Winston A. Vadino

Correlation of in Vitro Release Rate and in Vivo Absorption Characteristics of Four Chlorpheniramine Maleate Extended-Release Formulations

An in vitro/in vivo correlation was established for four formulations of chlorpheniramine maleate (histamine, H1-blocker) extended-release tablets exhibiting different in vitro release rate characteristics. In vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2, paddle stirrer at 50 rpm in 1000 ml of distilled water at 37.0 ± 0.5°C. Inspection of the individual and mean release rate data indicated that the in vitro release rate of chlorpheniramine maleate was consistent with the intended design of the four extended-release formulations. The in vivo bioavailability and pharmacokinetics of these formulations were evaluated in 24 healthy subjects under fasting conditions. Wagner Nelson analyses of the in vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in vitro release resulted in a statistically significant correlation (r2 > 0.98, P < 0.001) for each formulation. Qualitative rank-order correlations were observed among all combinations of in vitro and in vivo parameters. These data support a Level A correlation between the in vitro release rate profiles and the in vivo absorption for chlorpheniramine maleate determined under fasting conditions.

In-vivo/in-vitro correlation of four extended release formulations of pseudoephedrine sulfate.

An in-vivo/in-vitro correlation was established for four formulations of pseudoephedrine sulfate modified release tablets exhibiting different in-vivo and in-vitro release rate and absorption characteristics. In-vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2 paddle stirrer at 50 rev min-1 in 1000 ml 0.1 N hydrochloric acid for the first hour followed by 0.1 M phosphate buffer at pH 7.5 for hours 2-16. Inspection of the individual and mean release rate data indicated that the in-vitro release rate of pseudoephedrine sulfate was consistent with the intended design of the four extended release formulations. The in-vivo bioavailability and pharmacokinetics of these formulations were evaluated in 20 healthy volunteers under fasted conditions. Wagner-Nelson analyses of the in-vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in-vitro release resulted in statistically significant correlations (r2 > 0.99, p < 0.0001) for each formulation. Qualitative rank order correlations were observed among all combinations of in-vivo and in-vitro parameters. These data support a Level A correlation between in-vivo absorption profiles and in-vitro release rates of four pseudoephedrine sulfate extended release formulations determined in fasted healthy volunteers.

A Simple Method for Differentiating Sources of Pregelatinized Starch Nf

AbstractA simple test procedure to differentiate between sources of pregelatinized starch NF has been developed. The procedure is based on the swelling characteristics of the materials. Three pregelatinized starch NF products were distinguished by observing their sedimentation volumes. Microscopic differences in the particle morphology of each starch product were also observed. The study indicates that sedimentation testing can be used as an addition to the current compendial identity tests for pregelatinized starch NF.

Evaluation of the Flow-Through Cell Dissolution Apparatus: Effects of Flow Rate, Glass Beads and Tablet Position on Drug Release from Different Type of Tablets

AbstractSeveral factors affecting the dissolution performance of various solid dosage forms tested using the flow-through cell method have been evaluated in this study. These factors include the flow rate, the position of tablets in the flow through cell and the glass beads, as well as the physical properties of the dosage forms. The experimental results indicated that the flow rate through the cell greatly affects drug release from disintegrating tablets. Drug release increases with increasing the flow rate of the dissolution medium, as expected. However, the flow rate does not significantly influence drug release from tablets which are not disintegratable, for example, an erodible tablet. The position of the tablets in the flow cell without glass beads is also of importance. Drug release from horizontally positioned tablets is different from vertically positioned tablets in the flow-through cell. It was also observed that the use of glass beads in the flow cell can make the flow pattern more laminar. Th...

Monitoring the granulation process in a high shear mixer/granulator: An evaluation of three approaches to instrumentation

AbstractA high shear vertical mixer/granulator was instrumented to monitor power consumption, direct torque and reactive torque. All three methods were used to determine their ability in describing the granulation operation. Of the three methods used, direct torque generated the most descriptive profile of the granulation process.Two formulations were manufactured making use of direct torque in detailing the massing process. End-points were determined and the granulations produced were shown to yield tablets with acceptable hardnesses. One formulation was intentionally overwetted and the change in direct torque monitored to demonstrate the ability of the transducer to detail the massing process. Large fluctuations in torque, during the terminal phase of granulating, were seen and related to the doughy consistency of the final product.It was concluded that torque measurements, preferably direct, are needed to more precisely define granulation end-points. These types of measurements are needed to optimize t...

Determinaion of Hard Gelatin Capsule Brittlenss Using a Motorized Compression Test Stand

AbstractHard gelatin capsules are solid dosage forms containing powders, granulations, or pellets enclosed in a hard soluble shell. Recent guidelines for submitting documentation for the stability of human drugs and biologics to the FDA have requested test data for capsule brittleness. A simple test has been developed using a compression gauge to quantify the force required to fracture and/or shatter hard gelatin capsules. The data generated from this test can be utilized for dosage form stability assessment as well as quality control and quality assurance of capsules prior to their use in dosage from manufacture.