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Biomedical subjects

D A Piscitelli

Publications and source records attributed to D A Piscitelli.

5 recordsLinked to original sources
PubMed1998

The impact of formulation and process changes on in vitro dissolution and the bioequivalence of piroxicam capsules.

The purpose of this research was to determine the effect of major compositional changes on the bioavailability of piroxicam from immediate-release formulations filled in hard gelatin capsules. The capsules were manufactured according to a 2(5-1) + star point (resolution V) experimental design to investigate the effects of sodium lauryl sulfate level, magnesium stearate level, lactose/microcrystalline cellulose ratio, piroxicam particle size, and lubricant blending time. Sodium lauryl sulfate level, lactose level, and piroxicam particle size were the most important main effects affecting dissolution. Lubricant level and lubricant blending time were either not significant (5% level) or were among the lowest ranking of factors affecting dissolution in standardized pareto analysis. Three of these formulations exhibiting slow, medium, and fast dissolution were compared to a single lot of the Innovator (commercial) product in a small bioavailability study. The slow formulation did not meet the USP dissolution specification for piroxicam capsules. Compositionally, the experimental formulations represented major changes in piroxicam particle size, level of filler, and level of sodium lauryl sulfate. Sixteen healthy volunteers received each formulation (20 mg) in a four-way crossover design. The three Maryland manufactured formulations were bioequivalent with the commercial product and were also bioequivalent among themselves. The major changes incorporated into these formulations did not result in major differences in bioavailability. The dissolution profiles which discriminated between the formulations in vitro did not accurately represent the in vivo bioavailability results. The results of this study are part of the research database that supports SUPAC-IR, an FDA guidance that provides relaxed testing and filing requirements for scale-up and post-approval changes to immediate-release oral solid dosage forms.

Adult↗
PubMed1997

Setting dissolution specifications for modified-release dosage forms.

Dissolution specifications are used for quality assurance and may also serve as a surrogate for in vivo bioavailability. These limits can guide formulation development and eliminate the need for bioavailability studies for scale up and post approval changes. Several methods for setting dissolution specifications have been reviewed in this chapter. A summary of the advantages and disadvantages for each method can be found in Table 1. When choosing a method for setting dissolution specifications, it is important to 1) have a discriminating dissolution system, 2) incorporate in vivo data, 3) include intersubject variability, and 4) predict plasma concentration-time profiles. Predicting plasma concentration curves allows one to see how the change in formulation or dissolution limits perform in vivo. Dissolution specifications should be set so that all formulations that have dissolution profiles within the limits of the specifications are bioequivalent. This can be assured if the boundaries are tested for bioequivalence. Minimally, the formulations that have dissolution profiles within the limits of the specifications should be bioequivalent to the pivotal batch. A population prediction of the plasma concentration-time profiles for the upper and lower limit would incorporate the true intersubject variability for the formulation.

Data Interpretation, Statistical↗
PubMed1994

Bioavailability of total and unbound disopyramide: implications for clinical use of the immediate and controlled-release dosage forms.

This study further characterized the impact of concentration-dependent protein binding on the bioavailability and clinical use of the immediate-release (IR) and controlled-release (CR) dosage forms of disopyramide after single doses and during steady-state conditions in ten healthy volunteers. Consistent with the clinical use of these products, steady state has incorporated an IR to CR conversion step. Side effects and electrocardiographic actions were quantitated using a visual analog scale and serial Holter monitor recordings, respectively. Significant decreases resulted in area under the curve for total disopyramide between single dose and steady state: IR, 47.8 +/- 13.6 versus 33.0 +/- 6.4 mg/Lxh (P < .05); and CR, 46.9 +/- 9.5 versus 31.7 +/- 5.9 mg/Lxh (P < .05). In contrast, there were no differences in area under the curve for unbound disopyramide between phases or products. During conversion, the mean IR peak significantly decreased (P < .05) to the nadir before the first CR dose for total (37%) and unbound (60%) concentrations. There were no major differences in change in QT interval or side effects detected between products or phases. These findings indicate that, because of concentration-dependent protein binding, unbound, not total, concentrations should be used to estimate the bioavailability of disopyramide. Also, although the previously recommended conversion method (first CR dose 6 hours after the last IR dose) should provide an adequate transition in most, an alternative method (combined first CR with last IR dose) is indicated in select patients.

Adolescent↗