METHODS AND PRODUCTS FOR ERROR DETERMINATION OF DRUG DOSE IN PHARMACEUTICAL MIXTURES

• US 20080046188A1
• Filed: 08/18/2006
• Published: 02/21/2008
• Est. Priority Date: 08/18/2006
• Status: Active Grant

• Current Assignee: Vagma, LLC
• Original Assignee: Vagma, LLC
• Inventors: Savva, Michalakis
• Granted Patent: US 7,831,393 B2
• Time in Patent Office: Days
• US Class Current: 702/19
• CPC Class Codes: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12

Abstract

The present invention discloses a computer program and a method including an algorithm for computing the uncertainty of drug concentration in pharmaceutical dosage forms. The invention also provides a computer system, a website and an IC chip incorporating the program product. The invention determines the allowable sensitivity of the instruments measuring each of the components and the least allowable weight (LAW) within a maximum allowable error of each ingredient at the predetermined assay standard. The method and products allow the accurate error evaluation of drug dose in pharmaceutical mixtures and unit dosage forms, which may be composed of an infinite number of ingredients that are measured on multiple equipments of variable sensitivities. Thus this invention provides instant guidance on the pharmaceutical ingredient preparation.

Claims

1. A program product for determining the error in ingredient'"'"'s quantities in a multi-component pharmaceutical formula measured by multiple analytical instruments, including a computer readable computer program encoded in a storage medium, said program product employs steps of:

setting a computing mode according to a selection by a user on a type of error analysis;

receiving a value for a quantity of an ingredient of a composition to be measured by an instrument;

receiving a value for a sensitivity of the analytical instrument measuring the quantity of the ingredient;

repeating the above two receiving steps for any remaining ingredients to be measured that compose the pharmaceutical formula;

executing an algorithm based on following equations to relate;

the quantities of measurements and sensitivities of instruments to a value of variation of the final concentration of any ingredient in the pharmaceutical formula;

$\begin{array}{c}\mathrm{df}=<br><br>\frac{y+z+\mathrm{\dots <br><br>}}{{(x+y+z+\mathrm{\dots <br><br>}<br><br>)}^2}<br><br><br><br>\mathrm{dx}+<br><br>\frac{-x}{{(x+y+z+\mathrm{\dots <br><br>}<br><br>)}^2}<br><br><br><br>\mathrm{dy}+<br><br>\frac{-x}{{(x+y+z+\mathrm{\dots <br><br>}<br><br>)}^2}<br><br><br><br>\mathrm{dz}+\mathrm{\dots <br><br>}<br><br><br><br>{\mathrm{\sigma <br><br>}}_f^2\cong <br><br>{{\mathrm{\sigma <br><br>}}_x^2<br><br>\left(\frac{\partial <br><br>f}{\partial <br><br>x}\right)}^2+{{\mathrm{\sigma <br><br>}}_y^2<br><br>\left(\frac{\partial <br><br>f}{\partial <br><br>y}\right)}^2+{{\mathrm{\sigma <br><br>}}_z^2<br><br>\left(\frac{f}{z}\right)}^2+\mathrm{\dots <br><br>}\\ \frac{\mathrm{df}}{f}=\frac{y+z+\mathrm{\dots <br><br>}}{x}·<br><br>\frac{\mathrm{dx}}{(x+y+z+\mathrm{\dots <br><br>}<br><br>)}+\frac{\mathrm{dy}+\mathrm{dz}+\mathrm{\dots <br><br>}}{(x+y+z+\mathrm{\dots <br><br>}<br><br>)}<br><br><br><br>\mathrm{and}<br><br>\text{/}<br><br>\mathrm{or}<br><br><br><br>\frac{{\mathrm{\sigma <br><br>}}_f}{f}={\left[{\left(\frac{y+z+\mathrm{\dots <br><br>}}{x}\right)}^2·<br><br>\frac{{\mathrm{\sigma <br><br>}}_x^2}{{(x+y+z+\mathrm{\dots <br><br>}<br><br>)}^2}+\frac{{\mathrm{\sigma <br><br>}}_y^2+{\mathrm{\sigma <br><br>}}_z^2+\mathrm{\dots <br><br>}}{{(x+y+z+\mathrm{\dots <br><br>}<br><br>)}^2}\right]}^{1/2}\end{array}$

where df and σ

_f are the absolute variation of the concentration of a ingredient in the pharmaceutical formula,

$\frac{\mathrm{df}}{f}<br><br><br><br>\mathrm{and}<br><br><br><br>\frac{{\mathrm{\sigma <br><br>}}_f}{f}$

are the relative variation of the dosage percentage of a ingredient in the pharmaceutical formula, x, y, z, . . . are quantities of ingredients of the dosage form, dx, dy, dz, . . . are sensitivities of the analytical instruments;

optionally plotting the relationship between quantities of measurements of a ingredient, sensitivities of the instruments measuring the ingredient and the variation of final concentration of the ingredient in a mixture in 2D or 3D chart; and

outputting said value of variation of concentration for a validation under an assay standard.

2. A method for determining the error in ingredient'"'"'s quantities in a multi-component pharmaceutical formula measured by multiple analytical instruments by using the program product according to claim 1, comprises steps of:

selecting a type of error analysis;

inputting a quantity value of an ingredient of a composition to be measured by an instrument;

inputting a sensitivity value of the analytical instrument measuring the quantity of the ingredient;

repeating the two inputting steps for any remaining ingredients to be measured that compose the pharmaceutical formula;

executing said program product to relate;

the quantities of measurements and sensitivities of instruments to a value of variation of the final concentration of any ingredient in the pharmaceutical formula; and

determining the value of variation according to an assay standard based on the plot or output values of variation.

3. A computer system incorporating the program product according to the claim 1, wherein said system comprises:

an input device for selecting a type of analysis and inputting the values of quantities and sensitivities;

a storage device storing the input values and said program product;

a computing device executing said program product on the input values; and

an output device for displaying or outputting said value of variation.

4. A website incorporating the program product according to the claim 1, wherein said website comprises:

a first set of webpages for selecting a type of analysis and inputting the values of quantities and sensitivities;

a second set of webpages for displaying said values of variation. and

a server device executing said program product and storing the two sets of webpages and said program product;

5. An IC chip incorporating the program product according to the claim 1, wherein said chip comprises:

an input interface for receiving the selection of a type of analysis and the values of quantities and sensitivities;

a storage device storing said program product and input values;

a computing device for executing said program product; and

an output interface for outputting the values of variation.