Dexamethasone solubility

Suspension. If the drug is not sufficiently soluble, it can be formulated as a suspension. A suspension may also be desired to improve stability, bioavailability, or efficacy. The major topical ophthalmic suspensions are the steroid anti-inflammatory agents prednisolone acetate, dexamethasone, fluorometholone, and rimex-olone. Water-soluble salts of prednisolone phosphate and dexamethasone phosphate are available however, they have a lower steroid potency and are poorly absorbed. 

We describe below the use of halloysite nanotubules for entrapment and the subsequent release of three drugs Nifedipine (anti-anginal), Furosemide (anti-hypertension and diuretic), and Dexamethasone (synthetic corticosteroid). To increase the loading of these poorly soluble drugs in the tubules, we loaded them into a water-alcohol co-solvent solution (0, 10, and 50% ethanol). 

Both drugs are highly lipid soluble and as such are prepared and administered in dilutants (paclitaxel in Cremophor EL and docetaxel in polysorbate 80). Both medications are normally administered with dexamethasone, H, and H2 antagonists as premedications to decrease the incidence of the acute hypersensitivity reaction (HSR) (dyspnea with bronchospasm, urticaria, and hypotension) that has been observed to occur... 

Partition coefficient Octanol/water ca 70. The drug does not ionise so that the partition coefficient is unaffected by pH. Despite being neutral compound the hydroxyl groups in prednisolone give it a water solubility of ca 0.5 mg/ml. Closely related compounds dexamethasone, betamethasone, triamcinolone, hydrocortisone, betamethasone valerate, betamethasone dipropionate. 

A 5-year-old child with diabetes, Pierre Robin syndrome, cleft palate, allergic rhinitis, recurrent sinusitis, and obstructive sleep apnea, who had previously had skin rashes after penicillin, sulfonamides, and clindamycin, was given soluble and isophane human insulins (131). Three years later she developed local reactions, 2-5 cm areas, 30-120 minutes after injection. Skin-prick tests were negative for the diluent, isophane, and soluble insulin, but intradermal testing was positive with both insulins. Cetirizine and dexamethasone added to the insulin gave temporary relief. She was... 

Diabetes mellitus in a 36-year-old man with acute pancreatitis could not be controlled with continuous subcutaneous insulin infusion, even with doses up to 1800 U/ day, because of insulin resistance (168). Intravenous insulin by pump had to be stopped because of a catheter infection. The continuous subcutaneous infusion of freeze-dried insulin and the addition of aprotinin, a protease inhibitor, soluble dexamethasone or prednisolone, and intravenous immunoglobulin was ineffective. An implantable pump for intraperitoneal delivery established good regulation at a dosage of 30 U/day. 

Schroder and co-workers (Schroder etal., 1999,2000) studied PolyP metabolism in bone tissues and osteblast cultures. They revealed that PolyP metabolism in human osteoblasts was modulated by stimulators of osteoblast proliferation and differentiation (Leyhausen et al., 1998). A combined treatment of the cells with dexamethasone, ft-glycerophosphate, epidermal growth factor (EGF), and ascorbic acid resulted in a dramatic decrease in PolyP content. This decrease is caused mainly by a decrease in the amount of soluble long-chain PolyPs. The amount of this PolyP fraction, but not the amount of insoluble long-chain PolyPs, further decreases after additional treatment of the cells with la, 25-dihydroxy vitamin D3. The decrease in PolyP content during treatment with dexamethasone, ft-glycerophosphate, EGF and ascorbic acid is accompanied by a decrease in exopolyphosphatase activity. However, additional treatment with la, 25-dihydroxyvitamin D3 results in a significant increase of the enzyme activity. Therefore, it is reasonable to assume that PolyP... 

Figure 6.17 The classification of 42 drugs in the (solubility-dose ratio, apparent permeability) plane of the QBCS. The intersection of the dashed lines drawn at the cutoff points form the region of the borderline drugs. Key 1 acetyl salicylic acid 2 atenolol 3 caffeine 4 carbamazepine 5 chlorpheniramine 6 chlorothiazide 7 cimetidine 8 clonidine 9 corticosterone 10 desipramine 11 dexamethasone 12 diazepam 13 digoxin 14 diltiazem 15 disopyramide 16 furosemide 17 gancidovir 18 glycine 19 grizeofulvin 20 hydrochlorothiazide 21 hydrocortisone 22 ibuprofen 23 indomethacine 24 ketoprofen 25 mannitol 26 metoprolol 27 naproxen 28 panadiplon 29 phenytoin 30 piroxicam 31 propanolol 32 quinidine 33 ranitidine 34 salicylic acid 35 saquinavir 36 scopolamine 37 sulfasalazine 38 sulpiride 39 testosterone 40 theophylline 41 verapamil HC1 42 zidovudine.

Tanaka S, Takashima Y, Murayama H, Tsuchiya S. Solubility and distribution of dexamethasone acetate in oil-in-water creams and its release from the creams. Chem Pharm Bull 1985 33 3929— 3934. 

Dexamethasone and betamethasone are isomeric fluorinated derivatives of methyl-prednisolone, but their solubilities are not identical, which might be a crystal property or a solution property. A simpler example of differences in isomeric solubility is that of the 0-, m-, and p-dihydroxybenzenes referred to above. A steric argument may be applied to the case of dexamethasone, water molecules being less able to move close to the 17-OH group than in the case of betamethasone. 

Orally administered corticosteroids are effective in the treatment of chronic bronchial asthma. The inhalation route has been widely used in attempts to avoid systemic side-effects, such as adrenal suppression, but evidence suggests that inhaled steroids are absorbed systemically to a significant extent. The respiratory tract epithelium has permeability characteristics similar to those of the classical biological membrane, so lipid-soluble compounds are absorbed more rapidly than lipid-insoluble molecules. Cortisone, hydrocortisone and dexamethasone are absorbed rapidly by a nonsaturable diffusion process from the lung, the half-time of absorption being of the order of 1-1.7 min. Quaternary ammonium compounds, hippurates and mannitol have absorption half-times, in contrast, of between 45 and 70 min. 

There are three aerosolized corticosteroid preparatioias available in MDI formulation for administration to horses via the Equine AeroMask beclometasone dipropionate, fluticasone propionate and flunisolide (Table 16.2). In terms of the relative potency, fluticasone is more potent than beclometasone, which is more potent than flunisolide, which is equipotent to triamcinolone. Using dexamethasone as the standard (1.0), the relative glucocorticoid receptor affinity of the common corticosteroids is flunisolide 1.9, triamcinolone 2.0, beclometasone (active metabolite) 13.5 and fluticasone propionate 22.0 (Barnes et al 1998). The pulmonary residence time of the aerosolized corticosteroids is determined by the lipophilicity of each drug. Flunisolide has intermediate water solubility (lOmg/ml), simitar to... 

Fluocinolone acetonide is a lipophilic, synthetic corticosteroid with a potency similar to dexamethasone. However, fluocinolone acetonide is 1 /24th as soluble as dexamethasone, which makes it very insoluble. Thus it can be released over a much longer period of time than dexamethasone without an excessively bulky polymer system (23 see also Chapter 14). A prospective, noncomparative interventional case... 

Paclitaxel has very limited solubility and must be administered in a vehicle of 50% ethanol and 50% polyethoxylated castor oil (CREMOPHOR EL), a formation likely responsible for a high rate of hypersensitivity reactions. Patients receiving this formulation are protected by pretreatment with a histamine Hj receptor antagonist such as diphenhydramine, an receptor antagonist such as cimetidine fsee Chapter 24), and a glucocorticoid such as dexamethasone (see Chapter 59). Docetaxel, which is somewhat more soluble, is administered in polysorbate 80 and causes a lower incidence of hypersensitivity reactions. Pretreatment with dexamethasone is required to prevent progressive, and often disabling, fluid retention. 

The two crystal forms have essentially the same solubility in water and essentially the same decomposition temperature. Form B is the more usually observed form. No solvates or polymorphic modifications of dexamethasone were reported by Mesley for dexamethasone crystallized from chloroform, acetone and ethanol using X-ray diffraction patterns and solid state I.R. spectra to evaluate samples. 

Phase Solubility Analysis - See Section 5.1 for discussion of a phase solubility system for dexamethasone. 

O/W emulsion technique is suitable for the encapsulation of hydrophobic (poorly water soluble) compounds since they partition favorably into the oil phase, and the technique has been employed for the encapsulation of various drugs, such as steroids, thioridazine, dexamethasone, chlorproma-zine, methadone, and anticancer agents—aclarubicin, lomustine, " " and paclitaxel." " ... 

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