*
`
`of Pharmacy
`
`Remington: The
`Science and Practice
`
`Volume II
`
`Page 1 of 5
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`V
`
`LUPIN EX 1050
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`LUPIN EX 1050
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`Page 1 of 5
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`

`

`1 9TH
`
`EDITION
`
`Remington:
`Practice of
`
`ALFONSO R GENNARO
`
`Chairman of the Editorial Board
`and Editor
`
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`
`
`Page 2 of 5
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`

`

`1995
`
`MACK PUBLISHING COMPANY
`Easton, Pennsylvania 18042
`
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`Page 3 of 5
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`

`

`1264
`
`CHAPTER 76
`
`Table 1———Classes of Antiseptic Agents
`
`
`
` Class and agent Concentration (%) Uses
`
`
`
`0.1-5
`2.17, 5 and 10
`
`Irrigant
`Irrigant
`
`70, 91 and 100
`70
`
`Antiseptic
`Antiseptic, rubefacient
`
`Acids
`Acetic acid
`Boric acid
`Alcohols
`Ethyl alcohol
`Isopropyl alcohol
`Aldehydes
`Formaldehyde
`Glutaraldehyde
`Biguanide
`Chlorhexidine
`gluconate
`Carbanilide
`Triclocarban
`Chlorine Compounds
`Sodium
`hypochlorite
`Oxychlorosene
`Iodine Compounds
`Iodine
`Povidone-Iodine
`Metals
`Organic Mercurial
`Compounds
`Phenylmercuric
`acetate
`Phenylmercuric
`nitrate
`Thimerosal
`Silver Compounds
`Mild silver protein
`Oxidizing Agents
`Hydrogen peroxide
`
`3 7
`2-3.2
`
`0.12-4
`
`1.5
`
`0.1-0.2
`
`0.1 -O. 5
`
`2
`0.5—1 0
`
`0.02—0.2
`
`00025-0004
`
`0.1
`
`1 0
`
`1 .5-3
`
`Potassium
`permanganate
`Phenols
`Hexylresorcinol
`
`00025-0007
`
`0.1
`
`Disinfectant
`Disinfectant
`
`Antiseptic,
`mouthwash
`
`Antiseptic soap
`
`Wound irrigant
`
`Irrigant
`
`Antiseptic
`Antiseptic
`
`Irrigant, antiseptic,
`preservative
`Irrigant, antiseptic,
`preservative
`Irrigant, antiseptic
`
`Antiseptic
`
`Wound cleanser,
`irrigant
`Antiseptic, disinfectant
`
`Mouthwash, wound
`cleanser
`Soap, shampoo
`Irrigant, antiseptic
`Handwashes, shampoo
`
`Irrigant, antiseptic
`Irrigant, antiseptic
`Antiseptic soap
`Antiseptic soap
`Preservative
`
`3
`0.5
`0.5—2.0
`
`1
`0.5- 1.0
`0.5-1.5
`0 1-2.0
`0 05—025
`
`Hexachlorophene
`Menthol
`Parachlorometaxy—
`lenol
`Phenol
`Thymol
`Triclocarban
`Triclosan
`Parabens
`Quaternary Ammonium
`Compounds
`Mouthwash, irrigant
`0.0 1 -0.5
`Benzalkonium choice
`Cetylpyridinum chloride 0.05-0.5
`Mouthwash, irrigant
`Benzethonium chloride
`0.01-0.3
`Mouthwash, irrigant
`
`will exert a greater antimicrobial effect at a given pH than will a mineral
`acid. This is used to discourage bacterial infections in surgical wounds,
`to suppress growth by Pseudomonas aeruginosa in extensive burns of
`the skin, as a component of a number of dermatological lotions.
`It is used
`to treat external otitis caused by Pseudomrmas, Candida and Aspergil-
`lus and vaginal infections caused by Candida, Trichomonas or Hemophi-
`lus oaginalis. Acetic acid has a long history of lay use as a spermicide.
`The 0.25% solution is used for bladder irrigation, especially during
`catheterization.
`It also is used in mouthwashes/gargles, but the contact
`time is much too short for the acid to have an effect.
`It can cause irritation and inflammation, especially in the vagina.
`Dose—Topical, as a 1% surgical dressing, 5% solution in burn therapy,
`0.1% dermatological lotion, 1 to 5% solution for otitis and 0.25% for
`irrigation.
`
`Acrisorcin—see RPS—17, page 1226.
`Alcohol—page 1404.
`
`Rubbing Alcohol
`
`Rubbing alcohol, and all preparations coming under the classification of
`Rubbing Alcohols, must be manufactured in accordance with the require—
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`ments of the US Treasury Department, Bureau of Alcohol, Tobacco and
`Firearms, using Formula 23—H (8 parts by volume of acetone, 1.5 parts b
`volume ofmethyl isobutyl ketone and 100 parts by volume of ethyl alcohol).
`It contains 68.5—71.5% by volume of absolute ethyl alcohol, the remainder
`consisting of water and the denaturants, with or without color additiVeS
`and perfume oils. Rubbing Alcohol contains in each 100 mL not less that;
`355 mg of sucrose octaacetate or not less than 1.40 mg of denatomum
`benzoate. The preparation may be colored with one or more color addi—
`tives, listed by the FDA for use in drugs. A suitable stabilizer also may he
`added. RubbingAlcohol complies with the requirements ofthe Bureau of
`Alcohol, Tobacco, and Firearms, of the US Treasury Department.
`Note—RubbingAlcohol must bepackaged, labeled, and sold in accw.
`dance with the regulations issued by the US Treasury Departmem
`Y
`Bureau ofAlcohol, Tobacco, and Firearms.
`Description—Transparent, colorless or colored as desired, mobile,
`volatile liquid; extremely bitter taste; in the absence of added odorons
`substances, a characteristic odor; flammable; specific gravity ofFormulg,
`23-His between 0.8691 and 0.8771 at 15.563
`Uses—Applied externally as a cooling, soothing application for bedrid.
`den patients and athletes.
`It also is used widely for cleansing the Sur-
`geon’s hands and instruments and for disinfection of the skin prior to
`penetration of the skin by a hypodermic needle. As an antiseptic it is
`good against vegetative bacteria and fair against fungi and viruses.
`It is
`ineffective against spores.
`It is believed widely that 70% ethanol pro.
`vides the greatest reduction in bacterial count; however, this is in error,
`Other concentrations may be more effective, but their rate of kill is slower,
`In order to reduce the skin bacterial count to 5% of normal, 70% ethanol
`must be left on the skin for at least 2 min.
`It is also a feeble anesthetic
`and a mild counterir'ritant.’ See Alcohol (page 1404).
`It is not pa.
`table.
`
`Aluminum Acetate Solution—~page 871.
`Aluminum Subacetate Solution—see RPS-17, page 778.
`Aminacrine Hydrochloride—see RPS—18, page 1170.
`Bacitracin—page 1305.
`
`Benzalkcnium Chloride
`
`Ammonium, alkyldimethyl(phenylmethyl)-, chloride; Zephiran
`Chloride (Winthrop); (Various Mfrs)
`
`
`
`It
`uch.
`ngestion
`dermatitil
`imitation
`
`some virl
`
`agents an
`which ba«
`
`drug, so
`
`adsorbed
`sterilizing
`non of St
`irritation
`view Of t
`tics, ther
`Dose—
`0.01 % a
`skin or ti
`ous solul
`branes a
`of the v0
`denudet
`to 1 :50(
`urethra
`t0 1:40,l
`deep wt
`areas w
`insolubl
`and rub
`other ad
`of meta
`prevent
`Dosa
`0.133%
`0.133%
`ture.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
`
`
`
`
`Benz
`met
`
`
`
`Alkylbenzyldimethylammonium chloride [8001—54—5]; a mixture
`
`of alkylbenzyldimethylammonium chlorides of the general formula
`
`[06H5CH2N(CH3)2R]Cl, in whichR represents a mixture of alkyls, includ-
`
`ing all or some of the group beginning with n-Cng 7 and extending through
`
`higher homologs, with n-012H25, n-CMHZQ and n-CIGH33 comprising the
`
`major portion. On the anhydrous basis, the content of 11-0 12H25 homolog
`
`is not less than 40%, and the content of the n-CMHzg homolog is not less
`
`than 20%, of the total alkylbenzyldimethylammonium chloride content.
`
`The amounts of the WC, 2Hg5 and n—CI4H29 homolog components comprise
`together not less than 70% of the total alkylbenzyldimethylammonium ‘
`chloride content.
`
`Preparation—43y treating a solution of N—alkyl-N-methylbenzylamine
`in a suitable organic solvent with methyl chloride, the solvent being 50
`chosen that the quaternary compound precipitates as it is formed.
`Description—«White or yellowish white, thick gel or gelatinous pieces;
`aromatic odor and a very bitter taste; solutions are alkaline to litmus and ‘
`foam strongly when shaken.
`Solubility—Very soluble in water and alcohol; 1 g of the anhydrous
`form dissolves in about 6 mL benzene and in about 100 mL ether.
`Incompatibilities—Like other cationic surface~active agents, benzal—
`konium chloride is incompatible with soap and other anionic agent?"
`The large organic ions of the two agents are oppositely charged and: 1“
`sufficient concentration, can precipitate from solution. Nitric acid and
`nitrates cause precipitation.
`Uses—A bacteriostatic in low and bactericidal in high concentratiorls-
`Gram-positive bacteria are more sensitive than gram-negative bacteria-
`Indeed, some gram-negative bacteria, especially Pseudomonas CBPan"
`have been known to grow in solutions of this drug and thus to cause
`epidemics of hospital infections. Mycobacterium tuberculosis is 3150
`relatively resistant. The antiseptic has a slow action.
`It requires 7 ml“
`for the bacterial count on the skin to be decreased by a mere 50%, While -
`only 36 sec is required by 70% ethanol; to effect a 90% reduction, 25 min ‘5
`required for this compared to 2 min for the 70% ethanol. Some grant
`negative bacteria require hours of exposure to be killed. Tinctures We
`more rapidly acting and effective.
`It is Used _
`It is used for application to skin and mucous membranes.
`widely in OTC ophthalmic solutions and as applications to contact lenéesi
`It also is used for the sterilization of inanimate articles, such as surg‘cé‘
`instruments.
`Its solutions have low surface tension and possess detel
`gent and emulsifying actions.
`It is also a mild astringent and is used as :
`
`
`
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`Page 4 of 5
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`

`

`It has relatively low systemic toxicity, but poisoning from oral
`sach-
`ingestion has been reported. After repetitive use it sometimes may cause
`dermatitides. Like other cationic surface~active agents, it has certain
`limitations.
`It does not destroy bacterial spores, it is ineffective against
`some viruses, it is inactivated by soap and other anionic surface-active
`‘a exits and, when applied to the skin, it has a tendency to form afilm under
`whiCh bacteria remain viable. Organic matter from tissue inactivates the
`drug: so that it has limited efficacy in the disinfection of wounds.
`It is
`adsorbed by various organic substances, so that the concentration in a
`sterilizing solution may drop below the antibacterial level, and the steriliza-
`tion of surgical gloves, sponges, etc. may be erratic. The drug can cause
`irritation and damage the epidermis, and it also can cause allergies.
`In
`view of the availability of more reliable and more rapidly acting antisep-
`tics, there is little to commend its continued use.
`poser—Topical, 0.02 to 0.5% solution; to the conjunctiva, 0.1 mL of
`0,01% aqueous solution. For preoperative disinfection of unbroken
`skin or treatment of superficial injuries or fungus infections, 1:750 aque-
`ous solution or tincture. Forpreoperative disinfection of mucous mem-
`branes and denuded skin, 1:1 0,000 to 1 :2000; for instillation or irrigation
`of the vagina, 1 :5000 to 1:2000 aqueous solution; for irrigation ofwidely
`denuded surfaces, 1:10,000 or 125000; for irrigation of the eye, 1:10,000
`to 125000 aqueous solution; for irrigation of the urinary bladder and
`urethra, 120,000 to 125000; for retention lavage of the bladder, 120,000
`to 1:40,000; for disinfection of deep lacerations, 121000; for irrigation of
`deep wounds, 120,000 to 1:3000; for treatment of infected denuded
`areas with wet dressings, 125000; as a detergent solubilizer of water—
`insoluble drugs, up to 0.5%; for sterile storage of metallic instruments
`and rubber articles, 1:1000 to 1:750; for sterilization of catheters and
`other adsorbent articles, 1:500. When the drug is used for sterile storage
`of metal instruments, sodium nitrite (0.5%) is added to the solution to
`L prevent corrosion of metal.
`0.1 (l in 1000),
`0.05%; Solution:
`Dosage Forms—Vaginal Gel:
`0.133% (1 in 750) and 50%; Tincture:
`0.183%; Tincture Spray:
`0.133%; Concentrates:
`12.8, 17, 17.5 and 50% aqueous, and 17% tinc-
`ture.
`
`Benzethonium Chloride
`
`Benzenemethanaminium, MN—dimethyl-N—[Z-[ZM-G ,1 ,3,8-tetra-
`methylbutyl)phenoxy]ethoxylethyl ]-, chloride; (Various Mfrs)
`
`CH3
`I
`(CH3)3CCH2$‘@—OCHZCHZOCH2C\Hz
`CH,
`/N+(CH3)2
`
`_
`
`m
`
`Benzyldimethyl[2~[2—[p-(1,1,3,3—tetramethylbutyl)phenoxyi-
`
`ethoxy]ethyl]ammonium chloride. [121-54-0] CZ7H42C1N02 (448.09).
`Preparation From p-diisobutylphenol with dichlorodiethyl ether, di-
`methylamine and benzyl chloride.
`' Description—~White crystals; mild odor; very bitter taste; melts at
`about 160°; aqueous solution (1%) slightly alkaline and foams strongly
`When shaken.
`‘
`Solubility—1 g in 0.6 mL water, 0.6 mL alcohol, 1 ml chloroform or
`6000 mL ether.
`«Uses—A quaternary ammonium detergent antiseptic and spermi—
`Cide once used widely.
`It has the same limitations and erratic behavior
`that characterize Benzalkoniurn Chloride (page 1264).
`Its present uses
`are as as a preservative in ophthalmic preparations, vaginal contraceptive
`f0Elms and nursing lubricants;
`Dose—To the vagina, as a 3.17% solution of the monohydrate; as a
`mesewatioe, 0.01%.
`Dosage Form—Solution:
`
`0.01 and 3.1 7%.
`
`Benzoic Acid—see RPS-18, page 1235.
`Behzyl Alcohol—page 1 151.
`Blsmuth Tribromophenate—see RPS-18, page 1170.
`Boric Acid—page 1407.
`Blltlilp'ciraben—see RPS-18, page 1170.
`P‘iEri-Butylphenolmsee RPS-18, page 1170.
`
`Carbamide Peroxide
`
`Urea Peroxide; (Various Mfrs)
`
`
`
`BUrea, compound with hydrogen peroxide (1:1); [124-43-6] CH6N203
`( 4-07); contains about 35% H202.
`
`Page 5 of 5
`
`ANTI-lNFECTIVES
`
`1265
`
`Description—White crystals or crystalline powder; decomposes in air
`to urea, oxygen and water.
`Solubility—1 g in 2.5 mL water; incompatible with alcohol or ether,
`which cause partial decomposition.
`Uses—An oxidant much like hydrogen peroxide. Peroxide ion in
`sufficient concentration is bactericidal to most bacteria; low concentra—
`tions are lethal to anaerobes and microaerophiles.
`It is used to relieve
`minor irritation of the gingivae and oral mucosae. The action may be, in
`part, an antibacterial action against organisms that produce irritating
`substances, but relief of irritation also may be attributed partly to the high
`glycerin content of the gel. There may be some efficacy against cankers.
`Dose——Topical, to the gums and oral mucosae, as a 11% gel in a
`water-free gel base, or as a 10% solution in anhydrous glycerol.
`Dosage Forms—Gel:
`11%; Solution:
`10%.
`
`Cetyldimethylethylammonium Bromide—see RPS~18, page
`1 170.
`
`Cetylpyridinium Chloride—see RPS-18, page 1171.
`
`Chlorhexidine Giuconaie
`
`D-Gluconic acid, compd with N,N "-bis(4-chlorophenyl)—3,12-diimino—
`2,4,11,18-tetraazatetradecanediimidamide (2: 1);
`Hibiclens, Hibistat (Stuart)
`
`'11“
`t‘“
`t‘“
`'11“-
`C1©NH c NH c NH (CHzisNH CNHC NH©CI
`
`1,1 ’-Hexamethylenebis[5-(p—chlorophenyl)biguanide] di-D—gluconate
`[18472-510] CZZH30C12N10206H1207 (897.77).
`Preparation—Chlorhexidine base may be prepared by refluxing a
`mixture of hexamethylenebis[dicyandiamide],
`[NCNHC(:NH)-NH—
`(CH2)3]2, and p—chloroaniline hydrochloride in 2-ethoxyethanol at 130°-
`140° for two hours (Rose and Swain, CA 50: 1082h, 1956). The diglu-
`conate, diacetate, and dihydrochloride salts may be obtained by neutralizing
`the base with the respective acids.
`Description—Colorless to pale~yellow solution. Usually available in
`5 or 20% aqueous solution.
`pH (5% aqueous solution) 5.5 to 7.0.
`Solubility—«Very soluble in water; 1 g in 5 mL alcohol or 8 mL acetone.
`Uses—Bactericidal to both gram-positive and gram-negative bacteria,
`although it is not as potent against the latter.
`It disrupts the plasma
`membrane of the bacterial cell, and cellular contents are lost.
`In a 4% aqueous solution as a surgical scrub, it decreases the cutaneous
`bacterial population more than either hexachlorophene or povidone-iodine.
`It is slightly less effective than povidone—iodine if the skin is contaminated
`with certain gram-negative bacteria. A 1% aqueous solution has erratic
`antiseptic effects, but a 0.5% solution in 95% ethanol is more effective than
`a 4% aqueous solution. Chlorhexidine solutions leave a residue on the
`skin which gives a persistent antibacterial effect lasting 1 or 2 days.
`Its
`actions are not affected by blood, pus or soaps.
`It is used for the preoperative preparation of both surgeon and patient,
`for the treatment of superficial skin infections, burns, acne vulgaris
`and the irrigation ofwounds and surgical infections.
`It can be used in
`the hospital nursery to bathe neonates for prophylaxis against staphylococ~
`cal and streptococcal infections. Abroad, it is used as a mouthwash for
`oral hygiene and oropharyngeal infections, especially aphthous ulcers.
`It is absorbed onto tooth enamel, where it exerts a persisting action to
`decrease the growth ofdental plaque.
`It is absorbed negligibly from the skin and mucous membranes; it has
`low systemic toxicity. Thus, it would not be expected to cause systemic
`intoxication from topical application. However, serious injury may occur
`when it enters open wounds of the eye and deafness may occur if it enters
`the middle ear through a perforated eardrum. A few cases of sensitiza-
`tion have been reported. Bacterial resistance to the drug has not been
`reported, but overgrowth (superinfection) by naturally resistant gram—
`negative bacteria may sometimes occur.
`Instances of hospital epidemics
`caused by Pseudornonas maltophilia actually growing in its aqueous
`solutions have been reported. The substance is considerably adsorbed
`by new glass, and the concentration of weak solutions may thus be low-
`ered; it is not adsorbed by polyethylene.
`Dose—Topical, as a 4% cleanser or sponge or 0.5% tincture.
`Dosage Forms—Aqueous Emulsion:
`4%; Tincture Rinse:
`
`0.5%.
`
`ChlorothymoI—see RPS-18, page 1171.
`Cioflucarban—see RPS-18, page 1171.
`Ciorophene—see RPS—18, page 1171.
`Cloroxine—see RPS-18, page 1171.
`
`Page 5 of 5
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