Oxycodone hydrochloride immediate-release analgesic for managing severe pain: abuse-deterrent formulations.

This paper is an expert opinion in response to the development of abuse-deterrent immediate-release tablets containing oxycodone HCl. There is a potential impact, both positive and negative, of this type of dosage form on patients, those suffering from the disease of addiction, health care providers, and the cost of health care.

Pharmacists' compensation and work patterns, 1990-91.

Several major trends were observed in these findings from the 1990-91 National Pharmacists' Compensation Survey (for details see the final report). Only 72.6% of licensed pharmacists were working full-time in pharmacy; another 14.4% were working part-time in pharmacy, and nearly 13.0% were either not working in pharmacy or not working at all. Although 90.0% of active men pharmacists were working full-time, only 70.7% of active women pharmacists were working full-time. Men were more likely to be working in independent and chain pharmacies as a manager or owner. Women were more likely to be working in hospital or chain pharmacies as a staff pharmacist. Pharmacists' base salary in 1990 was substantially higher for men than for women with averages of $46,661 versus $42,668. Total pharmacy compensation showed a similar pattern but an even greater spread between men and women with averages of $51,032 versus $44,751. However, after adjusting for years in practice and number of hours worked per week, the base HWE for employee pharmacists shows that men and women pharmacists do get "equal pay for equal work" in the first 20 years of practice. The difference that develops between men and women with more years in practice is probably due to the higher proportion of men in management positions and to differences in practice setting preferences.(ABSTRACT TRUNCATED AT 250 WORDS)

An in vitro method of evaluating tolnaftate release from topical powder.

A dissolution apparatus was constructed to evaluate tolnaftate release from topical powders. It consisted of a mesh unit to support the powder, a receptor phase, and a sink. This report describes three parameters that were used to evaluate this technique. First, three different areas of contact were examined using 52-, 41-, or 30-µm mesh supports. Second, the effect of the pH on the dissolution rate was studied, using aqueous buffers of pH 3, 5, 7, or 8 as the receptor phase. Finally, different topical powder formulations containing different amounts of tolnaftate were tested. The results obtained showed that the percentage of tolnaftate released from topical powders increased at low pH levels and with the larger mesh support. The percentage released was greater in a starch-talc preparation than in a talc-only preparation. The mesh was replaced by a semipermeable membrane (2.5- to 4 nm pore size) to function as an in vitro model for intradermal diffusion. The results showed that a cream initially released more drug than powder formulations.

The effect of previous d-amphetamine treatment on the disposition and lethality of fenfluramine in the rat.

In an earlier study, it was found that a 15-day ip postfeeding session d-amphetamine treatment rendered an apparent "tolerance" to the feed intake suppressant effects of fenfluramine. The purpose of the present study was to determine if such d-amphetamine treatment altered the disposition of fenfluramine in a way which might account for this decrement in the feed intake suppressant effect of fenfluramine. In addition, the effect of d-amphetamine on fenfluramine toxicity was also examined in an attempt to further characterize and correlate fenfluramine dispositional changes. It was found that plasma and, to some extent, brain concentrations of fenfluramine were elevated in the d-amphetamine-treated rats as compared to a saline control group. The acute, ip LD50 for fenfluramine in d-amphetamine-treated rats was 68 mg/kg (95% CI = 64.8 to 71.4), a value significantly lower than that observed in the saline-treated animals (97 mg/kg; 95% CI = 93.3 to 100.9). The overall results of this study suggest that the anorectic tolerance conferred toward fenfluramine by previous subchronic treatment with d-amphetamine does not result from decreased plasma or brain concentrations of fenfluramine. In fact, such concentrations are increased by prior d-amphetamine treatment, and this increase may in part account for the increased lethality of fenfluramine observed in these animals.

Development and evaluation of enteric-coated penicillamine tablets.

Commercially available 250-mg penicillamine tablets were converted into enteric-coated tablets. Based on in vitro dissolution and disintegration tests, tablets coated with five layers of a cellulose acetate phthalate formulation by a modified pan coating technique were judged to be superior to other coated tablets. These tablets resisted disintegration in simulated gastric fluid over a 4-h period and disintegrated in an average of 21 min in simulated intestinal fluid. Enteric-coated penicillamine tablets were tested in vivo in nine weanling pigs divided into three groups: a negative control group, a test group dosed with enteric-coated penicillamine tablets, and a positive control group dosed with uncoated tablets. The incidence of GI tract bleeding, as determined by daily occult blood tests of the stools, was significantly less in the animals receiving the enteric-coated tablets when compared with the positive control group. The enteric-coated dosage form appeared to decrease GI tract irritation caused by penicillamine. Plasma concentration-time curves for penicillamine in the pigs were similar in shape to those reported in humans. Atypical double peaks occur in both species. Relative bioavailability of the enteric-coated tablet was found to be 67% when compared with the uncoated tablet. This apparent reduction is probably due to a large intrasubject variation in areas under the plasma concentration-time curves and not to a dosage form effect.

Dermatologic prescriptions requiring compounding.

Dermatologists responding to a mail survey supplied 520 prescriptions as examples of prescriptions requiring compounding. A total of 195 different ingredients were used, with an average of 2.5 ingredients per prescription. Anti-inflammatory agents were most frequently used. Brand-name medications were frequently incorporated with other ingredients.

Comparison of high-performance liquid chromatography and radioimmunoassay in the determination of content uniformity of digoxin tablets.

Digoxin 0.25-mg tablets were dissolved and assayed by the standard high-performance liquid chromatography (HPLC) method specified in USP XX and by a radioimmunoassay (RIA) method modified for the assay of tablet solutions. For the RIA method, the filtrate was diluted to a theoretical concentration of 5 ng/ml. Aliquots of this dilution were then assayed for digoxin content using a commercial digoxin 125I RIA kit. Results from both methods were extrapolated to total tablet content and compared with the labeled amount for 20 individual tablets. All tablet assay results were within the USP standards for content uniformity of individual tablets. The individual tablet deviations from labeled amount by the RIA method were smaller when compared with the USP XX-specified HPLC method. Comparison of individual tablet assays show the RIA method to be both as precise and as accurate as the USP XX-specified HPLC method.

Pharmacokinetic interactions of tolazamide and oxyphenbutazone in dogs.

The described pharmacokinetic analysis involved two separate studies on nine dogs randomly assigned to three groups of three dogs each. In the first study, the effect of varying the dosage of tolazamide was examined. The second study concerned the effect of varying the dosage of oxyphenbutazone on tolazamide. A 3 x 3 Latin square was used to study both effects. Each group received each treatment, with a minimum of 1 week separating each session. THe pharmacokinetics of tolazamide followed a two-compartment open model. The hybrid rate constants, alpha and beta, were not significantly different at the three dosages when measured by a three-way analysis of variance. The only significant difference at the three dosage levels of tolazamide was in the apparent volume of distribution. In the pharmacokinetic interaction associated with intravenous administration of one dose of tolazamide and three doses of oxyphenbutazone, the apparent volume of distribution and the hybrid rate constant alpha did not change significantly while the hybrid rate constant for tolazamide, beta, seemed to decrease with increasing oxyphenbutazone.

Effect of docusate sodium on drug release from a controlled-release dosage form.

This study was designed to determine the effect of a clinically used surfactant, docusate sodium, on the release of chlorpheniramine from a controlled-release dosage form (encapsulated coated pellets). In vivo treatments consisted of the controlled-release capsule alone or with 200 mg of docusate sodium. Plasma chlorpheniramine levels were determined, and the AUC was calculated. No significant difference in AUC values was observed between the two treatments. At a concentration below the CMC, docusate sodium enhanced the in vitro drug release rate. The surfactant exerted a greater effect on the release of the first one-third of the drug contained in nonwax-coated pellets. At the CMC, 0.02% (w/v), docusate sodium rapidly entrapped chlorpheniramine in micelles. The overall enhanced dissolution rate in vivo may have been offset by micellar drug entrapment.

Brief communication. Comparative pharmacology of norcocaine in M. mulatta and M. fascicularis.

Norcocaine was administered intravenously (0.05, 0.5, 5.0 mg/kg) to three chaired unanesthetized male rhesus monkeys and to three chaired male cynomolgus monkeys. Respiration rate, heart rate and rectal temperature were monitored. In the rhesus monkeys tachycardia and hyperventilation resulted. However, similar qualitative and quantitative changes were not observed in the cynomolgus species. There was a statistically significant difference in the response to norcocaine across species. These results indicate that cynomolgus monkeys are either less sensitive or respond differently than rhesus monkeys to some of the pharmacological effects of norcocaine. Furthermore, these data confirm that norcocaine is an active derivative of cocaine in both rhesus and cynomolgus monkeys.

Chronic intravenous dosing and blood collection in the unanesthetized monkey.

A procedure is described which allows chronic dosing and blood collection from awake monkeys. The procedure involves only minor surgical anesthesia and allows the same vein of the animal to be used several different times with home-cage recuperation periods intervening between sequential chronic catheterizations.

Biological effects of cocaine derivatives I: Improved synthesis and pharmacological evaluation of norcocaine.

An improved synthesis of norcocaine, a metabolite of cocaine, is reported. Following intravenous administration to a rhesus monkey, respiratory effects were similar to those observed following cocaine treatment. In addition, clonic convulsions, hypothermia, and mydriasis resulted. Norcocaine could be responsible for part of the pharmacological activity of cocaine.