rhe relative retention ·
`,r isopilocarpine, O. 76 .
`1.0 for isopilocarpic
`·:
`lumes (about 40 µL) 0
`oaration into the c
`.(cid:173)
`easure the responses for
`lf pilocarpine (C 11H,.
`formula:
`
`'(ru l rs),
`
`:ular weights of pit
`he concentration, in mg
`Standard preparatio11
`,carpine obtained fro~
`aration, respectively.
`
`m
`
`iins not less than 8S
`percent of the labe
`>2)- It is sterile.
`'
`
`P Pilocarpi11e RS.
`;arpine Nitrate RS.
`rgin of the Ocular Sy
`cular System, extract
`101 in a small capped
`porate the methanol
`in film: the IR abso '
`at the same wavelen
`'
`arpine RS.
`
`Ocular Systems in s ·
`. and suspend each
`attach a tag identify'
`1be containing 27.0 . .
`-ottom of the tube an
`of the tube. Put the
`1 which the tempera
`tubes with a hori
`:y of about 35 cycles'
`1rs, remove the assem
`:e them in similar
`Determine the am
`ijusting the volume IQ
`.es, by measuring the,
`h of maximum abso
`Jtometer, against saJ' . ·
`absorbance of a S
`:ide RS having a
`of saline TS. Calcu
`1tion taken by the fo
`
`.
`
`ls)27C,
`
`lllar weights ofpil
`1ely, Au and As are·
`the Standard sol
`, in µg per mL. of
`lard solution. Calcul
`s by adding the pil
`· 168 hours.
`from each Ocular S
`ed conforms to Ace
`irug release range
`t more than 120.0¾_
`
`· r-;, solution, Mobile phase, Standard preparation, System
`
`. bi/ity preparation, and Chromatographic system-Proceed as
`in the Assay under Pilocarpine.
`ay preparation-Select not less than IO Ocular Systems. Cut
`Ass system into 4 J!ieces, tran~fer quan_titati~ely to a 500-mL
`tric flask, and nnse all cutting utensils with 20 to 30 mL of
`ol into the flask. Make additional rinses of the utensils with
`t 250 mL of Mobile phase, and collect all the rinses in the flasks.
`w the flasks to stand for 30 minutes, sonicate for about 15
`. tes dilute with water to volume, and mix. Transfer an aliquot of
`sup~matant, e9uivale?t to 6 mg of pilocary,ine to a 200-mL
`etric flask, dilute with water to volume, mix, and filter.
`p,.ocedure-Proceed as directed for Procedure in the Assay under
`,pine. Calculate the quantity, in mg, of Pilocarpine. Calculate
`quantity, in mg, of Pilocarpine in each ocular system taken by the
`ula:
`
`(208.26/271.27)(10/ V)(C/ N)(rulrs),
`
`'
`
`which 208.26 and 271.27 are the molecular weights ofpilocarpine
`pilocarpine nitrate, respectively, Vis the volume, in mL, of the
`tant taken (see Assay preparation), C is the concentration, in
`· per mL, of USP Pilocarpine Nitrate RS in the Standard
`tion, N is the number of Ocular Systems taken, and ru and
`are the peak responses for pilocarpine obtained from the Assay
`ration and the Standard preparation, respectively.
`
`ocarpine Hydrochloride
`
`16N,01 • HCI 244.72
`H)-Furanone, 3-ethyldihydro-4-[( I-methyl- I H-imidazol-5-
`yl)methyl]-, monohydrochloride, (3S-cis)-.
`[54-71-7].
`ine monohydrochloride
`
`· ocarpine Hydrochloride contains not less than 98.5
`rcent and not more than IO l.O percent of
`11H16N2O2 · HCI, calculated on the dried basis.
`·ng and storage-Preserve in tight, light-resistant containers.
`Reference standards (11)-USP Pilocarpine Hydrochloride
`
`cation-
`lefrared Absorption ( 197M) .
`A solution ( I in 20) responds to the tests for Chloride ( 191).
`range (741): between 199° and 205°, but the range
`beginning and end of melting does not exceed 3 °.
`c rotation (781S}: between +88.5° and +91.5°.
`solution: 20 mg per mL, in water.
`on drying (731 }-Dry it at I 05° for 2 hours: it loses not more
`3.0% of its weight.
`~rbonizable substances (271 )-Dissolve 250 mg in 5 mL
`func acid TS: the solution has no more color than Matching
`. B.
`ary impurities (466)(cid:173)
`solution: dehydrated alcohol.
`ard solution: dehydrated alcohol.
`t: a mixture of hexanes, dehydrated alcohol, and ammo(cid:173)
`h
`ydroxide (70 : 30 : I).
`lization: 17.
`'ts: not more than I%.
`. •l~Ioids-Dissolve 200 mg in 20 mL of water, and divide the
`~ into two portions. To one portion add a few drops of 6 N
`•um hydroxide, and to the other add a few drops of potassium
`le TS: no turbidity is produced in either solution.
`Disso_lve about 500 mg of Pilocarpine Hydrochloride,
`ly weighed, in a mixture of 20 mL of glacial acetic acid
`0
`· ml of mercuric acetate TS, warming slightly to effect
`·. Cool the solution to room temperature, add 2 drops of
`
`,.
`
`t 0let _TS, and titrate with 0.1 N perchloric acid VS. Perform a
`
`cterrnmation, and make any necessary correction. Each mL of
`, l>Crchlonc acid is equivalent to 24.47 mg of C 11H 16N10 1 · HCI.
`
`Official Monographs I Pilocarpine
`
`1561
`
`Pilocarpine Hydrochloride Ophthalmic
`Solution
`
`» Pilocarpine Hydrochloride Ophthalmic Solution is a
`sterile, buffered, aqueous solution of Pilocarpine Hydro(cid:173)
`chloride. It contains not less than 90.0 percent and not
`more than 110.0 percent of the labeled amount of
`C11H16N2O2 · HCL It may contain suitable antimicrobial
`agents and stabilizers, and suitable additives to increase
`its viscosity.
`Packaging and storage-Preserve in tight containers.
`USP Reference standards (11)-USP Pilocarpine Hydrochloride
`RS.
`Identification-The retention time of the major peak in the
`chromatogram of the Assay preparation corresponds to that in the
`chromatogram of the Standard preparation, as obtained in the Assay.
`Sterility (7 I): meets the requirements.
`pH (791): between 3.5 and 5.5.
`Assay-
`Mobile phase-Mix 300 mL of a I in 50 solution of ammonium
`hydroxide in isopropyl alcohol and 700 mL of n-hexane. Filter
`through a 0.5-µm filter before using.
`Standard preparation-Using an accurately weighed quantity of
`USP Pilocarpine Hydrochloride RS, prepare a solution having a
`known concentration of about 1.6 mg per mL.
`Assay preparation-Transfer an accurately measured volume of
`Ophthalmic Solution, equivalent to about 80 mg of pilocarpine
`hydrochloride, to a 50-mL volumetric flask. Dilute with methanol to
`volume, and mix.
`Chromatographic system (see Chromatography (621 )}-The
`liquid chromatograph is equipped with a 220-nm detector and a
`4.6-mm x 25-cm column that contains packing L3. The flow rate is
`about 2 mL per minute. Chromatograph three replicate injections of
`the Standard preparation, and record the peak responses as directed
`for Procedure: the relative standard deviation is not more than 2.0%.
`Procedure-Separately inject equal volumes ( about 10 µL) of the
`Standard preparation and the Assay preparation into the chromat(cid:173)
`ograph by means of a suitable microsyringe or sampling valve, record
`the chromatograms, and measure the responses for the major peaks.
`The retention time is about 16 minutes for pilocarpine hydrochloride .
`Calculate the quantity, in mg, of C 11 H 16N20, · HCI in each mL of the
`Ophthalmic Solution taken by the formula:
`50(C I V)(rul rs),
`in which C is the concentration, in mg per mL, of USP Pilocarpine
`Hydrochloride RS in the Standard preparation, Vis the volume, in
`mL, of Ophthalmic Solution taken, and ru and rs are the peak
`responses obtained from the Assay preparation and the Standard
`preparation, respectively.
`
`Pilocarpine Nitrate
`
`C 11H 16N,02 • HN03 271.27
`2(3H)-Furanone, 3-ethyldihydro-4-[( I-methyl- I H-imidazol-5-
`yl)methyl]-, (3S-cis)-, mononitrate.
`[148-72-1].
`Pilocarpine mononitrate
`
`» Pilocarpine Nitrate contains not less than 98.5 percent
`and not more than 101.0 percent of C11H16N2O2 · NO3,
`calculated on the dried basis.
`Packaging and storage-Preserve in tight, light-resistant containers.
`USP Reference standards {11 )-USP Pilocarpine Nitrate RS.
`Identification-
`A:
`Infrared Absorption ( 197K).
`
`Slayback Exhibit 1055, Page 60 of 78
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`1562
`
`Pilocarpine / Official Monographs
`
`B: Mix a solution (1 in 10) with an equal volume of ferrous
`sulfate TS, and superimpose the mixture upon 5 mL of sulfuric acid
`contained in a test tube: the zone of contact becomes brown.
`Melting range (741 }: between 171° and 176°, with decomposition,
`but the range between beginning and end of melting does not exceed
`30_
`Specific rotation {781S): between +79.5° and +82.5°.
`Test solution: 20 mg per mL, in water.
`Loss on drying (731 )-Dry it at 105° for 2 hours: it loses not more
`than 2.0% of its weight.
`Readily carbonizable substances (271 }-Dissolve I 00 mg in 5 mL
`of sulfuric acid TS: the solution has no more color than Matching
`Fluid A.
`Chloride-To 5 ml ofa solution (I in 50), acidified with nitric acid,
`add a few drops of silver nitrate TS: no opalescence is produced
`immediately.
`Other alkaloids-Dissolve 200 mg in 20 mL of water, and divide the
`solution into two portions. To one portion add a few drops of _6 N
`ammonium hydroxide and to the other add a few drops of potassmm
`dichromate TS: no turbidity is produced in either solution.
`Assay-Dissolve about 600 mg of Pilocarpine Nitrate, accurately
`weighed, in 30 mL of glacial acetic acid, warming slightly to effect
`solution. Cool to room temperature, and titrate with 0.1 N perchloric
`acid VS, detennining the endpoint potentiometrically. Perform a
`blank detennination, and make any necessary correction. Each mL of
`0. IN perchloric acid is equivalent to 27.13 mg of C 11H,.N2O2 · NO,.
`
`Pilocarpine Nitrate Ophthalmic Solution
`
`» Pilocarpine Nitrate Ophthalmic Solution is a sterile,
`buffered, aqueous solution of Pilocarpine Nitrate. It
`contains not less than 90.0 percent and not more than
`110.0 percent of the labeled amount of
`C 11H 16N2O2 · HNO3. It may contain suitable antimicro(cid:173)
`bial agents and stabilizers, and suitable additives to
`increase its viscosity.
`
`Packaging and storage-Preserve in tight, light-resistant containers.
`USP Reference standards ( 11 }-USP Pilocarpine Nitrate RS.
`Identification-
`A: The retention time of the major peak in the chromatogram of
`the Assay preparation corresponds to that in the chromatogram of the
`Standard preparation obtained as directed in the Assay.
`B:
`It responds to Identification test B under Pilocarpine Nitrate.
`Sterility {71 ): meets the requirements.
`pH (791 ): between 4.0 and 5.5.
`Assay-Proceed with Ophthalmic Solution as directed in the Assay
`under Pilocarpine Hydrochloride Ophthalmic Solution, except_ to
`read pilocarpine nitrate instead of pilocarpine hydrochlonde
`throughout and to calculate the quantity, in mg, ofC 11H 16N202 · ~O,
`in each mL of the Ophthalmic Solution taken by the fonnula given
`therein.
`
`Pimozide
`
`C2,H2.F2N 10 461.55
`2H-Benzimidazol-2-one, 1-( 1-[ 4,4-bis( 4-fluorophenyl)buty(
`piperidinyl)-1,3-dihydro-.
`.
`1-( 1-(4,4-Bis(p-fluorophenyl)butyl]-4-piperidyl]-2-benzimi
`'
`[2062-78-4].
`none
`
`"
`» Pirnozide contains not less than 98.0 percent and:
`more than I 02.0 percent of C2sH29F2N3O, calculat
`the dried basis.
`
`·
`
`Packaging and storage-Preserve in tight, light-resistant con · 1
`USP Reference standards ( 11 }-USP Pimozide RS.
`Identification-
`A:
`Infrared Absorption (197K) .
`B: Ultraviolet Abs01ption (197U)-
`Solution: 35 µg per mL.
`Medium: 0.1 N hydrochloric acid in methanol (I in 10).
`Melting range, Class I (741}: between 216° and 220°.
`_
`Loss on drying (731 }-Dry it in vacuum at 80° for 4 hours: ii-..
`not more than 0.5% of its weight.
`, .
`Residue on ignition (281): not more than 0.2%, a 2-g portion'.
`platinum crucible being used for the test.
`Heavy metals, Method II (231} : 0.002%.
`Ordinary impurities (466)-
`Test solution: chlorofonn.
`Standard solution: chloroform.
`Eluant: a mixture of cyclohexane and acetone ( I : I).
`l, then 17.
`Visualization:
`Limit- The total of any ordinary impurities observed
`exceed 1.0%.
`Organic volatile impurities, Method V (467}: meets the
`ments.
`Solvem-Use dimethyl sulfoxide.
`Assay-Dissolve about 320 mg of Pimozide, accurately ~ei
`40 mL of glacial acetic acid. Titrate with 0.1 N perchlonc
`determining the endpoint potentiometrically. ~erfonn ha 1
`determination, and make any necessary correction. Eac
`0.1 N perchloric acid is equivalent to 46.16 mg of C2,H,.F2N3 :.
`
`Pimozide Tablets
`
`» Pimozide Tablets contain not less than 90.0 .
`and not more than I 10.0 percent of the labeled aJll~ ·
`C2sH29F2N3O.
`Packaging and storage-Preserve in tight, light-resistant co~ .
`USP Reference standards( 11 )-USP Pimozide RS.
`•!I
`Identification-The retention time . of the major P~,
`·
`chromatogram of the Assay preparation corresponds to
`Standard preparation, both relative to the internal stan ·
`obtained in the Assay.
`
`tion, Procedure J
`J,ledium: 0.01 N hyd
`ratus 2: 50 rprr
`• 1111e: 30 minutes.
`ndard preparation(cid:173)
`accurately weighed,
`oflactic acid. Heat 01
`t water, and shake. (
`e the solution quan·
`· a solution having
`as that of the s
`ution).
`edure-Transfer a
`le container, and ce
`atant, estimated ·
`· g complete dissc
`volume of the Stand
`container add 20 ml
`· fonn. Shake each
`· es, and centrifuge.
`transfer the chloro.
`·ne the amount of
`chloroform layers ol
`preparation, in :
`ce at about 277 n
`/erances-Not less t
`2N30 is dissolved i
`'ty of dosage un,
`edure for content u;
`5.0 mL of 0.1 N hyd
`for 30 minutes. A
`ical means for 20 n
`methanol to obtain a s
`of pimozide per mI
`·ne the absorbance
`. Pimozide RS in the sa:
`t40µgpermLin l
`ce at about 277 nn
`of 0.1 N hydrocl
`Calculate the quant
`. by the formula:
`
`(:
`Tis the labeled qu
`concentration, in µ1
`solution, D is the ,
`solution from the Ta
`and the extent of dilu
`lion from the Table•
`NOTE-Protect all
`nium acetate solu
`in 100 mL of water,
`P! phase-Prepare
`le and Ammoniu
`ts if necessary (s,
`(62)}).
`al standard solutio
`· lure of methanol
`having a concentra1
`rd preparation-T
`tely weighed, to 1
`standard solution,
`furan (I : I) to vol
`preparation-Weig
`Transfer an accun
`t to about 25 mg o1
`rnL of Internal stanG
`l_and tetrahydrofum
`'llllnutes. Dilute with
`: I) to volume, and ,
`preparation.
`tographic system
`matograph is eq1
`l< 25-cm column th
`ut 2 mL per minute
`preparation, an
`ure: the relative st.
`
`Slayback Exhibit 1055, Page 61 of 78
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`1578
`
`Polymyxin / Official Monographs
`
`Polymyxin B Sulfate and Bacitracin Zinc
`Topical Powder
`
`» Polymyxin B Sulfate and Bacitracin Zinc Topical
`Powder contains not less than 90.0 percent and not more
`than 130.0 percent of the labeled amounts ofpolymyxin
`B and bacitracin.
`
`Packaging and storage--Preserve in well-closed containers.
`USP Reference standards ( 11 )-USP Polymyxin B Sulfate RS. USP
`Bacitracin Zinc RS.
`Microbial limits---Collect aseptically in a suitable container about
`I g from not less than 5 containers, dissolve in 500 mL of Fluid A,
`filter through a membrane filter as directed for Membrane Filtration
`under Test for Sterility of the Product to be Examined under Sterility
`Tests (71), except to place the filter on the surface of Soybean-Casein
`Digest Agar Medium in a Petri dish, incubate for 7 days at 30° to 35°,
`and count the number of colonies on the filter. Similarly prepare a
`second specimen, except to incubate at 20° to 25°. Not more than 20
`colonies are observed from the two specimens. It meets also the
`requirements of the tests for absence of Staphylococcus aureus and
`Pseudomonas aeruginosa under Microbial Limit Tests ( 61 ).
`Water, Method I (921 ): not more than 7.0%.
`Assay for polymyxin B-Proceed as directed for polymyxin B under
`Antibiotics-Microbial Assays (81), using an accurately weighed
`portion of Topical Powder, equivalent to about 5000 USP Polymyxin
`B Units, shaken with 20 mL of water in a suitable volumetric flask.
`Dilute with Buffer No. 6 to volume, and mix. Dilute an accurately
`measured volume of the solution so obtained quantitatively with
`Buffer No. 6 to obtain a Test Dilution having a concentration of
`polymyxin B assumed to be equal to the median dose level of the
`Standard.
`Assay for bacitracin-Proceed as directed for bacitracin under
`Antibiotics-Microbial Assays (8 I), using an accurately weighed
`portion of Topical Powder, equivalent to about 800 USP Bacitracin
`Units, added to a 100-mL volumetric flask, dilute with 0.01 N
`hydrochloric acid to volume, and mix. Dilute this solution
`quantitatively with Buffer No. 1 to obtain a Test Dilution having a
`concentration assumed to be equal to the median dose level of the
`Standard. In preparing each test dilution of the Standard, add
`additional hydrochloric acid to each to obtain the same concentration
`of hydrochloric acid as in the Test Dilution.
`
`Polymyxin B Sulfate and Hydrocortisone
`Otic Solution
`
`» Polymyxin B Sulfate and Hydrocortisone Otic
`Solution is a sterile solution containing not less than
`90.0 percent and not more than 130.0 percent of the
`labeled amount of polymyxin B, and not less than 90.0
`percent and not more than 110.0 percent of the labeled
`amount of hydrocortisone (C21 H 300 5). It may contain
`one or more suitable buffers and preservatives.
`NOTE-Where Polymyxin B Sulfate and Hydrocortisone
`Otic Solution is prescribed without reference to the
`quantity of polymyxin B or hydrocortisone contained
`therein, a product containing I 0,000 Polymyxin B Units
`and 5 mg of hydrocortisone per mL shall be dispensed.
`
`Packaging and storage--Preserve in tight, light-resistant containers.
`USP Reference standards ( 11 )-USP Polymyxin B Sulfate RS. USP
`Hydrocortisone RS.
`Sterility (71) : meets the requirements.
`
`pH (791) : between 3.0 and 5.0.
`Assay for polymyxin-Proceed with Otic Solution as directed
`Antibiotics-Microbial Assays (81}, using an accurately m
`volume of Otic Solution diluted quantitatively with Buffer N, 6
`yield a Test Dilution having a concentration assumed to be ~~
`,,
`the median dose level of the Standard.
`Assay for hydrocortisone--
`,11
`Mobile phase-Prepare a suitable solution of about 500 volumes
`methanol, 500 volumes of water, and I volume of glacial acetic
`•
`su~h that the retention time of hydrocortisone is between 6 and l
`mmutes.
`Standard preparation-Dissolve a suitable quantity of tJ
`Hydrocortisone RS, accurately weighed, in a mixture of me
`and water (I : I) to obtain a solution having a known concentration
`about 0.15 mg per mL.
`1ssay p_reparat(on-Transfer an accurately measured volume ·
`Otic Solut1on, equivalent to about 15 mg ofhydrocortisone, to a I ·
`ml volumetric flask, dilute with a mixture of methanol and
`(l : I) to volume, and mix.
`Chromatographic system (see Chromatography (621)}- '
`chromatograph is equipped with a 254-nm detector and a 4-nun .
`30-cm column that contains packing LI . The flow rate is about 2° '
`per minute. Chromatograph five replicate injections of the Stan
`preparation, and record the peak responses as directed for Proce
`·1
`the relative standard deviation is not more than 2.0%.
`Procedure-Separately inject equal volumes (about 10 µL) of
`Standard preparation and the Assay preparation into the ch
`.,
`ograph by means of a suitable microsyringe or sampling v
`adjusting the specimen size and other operating parameters such
`the peak obtained from the Standard preparation is about 0.6
`scale. Record the chromatograms, and measure the responses fo{
`major peaks. Calculate the quantity, in mg, ofC1,H300, in each
`the Otic Solution taken by the formula:
`
`· 1-r
`
`(!00C/ VXHvl Hs),
`in which C is the concentration, in mg per ml, of
`Hydrocortisone RS in the Standard preparation, V is the vol ·
`in mL, of the portion of Otic Solution taken, and Hv and H., are
`peak responses obtained from the Assay preparation and ·
`Standard preparation, respectively.
`
`Polymyxin B Sulfate and Trimethoprim.
`Ophthalmic Solution
`; u
`
`» Polymyxin B Sulfate and Trimethoprim Ophth -
`Solution is a sterile, isotonic, aqueous solution
`Polymyxin B Sulfate and Trimethoprim Sulfate or
`Polymyxin B Sulfate and Trimethoprim that has
`solubilized with Sulfuric Acid. It contains not less
`90.0 percent and not more than 130.0 percent of
`labeled amount of polymyxin B and the equivalent of .
`less than 90.0 percent and not more than 110.0 percent
`the labeled amount of trimethoprim (C14H1sN403).'
`contains one or more preservatives.
`
`Packaging and storage--Preserve in tight, light-resistant con
`and store at controlled room temperature.
`Labeling-Label it to indicate that it is to be stored at 15° to
`protected from light.
`USP Reference standards ( 11 )-USP Polymyxin B Sulfate RS.
`Trimethoprim RS.
`Identification-
`A:
`It meets the requirements for polymyxin B under Thin·
`Chromatographic Identification Test (201BNP).
`.
`B: The retention time of the trimethoprim peak 1~
`chromatogram of the Assay preparation corresponds t~ that
`·
`chromatogram of the Standard preparation, as obtained in the .
`for trimethoprim.
`
`··
`
`· ·ty (7 I )-It meet
`rane Filtration l
`ined.
`(791) : between '
`y for polymyxin :E
`· iotics-Microbial
`e of Ophthalmic
`· Buffer No. 6, to ot
`yxin B assumed
`
`y for trimethopri
`'/uent-Prepare a
`nitrile (870 : 130).
`obile phase-Dissc
`a mixture of water a
`·um hydroxide or 0.
`· n through a filter
`e adjustments if
`atography {621)
`ndard preparation
`Trimethoprim RS i
`tration of about c
`Assay preparation-·
`lmic Solution, ec
`volumetric flask
`Chromatographic SJ
`·d chromatograph i
`x 30-cm colun
`t 1.5 ml per minut
`_ record the peak res1
`is not more than
`· and the relative st:
`than 2.0%.
`edure-Separatel
`ard preparation a:
`record the chron
`· r peaks. Calculat
`11N,03) in each m
`la:
`
`· ich C is the concen
`_' in the Standard p
`lmic Solution ta1<
`rs are the trimethop
`preparation and (
`
`I
`
`. hich the averag
`• It is prepan
`lysis of polyvi
`tipoises, at 2(
`inyl Alcohol i
`t and not more
`I.
`
`Slayback Exhibit 1055, Page 62 of 78
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`lution as directed
`n accurately m
`ly with Buffer No.
`assumed to be equa)
`
`,f about 500 vol
`1e of glacial ac
`1e is between 6
`
`·ography (621))--.: '
`.etector and a 4-mm .
`flow rate is about 2
`ections of the Stan ·
`directed for Proc
`an 2.0%.
`es (about 10 µL) of
`:ztion into the chro ·
`ge or sampling v
`ng parameters such
`·ation is about 0.6
`ire the responses for_
`·c2,H30Os in each
`
`ng per mL, of
`1tion, V is the vol
`, and Hu and H., are
`· preparation and.
`
`•ty (71 )-It meets the requirements when tested as directed for
`rane Filtration under Test for Sterility of the Product to be
`ined.
`,. (791):
`.
`.
`between 4.0 and 6.2.
`for polymyxin B-Proceed as d1~cted for polymyxm B under
`.
`. ~otics-Microbial Assays (81), usmg an accurately measu~ed
`1
`of Ophthalmic Solution, diluted quantitatively and stepwise
`Buffer No. 6, to obtain a Test Dilution having a concentration of
`yxin B assumed to be equal to the median dose level of the
`
`· y for trimethoprim-:-
`i/uent-Prepare a mixture of 0.01 N hydrochloric acid and
`itrile (870 : 130).
`.
`.
`.
`obile phase-Dissolve 1.65 g_ o~ ethanesulfomc ac!d m I _000 mL
`· 8 mixture of water and acetomtnle. (87~ : 130). Adjust with l 0 ~
`·um hydroxide or0.l N hydrochlonc acid to a pH of3.5. Pass this
`· n through a filter having a 0.5-µm or finer porosity, and degas.
`e adjustments if necessary (see System Suitability under
`matography (621)).
`.
`_
`andard preparation-Dissolve an accurately ~e1ghe~ quantity of
`Trimethoprim RS in Diluent to obtain a solution havmg a known
`ntration of about 0.04 mg per mL.
`. Assay preparation-Transfer an accurately me~ured vol~me of
`thalmic Solution, equivalent to about l mg oftnmethopn~, to a
`volumetric flask, dilute with Diluent to volume, and mIX.
`Chromatographic system (see Chromatography (621))-The
`· chromatograph is equipped with a 254-nm detector and _a
`x 30-cm column that contains packing L 11. The flow rate 1s
`t 1.5 mL per minute. Chromatograph the Standard prepara~i<;>n,
`record the peak responses as directed for Procedure: the ta1hng
`· r is not more than 1.5, when calculated a~ 10'!:o _hei~ht ~f the
`· • and the relative standard deviation for replicate m1ect10ns 1s not
`·' than 2.0%.
`edure-Separately inject equal volumes (about 10 µL) of the
`' ard preparation and the Assay preparation into the chromat(cid:173)
`b, record the chromatograms, and measure the resp~nses for ~e
`dor peaks. Calculate the quantity, i~ mg, ?f tnmethopnm
`J{,.N,03) in each mL of the Ophthalmic Solution taken by the
`ula:
`
`25(CIV)(rul rs),
`ich C is the concentration, in mg per mL, of USP Trimethoprim
`· in the Standard preparation; V is the volume, i_n mL, of
`·thalmic Solution taken to prepare the Assay prepa~atzon; and ru
`r5 are the trimethoprim peak area responses obtame~ from the
`preparation and the Standard preparation, respectively.
`
`.
`
`b.oprirn Ophth
`1ueous solution
`,prim Sulfate or
`prim that has
`ntains not less
`30.0 percent of
`he equivalent of
`1an 11 O. O percent'
`m (C14H1sN403).;
`
`.
`
`1JCin B under Thin(cid:173)
`'1/P).
`.
`~thoprim peak 1~
`,rresponds to that 111 -
`as obtained in the
`
`Official Monographs I Potash
`
`1579
`
`Packaging and storage-Preserve in well-closed containers.
`Viscosity-After determining the Loss on drying, weigh a q?antity ~f
`undried Polyvinyl Alcohol, equivalent to 6.00_g on ~e dned_ basis.
`Over a period of seconds, transfer the test spe~1me~ with ~ontmuous
`slow stirring to about 140 mL of water C?ntamed m a smtable_ ~red
`flask. When the specimen is well-wetted, 1_ncrease the rate of stl~n~,
`avoiding mixing in excess air. Heat the mIXture to 90°, and mamtam
`the temperature at 90° for about 5 minutes. Discontinue _heating, ~d
`continue stirring for I hour. Add water to make the ~1xtu~ weigh
`150 g. Resume stirring to obtain a hom~genous solution. ~liter the
`solution through a tared I 00-mesh screen mto a 250-mL corneal flask,
`cool to about 15°, mix, and proceed as directed under Vzscosity (911).
`pH (791): between 5.0 and 8.0, in a solution (l in 25).
`Loss on drying (731 )-Dry it at 110° to constant weight: it loses not
`more than 5.0% of its weight.
`Residue on ignition {281 ): not more than 2.0%.
`Water-insoluble substances-Wash the tared 100-mesh screen used
`in the test for Vzscosity with two 25-mL portions of water, and dry at
`110° for 1 hour: not more than 6.4 mg of water-insoluble substances
`is found (0.l %).
`Organic volatile impurities, Method I (467): meets the require(cid:173)
`ments.
`Degree of hydrolysis-
`Procedure-Transfer about I g of Polyvinyl Alcohol, previously
`dried at ll 0° to constant weight and accurately wei~ed, to a ""'.i~e(cid:173)
`mouth, 250-mL conical flask fitted by means of a su1ta?le glass JOI~!
`to a reflux condenser. Add 35 mL of dilute methanol (3 m 5), and mix
`gently to assure complete wetting of the s~lid .. Add 3 drop~ of
`phenolphthalein TS, and add 0.2 N_ hydrochlonc acid or 0.2 N sod!um
`hydroxide, if necessary, to neutrahze. Add 25.0 mL of 0.2 N sodium
`hydroxide VS, and reflux gently on a h_ot plate for l_ ho~. Wash the
`condenser with l 0 mL of water, collecting the washmgs m the flask,
`cool and titrate with 0.2 N hydrochloric acid VS. Concomitantly
`perf~rm a blank dete!'18ination i~ the same manner, using the same
`quantity of 0.2 N sodium hydroxide VS.
`.
`.
`Calculation of saponification value-Calculate the sapomfication
`value by the formula:
`
`[(B -A)N56. l l] I W,
`
`in which B and A are the volumes, in mL, of 0.2 N hydrochloric ~cid
`VS consumed in the titration of the blank and the test preparation,
`respectively, N is the exact normality ~f the hydro~hloric acid
`solution, W is the weight, in g, of th~ portion of ~olyvmyl A\cohol
`taken, and 56. l l is the molecular weight of potassrnm hydroxide.
`Calculation of degree of hydrolysis-Calculate_ the degree_ of
`hydrolysis, expressed as percentage of hydrolysis of polyvmyl
`acetate, by the formula:
`
`100- [7.84S/(100- 0.075S)],
`
`in which Sis the saponification value of the Polyvinyl Alcohol taken:
`between 85% and 89% is found.
`
`Sulfurated Potash
`
`[9002-89-5].
`
`-!olyvinyl Alcohol is a water-soluble synthetic resin,
`sented by the formula:
`
`(C2140).,
`•
`Which the average value of n lies between 500 and
`· It_ is prepared by 85 percent to 89 _perc~nt
`lys1s of polyvinyl acetate. The apparent v1scos1ty,
`tentipoises at 20° of a solution containing 4 g of
`, inyl Aldohol in 'each 100 g is not less than 85.0
`t and not more than 115.0 percent of that stated on
`label.
`
`Thiosulfuric acid, dipotassium salt, mixture with potassium sulfide
`(K2S,).
`'th
`·
`Dipotassium thiosulfate mixture w1
`[39365-88-3].
`
`lfid (K S )
`·
`potassium su
`e
`2
`,
`
`» Sulfurated Potash is a mixture composed chiefly of
`potassium polysulfides and potassium thiosulfate. It
`contains not less than 12.8 percent of sulfur (S) in
`combination as sulfide.
`
`Packaging and storage-Preserve_ in tig_ht contai~ers. Contain_ers
`from which it is to be taken for nnmed1ate use m compounding
`prescriptions contain not more than 120 g.
`Identification-
`.
`.
`A: To a l in l 0 solution add an excess of 6 N acetic acid:
`hydrogen sulfide is evolved, and sulfur is precipitated.
`
`Slayback Exhibit 1055, Page 63 of 78
`Slayback v. Eye Therapies - IPR2022-00142
`
`

`

`1m Phosphate
`
`, 17-dihydroxy-21-(phospho
`
`)Sphate contains not less
`ore tha~ 102.0 percent
`n the dried basis.
`'e in tight containers.
`-USP Prednisolone RS.
`
`·
`
`reparation obtained as d.
`J-mL volumetric flask m1
`·
`,
`IX
`("
`! ion Pr:epared as directed • ,
`e chlonde. Insert the stop ii!
`tie inversion (about once e,.
`.
`:thylene chloride layer th
`the filtrate to dryness: the
`·:m test A under Predniso/o
`1 of about 20 mg of it res ""
`~hosphate (191).
`1 +95° and +102•
`1 a mixture of pH. 7.0 pho
`: (9 : I).
`n a solution ( I in IOO).
`han 6.5%.
`
`>issol"'.e 143.3 mg of
`,PO,, m water to make I
`alent of O. Jo mg of pho
`
`~ of ammonium molybdtft
`
`·
`· ·
`
`> mg of p-methylamino
`of sodium bisulfite
`mL.
`'
`,_g of Prednisolone s
`1xture of IO mL of water
`a 25-mL volumetric fl
`·
`of Phosphate reagent A
`to 25 mL, mix, and allo ·
`it~s. Similarly and co
`ISlng 5.0 mL of S~
`: of the substance under ·
`es of both solutions in I
`IO_tometer, using water as.
`1 is not more than that o
`•hosphate (PO,).
`.
`,t specimen being used.
`: of Prednisolone
`·
`·
`to make 25.0 mL.
`, 50-mL tube, add 25.0
`mix by gentle shakin :.
`~e layer is clear ( a
`· the methylene
`uitable spectrophoto
`_culate the quantity, in.
`1solone Sodium P
`rbance of the un
`nisolone RS obta.
`g is found (1.0%).
`
`siondard preparation-Dissolve a suitable, accurately weighed
`tity of USP Prednisolone RS in methylene chloride, and dilute
`titarively and stepwise with methylene chloride to obtain a
`rion having a known concentration of about 16 µg per mL. Pipet
`rnL of the solution into a glass-stoppered, I 00-mL cylinder, and
`1.0 rnL of Alkaline phosphatase solution and 1.0 mL of water.
`w 10 stand, with occasional gentle inversion, for 2 hours.
`,4ssaJ preparation-Dissolve about 100 mg of Prednisolone
`·um Phosphate, accurately weighed, in water that has been
`ted with methylene chloride, to make 50.0 mL, and mix. Pipet
`inL of this solution into a 125-mL separator, and shake with two
`portions of water-washed methylene chloride, discarding the
`ylene chloride layers.
`p,ocedure-Pipet I mL of the Assay preparation into a glass(cid:173)
`d, 100-mL cylinder, add 1.0 mL of Alkaline phosphatase
`·on and about 50 mL of methylene chloride, insert the stopper,
`allow to stand, with occasional gentle inversion (about once
`15 minutes), for 2 hours. Add methylene chloride to volume,
`and allow to stand until the methylene chloride layer is clear
`20 minutes). Concomitantly and without delay, determine the
`ces of the methylene chloride solution obtained from the
`preparation and the Standard preparation at 241 nm, with a
`le spectrophotometer, using methylene chloride as the blank.
`late the quantity, in mg, of C2,H27Na2O1P in the portion of
`isolone Sodium Phosphate taken by the formula:
`
`l.344[5C(Aul As)],
`·· which 1.344 is the ratio of the molecular weight of prednisolone
`phosphate to that of prednisolone, C is the concentration, in
`· per mL, of USP Prednisolone RS in the Standard preparation, and
`and As are the absorbances of the solution from the Assay
`ation and the Standard preparation, respectively.
`
`nisolone Sodium Phosphate Injection
`
`·
`
`Prednisolone Sodium Phosphate Injection is a sterile
`tion of Prednisolone Sodium Phosphate in Water for
`ion. It contains not less than 90.0 percent and not
`than 110.0 percent of the labeled amount of
`isolone phosphate (C2 1H29O8P), present as the
`ium salt.
`
`·ng and storage-Preserve in single-dose or in multiple-dose
`, preferably of Type I glass, protected from light.
`·
`Reference standards ( 11 )-USP Prednisolone RS. USP
`xin RS.
`tion-
`Dissolve 65 mg ofphenylhydrazine hydrochloride in 100 mL
`, ute sulfuric acid (3 in 5), add 5 mL of isopropyl alcohol, and
`. _Heat 5 mL of this solution with 1 mL of Assay prepar