Hydrocortisone solution preparation

Crystallization and Purification Solvent. Dimethylacetamide is useful ia the purification by crystallization of aromatic dicarboxyHc acids such as terephthahc acid [100-21-0] and/vcarboxyphenylacetic acid [501-89-3]. These acids are not soluble ia the more common solvents. DMAC and dibasic acids form crystalline complexes containing two moles of the solvent for each mole of acid (16). Microcrystalline hydrocortisone acetate [50-03-3] having low settling rate is prepared by crystallization from an aqueous DMAC solution (17). 

The principal OTC pharmaceutical products include cold remedies, vitamins and mineral preparations, antacids, analgesics, topical antibiotics, antiftingals and antiseptics, and laxatives. Others include suntan products, ophthalmic solutions, hemorrhoidal products, sleep aids, and dermatological products for treatment of acne, dandmff, insect parasites, bums, dry skin, warts, and foot care products (11). More recent prescription-to-OTC switches have included hydrocortisone, antihistamine and decongestant products, antiftingal agents, and, as of 1995, several histamine H2-receptor antagonists. 

Materials Required Hydrocortisone acetate 0.350 g aldehyde-free absolute ethanol 100 ml triphenyltetrazolium chloride solution [a 0.5% w/v solution of 2,3,5, -triphenyltetrazolium chloride in aldehyde-free ethanol (96%)] 10 ml dilute tetramethylammonium hydroxide solution [Dilute 10 ml of tetramethylammonium hydroxide solution (10%) to 100 ml with aldehyde-free ethanol (96%). It contains about 1% w/v of C4H13NO. To be prepared immediately before use] 10 ml. 

Excellent separations of corticosteroids can be achieved on an ODS column with a suitable ratio of methanol/water as an eluent. In this assay hydrocortisone is quantified using betamethasone as an internal standard. The structure of betamethasone is close to that of hydrocortisone but since it is more lipophilic it elutes from the ODS column after hydrocortisone (Fig. 12.12). The assay is a modification of the BP assay for hydrocortisone cream. In the assay described here the internal standard is added at the first extraction step rather than after extraction has been carried out in order to ensure that any losses in the course of sample preparation are fully compensated for. Extraction is necessary in the case of a cream because the large amount of oily excipients in the basis of the cream would soon clog up the column if no attempt was made to remove them. The corticosteroids are sufficiently polar to remain in the methanol/water layer as they have a low solubility in hexane, while the oily excipients are removed by extraction into hexane. The sodium chloride (NaCl) is included in the sample extraction solution to prevent the formation of an emulsion when the extract is shaken with hexane. Solution 2, where the internal standard is omitted, is prepared in order to check that there are no excipients in the sample which would interfere with the peak due to the internal standard. 

Stated content of hydrocortisone cream = 1% w/w Weight of hydrocortisone cream used to prepare solution 3 = 1.173 g Area of hydrocortisone peak in Solution 1 = 103 026 Area of betamethasone peak in Solution 1 = 92 449 Area of hydrocortisone peak in Solution 3=113 628 Area of betamethasone peak in Solution 3 = 82 920 Concentration of hydrocortisone in the solution used in the preparation of Solution 1 = 0.1008% w/v... 

When first seen, the infant with congenital adrenal hyperplasia may be in acute adrenal crisis and should be treated as described above, using appropriate electrolyte solutions and an intravenous preparation of hydrocortisone in stress doses. 

Sample preparation for complex formulations, such as creams, can frequently be as simple as dissolving the cream in the totally organic mobile phase such as the ones typically used in normal-phase chromatography. Organic solutions of flurometholone [3, p. 677] and hydrocortisone acetate [3, p. 758] creams were assayed by HPLC and hydroquinone cream by TLC [3, p. 769]. A similiar approach has been applied to sample preparation of ointments. 

Sample preparation Dilute solution 10-fold with mobile phase. Mix 100 p-L with 100 xL 300 pg/mL hydrocortisone, inject 10 pL. 

Sample preparation Ointment. 1 g Ointment + 5 mL MeOH + 5 mL water + 800 pL 1 mg/mL hydrocortisone in EtOH, stir until a clear solution forms, make up to 25 mL with water, inject a 20 (xL aUquot. Solutions. 8 mL Solution -I- 800 jxL 1 mg/mL hydrocortisone in EtOH + 5 mL MeOH, make up to 25 mL with water, iiyect a 20 p.L aliquot. 

Bacitracin is available in ophthalmic and dermatologic ointments the antibiotic also is available as a powder for the preparation of topical solutions. The ointments are applied directly to the involved surface one or more times daily. A number of topical preparations of bacitracin, to which neomycin or polymyxin or both have been added, are available, and some contain the three antibiotics plus hydrocortisone. For open infections such as infected eczema and infected dermal ulcers, the local application of the antibiotic may be of some help in eradicating sensitive bacteria. Bacitracin rarely produces hypersensitivity. Suppurative conjunctivitis and infected comeal ulcer respond well to the topical use of bacitracin when caused by susceptible bacteria. Bacitracin has been used with limited success for eradication of nasal carriage of staphylococci. Oral bacitracin has been used with some success for the treatment of antibiotic-associated diarrhea caused by C. difficile. Serious nephrotoxicity results from the parenteral use of bacitracin. Hypersensitivity reactions rarely result from topical application. 

Pyka separated six selected steroids (corticosterone acetate, 11-dehydrocorticosterone acetate, corticosterone, 11-dehydrocorticosterone, hydrocortisone, and cortisone) by RP-HPLC on Separon Six Cig column. Column void time was determined using the peak derived from a solution of sodium nitrite in methanol. The mobile phase was prepared from analytical grade methanol and redistilled water (3 2, v/v). The Randic (, Wiener... 

Dexamethasone, prednisolone and hydrocortisone are systemically active via the rectal route. The best chemical form of the active substance must be chosen and a dosage form that provides good release of the active substance. A corticosteroid as salt in solution is often optimal for an enema and the preparation is easy. As a solution in water it avoids problems such as release from a fatty base and subsequent dissolution. Dexamethasone and prednisolone for instance are used as sodium phosphate salts. Conversion and factorisation must not be forgotten. For stability reasons... 

In aqueous solution, prednisolone sodium phosphate and dexamethasone sodium phosphate are more stable than hydrocortisone sodium succinate. At a pH of about 8, the acid groups are sufficiently ionised to make the substance very soluble, while the phosphate ester is reasonably stable at this pH. Water soluble corticosteroids are mainly used in parenteral preparations, eye drops, oral mixtures and enemas. Examples are prednisolone oral mixtures and dexamethasone injections. 

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