No abstract

No abstract

Aprepitant, a selective high-affi nity antagonist of human substance P/neurokinin 1 (NK 1 ) receptors, is the active ingredient of EMEND ® which has recently been approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting (CINV). Aprepitant undergoes extensive metabolism, primarily via CYP3A4 mediated oxidation. It is eliminated primarily by metabolism and is not renally excreted. The apparent terminal half-life in humans ranged from 9 to 13 hours. Early development studies led to the development of a nanoparticle formulation to enhance exposure and minimize food effects. Two large randomized trials accruing 1099 patients studied the effect in patients receiving cisplatin of adding aprepitant to ondansetron and dexamethasone on day 1 then to dexamethasone on days 2 and 3 to control delayed emesis. The complete response of no vomiting and no rescue medication overall from days 1 to 5 improved from 48% to 68% (p<0.001), a 13% improvement in acute emesis but a 21% improvement in delayed emesis with the improvement from 51% to 72% (p<0.001).Similarly, 866 patients treated with cyclophosphamide plus either doxorubicin or epirubicin, received either ondansetron, dexamethasone, and aprepitant on day 1 followed by aprepitant on days 2 and 3 or ondansetron and dexamethasone on day 1 and dexamethasone on days 2 and 3. The overall complete response rate over 5 days was better for the aprepitant group 50.8% vs 42.5% (p=0.015). Complete responses were reported in more patients taking aprepitant in both the acute (76% vs 69%, p=0.034) and delayed (55% vs 49%, p=0.064) phases of vomiting. There were no clinically relevant differences in toxicity by adding aprepitant and improvements in the quality of life of patients on chemotherapy were recorded.

AFM is demonstrated to be a valuable tool in visualization and quantification of drug nanoparticle crystals in formulations. In addition to accurate size measurement, AFM readily provides shape and structural information of nanoparticles, which cannot be obtained by light scattering. Ultramicrotomy is a good sample preparation method to expose the interior of solid dosage forms with minimal structural alteration for microscopic examination.

The control of tablet-to-tablet variation that occurs during batch coating operations is important in the pharmaceutical industry. This is particularly true when the coating substance contains an active ingredient (drug). The current work focused on evaluating the effect of tablet deflectors in the spray zone on the variation of coating material received by individual tablets as they pass through the spray. Digital video imaging was used to show how these deflectors changed the solids' velocity and voidage profiles near the spray nozzle. A series of coating experiments was conducted to establish how such deflectors affected the coating variation per tablet per pass and the overall variation in coating received per tablet in a batch coating process. For the optimum deflector considered in this work, the relative standard deviation of coating mass was reduced from 11.3% without any deflector to 6.7%.