Implant pellets I: effects of compression pressure on in vivo dissolution of delmadinone acetate pellets.

A formulation containing 95% delmadinone acetate was compressed at three different pressures. These pressures resulted in a pellet density difference of 19%. In vivo dissolution profiles were determined for five lots of pellets. The pellets were implanted subcutaneously in rats, removed periodically, and assayed chemically for remaining steroid. The resulting data were fit, using the computer program NONLIN, to a dissolution model. The dissolution rate for the lot with the lowest density made at the lowest compression was statistically (p less than 0.05) different from the four other lots. A possible explanation for this increased dissolution rate could be that channeling occurs within the pellet, thereby increasing the effective dissolving surface. The results also indicate that equivalent dissolution rates between lots are reached at a certain compression and density.

PIP: Effects of compression pressure on in vivo dissolution of delmadinone acetate implant pellets were investigated in rats. A formulation containing 95% delmadinone acetate was compressed at 3 different pressures which resulted in a pellet density difference of 19%. Pellets from 5 different lots were implanted sc, removed periodically, and assayed chemically for remaining steroid. The results were fit, using the computer program NONLIN, to a dissolution model. The dissolution rate for the lot with the lowest density made at the lowest compression was significantly (p less than .01) greater than that of the other 4 lots. A possible explanation could be that channeling occurs within the pellet, thereby increasing the effective dissolving surface. These results also suggest that equivalent dissolution rates between lots are reached at a certain compression and density.

Design and evaluation of an automated system for in vitro dissolution testing utilizing a high-pressure liquid chromatographic multiport switching valve.

An automated system for the simultaneous dissolution testing of six samples was developed consisting of four basic units: dissolution vessels and stirring unit, a peristaltic pump, a rotary stream multiport switching valve and programmer, and a UV spectrophotometer with recorder. Among the major advantages of such a system are: (a) paddle or basket stirring with variable speed is used, (b) the tablet or capsule (wire coil required) locates reproducibly at the bottom of a round-bottom reaction flask when utilizing paddle-type stirring, (c) a USP basket for tablet or capsule dissolution testing can be used, (d) continuous or intermittent sampling is possible, (e) the flow system readily adapts to UV-visible detector or fluorescence spectroscopy, (f) the system readily adapts to automated determination of the intrinsic dissolution of a material, and (g) the cost is low because of the multiport switching valve and inexpensive UV monitor required. Studies were performed using this apparatus to demonstrate the response characteristics of the system, its reproducibility, potential problems, and precautions required. This dissolution system was used to determine the dissolution characteristics of a new steroid tablet formulation, including a formulation and lot demonstrated to be bioavailable.

Controlled release of a luteinizing hormone-releasing hormone analogue from poly(d,l-lactide-co-glycolide) microspheres.

The performance in vivo of nafarelin acetate, a potent analogue of luteinizing hormone-releasing hormone, microencapsulated in poly(d,l-lactide-co-glycolide), was evaluated. The influence of polymer composition and molecular weight on the estrus-suppressing activity of the microspheres in female rats was determined. Compound release was shown to be effected by polymer erosion rather than by diffusion. A triphasic release of compound was observed, which was adjusted by altering the critical parameters of the polymer. A mechanism for the release of the compound was proposed. The primary release phase was compound loss by diffusion from the surface of the microspheres. The secondary phase of subeffective rates of release occurred concomitantly with polymer hydrolysis and a decrease in its molecular weight, although it remained insoluble. Dissolution of low-molecular weight fragments and erosion of the bulk of the polymer then initiated the tertiary phase of release of compound.

Absorption, excretion and tissue residue in feedlot heifers injected with the synthetic prostaglandin, fenprostalene.

Preliminary studies on use of the synthetic prostaglandin, fenprostalene, as an abortifacient had indicated that maximum effectiveness was dependent upon slow delivery. Because both route of administration and formulation control delivery rates, the influences of intramuscular (im) vs subcutaneous (sc) injections, and aqueous acetate buffer (AAB) vs polyethylene glycol-400 (PEG) vehicles on the plasma concentration and urinary excretion of fenprostalene were compared. Feedlot heifers were administered 1 mg injections of [13,14-3H]-fenprostalene. Blood samples and total urine excretion were collected during the following 96 h. The maximum concentration of tritium in plasma occurred at 2 h for AAB-im (.90 ng eq/ml), PEG-im (.75 ng eq/ml) and AAB-sc (.64 ng eq/ml), and then declined throughout 24 h with t 1/2 values of 6.1, 9.4 and 9.2 h, respectively. The peak concentration from PEG-sc was lower (.37 ng eq/ml, P less than .05), observed later (4h, P less than .05) and declined more slowly following peak concentration (t 1/2 = 15.1 h, P less than .05). Consistent with delayed absorption, a smaller fraction (P less than .05) of the total radioactivity excreted in urine was recovered during the first 24 h after injection for PEG-sc (85%) than for PEG-im (95%), AAB-sc (97%) or AAB-im (99%). In a tissue distribution study, plasma, urine and fecal samples were collected and heifers were slaughtered at various times following sc injection of 1 mg of [3H] fenprostalene in PEG. Peak concentrations of tritium in plasma occurred between 4 and 8 h and declined with a t 1/2 of 15.2 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical features distinguishing angle closure from pseudoplateau versus plateau iris.

PURPOSE: To evaluate clinical aspects of patients with the diagnosis of plateau iris (PI) or pseudoplateau iris (PPI) made by ultrasound biomicroscopy (UBM) in order to determine if there are any clinical factors that can help differentiate between these two entities. METHOD: A retrospective cohort of consecutive UBM patients with the diagnosis of PI or PPI. The diagnosis of PI was based on an anteriorly positioned ciliary body that abutted the peripheral iris, a narrow (<10 degrees) or closed angle for at least 180 degrees, and the anterior portion of the iris positioned anterior to scleral spur. The diagnosis of PPI was similar to plateau except that large or a cluster of small cysts had to be present in the iridociliary sulcus. RESULTS: There were a total of 76 patients (29% male), 21 with PPI and 55 with PI. Patients with PPI were more likely to be male (p = 0.005), slightly younger (51.5 (SD 10.7) vs 57.9 (10.2) p = 0.0190), have a "bumpy" peripheral iris appearance (p = 0.003), have greater trabecular meshwork pigmentation (2.0 (0.7) vs 1.3 (0.6) p = 0.004) and have fewer clock hours of gonioscopic angle closure versus plateau iris patients (5.1 (4.3) vs 9.2 (4.2) p = 0.0009). Spherical equivalent was not significantly different between groups (0.50D (1.69) PPI vs 1.33D (2.42) PI; p = 0.187). CONCLUSIONS: In patients being referred to a UBM clinic for evaluation of angle-closure mechanism, younger males with a bumpy peripheral iris have a higher likelihood of having a diagnosis of pseudoplateau iris. However, clinical factors do not appear to discriminate well between PPI and PI. UBM is extremely helpful in confirming underlying mechanism and guiding therapy.

Bulimia: a comparison of psychological adjustment and familial characteristics in a nonclinical sample.

This study examined the relation of eating attitudes and behaviors to family dynamics and psychological adjustment in a nonclinical group of female university freshmen. Family dynamics variables, which were measured by the Family Environment Scale (FES), included Control, Cohesion, Conflict, Organization, Expressiveness, Independence, Achievement-Orientation, Intellectual-Cultural Orientation, Active-Recreational Orientation, and Moral Religious Emphasis. Psychological adjustment was measured by the Hopkins Symptom Checklist (HSC). Variables on this scale included Anxiety, Depression, Somatization, Obsessive-Compulsive, and Interpersonal Sensitivity. Eating attitudes and behaviors were measured by the Bulimia Test (BULIT), a 32-item self-report inventory. Multivariate analysis of variance indicated that bulimics, subclinical bulimics, and normals could be differentiated on the Hopkins Symptom Checklist. Univariate analyses revealed differences between the groups on all of the HSC measures and the Organization scale of the FES. The results suggest that conclusions about the causal relationships between maladaptive family patterns and bulimia presented in previous research should be viewed with caution.

Bulimic women's perceptions of their family relationships.

This study examined the relationship between bulimia and family variables. Eight hundred twenty female college students completed a personal history questionnaire, the Bulimia Test, and the Eating Disorders Inventory. Twenty-four subjects who met the DSM-III-R criteria for bulimia were compared with 24 subclinical bulimics and 24 symptom-free subjects on demographic and family variables, including subscales from the Family Environment Scale and the Parental Bonding Instrument. Significant group differences indicated that the families of bulimics differ from other families. However, in contrast to the findings of research done in treatment settings, bulimics in this nonclinical setting did not report more family conflict or less caring from their parents than did symptom-free subjects.

Manipulation of duration of action of a synthetic prostaglandin analogue (TPT) assessed in the pregnant beagle bitch.

Beagle bitches were treated on days 20-22 of pregnancy with TPT as an aqueous solution administered subcutaneously via a minipump at a rate of 10 micrograms per hour for either 24 (I) or 48 hours (II). Additional animals received a single subcutaneous injection of 200 micrograms of TPT as an aqueous solution (III) or dissolved in polyethylene glycol 400 (IV) or the methyl ester of TPT dissolved in polyethylene glycol 400 (V). The duration of action was assessed by the nadir in circulating progesterone levels. By this criterion the duration of action in the different groups ranked I=III