In vitro release rate

In an extension of this work, pellets of a blend of PCL and hy-droxypropylcellulose containing fluridone were prepared by grinding, blending, and then melt-spinning the mixture with a Berstorff twin screw extruder (78). The extruded rod was subsequently water-quenched and pelletized. Pellets were also prepared by coating bundles of extruded rods with the water-soluble excipients PEG 3350 and PEG 600 (95 5). In vitro release rate measurements were conducted in the simulant medium of 50% aqueous ethanol or hardened water. 

GS Rekhi, ND Eddington, MJ Fossler, P Schwartz, LJ Lesko, LL Augsburger. Evaluation of in vitro release rate and in vivo absorption characteristics of four metoprolol tartrate immediate release tablet formulations. Pharm Devel Tech 2(1) 11-24, 1997. 

This optimization method, which represents the mathematical techniques, is an extension of the classic method and was the first, to our knowledge, to be applied to a pharmaceutical formulation and processing problem. Fonner et al. [15] chose to apply this method to a tablet formulation and to consider two independent variables. The active ingredient, phenylpropanolamine HC1, was kept at a constant level, and the levels of disintegrant (corn starch) and lubricant (stearic acid) were selected as the independent variables, X and Xj. The dependent variables include tablet hardness, friability, volume, in vitro release rate, and urinary excretion rate in human subjects. 

Panel b shows two lines, one for the in vitro release rate... 

Transdermal Patches In vitro release rates, leakage, microbial bioburden/ sterility, and peel and adhesive forces. 

An in vitro release rate can reflect the combined effect of several physical and chemical parameters, including solubility and particle size of the active ingredient and rheological properties of the dosage form. In most cases, in vitro release rate is a useful test to assess product sameness between prechange and postchange products. However, there may be instances where it is not suitable for this purpose. In such cases, other physical and chemical tests to be used as measures of sameness should be proposed and discussed with the Agency. With any test, the metrics and statistical approaches to documentation of sameness in quality attributes should be considered. 

The in vitro release rate should not be used for comparing different formulations across manufacturers. 

II. In Vitro Release Documentation. The in vitro release rate of a lot of the dosage form prepared in new equipment should be compared with the re-... 

II. In Vitro Release Documentation. The in vitro release rate of a lot of the dosage form prepared by the new/modified process should be compared with the in vitro release rate of a recent lot of comparable age of the dosage form prepared by the prechange process. The median in vitro release rates (as estimated by the estimated slope from each cell, see VII) of the lots prepared by the two processes should be demonstrated to be within acceptable limits, using the testing procedure described in section VII (IN VITRO RELEASE TEST) below. 

In Vitro Release Rate A plot of the amount of drug released per unit membrane area (mcg/cm) versus square 2 root of time should yield a straight line. The slope of the line (regression) represents the release rate of the product. An X intercept typically corresponding to a small fraction of an hour is a normal characteristic of such plots. 

The in vitro release comparison should be carried out as a two-stage test. At the first stage, two mns of the (six cells) in vitro apparatus should be carried out, yielding six slopes (estimated in vitro release rates) for the prechange lot (R) and six slopes for the postchange lot (T). A 90% confidence interval (to be described below) for the ratio of the median in vitro release rate (in the population) for the postchange lot over the median in vitro release rate (in the population) for the... 

In the third step, the 8th saA29th ordered individual ratios are the lower and upper limits, respectively, of the 90% confidence interval for the ratio of the median in vitro release rate (slope) for T over the median in vitro release rate for R. In the example, this confidence interval is 1.0343 to 1.2863, or in percentage terms, 103.43% to 128.63%. 

In Vitro Release Rate Rate of release of the active drug from its formulation, generally expressed as amount/unit arca/limc° . 

In vitro release rate compared to recent lot of comparable age prechange product. Median in vitro release rates 1 of the two formulations should be within acceptable limits. ... 

In vitro release rate of new/modi-fied formulation established as point of reference. In vitro release documentation not required, but this information should be developed for use in subsequent changes. 

Fig. 11 Comparative in vitro release rate profile of levonor-gestrel from a vaginal ring containing a homogeneous dispersion of drug in a silicone-based polymer matrix (O) and from one containing an inert overcoat covering the drug reservoir layer ( and ). The effect of overcoat thickness fijii on the release rate of levonorgestrel is also shown. (From RefP l)...

Figure 8.39 In vitro release rate of potassium chloride from elementary osmotic pumps in water at 37°C.

In vivo release rate (X(,ivo) can also be expressed as a function of in vitro release rate (XJ-gi itro) with parameters a, b), which may be empirically selected... 

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