An Anti-Inflammatory Adrenocorticalsteroid Hydrocortisonesodiumsuccinate, Hydrocortisone Preparation and Validated for the Confirmation/Determination and Quantification of Hydrocortisone

Hydrocortisone sodium succinate is an anti-inflammatory adrenocortical steroid. This highly water-soluble sodium succinate ester of hydrocortisone permits the immediate intravenous administration of high doses of hydrocortisone in a small volume of diluent and is particularly useful where high blood levels of hydrocortisone are required rapidly. A-Hydrocort sterile powder is available for intravenous or intramuscular administration. 100 mg− Vials containing hydrocortisone sodium succinate equivalent to 100 mg hydrocortisone, also 0.8 mg monobasic sodium phosphate anhydrous, 8.73 mg dibasic sodium phosphate anhydrous. When necessary, the pH was adjusted with sodium hydroxide so that the pH of the reconstituted solution is within the USP specified range of 7 to 8 (Figure 1). Abstract


Introduction
Hydrocortisone sodium succinate is an anti-inflammatory adrenocortical steroid. This highly water-soluble sodium succinate ester of hydrocortisone permits the immediate intravenous administration of high doses of hydrocortisone in a small volume of diluent and is particularly useful where high blood levels of hydrocortisone are required rapidly. A-Hydrocort sterile powder is available for intravenous or intramuscular administration. 100 mg− Vials containing hydrocortisone sodium succinate equivalent to 100 mg hydrocortisone, also 0.8 mg monobasic sodium phosphate anhydrous, 8.73 mg dibasic sodium phosphate anhydrous. When necessary, the pH was adjusted with sodium hydroxide so that the pH of the reconstituted solution is within the USP specified range For intravenous infusion, vial should be reconstituted with Bacteriostatic Water for Injection. Hydrocortisone and hydrocortisone salts are known for use as anti-inflammatory agents. It is common to use these active substances in the treatment of asthma in particular, endocrine disorders, dermatological disorders and allergic conditions, and acute adrenal insufficiency.
Hydrocortisone and its salts belong to the family of corticosteroids.
Hydrocortisone and its salts are susceptible to oxidation. Therefore, pharmaceutical solutions of these active ingredients always include at least one antioxidant. However, antioxidants used in these pharmaceutical solutions are themselves unstable. Therefore, it is known that these pharmaceutical solutions comprise a 2 nd antioxidant is disodium ethylenediamine tetraacetate (hereinafter abbreviated as "disodium EDTA"). The disodium EDTA serves to stabilize (or otherwise preserve) the antioxidant which is itself chosen to keep the hydrocortisone thus preserving oxidation.

C.
Step   A search of the literature revealed that few analytical methods such as ultraviolet spectrophotometry [2], electrokinetic capillary chromatography [3,4], photochemically enhanced fluorescence [5], thin-layer chromatography-(TLC-) densitometry [1,6], and high-performance thin-layer chromatography (HPTLC) [7]  The upsurge of autoimmune diseases such as adrenal insufficiency is a major health concern and the long-term use of conventional hydrocortisone tablets in the management of such a condition is problematic. The twice or thrice daily dosing of conventional hydrocortisone tablets to patients with adrenal insufficiency disease is incapable of mimicking the unique diurnal cortisol circadian pattern. Thus, most persons with adrenal insufficiency continue to suffer from poor therapeutic management resulting in poor quality of life and increased mortality. There is therefore the need for the development of creative and innovative treatment models for hydrocortisone replacement therapy in such dire situations. The use of controlled-release hydrocortisone oral dosage forms holds great promise with the capability to replicate the unique physiological pattern of hydrocortisone. In addition, such formulations are better able to manage and control the levels of morning androgen levels. The accurate monitoring of the quality of these promising new drug therapies is an important prerequisite to obtain quality healthcare [14]. The improved therapy will enhance patient compliance and ensure the delivery of controlled amounts of hydrocortisone at the absorption site compared to the immediate release pattern of conventional tablets [15].

Standards and Reagents
The reference material of hydrocortisone (Sigma Aldrich, USA), HPLC grade methanol (Fisher Scientific, UK), glacial acetic acid (Fluka, Germany), and water (double distilled) were used. All stock and working solutions were freshly prepared with distilled water for HPLC analyses.

Instrumentation and Optimized Chromatographic Conditions
A chromatograph comprising a P100 Spectra Series pump with a 785A Programmable Perkin Elmer UV/VIS absorbance detector was employed in the study. Isocratic mode of elution was employed.

Analytical Method Validation
The new HPLC method was validated in terms of linearity, limits of detection and quantification, accuracy, precision (intraday and interday), specificity, robustness, and stability, in compliance with International Conference on Harmonization (ICH) guidelines [16].

Assay of Hydrocortisone Preparations
An amount of finely powdered hydrocortisone powder from each of the nine commercial conventional tablet formulations equivalent to 2.5 mg hydrocortisone was individually weighed accurately and transferred to a 25 ml volumetric flask containing 10 ml of methanol. The solution was sonicated for 5 min and made up to volume with methanol. The resulting solution was then filtered using Whatman filter paper number 41. The filtrate obtained was analyzed by making triplicate injections. The controlled-release hydrocortisone tablet and capsule formulations were analyzed in a similar way. In the analysis of the hydrocortisone injections, aliquots equivalent to 2.5 mg hydrocortisone were pipetted from the six (6) injectable preparations into 25 ml volumetric flasks and treated similarly to above. The peak areas of sample were determined, and the amount of hydrocortisone was estimated from the linear regression calibration curves using the developed method. The official United States Pharmacopoeia method [11] was employed in analyzing the commercial samples. Statistical comparison between the official and developed methods was done using Student's -test.

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formulations results in more stable cortisol concentrations during the diurnal cortisol circadian pattern than conventional hydrocortisone products [17]. It is however essential that suitable and accurate analytical methods are made available to assess the quality of the products with regard to their content. The development and validation of a simple isocratic RP-HPLC method for the determination of hydrocortisone in both conventional and controlled-release pharmaceutical formulations were the focus of this study. Review of literature indicates the employment of normal phase stationary support material [18,19] and reverse phase stationary support material [20] for the development of HPLC       Table 2). The method was reproducible with good intraday and interday precision of less than 1% RSD (Tables 3 & 4). The new HPLC method showed high specificity and the robustness was less than 1% RSD (Tables 5 & 6).

Analytical Method Validation
The method also demonstrated good stability over a period of 8 h (<6% RSD) ( Table 7).          was successfully applied to commercial samples which indicate the ability of the analytical method to distinguish between good and poor-quality hydrocortisone products.