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Biomedical subjects

L V Allen

Publications and source records attributed to L V Allen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Iontophoresis of hydrocortisone across hairless mouse skin: investigation of skin alteration.

The effects of hydration, sodium dodecyl sulfate (SDS), and electric current on the permeability of hairless mouse skin was examined in vitro with a neutral solute, hydrocortisone, as a permeant. The study was carried out by pretreating the skin with (1) normal saline, (2) 0.06% SDS in 0.3% NaCl, (3) normal saline plus 0.5 mA anodic current, and (4) 0.06% SDS in 0.3% NaCl plus 0.5 mA anodic current for 8 h. The pretreated skin was then immediately used for passive or anodic transport of hydrocortisone. Results show that pretreatment of skin with either normal saline or 0.06% SDS resulted in a slightly increased passive penetration of hydrocortisone with a prolonged lag time, but did not significantly change the anodic transport of hydrocortisone. There was no significant difference between normal saline pretreatment and 0.06% SDS pretreatment, indicating that 0.06% SDS did not irreversibly alter the permeability of skin other than its hydration effect. Pretreatment of skin with current, and especially with current combined with 0.06% SDS, yielded a significant increase in both passive and anodic transport of hydrocortisone with reduced lag time, indicating that alteration of the skin structure had occurred. The reversibility of this alteration depends on the duration of exposure of the skin to the electric field. Short-term exposure (< 2 h) does not appear to change the permeability of skin in any significant way; long-term exposure may lead to slowly reversible or irreversible skin alteration.

Animals↗
PubMed1993

Stability of octreotide acetate in polypropylene syringes.

The stability of octreotide acetate in polypropylene syringes was studied. Polypropylene syringes were aseptically filled with 1 mL of octreotide acetate 0.2 mg/mL and stored at 3 or 23 degrees C under light protection or light exposure. Three syringes were prepared for each condition and each sampling time. Unopened 5-mL glass vials of the drug served as controls. Samples were removed immediately and at 8, 15, 22, and 29 days and analyzed by high-performance liquid chromatography. At 3 degrees C, octreotide stored in light-protected syringes maintained more than 90% of its initial concentration for up to 29 days. However, at 22 days the concentration in the syringes stored at that temperature and exposed to light was less than 90% when the standard deviation is considered. At 23 degrees C, the drug was stable for only up to 15 days (light protection) and 22 days (light exposure) when the standard deviation is considered. Octreotide acetate in polypropylene syringes was stable for up to 29 days when stored at 3 degrees C and protected from light and for up to 22 days when stored at 23 degrees C and exposed to light.

Chemistry, Pharmaceutical↗
PubMed1992

Iontophoretic permeation of sodium cromoglycate through synthetic membrane and excised hairless mouse skin.

The iontophoretic transport properties of sodium cromoglycate were characterized using a synthetic membrane and excised hairless mouse skin. The permeation rate of sodium cromoglycate through the synthetic membrane was found to be linearly dependent on the density of electrical current applied. Passive diffusion through the excised hairless mouse skin was not demonstrated for sodium cromoglycate; however, under iontophoresis, an appreciable permeation was exhibited by the drug through the animal skin, which was also found to be a function of the electrical current density.

Animals↗
PubMed1992

Stability of ondansetron hydrochloride in portable infusion-pump reservoirs.

The stability of ondansetron hydrochloride 0.24 and 2 mg/mL when delivered by portable infusion pump at near-body temperature over various time periods was investigated. Nine 100-mL drug reservoirs were prepared, three containing ondansetron hydrochloride 2 mg/mL and six containing ondansetron hydrochloride diluted with 0.9% sodium chloride injection to 0.24 mg/mL. Three of the reservoirs containing the diluted solution were refrigerated for up to 30 days at 3 degrees C before being attached to portable infusion pumps and pumped over 24 hours at 30 degrees C. The remaining six reservoirs were attached to pumps immediately after being filled, and the solutions were delivered for up to 24 hours (the diluted solution; three reservoirs) or up to seven days (the concentrated solution; three reservoirs) at 30 degrees C. Samples were taken initially and periodically and analyzed by high-performance liquid chromatography and with a pH meter. Both the diluted and the concentrated solutions of ondansetron hydrochloride retained at least 95% of the initial drug concentration under all the conditions studied. There was no appreciable change in pH. Ondansetron hydrochloride 0.24 mg/mL was stable when stored for up to 30 days at 3 degrees C and infused over 24 hours at 30 degrees C. Ondansetron hydrochloride 2 mg/mL was stable when infused for up to one week at 30 degrees C.

Chromatography, High Pressure Liquid↗
PubMed1992

Stability of ceftazidime (with arginine) and of cefuroxime sodium in infusion-pump reservoirs.

The stability of ceftazidime (with arginine) and cefuroxime sodium was studied after storage in infusion-pump reservoirs at freezing and refrigerated temperatures and subsequent simulated administration over 24 hours at near-body temperature. Polyvinyl chloride reservoirs and glass vials were filled with ceftazidime (with arginine) or cefuroxime sodium at various concentrations, diluted in sterile water. Three reservoirs each of ceftazidime 30 and 60 mg/mL and of cefuroxime 22.5, 30, 45, and 60 mg/mL were stored for various times and at various temperatures. Three glass vials each of ceftazidime or cefuroxime 30 and 60 mg/mL were stored for 30 days at -20 degrees C, followed by 4 days at 3 degrees C and 24 hours at 30 degrees C. Samples obtained periodically during storage and during simulated administration were analyzed with high-performance liquid chromatography. Both drugs maintained at least 90% of their initial concentration under all of the test conditions except simulated administration at 30 degrees C, during which degradation accelerated. In portable infusion-pump reservoirs, ceftazidime 30 and 60 mg/mL and cefuroxime 30 and 60 mg/mL were stable for 30 days at -20 degrees C followed by 4 days at 3 degrees C; ceftazidime 30 and 60 mg/mL was stable for 10 days at 3 degrees C; and cefuroxime 22.5 and 45 mg/mL was stable for 7 days at 3 degrees C. However, the drugs may need to be administered over less than 24 hours when the pump reservoir is worn on the patient's body.

Arginine↗
PubMed1992

Causes of non-medication-induced nasogastric tube occlusion.

In vitro simulation of nasogastric tube delivery of enteral formulas was used to study the mechanism and prevention of non-medication-induced nasogastric tube occlusion. Enteral nutrition products--Osmolite, Ensure, Vital High Nitrogen, and Vivonex T.E.N.--were placed in glass beakers and titrated with hydrochloric acid to determine the pH at which clotting would occur. Factors such as pH, protein content, viscosity, electrolyte composition, flow rate, and tube design were evaluated to determine their effects on coagulation of formula. Addition of simethicone emulsion and docusate sodium to the formulas and siliconization of the nasogastric tubes were studies for their effect on prevention of clog formation. Clumping began to occur at pH 4.6 (the isoelectric point for casein) for Ensure and Osmolite; addition of protein supplement did not change the pH at which coagulation occurred. Vital High Nitrogen and Vivonex T.E.N. formulations did not clump in the beakers. Ensure and Osmolite coagulated within 35 seconds at pH 4.6 or less and remained unchanged at pH greater than 6.0. Addition of sodium or calcium caseinate greatly increased the tendency of the formulas to coagulate. Viscosity of the formula increased markedly as pH decreased. Addition of electrolytes had no effect on precipitation or clumping. Slow or no flow rates within nasogastric tubes placed in simulated gastric juice decreased the pH and caused clumping of formulas within the tubes in a retrograde manner. Flow time or clog formation was not affected by the addition of simethicone or docusate sodium or siliconization of the nasogastric tube.(ABSTRACT TRUNCATED AT 250 WORDS)

Enteral Nutrition↗
PubMed1991

Gas production of three brands of ceftazidime.

Two sodium carbonate formulations of ceftazidime (Tazidime and Tazicef) and a new arginine formulation (Ceptaz) were evaluated for gas production and bubble formation within the drug reservoir and extension tubing of a portable infusion pump during a 24-hour delivery cycle. Triplicate samples of each brand of ceftazidime were studied under identical conditions. All formulations were constituted and diluted with sterile water for injection to a concentration of approximately 33 mg/mL, drawn into syringes, and expelled into infusion-pump drug reservoirs. Triplicate samples of degassed Tazidime and Tazicef were evaluated in the same manner. In one set of triplicate experiments, reservoirs for each formulation were attached to portable infusion pumps immediately after filling at room (23 degrees C) temperature and were programmed to deliver 25 mL over one hour every eight hours for a 24-hour delivery cycle. In a second experiment, reservoirs containing triplicate samples of each product were refrigerated (3 degrees C) for 24 hours before they were attached to the pumps for dose delivery. Visual observations were made for all pumping devices. In addition, multiple vials of each formulation were constituted, and the headspace pressure of the various formulations was monitored to compare the pressure build-up due to carbon dioxide. The presence of carbon dioxide was confirmed by gas chromatography. Pressure build-up due to carbon dioxide formation occurred in the ceftazidime sodium carbonate vials only. The sodium carbonate formulations required degrassing to reduce gas and bubble formation to a manageable level after constitution. Additionally, drug was lost because of spewing of some samples during withdrawal from the vial.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1990

Nefopam hydrochloride degradation kinetics in solution.

A stability-indicating reversed-phase high performance liquid chromatographic method was developed for the detection of nefopam hydrochloride and its degradation products under accelerated degradation conditions. The degradation kinetics of nefopam hydrochloride in aqueous solutions over a pH range of 1.18 to 9.94 at 90 +/- 0.2 degrees C was studied. The degradation of nefopam hydrochloride was found to follow apparent first-order kinetics. The pH-rate profile shows that maximum stability of nefopam hydrochloride was obtained at pH 5.2-5.4. No general acid or base catalysis from acetate, phosphate, or borate buffer species was observed. The catalytic rate constants on the protonated nefopam imposed by hydrogen ion and water was determined to be 7.16 X 10(-6) M-1 sec-1, and 4.54 X 10(-9) sec-1, respectively. The pKa of nefopam hydrochloride in aqueous solution was determined to be 8.98 +/- 0.33 (n = 3) at 25 +/- 0.2 degrees C by the spectrophotometric method. The catalytic rate constant of hydroxyl ion on the degradation of nefopam in either protonated or nonprotonated form was determined to be 6.63 X 10(-6) M-1 sec-1 and 4.06 X 10(-6) M-1 sec-1, respectively. A smaller effect of hydroxyl ion on the degradation of nonprotonated than on the degradation of protonated nefopam was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Buffers↗
PubMed1990

Stability of fentanyl citrate and bupivacaine hydrochloride in portable pump reservoirs.

The stability of fentanyl citrate and bupivacaine hydrochloride in an admixture with 0.9% sodium chloride injection in portable pump reservoirs with or without overwraps was investigated. Twelve 100-mL samples containing fentanyl 20 micrograms/mL and bupivacaine hydrochloride 1250 micrograms/mL were placed in the plastic drug reservoirs, and 1-mL quantities were withdrawn immediately after preparation and at intervals during 30 days of storage. Six reservoirs were refrigerated (3 degrees C) and six stored at room temperature (23 degrees C); three at each temperature were placed in overwraps. All samples were observed for precipitation and for change in color or pH and were analyzed for drug concentration by high-performance liquid chromatography. No precipitation or change in color or pH was observed during the 30-day storage period. No loss of fentanyl or bupivacaine was detected in either the wrapped or the unwrapped samples. Fentanyl citrate and bupivacaine hydrochloride in 0.9% sodium chloride injection appear to be compatible, and admixtures containing the two drugs at the concentrations studied can be stored without overwraps for up to 30 days at refrigerated or room temperature without any significant loss of potency.

Bupivacaine↗
PubMed1990

Uptake of trimethoprim and metronidazole in the seminal vesicle: experimental study.

A rat model for determining drug levels in the seminal vesicle was developed. In separate studies, trimethoprim and metronidazole were injected intravenously into rats and assays of seminal vesicle, plasma, and prostate performed. Drug levels were detected early in both the seminal vesicle and prostate. This appears to be the first study to report drug levels in the seminal vesicle. Metronidazole levels in the seminal vesicle were very low and short lived.

Animals↗
PubMed1990

Recovery of phenytoin suspension after in vitro administration through percutaneous endoscopic gastrostomy Pezzer catheters.

Various methods of administering phenytoin suspension through a percutaneous endoscopic gastrostomy (PEG) Pezzer catheter were evaluated in vitro to determine which method resulted in the most complete recovery of phenytoin. To determine the effect of temperature on phenytoin recovery, 12 mL of phenytoin suspension (Dilantin-125, 125 mg/5 mL) was administered through three separate 35.5-cm 20 French latex PEG Pezzer catheters under each of three temperature conditions (suspension 11.8 degrees C and catheter 22 degrees C, suspension and catheter 22 degrees C, and suspension 22 degrees C and catheter 37 degrees C). To determine the effect of the administration method, 12-mL aliquots of phenytoin suspension were injected into the catheter by seven methods that varied with respect to catheter temperature, dilution of suspension, and irrigation of catheter. Each method was tested in triplicate, and samples were assayed by high-performance liquid chromatography. Varying the temperature of the catheter or suspension had little effect on the recovery of phenytoin. There was no appreciable loss of phenytoin when the suspension was undiluted, regardless of whether the catheter was irrigated. The greatest losses were seen when the suspension was diluted before administration. Irrigation also caused a decrease in recovery, but to a lesser extent than dilution. Until the effects of administering multiple doses of phenytoin through PEG Pezzer catheters are investigated, phenytoin suspension should not be diluted before administration because of decreased recovery and increased administration time.

Catheterization↗
PubMed1990

Degradation mechanism of nefopam in solution under stressed storage conditions.

Nefopam, in pH 2.0 and pH 9.0 solutions, was forcibly degraded at 90 +/- 0.2 degrees C for 60 days. At least eight degradation products from the above solutions were collected from a reverse-phase high performance liquid chromatographic (HPLC) system with a C18 semipreparative column. Some minor peaks were considered insignificant, and no attempt was made to collect and identify their structures. The collected eluents under each major peak were further purified by extraction with methylene chloride from alkaline solutions. Proton nuclear magnetic resonance and fast atom bombardment mass spectroscopy were used to characterize the chemical properties of these degradates. The chemical structures of the major degradation products were proposed as (B) or (C) 2,3-dihydro-2(2'-hydroxyethyl)-N-methyl-1-phenyl-isoindole; (D) or (E) 1-hydroxy-3,4,5,6-tetrahydro-5-methyl-1-phenyl-1H-2,5-benzoxazocine++ +; (F) 2-(N-(2-hydroxyethyl)-N-methylaminomethyl) benzhydrol; (G) 2-(N-(2-hydroxyethyl)-N-methylaminoethyl) benzophenone; (H) 1-hydroxy-3,4,5,6-tetrahydro-5-methyl-1-phenyl-1H-2,5-benzoxazocine++ +, where B and C, D and E, are diasteromers. The possible pathways by which the nefopam degradation proceeded in acidic and basic solutions is postulated as Schemes I and II, respectively. The initial ring-opening process at the site of ether linkage appears to be the rate-determining step of degradation in both acidic and basic solutions.

Chemical Phenomena↗
PubMed1990

Osmolality of small-volume i.v. admixtures for pediatric patients.

The osmolalities of pediatric i.v. admixtures were measured to identify drug concentrations in selected vehicles that would conserve fluid while maintaining osmolality values of 400 mOsm/kg or less. Test solutions were prepared by diluting appropriate volumes of freshly reconstituted powdered drug products or commercially diluted drug products with 5% dextrose injection, 0.9% sodium chloride injection, or both to provide 5 mL of each admixture at desired drug concentrations. To reduce their osmolalities, trimethoprim-sulfamethoxazole and ampicillin sodium were also diluted in 0.45% sodium chloride injection; ticarcillin disodium was diluted only in 0.45% sodium chloride injection. A vapor pressure osmometer was used to measure osmolalities in triplicate for three solutions prepared for each admixture. Of the 63 different admixtures prepared with 5% dextrose injection or 0.9% sodium chloride injection or both, 47 (75%) had osmolalities of 400 mOsm/kg or less. At least one concentration of each selected drug diluted in these vehicles had an osmolality of less than 425 mOsm/kg, except for trimethoprim-sulfamethoxazole and ampicillin sodium. Selected concentrations of the latter two drugs and ticarcillin disodium in 0.45% sodium chloride injection resulted in acceptable osmolalities. For most drugs diluted to the same concentration in 5% dextrose injection and 0.9% sodium chloride injection, osmolalities were lower in the dextrose solutions. Selection of an appropriate vehicle and drug concentration can control the osmolality of i.v. admixtures when the volume of fluid must be minimized, as for pediatric patients.

Anti-Bacterial Agents↗
PubMed1990

Stability of fentanyl citrate in 0.9% sodium chloride solution in portable infusion pumps.

The stability of fentanyl citrate diluted with 0.9% sodium chloride injection for use in portable infusion pumps was studied. The commercially available injection containing 50 micrograms of fentanyl per milliliter was diluted to a concentration of 20 micrograms/mL. Twelve 100-mL portions of the dilute solution were placed in polyvinyl chloride infusion pump drug reservoirs; six were stored at 3 degrees C and six at 23 degrees C; three at each temperature were overwrapped with polypropylene-Mylar. Initially and after 5, 10, 20, and 30 days of storage, 1-mL samples were taken from each reservoir, inspected for color change and precipitation, and assayed for fentanyl concentration by high-performance liquid chromatography. Initially and on day 30, pH of the samples was checked. No precipitation or change in color or pH was observed. No substantial decrease in fentanyl concentration was found in either the wrapped or unwrapped samples at either temperature, although concentrations on day 30 in the samples at 23 degrees C were slightly lower than those at 3 degrees C. Under the conditions studied, fentanyl citrate solutions containing 20 micrograms of fentanyl per milliliter can be stored for 30 days in polyvinyl chloride reservoirs for portable infusion pumps.

Chromatography, High Pressure Liquid↗
PubMed1989

In vitro iontophoretic studies using a synthetic membrane.

In vitro iontophoretic administration of drugs through a microporous polyolefin membrane with hydrophilic urethane polymerfilled pores was done for the ionized drugs dexamethasone sodium phosphate, hydrocortisone sodium phosphate, and prednisolone sodium succinate, and for a nonionizable drug cortisone acetate. Currents between 0.2 and 0.8 mA were demonstrated to be effective in increasing the transmembrane transport rate compared with passive diffusion for all the ionizable drugs studied. However, these currents failed to show any significant effect on the transmembrane transport rate of the nonionizable drug, cortisone acetate. There was a good linear relationship between the applied current (I, mA) and the transmembrane transport rate (J, micrograms/mL) in the receptor cell for all the ionized drugs (J = 1.97I + 0.70 for dexamethasone sodium phosphate; J = 2.05I + 1.49 for hydrocortisone sodium succinate; J = 2.25I + 1.93 for prednisolone sodium succinate). This in vitro iontophoretic study demonstrated that electric fields interact more efficiently with charged than with uncharged molecules.

Chromatography, High Pressure Liquid↗