improvement. Moreover, following pilocarpine mouthwash treatment, the stimulated salivary flow rate appeared to be significantly increased, along with a predominant attenuation of side effects referred after pilocarpine mouthwash use to oral discomfort.
Park et al. [83]	2015	12	Mouthwash	The examined 2% pilocarpine solution as mouthwash increased salivary flow rate, compared to the placebo solution. Its efficacy was comparable to pilocarpine tablet, yet with the comparative advantage of presenting reduced side effects in healthy subjects.
Song et al. [84]	2017	30	Mouthwash	Pilocarpine mouthwash with at least 1.0% concentration and at a more-than- a-minute application might be clinically effective without any serious side effects.
Beatris et al. [85]	2018	36	Mouthwash	Treatment with pilocarpine mouthwash provided an increased salivation, without being followed any significant clinical adverse effect.
Watanabe et al.[93]	2018	24	Mouthwash	This new, low-dose pilocarpine formulation was well-tolerated and resulted to significant improvements in dry mouth symptoms and other xerostomic conditions in patients with Sjögren’s syndrome.
Santos Polvora et al. [87]	2018	28	Mouth spray	The pilocarpine spray significantly increased the salivary flow and alleviated xerostomia symptoms.
Pereira et al. [88]	2020	40	Mouth spray	The pilocarpine spray presented no significant differences as compared to placebo.
Sarideechaigul et al. [94]	2021	31	Artificial saliva	The evaluated formulations with were regarded as safe with minimum referred adverse effects. Specifically, while some adverse effects were in fact mentioned, they were not regarded as severe.
Gusmão et al. [95]	2021	25	Mucoadhesive tablets	The mucoadhesive tablets resulted to higher salivary concentrations of pilocarpine as compared to the conventional oral tablet.