Pilocarpine Ocular System
»Pilocarpine Ocular System contains not less than 85.0percent and not more than 115.0percent of the labeled amount of pilocarpine (C11H16N2O2).It is sterile.
Packaging and storage— Preserve in single-dose containers,in a cold place.
Identification— Cut around the inside margin of the Ocular System,then discard the ring encircling the Ocular System,extract the remaining portion with 0.5mLof methanol in a small capped vial,shaking vigorously for 1to 2minutes.Evaporate the methanol extract on a sodium chloride plate forming a thin film:the IRabsorption spectrum of the film exhibits maxima only at the same wavelengths as that of a similar preparation of USP Pilocarpine RS.
Sterility á71ñ: meets the requirements.
Uniformity of dosage units á905ñ: meets the requirements for capsules.
Drug release pattern— Place each of the Ocular Systems in suitable porous holders made of an inert material,and suspend each from a nickel wire.To the upper end of the wire attach a tag identifying the specimen.Put each assembly into a test tube containing 27.0mLof saline TSso that the system lies at the bottom of the tube and the identifying tag extends from the open top of the tube.Put the tubes into a horizontally reciprocating shaker in which the temperature is maintained at 37±0.5.Agitate the tubes with a horizontal amplitude of about 4cm and a frequency of about 35cycles per minute.At 7,24,48,72,96,and 168hours,remove the assemblies from their tubes,and each time replace them in similar tubes containing 27.0mLof fresh saline TS.Determine the amount of pilocarpine in solution in each tube,after adjusting the volume to 27.0mLto make up for any evaporative losses,by measuring the UVabsorbance in 1-cm cells at the wavelength of maximum absorbance at about 215nm,with a suitable spectrophotometer,against saline TSas the blank.Concomitantly measure the absorbance of a Standard solution of USP Pilocarpine Hydrochloride RShaving a known concentration of about 20µg in each mLof saline TS.Calculate the quantity,in µg,of C11H16N2O2in each solution taken by the formula:
(208.26/244.72)(AU/AS)27C,
in which 208.26and 244.72are the molecular weights of pilocarpine and pilocarpine hydrochloride,respectively,AUand ASare the absorbances of the test solution and the Standard solution,respectively,and Cis the concentration,in µg per mL,of USP Pilocarpine Hydrochloride RSin the Standard solution.Calculate the amount of pilocarpine released in 168hours by adding the pilocarpine content of each set of tubes collected over 168hours.
Tolerances— The amount of C11H16N2O2from each Ocular System released during the total 0to 168hours tested conforms to Acceptance Table 4under Drug Release á724ñ.The drug release range for this time period is not less than 80.0%and not more than 120.0%of the labeled release pattern.
Assay—
Buffer solution,Mobile phase,Standard preparation,System suitability preparation,andChromatographic system— Proceed as directed in the Assayunder Pilocarpine.
Assay preparation— Select not less than 10Ocular Systems.Cut each System into 4pieces,transfer quantitatively to a 500-mLvolumetric flask,and rinse all cutting utensils with 20to 30mLof methanol into the flask.Make additional rinses of the utensils with about 250mLof Mobile phase,and collect all the rinses in the flasks.Allow the flasks to stand for 30minutes,sonicate for about 15minutes,dilute with water to volume,and mix.Transfer an aliquot of the supernatant,equivalent to 6mg of pilocarpine to a 200-mLvolumetric flask,dilute with water to volume,mix,and filter.
Procedure— Proceed as directed for Procedurein the Assayunder Pilocarpine.Calculate the quantity,in mg,of Pilocarpine.Calculate the quantity,in mg,of Pilocarpine in each ocular system taken by the formula:
(208.26/271.27)(10/V)(C/N)(rU/rS),
in which 208.26and 271.27are the molecular weights of pilocarpine and pilocarpine nitrate,respectively,Vis the volume,in mL,of the supernatant taken (see Assay preparation),Cis the concentration,in µg per mL,of USP Pilocarpine Nitrate RSin the Standard preparation,Nis the number of Ocular Systems taken,and rUand rSare the peak responses for pilocarpine obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 1560
Phone Number:1-301-816-8389