Triphasic release

The influence of polymer composition and molecular weight on the estrus-suppressing activity of the microspheres in female rats was determined. A triphasic release pattern was observed. An initial rapid release over the first few days was attributed to diffusion from superficial areas of the microspheres. A second phase of lower release levels then occurs and continues until the onset of the third, major phase of release. This phase is facilitated by the onset of erosion of the polymer matrix. 

The volume of the inner aqueous solution relative to that of the organic solvent in W,/0/Wn emulsion was found affect the release characteristics of BSA, or an antigen from PLGA microspheres. At low aqueous to organic phase volume ratios ( 0.1 mL/mL), the microspheres exhibited a triphasic release initial burst, lag phase with little or no release, and a second release phase. 

The second phase occurs when the polymer undergoes significant biodegradation. Broad molecular weight compositions were proposed as one method of reducing the triphasic nature of these release patterns. ... 

LJ, a 25-year-old-woman with complex partial seizures, presents a prescription to the pharmacy for a triphasic oral contraceptive containing ethinyl estradiol and norgestimate. A review of her medication profile shows that she is taking carbamazepine extended-release 1200 mg/day. Her last refill for this prescription was 2 weeks ago. She reports that she has not had a seizure for a year and that she just became engaged. She is planning to be married in 4 months. 

In subacute thyroiditis, thyroid function tests typically run a triphasic course in this self-limited disease. Initially, serum T4 levels are elevated due to release of preformed thyroid hormone from disrupted follicles. The 24-hour RAIU during this time is less than 2% because of thyroid inflammation and TSH suppression by the elevated T4 level. As the disease progresses, intrathyroidal hormone stores are depleted, and the patient may become mildly hypothyroid with an appropriately elevated TSH level. During the recovery phase, thyroid hormone stores are replenished and serum TSH elevation gradually returns to normal. 

Methotrexate is well absorbed orally and at usual dosages is 50% bound to plasma proteins. The plasma decay that follows an intravenous injection is triphasic, with a distribution phase, an initial elimination phase, and a prolonged elimination phase. The last phase is thought to reflect slow release of methotrexate from tissues. The major routes of drug excretion are glomerular filtration andl active renal tubular secretion. 

Figure 4.15 Triphasic drug release kinetics from PLGA-based microparticles in phosphate buffer pH 7.4 experimental data (symbols) and fitted theory (curve). Reprinted from [91] with permission from Springer.

In several papers the Kunos group has reported observations that may represent a starting point for novel medicinal chemistry research in this area [167, 168], Anandamide (i.v. bolus 4 mg/kg) caused a triphasic blood pressure response, brief hypotension, followed by a transient pressor and then a prolonged depressor phase. The hypotensive effect was not initiated in the CNS, but was due to a presynaptic action that inhibited norepinephrine release from sympathetic nerve terminals in the periphery (heart and vasculature). The inhibitory effect (but not the pressor effect) was antagonized by SR141716A, indicating that this peripheral action was mediated by CB receptors. 

Early work in this area was published in several articles by Sanders and co-workers, who described the use ofpoly(D,L-lactide-co-glycolide) (PLGA) microcapsules for the delivery of the peptide nafarelin acetate, an LHRH analog [(D-Nal(2) Aza-Gly >)-LHRH Syntex] (Anik et al, 1984 Sanders et al, 1984, 1985, 1986). Microcapsules were produced by a coacervation microencapsulation technique, and the release of the peptide was shown to be predominately triphasic (Fig. 1)—high initial release lasting for several hours, followed by a period of low or limited release, and finally several days... 

Initially, light pressure is used so as not to collapse the vein (Fig. 4.33a). With the probe straddling both artery and vein, further pressure is subsequently applied. If the vein is patent, the walls collapse and appose each other completely (Fig. 4.33b). When the pressure is released, the lumen of the vein returns to normal. If the vein contains clots, it will not collapse but remains distended when applying probe pressure (Fig. 4.33a,b). In lower limb veins, Doppler imaging and spectral analysis reveal monophasic venous flow rather than triphasic waveforms. In contrast, upper limb veins demonstrate more pulsatile flow because of their closer proximity to the heart (Chin et al. 2005). The use of low velocity (3-6 cm/s)... 

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