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    Analgesic solubility

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    11095_2004_Article_305951

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    Analgesic solubility

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    9 views5 pages

    2004 Article 305951

    Uploaded by

    DownTheTheRabbitHole108
    Analgesic solubility

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 5
    Pharmaceutical Research, Vol. 6, No. 2, 1989 Report Solubility Behavior of Narcotic Analgesics in Aqueous Media: Solubilities and Dissociation Constants of Morphine, Fentanyl, and Sufentanil Samir D. Roy’? and Gordon L. Flynn’? Received June 30, 1988; accepted August 29,1988 ‘The pil dependence ofthe aqueous solubility of morphine, fentanyl, and sufentanil was investigated at 35°C. Dissociation constants and corresponding pK,’ values of the drugs were obtained from ‘measured free-base solubilities (determined a high pH's) and the concentrations of saturated soltions intermediate pH's. Morphine, fentanyl, and sufentanil exhibited pK,’ values of 8.08, 8.99, and 8, respectively. Over the pH range of 5 o 12.5 the apparent solubilities are determined by the intrinsic solubility ofthe free base plus the concentration of ionized drug necessary to satisfy the dissociation ‘equilibrium at a given pH. Consequently, the drug concentrations of saturated aqueous solutions fall ‘off precipitously asthe pH is raised and ionization is suppressed. Further, at low pHs the aqueous Solubility of morphine increased ina linear fashion wit increases in the molar strength of citric acid Which was added to acidfy the medium, suggesting the formation of a soluble morphine-ctrate complex. KEY WORDS: narcotic anlgesies; sociation constants; pH-solubility profiles; solubility; amines INTRODUCTION ‘Naturally occurring opioid alkaloids such as morphine and synthetic 4-anilinopiperidine analogues such as fentanyl and sufentanil (see Fig. 1) are used for the relief of postsur- gical pain, chronic cancer pain, and other pain (1). These drugs are commonly given orally and parenterally; however, ‘many of the narcotics are relatively short acting, necessitat ing frequent administration, with widely fluctuating blood levels. Therefore, it is desirable to attain steady plasma lev- els over long time periods. Transdermal delivery may repre- sent a suitable delivery route. ‘Skin permeation studies are generally performed using ‘aqueous vehicles. The rate of delivery of a drug from its vehicle through the skin is directly proportional to the drug's concentration. The maximum achievable rate and the rate used to determine delivery feasibility are therefore set by the

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