Pilocarpine is a naturally occurring alkaloid and an important pharmaceutical active ingredient belonging to the cholinergic or muscarinic agonist class. It is primarily obtained from plants of the genus Pilocarpus and is widely recognized for its parasympathomimetic activity. Pilocarpine has the CAS Number 92-13-7, molecular formula C11H16N2O2, and molecular weight 208.26 g/mol. The compound is also known by names such as Pilokarpin, Pilocarpol and Syncarpine.
Pilocarpine API is widely associated with ophthalmic pharmaceutical applications. As a muscarinic receptor agonist, it stimulates cholinergic activity and produces effects such as contraction of the pupil and increased aqueous humor outflow. This pharmacological activity has made Pilocarpine an established active ingredient in pharmaceutical preparations used for the management of elevated intraocular pressure and glaucoma.
Pilocarpine is also used in pharmaceutical products designed to stimulate salivary secretion. Its cholinergic activity can increase exocrine gland secretion, making Pilocarpine an important API for formulations intended to manage dry mouth conditions.
Pilocarpine is a stereochemically defined compound. The USP specification identifies the pharmaceutical substance as the (3S-cis) form and specifies a specific rotation of +102° to +107° under the prescribed test conditions. This stereochemical characteristic is important because Pilocarpine can undergo epimerization and degradation, producing related compounds such as isopilocarpine and pilocarpic acid.
Pilocarpine may occur as an oil or crystals. Reported physical data include a melting range around 195–205°C, although the material can also exist in a liquid form depending on its physical state. PubChem reports that Pilocarpine is soluble in water, alcohol and chloroform and sparingly soluble in ether.
The USP 2025 monograph specifies that Pilocarpine contains 95.0% to 100.5% of C11H16N2O2, calculated on the anhydrous basis. The USP analytical procedure uses liquid chromatography with UV detection at 215 nm. The chromatographic system uses a 4.6 mm × 12.5 cm column containing 3 µm L1 packing, with a flow rate of approximately 1.0 mL/min.
The USP monograph also provides numerical limits for water, related compounds and inorganic impurities. Water content is limited to NMT 0.5%. Isopilocarpine is limited to NMT 2.0%, while the total of all impurities, including isopilocarpine, is limited to NMT 5.0%. No individual impurity corresponding to the four specified system-suitability peaks may exceed 3.0%, and other individual impurities are limited to 0.5%.
Identification of Pilocarpine can be performed using infrared spectroscopy and ultraviolet-visible spectroscopy. The USP identification procedure uses a 20 µg/mL solution in water for UV testing. The monograph also specifies a refractive index of 1.5170–1.5210 at 25°C for a liquid specimen.
The USP specification additionally controls chloride at 0.25% and sulfate at 0.004% using comparative pharmacopoeial tests. Nitrate is limited to 0.005%. These controls are particularly relevant for maintaining the chemical purity of Pilocarpine API.
Pilocarpine Base should be distinguished from Pilocarpine Hydrochloride and Pilocarpine Nitrate. Pilocarpine Hydrochloride has CAS Number 54-71-7 and molecular weight 244.72 g/mol, while Pilocarpine Nitrate has CAS Number 148-72-1 and molecular weight approximately 271.3 g/mol. These salt forms have separate pharmacopoeial specifications and should not be treated as interchangeable with Pilocarpine Base.
USP recommends preserving Pilocarpine in tight, light-resistant containers and in a cold place. Appropriate storage is important because Pilocarpine can undergo degradation and epimerization under unsuitable environmental conditions. Controlled storage, suitable packaging and validated analytical testing are therefore important for maintaining API quality.
Pilocarpine API is consequently an established specialty pharmaceutical ingredient with defined chemical identity, stereochemical characteristics and pharmacopoeial quality requirements. Its controlled assay, water content, related substances, optical rotation and refractive index make it suitable for pharmaceutical development and manufacturing applications where consistent Pilocarpine quality is required.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 95.0% – 100.5% |
| Total Impurities | NMT 5.0% |
| Water Content | NMT 0.5% |
| Specific Rotation | +102° to +107° |