Standard Capsule Research Articles

Evaluation of sustained-release indomethacin in osteoarthritis

MULTICLINIC, double-blind study was conducted to compare two indomethacin regimens-a 75-mg sustained-release capsule INDOCIN@ SR (Indomethacin, MSD) given once daily and standard 25-mg capsules INDOCIN given three times daily-in 234 patients with active moderate to severe osteoarthritis of the hip or knee. During the 6-wk trial, significant improvement occurred with each treatment according to pain ratings, measurements of range of passive movement, and estimates of duration of inactivity stiffness. Overall, no clinically important differences were found with respect to either efficacy or tolerability between the two formulations. The availability of indomethacin in a sustained-release capsule that can be administered once daily may provide a convenient, high-compliance regimen for many patients. Indomethacin has been used for the treatment of rheumatic disorders for over 15 yr, and recently has become a reference agent in the field of prostaglandin synthetase inhibition. Indomethacin has been shown to be a potent inhibitor of prostaglandin synthetase both in vitro and at concentrations which are achieved in vivo. lndomethacin has been used in the treatment of moderate to severe osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, and acute gouty arthritis and acute painful shoulder (bursitis and tendinitis). The sustained-release formulation of indomethacin consists of 25-mg immediate-release indomethacin, with 50 mg pelletized for release over time. When normal volunteers in a crossover

Study of an anti-arrhythmic agent, disopyramide, in delayed action form ('Ritmoforine' Retard).

A study was carried out in 10 patients with ventricular dysrhythmias to determine serum levels and effectiveness of treatment with a new delayed-action formulation of disopyramide. Patients received 1 tablet (322.5 mg disopyramide phosphate) twice daily and were monitored constantly. A therapeutically effective level of 3 mg/l was achieved in most cases after 24 hours and in 8 out of the 10 patients the levels remained reasonably stable during the 4 days of observation. It is suggested that adjustment of dosage is advisable in patients with renal dysfunction or left heart failure. Although the new formulation provided a good alternative to the standard preparation of disopyramide, which is usually given on a 4-times daily regimen, it is recommended that the standard capsules should be used during the first 24 hours of treatment to ensure that effective blood levels are achieved rapidly.

Two-point calibration of standard capsule platinum resistance thermometers for the range 13.81 K to 273.15 K

A method of calibrating a standard capsule platinum resistance thermometer (prt) over the range 13.81 K to 273.15 K is described. Measurements of the resistance of the prt are needed at only two fixed points, the boiling point of He 4 (4.2 K) and the ice-point (273.15 K), both of which are easy to realize. For a prt with a residual resistance ratio ( R 4.2 K / R 273.15 K ) of less than 4 × 10 −4, the method provides a calibration on ipts 68 with an uncertainty of 20 mK over the entire range 13.81 K to 273.15 K. For prts with residual resistance ratios between 4 × 10 −4 and 7 × 10 −4, the calibration uncertainty is 75 mK from 13.81 K to 40 K and 20 mK from 40 K to 273.15 K.

BIOAVAILABILITY OF DIGOXIN FROM RAPIDLY DISSOLVING PREPARATIONS

1 Intestinal absorption of digoxin was assessed by determination of peak plasma concentrations, areas under plasma concentration curves over 80 h, and 10 day urinary excretion. Absorption was equal after ingestion of single doses of standard Lanoxin (Wellcome) tablets, tablets and capsules of ultra-rapid dissolution rate material, or an oral solution of digoxin in water. 2 Mean plasma concentrations and dosage-interval urinary excretion were highly similar during 14 day courses of either Lanoxin or ultra-rapid dissolution tablets. Increased bioavailability does not result from encapsulation of solid dosage presentations, nor from increasing tablet dissolution rate beyond 75% in 15 minutes. 3 Fourteen day courses of tablets of slow dissolution rate produced lower and less consistent mean plasma concentrations and urinary excretion. Slow dissolution rates are associated with greater individual variability in absorption.

Hormonal Therapy with Steroid-Filled Silastic Rubber Implants

A new method of hormone administration was tested in the human male. PDS (silastic) capsules filled with dry, milled steroid and implanted subcutaneously, release the hormone at a relatively constant rate over a longer period of time. A standard capsule of 20 mm length, a membrane thickness of ∼0.8 mm and a surface area of about 150 mm2 was used. Capsules filled with 22–23 mg ethinyl estradiol and implanted in patients with carcinoma of the prostate had a releasing factor of approximately 45 µg/24 h/capsule, and a therapeutic effect of about 17 months. Capsules filled with 21–23 mg testosterone and implanted in castrates, hypogonadal and subfertile men had a releasing factor of approximately 55 µg/24 h/capsule and a therapeutic effect of about 13 months. The clinical results of testosterone substitution in castrates and hypogonadal men were good as judged by clinical observation and regular determinations of plasma testosterone levels. There was a definite improvement of the sperm qualities of subfertile men with moderate forms of Leydig’s cell insufficiency. The observation period of the cases of prostatic carcinoma treated with ethinyl estradiol capsules still is too short for exact clinical evaluation, but the results seem to be encouraging.

Spectrum of the radiation from a cobalt 60 teletherapy unit

The spectrum of the degraded radiation in the beam from a 60Co therapy unit has been determined from measurements of the once-scattered radiation at various angles. The therapy unit contained a source 2·5 cm diameter and 0·65 cm thick in a standard capsule. The once-scattered spectra were measured with a scintillation spectrometer and corrected using theoretical response functions. Changing the size of the beam from the unit produced very little change in the spectrum indicating that there was little radiation scattered from the inside of the collimating system. For photon energies below 0·5 MeV the measured spectrum agrees well with the calculations of Cormack and Johns (1958) for a 60Co source 2·5 cm in diameter and 1·3 cm thick with no collimator but at higher energies the experimental curve falls considerably below the calculated curve. The spectrum is also in satisfactory agreement with spectra measured recently by Costrell.

Leaks in standard sealed teletherapy sources.

Teletherapy sources encapsulated in the United States and Canada from 1954 to 1959 were generally of the standard, single capsule, sealed type. One feature of the standard capsule was believed to be its tight seal and its ability to maintain tais integrity. Late in 1958, a standard capsule source at the Oak Ridge Institute of Nuclear Studies (encapsulated 1.5 years earlier with Co/sup 60/ metal pellets) developed a leak. This leak resulted in from 30 to 100 mc of activity being released before it was detected. Subsequent investigation of other sealed sources in the United States revealed that thirteen of 200 standard teletherapy capsules had developed leaks. A review of the possible causes of leakage, and of the standard capsule design, fabrication, sealing and initial and subsequent leak testing, has resulted in recommended changes to reduce the probability of future capsule failures. The incidence of failures already encountered, however, has made apparent the importance of routine leak testing of encapsulated sources. (auth)

THE GAMMA-RAY MEASUREMENT OF RADIUM ORE CONCENTRATES

A method is described for measuring the radium content of substances in which the radium concentration is of the order of micrograms per gram of material. The gamma-ray activities of the unknown material and of a standard radium capsule are compared by means of Geiger-Müller counters. Corrections for self-absorption and distance are given for rectangular and cylindrical sources. The effect of radiation scattered by the source into the detector is discussed. Synthetic bulk sources made up with known quantities of radium were used for the experimental work.