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Biomedical subjects

L V Allen

Publications and source records attributed to L V Allen.

At least 19 recordsLinked to original sources

Stability of labetalol hydrochloride, metoprolol tartrate, verapamil hydrochloride, and spironolactone with hydrochlorothiazide in extemporaneously compounded oral liquids.

The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Labetalol hydrochloride 40 mg/mL, metoprolol tartrate 10 mg/mL, verapamil hydrochloride 50 mg/mL, and spironolactone 5 mg/mL plus hydrochlorothiazide 5 mg/ mL were prepared in a 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in polyethylene terephthalate bottles. The sources of the drugs were tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle initially and at intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. At least 91% of the initial drug concentration was retained in all the oral liquids for up to 60 days. There were no substantial changes in the appearance or odor of the liquids, or in the pH. Labetalol hydrochloride 40 mg/mL, metoprolol tartrate 10 mg/mL, verapamil hydrochloride 50 mg/mL, plus hydrochlorothiazide 5 mg/ mL in three oral liquids compounded extemporaneously from sweetened vehicles and tablets were stable for up to 60 days when stored without light at 5 and 25 degrees C.

Antihypertensive Agents

Stability of baclofen, captopril, diltiazem hydrochloride, dipyridamole, and flecainide acetate in extemporaneously compounded oral liquids.

The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Baclofen 10 mg/mL, captopril 0.75 mg/mL, diltiazem hydrochloride 12 mg/mL, dipyridamole 10 mg/mL, and flecainide acetate 20 mg/mL were prepared in a 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in 120-mL amber, clear polyethylene terephthalate bottles. The source of all the drugs was tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle immediately after preparation and at various intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. A mean of at least 92% of the initial drug concentration was retained for up to 60 days in the baclofen, diltiazem hydrochloride, dipyridamole, and flecainide acetate liquids at both 5 and 25 degrees C. There were no substantial changes in the appearance or odor of any of the liquids or in the pH. Baclofen 10 mg/mL, diltiazem hydrochloride 12 mg/mL, dipyridamole 10 mg/mL, and flecainide acetate 20 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three extemporaneously compounded oral liquids.

Baclofen

Stability of ketoconazole, metolazone, metronidazole, procainamide hydrochloride, and spironolactone in extemporaneously compounded oral liquids.

The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Ketoconazole 20 mg/mL, metolazone 1 mg/mL, metronidazole 50 mg/mL, procainamide hydrochloride 50 mg/ mL, and spironolactone 25 mg/mL were prepared in a 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in 120-mL polyethylene terephthalate bottles. The sources of the drugs were powder, capsules, and tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle immediately after preparation and at intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. At least 93% of the initial drug concentration was retained in all the oral liquids for up to 60 days. There were no substantial changes in the appearance or odor of the liquids, or in the pH. Ketoconazole 20 mg/mL, metolazone 1 mg/mL, metronidazole 50 mg/mL, procainamide hydrochloride 50 mg/ mL, and spironolactone 25 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three extemporaneously compounded oral liquids. INDEX TERMS: Anti-infective agents; Antifungals; Capsules; Cardiac drugs; Cherry syrup; Compounding; Containers; Diuretics; Incompatibilities; Ketoconazole; Liquids; Metolazone; Metronidazole; Polyethylene terephthalate; Powders; Procainamide hydrochloride; Spironolactone; Stability; Storage; Suspending agents; Tablets; Temperature; Vehicles.

Administration, Oral

Stability of acetazolamide, allopurinol, azathioprine, clonazepam, and flucytosine in extemporaneously compounded oral liquids.

The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Acetazolamide 25 mg/mL, allopurinol 20 mg/mL, azathioprine 50 mg/mL, clonazepam 0.1 mg/mL, and flucytosine 10 mg/mL were prepared in 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in polyethylene terephthalate bottles. The sources of the drugs were capsules and tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle initially and at intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. At least 94% of the initial drug concentration was retained in all the oral liquids for up to 60 days. There were no substantial changes in the appearance or odor of the liquids, or in the pH. Acetazolamide 25 mg/mL, allopurinol 20 mg/mL, azathioprine 50 mg/mL, clonazepam 0.1 mg/mL, and flucytosine 10 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three extemporaneously compounded oral liquids.

Acetazolamide

Stability of cefpirome sulfate in the presence of commonly used intensive care drugs during simulated Y-site injection.

The stability of cefpirome sulfate during simulated Y-site injection with drugs commonly used in the intensive care unit was studied. Cefpirome sulfate was constituted and diluted to 50 mg/mL with 0.9% sodium chloride injection, 0.45% sodium chloride injection, 5% dextrose injection, and lactated Ringer's injection. Each cefpirome sulfate solution was mixed 1:1 (simulating Y-site injection) with amikacin 5.0 mg/mL (as the sulfate salt), amphotericin B 0.1 mg/mL, cefazolin 10 mg/mL (as the sodium salt), clindamycin 12.0 mg/mL (as the phosphate ester), dexamethasone phosphate 4.0 mg/mL (as the sodium salt), dopamine hydrochloride 0.8 mg/mL, epinephrine 0.1 mg/mL (as the hydrochloride salt), fluconazole 2.0 mg/mL, gentamicin 1.0 mg/mL (as the sulfate salt), and vancomycin 5.0 mg/mL (as the hydrochloride salt). All the drug combinations were prepared in triplicate and maintained at 23 degrees C. The combinations were observed visually at intervals up to eight hours, pH was measured, and samples were tested for drug concentration by high-performance liquid chromatography. Cefpirome was stable in the presence of each of the secondary drugs throughout the study period. All the secondary drugs except amphotericin B were stable in the presence of cefpirome. There were no visual phenomena indicating incompatibility. Changes in pH were minimal. Cefpirome 50 mg/mL (as the sulfate salt) in four different diluents was stable in the presence of each of 10 commonly used intensive care drugs for at least eight hours during simulated Y-site administration. Amphotericin B 0.1 mg/mL was not stable in the presence of cefpirome sulfate.

Amphotericin B

Stability of ramipril in water, apple juice, and applesauce.

The stability of ramipril in water, in apple juice, and in applesauce was studied. The contents of a single capsule each of ramipril 1.25, 2.5, and 5 mg were mixed in glass beakers with 120 mL of deionized and filtered water, apple juice, or applesauce. Each mixture was apportioned into 10 120-mL amber polyethylene terephthalate (PET) containers. Five of the containers in each set were stored at 23 degrees C, and samples were taken at 0, 1, 2, 6, 12, and 24 hours. The other five containers were stored at 3 degrees C, and samples were taken at 4, 8, 12, 24, and 48 hours. The samples were analyzed for ramipril concentration by stability-indicating high-performance liquid chromatography (HPLC). The quantity of drug remaining in the PET container after "administration" was determined by mixing the contents of single 5-mg ramipril capsules with 60 mL of apple juice, pouring the mixture into a waste receptacle, rinsing the PET container three separate times with 10 mL of water, and analyzing the pooled fluid from these rinses for ramipril concentration by HPLC. Under no condition did the percentage of ramipril remaining drop below 90%. No peaks for degradation products appeared in the chromatograms. The mean +/- S.D. quantity of ramipril remaining in the PET containers after draining was 0.3 +/- 0.3% for the apple juice. Ramipril from 1.25-, 2.5-, and 5-mg capsules mixed in water, in apple juice, and in applesauce was stable for 24 hours at 23 degrees C and for 48 hours at 3 degrees C.

Angiotensin-Converting Enzyme Inhibitors

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

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

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

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