Design and evaluation of prednisolone acetate eye drops with prolonged effect

The potentiality of interaction of prednisolone acetate with six cyclodextrins [CyDs], namely alph-, beta-, gamma-, dimethyl-beta-CyD [DM-beta-CyD], trimethyl-beta-CyD [TM-beta-CyD] and hydroxypropyl-beta-cyclodextrin [HP-beta-CyD] was monitored by spectrophotometric measurements. The results revealed formation of equimolar complexes in these systems. The apparent solubility of prednisolone acetate in water was found to increase linearly with increasing CyD concentration or CyD combined with 0.25% polyvinylpyrrolidone [PVP] or hydroxyethylcellulose [HEC]. The partition coefficient of prednisolone acetate and its complexes between n-octanol and phosphate buffer of pH 6.7 was determined. The effect of CyDs on the permeation of prednisolone acetate through semi-permeable membrane was also investigated. The results revealed that all investigated CyDs increase the permeation of prednisolone acetate. The effect of CyDs or CyDs combined with 0.25% PVP or HEC on the bioavailability of prednisolone acetate eye drops was assessed by measuring the intraocular pressure [IOP] in rabbits. The results indicated the possibility of utilizing a formula containing beta-CyD together with 0.25% PVP or HEC for preparing prednisolone acetate eye drops characterized by an increased biological availability of the drug as well as a marked prolongation of its effect extending up to a period of 18 hr

Dissolution rate measurements as a predictory tool for assessing comparative bioavailability of generic ampicillin capsules

The dissolution rate of 12 batches of commercial ampicillin capsules manufactured by four leading pharmaceutical companies was determined by both closed and open dissolution systems. The most consistent results were those obtained by the USP method. The beaker as well as flow-through methods showed higher discriminating ability for differentiating the dissolution behavior of different batches of ampicillin capsules of the same brand. On the other hand, the flow- through method provided best discrimination of the dissolution characteristics of different brands. At the same time, the USP rotating basket method did not afford good discriminating ability for different lots belonging to the same brand or for different brands. The bioavailability of these products was assessed in human subjects according to a Latin square design

Solubilization of certain Analgesics by cetomacrogol 1000

Solubilization of certain nonsteroidal anti-inflammatory drugs, viz., phenacetin, ibuprofen and indomethacin by Cetomacrogol 1000 [Cetomacrogol] has been investigated. The values of the ratio of mole drug solubilized per mole micellar Cetomacrogol revealed that the solubilizing power of Cetomacrogol towards ibuprofen is higher than that for phenacetin or indomethacin. One Cetomacrogol micelle solubilizes 38, 17 and 6 molecules of ibuprofen, phenacetin and indomethacin, respectively. Spectrophotometry as well as solubility measurements in different solvents have been used to provide evidence on the environment of the solubilizate molecule in the micelle. On the basis of the results obtained, it was concluded that these drugs are solubilized as follows: Phenacetin and ibuprofen are solubilized in the hydrocarbon core and in the polyoxyethylene region adjacent to the hydrocarbon core. Indomethacin is wholly solubilized in the polyoxyethylene layer adjacent to the hydrocarbon core. The ability of the surfactants to accelerate the dissolution rate of the drug was also investigated. The dissolution profiles of these drugs in Cetomacrogol revealed marked enhancement of dissolution and there is a good correlation between the dissolution efficiency of the three drugs and their solubility in Cetomacrogol at the same temperature

Interaction of dicumarol with beta-cyclodextrin

The potentiality of interaction of dicumarol with beta-cyclodextrin was monitored by spectrophotometry, vapor pressure osmometry and DSC thermograms. The results revealed a very strong evidence for molecular interaction between dicumarol and beta-cyclodextrin

Interaction of hydrochlorothiazide with beta-cyclodextrin

Interaction of hydrochlorothiazide with beta-cyclodextrin was investigated by spectrophotometry, vapor pressure osmometry and differential scanning calorimetry. The results revealed a very strong evidence for molecular interaction between hydrochlorothiazide and cyclodextrin. The continuous variation method was utilized to elucidate the stoichiometry of molecular interaction via spectrophotometric as well as vapor pressure measurements. Both types of data are in full agreement and revealed the formation of 1:1 complex. The stability constant of the complex was determined at different temperatures by the vapor pressure osmometric method. The complex was found to undergo partial dissociation with increasing temperature above 25C and more or less complete dissociation at 60C. The apparent solubility of the drug in presence of beta-cyclodextrin was found to increase to a marked extent. The amount of drug solubilized in the form of complex was determined and the results revealed that the solubilizing effect of beta-cyclodextrin is entirely due to complex-formation. The dissolution profiles of the drug, physical mixture of the drug and beta-cyclodextrin as well as the prepared complex showed an enhancement of drug dissolution from the prepared complex or the physical mixture compared to the drug per se. The effect of beta-cyclodextrin on the bioavailability of hydrochlorothiazide was determined by quantifying the diuretic effect of the drug in healthy human volunteers. The data revealed that, coadministration of the drug with beta-cyclodextrin either in the form of physical mixture or complex leads to an increase in the diuretic response intensity and there is a good correlation between the in vivo performance of the drug and its dissolution rate determined according to the USP rotating basket method

Effect of aromatic hydrotropies on the solubility of carbamazepine part I: effect of sodium salt of hydroxy and amino derivatives of benzoic acid

It was found that the hydrotropic agents enhance the water-solubility of carbamazepine as a function of their concentration. The solubilizing power of these hydrotropes was shown to be highly dependent on their chemical structure. The solubilizing power of the amino derivatives is generally higher than that of the hydroxy derivatives. The position of the hydroxyl or amino groups relevant to the carboxylate group in the hydrotrope molecule plays a major role in its solubilizing effect. The spectral pattern of carbamazepine was found to undergo a change in presence of these compounds. Applying the continuous variation method revealed formation of 2:1 carbamazepine complex with each of sodium salicylate and sodium anthranilate as well as a 1:2 complex with sodium p-amino benzoate. Also, the drug forms 1:1 complexes with both sodium m-hydroxybenzoate and sodium p-hydroxybenzoate. On the other hand, two species of complexes appear to be formed in carbamazepine-sodium p- aminosalicylate system, viz., 1:2 and 2:1 complexes. An apparent correlation seems to exist between the solubilizing power of the investigated hydrotropes and the stability constant of their respective complexes with the drug. Calculating the amount of drug solubilized in free as well as in complexed forms in these systems revealed that the decrease in the activity coefficient of carbamazepine in presence of the investigated hydrotropes may be responsible for the increase in carbamazepine solubility beside complex-formation

Effect of aromatic hydrotropies on the solubility of carbamazepine part II effect of nicotinamide, sodium salts of benzoic naphthoic and nicotinic acids

The effect of nicotinamide and sodium benzoate, naphthoate and nicotinate on the solubility of carbamazepine in water was studied. The investigated hydrotropes were found to increase the solubility of carbamazepine. The solubilizing power of these hydrotropes was shown to be highly dependent on their chemical structure. The replacement of benzene ring by a naphthalene or pyridine ring enhances solubilization. Molecular interaction of carbamazepine with the investigated solubilizers was depicted via differential ultraviolet spectrophotometric measurements. Applying the continuous variation method revealed formation of 1:1 complex with sodium nicotinate, 2:1 complex with nicotinamide and sodium naphthoate and a mixture of 2:1 and 1:2 complexes with sodium benzoate. An apparent correlation seems to exist between the solubilizing power of these hydrotropic agents and the stability constant of their respective complexes. Calculating the amount of drug solubilized in free as well as complexed forms revealed that complex-formation as well as the decrease in activity coefficient of the drug are the two factors governing the hydrotropic behavior of these compounds towards carbamazepine

Interaction of glucocorticoids with xanthines

The potentiality of interaction of prednisone and prednisolone with xanthine derivatives, viz., caffeine, theophylline, dyphelline and acepifylline was investigated. Differential ultraviolet spectrophotometry revealed a marked effect of xanthines on the extinction coefficient of prednisone and prednisolone. The continuous variation method revealed the formation of 1:1 complexes between xanthine derivatives and prednisone or prednisolone with the exception of interaction between prednisone and acepifylline where two types of complexes 1:3 and 2:1 appear to be formed. Determination of the stability constant of the complexes revealed that theophylline and its derivatives acepifylline and dyphelline form more or less stable complexes with the two steroids compared to caffeine. The dissolution rate of the two steroids as well as their xanthine complexes was found to follow first order kinetics during the first 30 min of the dissolution run. On the other hand, the solubility power of theophylline and its derivatives is more or less higher than caffeine, this is more evident for prednisone. There is a lack of correlation between the solubility power of the complexing agents and the stability constant of the formed complexes, but there is a good correlation between the dissolution rate constant of prednisolone complexes and their stability constant [c.c. = 0.995]