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Biomedical subjects

L V Allen

Publications and source records attributed to L V Allen.

67 records · Page 4Linked to original sources

Dissolution rates of hydrocortisone and prednisone utilizing sugar solid dispersion systems in tablet form.

The utilization of ternary sugar solid dispersion systems and the incorporation of these systems into tablet dosage forms were investigated. The dispersion systems were prepared by the fusion method using 50% sucrose-50% mannitol and 50% sorbitol-50% mannitol. Other systems investigated utilized sorbitol, mannitol, and polyethylene glycol 6000 for comparison. The drug component was hydrocortisone or prednisone. The results from a modified NF XIII dissolution rate determination revealed that the mannitol system had the fastest dissolution rate, followed by sorbitol-mannitol, sucrose-mannitol, sorbitol, and finally, polyethylene gylcol 6000. The corticosteroids were stable and did not decompose during preparation of the dispersion systems or direct compression of the tablets. A short-term stability study revealed that the tablets retained their fast dissolution rates and that the tablet characteristic tests, i.e., tablet hardness, remained unchanged. The use of sugar combinations overcame some difficulties previously reported with single sugar systems.

Chemistry, Pharmaceutical↗

The protective effects of ethylestrenol against acute poisoning by organophosphorus cholinesterase inhibitors in rats.

Pretreatment of rats with 10 mg of ethylestrenol (17alpha-ethylestr-4-en-17beta-ol) by force feeding twice daily for three days and once on the fourth day decreased the severity of parathion (0,0-diethyl 0-4-nitrophenyl phosphorothioate) toxicity and caused a 150% increase in the parathion LD50 in male animals. It decreased by 51% cholinesterase inhibition in the brain caused by i.p. injection of 2 mg of parathion/kg body weight but not that of an equitoxic dose (0.5 mg/kg) of its active metabolite, paraoxon (0,0-diethyl 0-4-nitrophenyl phosphate). It decreased by 29% cholinesterase inhibition in plasma following i.p. administration of parathion but caused only a 16% decrease in cholinesterase inhibition following administration of the equitoxic dose of paraoxon. It did not protect against brain cholinesterase inhibition by 4 mg/kg of parathion given i.v.; however, brain parathion levels were 16% lower in rats pretreated with ethylestrenol than in control rats. It increased the rate of inactivation of both parathion and paraoxon by liver microsomal enzyme preparations. Thus enzyme induction seems to account for the protection afforded by ethylestrenol to toxicity following poisoning by organophosphates.

Animals↗

Dissolution rates of corticosteroids utilizing sugar glass dispersions.

A method of increasing the dissolution rates of some orally administered corticosteroids was investigated. This method involved glass dispersions using dextrose, galactose, and sucrose as the carriers. These dispersions were prepared by the fusion process and were subjected to a modified NF XIII dissolution rate determination. The results revealed a marked increase in the dissolution rate of the corticosteroids contained in the solid dispersions when compared to the dissolution rate of the plan corticosteroid powder. The increase in dissolution rates was attributed to the presence of the corticosteroid in a very fine state of subdivision and to the increased wettability of the corticosteroid powder.

Betamethasone↗

Detection of particles in intravenous fluids using scanning electron microscopy.

A study was conducted to compare the particles in intravenous solutions found in glass and plastic containers, and to investigate the use of scanning electron microscopy in detecting and identifying such particulate contamination. The method used was to filter one liter of each fluid from glass and plastic containers through a membrane filter, attach the membrane to aluminum studs and coat the specimens with a thin layer of gold-palladium in a vacuum evaporator. Scanning electron microscopy was then used to examine the specimens, and photomicrographs were prepared. The results showed that the particles found in glass and in plastic containers have distinctive differences and that scanning electron microscopy is useful in detecting and characterizing these particles.

Drug Contamination↗

Physicochemical stability of a preanesthetic mixture of hydroxyzine hydrochloride and atropine sulfate.

The stability of a combination of hydroxyzine hydrochloride and atropine sulfate stored in syringes was studied. Syringes containing the two drugs were stored at 25 C and 3 C for ten days and analyzed at specific time intervals. Absorption spectra, chromatographic characteristics and pH were determined. Results showed the admixture to be stable for ten days at room temperature or under refrigeration. The technique used would probably not detect any significant degradation of atropine sulfate unless the reaction occurred with the hydroxyzine hydrochloride.

Atropine↗

Specificity of the cannabinoid metabolite and phencyclidine EMIT d.a.u. assays.

An investigation to determine the specificity of the EMIT d.a.u. assays was conducted. Samples of drug-free urine from healthy volunteers were spiked individually with one of 162 drugs to a concentration of 1000 mg/L. These samples were analyzed with the EMIT d.a.u. assays for phencyclidine and cannabinoids. Although some of the assays yielded positive results at this concentration, negative results were obtained in all samples diluted to 100, 10, and 1 mg/L.

Cannabinoids↗

Effect of pH on the equilibrium dialysis of phenytoin suspension with and without enteral feeding formula.

Significant decreases have been reported in phenytoin absorption when the suspension is combined with continuous enteral feedings. Several theories for this interaction have been proposed including binding of phenytoin to the protein constituents of the enteral formula, phenytoin binding to the calcium in the enteral formula, and inadequate dissolution of the suspension when delivered with the enteral formula due to the high pKa of phenytoin and the acidic nature of the enteral formula. We therefore evaluated the effects of pH levels 2.0, 3.5, 6.0, and 8.0 on the interaction of phenytoin suspension with enteral formula (Osmolite) with equilibrium dialysis using a Spectra/Por 1 (MWCO 6000-8000) molecularporous dialysis membrane. Phenytoin concentrations in the dialysis membrane (internal phase) mimicked the expected stomach concentrations of a 100-mg dose administered in an adult stomach containing 200 ml of gastric fluid. External phase buffers were sampled at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 hr after the start of the dialysis. The phenytoin concentrations in the external phase were compared between buffer alone or buffer combined with enteral formula at the same pH and time intervals. With pH 2.0 and 3.5 the enteral formula formed an aggregate with suspension whereas no aggregate was formed with pH 6.0 and 8.0. The phenytoin concentrations with pH 2.0 were 26% to 44% lower and with pH 3.5 were 11.5 to 27% lower when phenytoin suspension was combined with enteral solution. However, at 24 hr there was no difference between the two conditions with both pH 2.0 and 3.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Dialysis↗

Phenytoin recovery from percutaneous endoscopic gastrostomy Pezzer catheters after long-term in vitro administration.

Four in vitro administration techniques were evaluated to determine which method would produce the least amount of phenytoin lost with long-term (14 days) dosing of Dilantin Kapseals (100 mg) or Dilantin suspension 125 mg/5 mL (92 mg) through 20 French percutaneous endoscopic gastrostomy Pezzer catheters. The four in vitro techniques were (1) no dilution or irrigation, (2) irrigation with 10 mL of deionized water, (3) dilution with 10 mL of deionized water, and (4) dilution with irrigation. Similar doses and volumes (3.68 mL) of suspension and capsules were delivered to three separate catheters for each method every 8 hours for 14 days. Each catheter was encased in a 200-mm glass water jacket and maintained at 37 degrees C for the entire 14 days. Samples were collected 1 hour after administration on days 1, 3, 7, 10, and 14 and analyzed by high-performance liquid chromatography. The total mean percent change in initial phenytoin for each method was as follows (S = suspension, K = Kapseals, subscript number = method number): S1, -4.23 +/- 20.20 (mean +/- SD); S2, -7.63 +/- 14.04; S3, -0.14 +/- 2.31; S4, 3.33 +/- 5.59; K1, -9.72 +/- 4.60, K2, 1.43 +/- 3.90; K3, -3.18 +/- 5.59; and K4, 1.39 +/- 4.57.(ABSTRACT TRUNCATED AT 250 WORDS)

Capsules↗