ABSTRACT
The evaluation of the benefit/risk ratio (BRR) for topical glucocorticoids (TGC) allows the comparison of active ingredients and thereby includes aspects of dosage (blanching response, BR) as well as adverse effects (skin atrophy). In the present study, the BRR of hydrocortisone aceponate, prednicarbate and betamethasone valerate was investigated according to an adapted procedure for investigating the BR. The main difference is the longer application period of the investigational substance without occlusion. Thus, the pharmacokinetic characteristics of all of the systems are considered more intensely and the penetration conditions are designed in a realistic way, namely oriented towards the preparation in order to improve the significance and relevance of the BRR for practical use. The results demonstrate that the investigated substances also show differences in the extent of the BR, but on the other hand they show that the improved penetration characteristics of the double-esterified compounds are clearly less effective. In comparison to the BRR, this results to a large extent in a balanced picture without relevant advantages for single preparations. Nevertheless, the already mentioned positive characteristics of the investigated TGC and the positive practical clinical experiences have been approved. Further investigations have to show whether the method presented here for investigating the BR offers advantages in the comparative assessment of TGC.
Subject(s)
Glucocorticoids/administration & dosage , Glucocorticoids/metabolism , Hydrocortisone/analogs & derivatives , Skin Absorption/drug effects , Skin Absorption/physiology , Administration, Topical , Adult , Double-Blind Method , Female , Follow-Up Studies , Glucocorticoids/therapeutic use , Humans , Hydrocortisone/administration & dosage , Hydrocortisone/metabolism , Hydrocortisone/therapeutic use , Male , Middle Aged , Reference Standards , Risk Factors , Young AdultABSTRACT
Lambda-carrageenan, a linear, high molecular weight sulfated polysaccharide, was successfully employed in both its native and sulfobutyl derivatized form as a chiral selector in capillary electrophoresis for the separation of enantiomers of basic pharmaceutical compounds. In order to characterize the chiral selectivity properties of this chiral selector, various structurally related racemic compounds were analyzed for enantiomeric interactions using capillary electrophoresis. The results of these studies were then rationalized and analyzed utilizing a general quantitative structure-property relationship (QSPR) evaluation in order to predict critical analyte structural requirements for successful enantiomeric separation. Important structural components of the analytes were found to include the aromatic content, the type of substitution on the aromatic ring, presence of a primary or secondary protonated amine, and an overall positive charge to the molecule.
Subject(s)
Carrageenan , Electrophoresis, Capillary/methods , Adrenergic beta-Antagonists/chemistry , Adrenergic beta-Antagonists/isolation & purification , Carrageenan/chemistry , Ethers/chemistry , Quantitative Structure-Activity Relationship , Stereoisomerism , Tryptophan/analogs & derivatives , Tryptophan/chemistry , Tryptophan/isolation & purificationABSTRACT
Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, was employed as a chiral selector in capillary electrophoresis for the separation of enantiomers of weakly basic pharmaceutical compounds. In order to improve the utility of the chiral selector, the purity and concentration of the lambda-carrageenan and other important capillary electrophoresis method parameters were investigated. The results indicated that the purity and concentration of the lambda-carrageenan, ionic strength of the buffer, and temperature were critical to successful enantioseparation. These new method conditions were then applied to previously investigated beta-blockers (such as propranolol HCl and pindolol) and racemic tryptophan derivatives. These studies were successful in identifying important method conditions for the improved enantioselectivity with lambda-carrageenan.
Subject(s)
Carrageenan , Electrophoresis, Capillary/methods , Pharmaceutical Preparations/isolation & purification , Carbohydrate Sequence , Carrageenan/chemistry , Carrageenan/isolation & purification , Pharmaceutical Preparations/chemistry , Propranolol/chemistry , Propranolol/isolation & purification , Spectrophotometry, Infrared , StereoisomerismABSTRACT
Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, has been employed as a chiral selector in capillary electrophoresis for the separation of enantiomers of weakly basic pharmaceutical compounds. The racemic compounds that were enantioresolved included propranolol, pindolol, tryptophanol, laudanosine and laudanosoline. In addition, the diastereomeric pair of cinchonine and cinchonidine were also resolved. Method conditions such as buffer pH, electrolyte concentration, column temperature, and chiral selector concentration were found to be important for improvement of enantioselectivity.
Subject(s)
Carrageenan , Electrophoresis, Capillary/methods , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/isolation & purification , Adrenergic beta-Antagonists/chemistry , Adrenergic beta-Antagonists/isolation & purification , Carrageenan/chemistry , Cinchona Alkaloids/chemistry , Cinchona Alkaloids/isolation & purification , Isoquinolines/chemistry , Isoquinolines/isolation & purification , Molecular Structure , Pindolol/chemistry , Pindolol/isolation & purification , Propranolol/chemistry , Propranolol/isolation & purification , Stereoisomerism , Tryptophan/analogs & derivatives , Tryptophan/chemistry , Tryptophan/isolation & purificationABSTRACT
Conventional reversed-phase HPLC conditions have been optimized for resolution of a mixture containing prostaglandins PGE(1), PGE(2), PGF(1alpha), and PGF(2alpha). Electroactive derivative-forming reagents, such as p-nitrobenzyloxyamine, 2-bromo-2'-nitroacetophenone, and 2,4-dinitrophenylhydrazine have been evaluated for use as precolumn reagents for forming prostaglandin derivatives. The results indicate that detection limits of 120 pg are achievable with amperometric detection. The utility of the procedures developed is illustrated by the detection of prostaglandins in human urine and plasma.