Percutaneous diffusion of cefalexin, sulfamethoxazole and diphenhydramine from ointments.

The effects of ointment base, drug concentration, and the presence of surfactant on the diffusion of cefalexin, sulfamethoxazole and diphenhydramine through excised mouse skin were studied. The total amount of diffused drug per ml against time and against the square root of time as plotted for the evaluation of results. As was expected from theory, a linear relationship was obtained for each drug when the square root of time was employed. The effect of the vehicle on the release of cefalexin was in the following decreasing order: o/w emulsion greater than water-soluble greater than hydrophilic greater than oleaginous greater than w/o emulsion base. That on the release of sulfamethoxazole was in the order: water-soluble greater than o/w emulsion greater than w/o emulsion = oleaginous = hydrophilic. The order in case of diphenhydramine was as follows: o/w emulsion greater than water-soluble greater than hydrophilic greater than oleaginous = w/o emulsion. The increase in drug concentration or the addition of a surfactant has caused an increase in the diffusion rate of each of the drugs.

Effect of some syrup constituents on the solubility of sorbic acid.

The effects of sucrose, glucose, sorbitol, and saccharin on the aqueous solubility of sorbic acid at 20 and 37 degrees C were determined. Sucrose, glucose, and sorbitol decreased the solubility of sorbic acid with increasing concentrations at both temperatures. Increasing the concentrations of these sweetening agents resulted in decreases in the dielectric constants. Calculation of the free energy and enthalpy changes indicated that the dissolution process for sorbic acid became progressively unfavorable with increasing sugar concentration.

An introductory course to facilitate the implementation of a clinical pharmacy programme in Iraq.

An introductory course in clinical pharmacy is discussed which is designed to implement the basic concepts of clinical pharmacy as well as assist in the stepwise transition from a pharmacy school, with primary emphasis on dispensing, to a more clinically (patient) oriented pharmacy programme. The course is composed of a 2-h didactic session and a 3-h observation session per week for 3 months followed by daily 3-h practical clerkships for 4 months in the following areas: in-patient and out-patient hospital pharmacy, clinical laboratory, internal medicine, paediatrics, surgery, and retail pharmacy. Weekly 2-hour discussion sessions at the college or site of the clerkship are scheduled to review these experiences and introduce additional topics such as patients rights, pharmacist-patient relations, and pharmacy relations with other health professionals. This course promotes the development of a clinically oriented attitude in students and staff members in the college, and decreases the trauma of direct change from a product-oriented to a more patient-oriented curriculum.

Percutaneous absorption and disposition of iodochlorhydroxyquin in dogs.

The percutaneous absorption and disposition of iodochlorhydroxyquin (5-chloro-7-iodo-8-quinolinol; I) from a 3% cream were studied in five dogs over a 28-d topical treatment period. Plasma levels, determined by HPLC, were 0.275-0.525 microgram/mL. The steady-state elimination rate of total I in urine was 2.4-3.0 mg/d. The apparent elimination rate constant and half-life were 0.25 +/- 0.05 d-1 and 3.1 +/- 0.5 d, respectively. Greater than 50% of topically applied I was absorbed over 16 h. Occlusion of the skin without the drug indicated that the skin acted as a reservoir for the drug. Feces analysis for iodochlorhydroxyquin from one dog showed that 27.1 +/- 8.5 mg/d was eliminated via this route. Tissue levels of I 15 d after the 28-d topical treatment were 0.7 microgram/g of liver, 0.2 microgram/g of kidney, and 0.8 microgram/g of mesenteric fat. The apparent rate constants of plasma level decline after a 100-mg iv bolus dose of I were alpha = 3.9 h-1 and beta = 0.6 h-1. The urinary elimination after intravenous administration was biphasic. The rate constant for the slow elimination phase was 0.4 +/- 0.1 d-1, and the half-life was 2.0 +/- 0.5 d. The primary neurological symptoms observed during topical treatment were ataxia and hind limb paralysis. Microscopic examination revealed liver necrosis. A weight loss of 15.3 +/- 2.7% was also observed over the 28-d topical treatment period. The results indicate that significant percutaneous absorption of I occurs, and that chronic high-dose topical treatment may lead to toxicity.

Percutaneous absorption of iodochlorhydroxyquin in humans.

Iodochlorhydroxyquin (I) is used in the treatment of diaper rash and other skin disorders, and is presumed to undergo little or no percutaneous absorption. The absorption of (I) from a 3% cream was studied in 5 normal male subjects after a single application of the cream for 12 h. Plasma levels of the drug were followed for 24 h after initial application while urinary excretion was measured for 54 h. (I) was extracted from plasma and urine and assayed by high-performance liquid chromatography. The drug in the range of 0.37-0.56 micrograms/ml was detected in plasma 2 h after application and persisted throughout the treatment period. The mean excretion rate after 12 h of application was 58.4 micrograms/h and the excretion rate was 8.8 micrograms/h at 42 h posttreatment. The elimination rate constant was calculated to be 0.15 h-1. Approximately 40% of the drug was absorbed over the 12-h application period. From the above results it is apparent that significant percutaneous absorption of (I) occurs.

High-performance liquid chromatographic analysis of iodochlorhydroxyquin and hydrocortisone in ointments and creams.

A simple isocratic, high-performance liquid chromatographic (HPLC) assay procedure was developed for the simultaneous determination of iodochlorhydroxyquin and hydrocortisone in ointments and creams using phenyl salicylate as an internal standard. Ointment samples were extracted by direct dissolution in ether. Homogeneous suspensions of the creams were prepared in the mobile phase. The samples were spiked by the addition of standard iodochlorhydroxyquin, standard hydrocortisone, and the internal standard and subsequently extracted with the mobile phase. HPLC was performed using a reverse-phase microparticulate C-18 column, a precolumn, and a UV detector set at 256 nm. A mobile phase containing methanol and 0.05 M phosphoric acid (70:30) was employed at a flow rate of 1 ml/min. The percent iodochlorhydroxyquin and hydrocortisone found to be present in eight commercial products is reported.

Analysis of iodochlorhydroxyquin in biological materials by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic system using a mobile phase of 0.05 M phosphoric acid--methanol (30:70) was developed for determination of iodochlorhydroxyquin (clioquinol, I) in biological material. I was extracted from samples with diethyl ether. Conjugates of I were hydrolyzed to free I and extracted by the same method. The ether phases were evaporated to dryness, reconstituted in the mobile phase and chromatographed using a microparticulate C18 column, a pre-column and a UV detector set at 256 nm. Quantitation of I in the range of 0.20-2.0 micrograms/ml of urine, 0.50-2.0 micrograms/g of liver, and 0.25-2.0 micrograms/g of feces was obtained with coefficients of variation of 0.02, 0.05, and 0.06, respectively. The detection limit of I was 0.2 micrograms. Extensive absorption of I upon topical application to dogs was also demonstrated.

High-performance liquid chromatographic analysis of iodochlorhydroxyquin in plasma.

A simple isocratic high-performance liquid chromatographic procedure for the analysis of iodochlorhydroxyquin in human plasma is described. Protein was precipitated using perchloric acid, and the supernatant and precipitated protein fractions were extracted with ether. The ether phases were evaporated to dryness, reconstituted in mobile phase, and chromatographed. A reversed-phase microparticulate C18 column, a precolumn, and a UV detector at 256 nm were used. A mobile phase containing 80% methanol and 20% of 0.05 M phosphoric acid was employed at a flow rate of 1 ml/min. Quantitation of iodochlorhydroxyquin in the 1--15-microgram/ml range in human plasma was demonstrated with a coefficient of variance of 0.1--0.06. Hydrocortisone, which is used in combination with iodochlorhydroxyquin in ointments and creams, does not interfere in the assay.