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.

Oxygen solubilization in egg lecithin dispersed in distilled water and physiological electrolyte fluids.

Gaseous oxygen solubilization in egg lecithin dispersed in distilled water, saline, and a multi-ion physiological electrolyte solution was determined and compared to controls deficient in egg lecithin. Significant oxygen solubilization occurred in the presence of egg lecithin. Oxygen solubilization was significantly greater in saline and in the multi-ion physiological electrolyte solution than in distilled water.

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.

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.

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.

Effect of surfactant on tetracycline absorption across everted rat intestine.

Absorption of tetracycline hydrochloride (500 micrograms/ml) from oxygenated modified Krebs buffer in randomized everted rat jejunal segments was determined alone and in the presence of calcium, polysorbate 80, and calcium plus polysorbate 80. Surfactant increased absorption of tetracycline in the presence and absence of calcium, with 0.01% (w/v) polysorbate 80 increasing transfer to the greatest extent of the concentrations examined(0.005, 0.01, 0.05, 0.1, and 1%); tetracycline hydrochloride + 12.5 mM CaCl2, 143 +/- 45 micrograms/ml; tetracycline hydrochloride + polysorbate 80, 389 +/- 18 micrograms/ml; tetracycline hydrochloride + 12.5 mM CaCl2 + polysorbate 80, 255 +/- 31 micrograms/ml. On the premise that the effective surfactant concentration is similar to the critical micelle concentration, an absorption mechanism based on micellar solubilization is postulated.

Degradation kinetics of phentolamine hydrochloride in solution.

The degradation kinetics of phentolamine hydrochloride in aqueous solution over a pH range of 1.2 to 7.2 and its stability in propylene glycol- or polyethylene glycol 400-based solutions were investigated. The observed rate constants were shown to follow apparent first-order kinetics in all cases. The pKa determination for phentolamine hydrochloride was found to be 9.55 +/- 0.10 (n = 5) at 25 +/- 0.2 degrees C. This indicated the protonated form of phentolamine occurs in the pH range of this study. The pH-rate profile indicated a pH-independent region (pH 3.1-4.9) exists with a minimum rate around pH 2.1. The catalytic effect of acetate and phosphate buffer species is ordinary. The catalytic rate constants imposed by acetic acid, acetate ion, dihydrogen phosphate ion, and monohydrogen phosphate ion were determined to be 0.018, 0.362, 0.036, and 1.470 L mol-1 h-1, respectively. The salt effect in acetate and phosphate buffers followed the modified Debye-Huckel equation quite well. The ZAZB value obtained from the experiment closely predicts the charges of the reacting species. The apparent energy of activation was determined to be 19.72 kcal/mol for degradation of phentolamine hydrochloride in pH 3.1, 0.1 M acetate buffer solution at constant ionic strength (mu = 0.5). Irradiation with 254 nm UV light at 25 +/- 0.2 degrees C showed a ninefold increase in the degradation rate compared with the light-protected control. Propylene glycol had little or no effect on the degradation of phentolamine hydrochloride at 90 +/- 0.2 degrees C; however, polyethylene glycol 400 had a definite effect.

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)

Pharmacokinetics of trimethoprim in the rat.

The pharmacokinetics of trimethoprim was studied in male Sprague-Dawley rats following the intravenous administration of trimethoprim at a dose of 25 mg/kg. Plasma and tissue levels of trimethoprim, as a function of time, were determined by reversed-phase high-performance liquid chromatography. The disposition of trimethoprim was described by both a two-compartment open model with elimination from a central compartment and a noncompartmental method. For the compartmental analysis, the terminal elimination rate constant, elimination half-life, apparent volume of distribution in the central compartment, apparent volume of distribution in the central compartment based on the area under the plasma concentration-time curve, and volume of distribution at steady state, were determined to be 0.007 min-1, 99 min, 2059 mL/kg, 5729 mL/kg, and 2473 mL/kg, respectively. Noncompartmental pharmacokinetic parameters were obtained by the statistical moment theory. The estimates for mean residence time, clearance, and volume of distribution at steady state of trimethoprim were calculated to be 52 min, 40 mL.min-1kg-1, and 2097 mL, respectively. Tissue distribution of trimethoprim followed a biphasic phenomenon with a maximum concentration at 30 min for heart, lung, spleen, liver, kidney, seminal vesicles, and muscle, and at 45 min for testicles, 20 min for prostate gland, and less than 10 min for brain. The data show that compared with the plasma concentration, higher levels of trimethoprim were found in heart, lung, spleen, liver, kidney, prostate gland, and seminal vesicles; a similar concentration was found for muscle, but lower levels of trimethoprim were found for brain and testicles.

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)

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)

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.

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.

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.

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.

Stability of bethanechol chloride, pyrazinamide, quinidine sulfate, rifampin, and tetracycline hydrochloride in extemporaneously compounded oral liquids.

The stability of five drugs commonly prescribed for use in oral liquids but not commercially available as such was studied. Bethanechol chloride 5 mg/mL, pyrazinamide 10 mg/mL, quinidine sulfate 10 mg/mL, rifampin 25 mg/mL, and tetracycline hydrochloride 25 mg/mL were each 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, and cherry syrup and placed in 120-mL amber clear polyethylene terephthalate bottles. Three bottles of each liquid were stored at 5 degrees C and three at 25 degrees C, all in the dark. Samples were taken initially and at various times up to 60 days for analysis by high-performance liquid chromatography and assessment of appearance and odor; pH was measured. A mean of at least 90% of the initial drug concentration was retained for 60 days in the liquids containing bethanechol chloride, pyrazinamide, or quinidine sulfate and for 28 days in the rifampin-containing liquids and the mixture of tetracycline hydrochloride and Ora-Sweet-Ora-Plus at both 5 and 25 degrees C. Tetracycline hydrochloride concentrations of 90% or more of the initial concentration were retained in the liquids prepared with Ora-Sweet SF-Ora-Plus for 10 days at 5 degrees C and 7 days at 25 degrees C and in those prepared with cherry syrup for 7 days at 5 degrees C and 2 days at 25 degrees C. No substantial changes in the appearance, odor, or pH of any liquid were observed. At 5 and 25 degrees C, bethanechol chloride 5 mg/mL, pyrazinamide 10 mg/mL, and quinidine sulfate 10 mg/mL were stable in three extemporaneously compounded oral liquids for 60 days and rifampin 25 mg/mL was stable for 28 days. The stability of tetracycline hydrochloride 25 mg/mL varied with the vehicle.

Stability of alprazolam, chloroquine phosphate, cisapride, enalapril maleate, and hydralazine hydrochloride in extemporaneously compounded oral liquids.

The stability of five drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Alprazolam 1 mg/mL, chloroquine phosphate 15 mg/mL, cisapride 1 mg/mL, enalapril maleate 1 mg/mL, and hydralazine hydrochloride 4 mg/mL were each 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, and cherry syrup and placed in 120-mL amber clear polyethylene terephthalate bottles. Three bottles of each liquid were stored at 5 degrees C and three at 25 degrees C, all in the dark. Samples were taken initially and at various times up to 60 days for analysis by high-performance liquid chromatography and assessment of appearance and odor; pH was measured. A mean of at least 91% of the initial drug concentration was retained for 60 days in the alprazolam, chloroquine phosphate, cisapride, and enalapril maleate liquids. The hydralazine hydrochloride liquids retained more than 90% of the initial concentration for only one day at 5 degrees C when prepared with Ora-Sweet-Ora-Plus and two days when prepared with Ora-Sweet SF-Ora-Plus and for less than a day in these preparations at 25 degrees C and in cherry syrup at 5 and 25 degrees C. No substantial changes in the appearance, odor, or pH of any liquid were observed. Alprazolam 1 mg/mL, chloroquine phosphate 15 mg/mL, cisapride 1 mg/mL, and enalapril maleate 1 mg/mL were stable in three extemporaneously compounded oral liquids for 60 days at 5 and 25 degrees C; hydralazine hydrochloride 4 mg/mL was stable at 5 degrees C for one day in Ora-Sweet-Ora Plus and for two days in Ora-Sweet SF-Ora-Plus.

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.

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.

Analysis of benzalkonium chloride and its homologs: HPLC versus HPCE.

Benzalkonium chloride (BAK) is a mixture of alkylbenzyldimethylammonium chloride homologs with n-C,2H25, n-C,4H29, and n-C16H33 comprising a major portion of the alkyl groups present. An analytical method for BAK must differentiate and quantitate the homologs in the BAK mixture. Reversed-phase high performance liquid chromatography (HPLC) separates compounds based on their affinity for a nonpolar column, which is a direct correlation to the compounds' polarity. High performance capillary electrophoresis (HPCE), however, separates compounds in an electric field according to their charge and size. The BAK homologs are suitable for separation by either of these methods because their polarity and sizes differ significantly. The HPLC method employed a mobile phase of 60% acetonitrile and 40% 0.1 M sodium acetate buffer pH 5 pumped at 1.0 ml min(-1), a 4.6 x 250 mm cyano column with 5 microm packing, and UV detection at 254 nm. The HPCE method utilized a run buffer of 30% acetonitrile and 70% 0.05 M sodium phosphate pH 3.06, a 50 microm x 20 cm open silica capillary, 7.5 kV electric field and UV detection at 214 nm. Both HPLC and HPCE demonstrated good linearity in the range of 0.025 to 0.8 mg ml(-1) with r2 values of approximately 0.99. The HPLC method produced good separation of the homolog peaks with a total analysis time of 25 min. HPCE run time was less than 5 min and demonstrated good separation of the three homologs. The HPLC method, however, was superior to HPCE in the areas of sensitivity and precision. The HPLC has been extensively used in the routine quantitation and qualitation of benzalkonium chloride concentrations in various products; however, long analysis times make this method inefficient. The HPCE method produced comparable results to the HPLC method but with much shorter analysis times. An HPCE analysis method, as presented here, may prove to be a much more useful and efficient method for the analysis of benzalkonium chloride and its homologs.