(dij'' i tal' is).
» Digitalis is the dried leaf of Digitalis purpurea Linné (Fam. Scrophulariaceae). The potency of Digitalis is such that, when assayed as directed, 100 mg is equivalent to not less than 1 USP Digitalis Unit.*
[noteWhen Digitalis is prescribed, Powdered Digitalis is to be dispensed. ]
Packaging, storage, and labeling Preserve in containers that protect it from absorbing moisture. Digitalis labeled to indicate that it is to be used only in the manufacture of glycosides is exempt from the moisture and storage requirements.
USP Reference standards 11
Unground Digitalis This occurs as more or less crumpled or broken leaves. The leaf blades are ovate, oblong-ovate to ovate-lanceolate, mostly 10 to 35 cm in length and 4 cm to 11 cm in width and contracted into a winged petiole. The apex is obtuse; the margin irregularly crenate or serrate; the lower surface densely pubescent, the upper surface wrinkled and finely hairy. The venation is conspicuously reticulate, the mid-rib and principal veins broad and flat, and the lower veins are continued into the wings of the petiole. The color of the upper surface is dark green, of the lower surface grayish from the dense pubescence, the larger veins often purplish. The odor is slight when dry, peculiar and characteristic when moistened.
Histology Digitalis shows an upper epidermis whose cells possess slightly wavy anticlinal walls, numerous hairs, and no stomata; a lower epidermis with wavy anticlinal walls, numerous oval stomata, and many hairs, and frequently not attached over irregular areas to the cell layer within, especially near the veins; a broad chlorenchyma of a single layer of short palisade cells and several layers of spongy parenchyma; and numerous vascular bundles in the larger veins and petioles, separated by vascular rays one cell in width. On the apex of each marginal tooth one or two water stomata occur.
Ground Digitalis This is dark green in color. Present are chiefly numerous irregular fragments of epidermis and chlorenchyma; nonglandular hairs that are frequently curved or crooked, up to 500 µm in length, uniseriate, two- to eight-celled, some of the cells collapsed so that the planes of adjoining cells may be at right angles, the terminal cell pointed or rounded; few, small glandular hairs, usually with a one- or two-celled stalk, and a one- or two-celled head; fragments of veins and petioles with annular, reticulate, spiral and simple pitted vessels and tracheids. Calcium oxalate is absent.
Acid-insoluble ash 561: not more than 5.0%.
Foreign organic matter 561 The proportion of stems, browned leaves, flowers, and other foreign organic matter does not exceed 2.0%.
Water, Method III, Procedure for Articles of Botanical Origin 921: not more than 6.0%.
Standard preparation Weigh the contents of 1 container of USP Digitalis RS to the nearest mg, either in the original container or in a weighing bottle, and transfer to a dry, hard-glass, glass-stoppered container or centrifuge tube of at least 50-mL capacity. Complete the weighing within 5 minutes after opening the ampul. Add a menstruum consisting of 4 volumes of alcohol and 1 volume of water so that the total volume of menstruum added corresponds to 10 mL for each g of powder. Insert the stopper, the upper third of which is greased lightly with petrolatum. Shake the mixture for 24 ± 2 hours at 25 ± 5 by mechanical means, which continuously brings the solid material into fresh contact with the liquid phase. Immediately thereafter transfer, if necessary, to a centrifuge tube, centrifuge, and decant the supernatant tincture into a dry, hard-glass bottle having a tight closure. Preserve under refrigeration, and use within 30 days.
Assay preparation Transfer about 5 g of Digitalis, reduced to a fine powder and accurately weighed, to a hard-glass, glass-stoppered container or centrifuge tube of at least 50-mL capacity. Proceed as directed under Standard preparation, beginning with Add a menstruum. Preserve under refrigeration, and use within 30 days.
Pigeons Employ adult pigeons free from gross evidence of disease or emaciation, and of such weight that the heaviest weighs less than twice the weight of the lightest. Divide the pigeons into groups as nearly alike as practicable with respect to breed and weight so that the average weight of the group assigned by random choice to the Standard preparation shall not differ by more than 30% from the average weight of the group assigned to the preparation to be assayed. Withhold food but not water during the period 16 to 28 hours prior to use. Preparatory to injection, lightly anesthetize the pigeon with ether, and immobilize it; expose an alar vein, and cannulate with a suitable cannula. Maintain the anesthesia during cannulation and throughout the subsequent injection period at such a level that pain is absent, the pupillary and corneal reflexes are present, and the voluntary musculature is not relaxed beyond permitting the pigeon to make some voluntary movement occasionally.
Preparation of test dilutions On the day of the assay, dilute portions of the Standard preparation and of the preparation to be assayed (Assay preparation) with isotonic sodium chloride solution in such a way that the estimated fatal dose of each dilution will be 15 mL per kg of body weight.
Injection of test dilutions Arrange to inject the appropriate test dilution by suitable means such as a small-bore buret calibrated to 0.05 mL. Start the injection after ensuring the absence of air bubbles from the injection apparatus, by infusing, within a few seconds, a volume of the test dilution equivalent to 1 mL per kg of body weight. Repeat this dose at 5-minute intervals thereafter until the pigeon dies of cardiac arrest.
Use a total of not less than 6 pigeons for the Standard preparation and not less than 6 pigeons for the preparation to be assayed. If the average number of doses for any given dilution required to produce death is less than 13 or greater than 19, or if the larger exceeds the smaller in the same assay by more than 4 doses, regard these data as preliminary. Use them as a guide, and repeat with a fresh, higher or lower dilution. Complete the assay within the period of 30 days for preservation of the Standard preparation and Assay preparation.
Calculation of potency Tabulate and average the number of doses of the Standard preparation, designating the average zS, and likewise obtain the corresponding average, zU, for the Assay preparation. Compute the potency in USP Digitalis Units per mL (i.e., per 100 mg) of the Assay preparation as:
Potency = zS R / zUwhere R equals vS / vU, in which vS is the number of USP Digitalis Units per mL of Standard preparation dilution, and vU is the volume, in mL, of Assay preparation per mL of dilution. Compute the confidence interval, L (see Equation (31) under Confidence Intervals for Individual Assays in Design and Analysis of Biological Assays 111). If L exceeds 0.30, repeat the assay or inject more pigeons with one or both preparations until the confidence interval is 0.30 or less.
The potency of Digitalis, calculated from that of the Assay preparation, is satisfactory if the result is not less than 0.85 USP Digitalis Unit per 100 mg.
* One USP Digitalis Unit represents the potency of 100 mg of USP Digitalis RS.
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USP35NF30 Page 2900