Pilocarpine Ocular System
» Pilocarpine Ocular System contains not less than 85.0 percent and not more than 115.0 percent of the labeled amount of pilocarpine (C11H16N2O2). It is sterile.
Packaging and storage Preserve in single-dose containers in a cold place.
USP Reference standards 11
Identification Cut around the inside margin of the Ocular System, then discard the ring encircling the Ocular System, extract the remaining portion with 0.5 mL of methanol in a small capped vial, shaking vigorously for 1 to 2 minutes. Evaporate the methanol extract on a sodium chloride plate forming a thin film: the IR absorption spectrum of the film exhibits maxima only at the same wavelengths as that of a similar preparation of USP Pilocarpine RS.
Sterility 71: meets the requirements.
Uniformity of dosage units 905: 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 27.0 mL of saline TS so 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 4 cm and a frequency of about 35 cycles per minute. At 7, 24, 48, 72, 96, and 168 hours, remove the assemblies from their tubes, and each time replace them in similar tubes containing 27.0 mL of fresh saline TS. Determine the amount of pilocarpine in solution in each tube, after adjusting the volume to 27.0 mL to make up for any evaporative losses, by measuring the UV absorbance in 1-cm cells at the wavelength of maximum absorbance at about 215 nm, with a suitable spectrophotometer, against saline TS as the blank. Concomitantly measure the absorbance of a Standard solution of USP Pilocarpine Hydrochloride RS having a known concentration of about 20 µg in each mL of saline TS. Calculate the quantity, in µg, of C11H16N2O2 in each solution taken by the formula:
(208.26 / 244.72)(AU / AS)27Cin which 208.26 and 244.72 are the molecular weights of pilocarpine and pilocarpine hydrochloride, respectively; AU and AS are the absorbances of the test solution and the Standard solution, respectively; and C is the concentration, in µg per mL, of USP Pilocarpine Hydrochloride RS in the Standard solution. Calculate the amount of pilocarpine released in 168 hours by adding the pilocarpine content of each set of tubes collected over 168 hours.
Tolerances The amount of C11H16N2O2 from each Ocular System released during the total 0 to 168 hours tested conforms to Acceptance Table 1 under Drug Release 724. 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.
Buffer solution, Mobile phase, Standard preparation, System suitability preparation, and Chromatographic system Proceed as directed in the Assay under Pilocarpine.
Assay preparation Select not fewer than 10 Ocular Systems. Cut each System into 4 pieces, transfer quantitatively to a 500-mL volumetric flask, and rinse all cutting utensils with 20 to 30 mL of methanol into the flask. Make additional rinses of the utensils with about 250 mL of Mobile phase, and collect all the rinses in the flasks. Allow the flasks to stand for 30 minutes, sonicate for about 15 minutes, dilute with water to volume, and mix. Transfer an aliquot of the supernatant, equivalent to 6 mg of pilocarpine to a 200-mL volumetric flask, dilute with water to volume, mix, and filter.
Procedure Proceed as directed for Procedure in the Assay under 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 208.26 and 271.27 are the molecular weights of pilocarpine and pilocarpine nitrate, respectively; V is the volume, in mL, of the supernatant taken (see Assay preparation); C is the concentration, in µg per mL, of USP Pilocarpine Nitrate RS in the Standard preparation; N is the number of Ocular Systems taken; and rU and rS are the peak responses for pilocarpine obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 4321Pharmacopeial Forum: Volume No. 31(1) Page 177