Pharmacokinetic modulations in NDDS...

This is the continuation of my previous blog....

NDDS for systemic drug delivery try to circumvent the problems of compliance and fluctuations in drug concentrations shown by conventional drug delivery systems. The intention in most cases is to maintain the drug concentrations within the therapeutic window for time periods that are significantly longer than that observed for conventional dosage forms and with minimum fluctuation in the drug concentrations.

In one approach, the steepness of the concentration - time curve is made graded by simply modulating the first order rate of release of drug from the NDDS. As a consequence, the rate of absorption is slowed or prolonged. The end result is that the interplay of Rate In and Rate Out yields a more gradual increase in the slope of the bell curve with the resultant maintenance of drug concentrations in the therapeutic window for longer periods of time, with a lesser degree of fluctuation that conventional dosage forms.

In the second approach, based on the knowledge of the pharmacokinetic parameters of the drug (Cl and V) and the target average concentration required, the rate of elimination
(Cl × Cav) when average drug concentration is achieved can be calculated. If one were to match this rate of output by delivering the drug in a zero order fashion, the consequence would be as follows,
Rate In (via the NDDS) = Rate Out (Cl × Cav.)
Under these conditions, dA/dt = Rate In - Rate Out (assuming instantaneous distribution) The amount of drug in the body would be maintained at a steady or stable state.

Of the two approaches, the second approach, obviously, allows for a better degree of control of drug concentrations with minimal fluctuations.

The caveats in the two approaches mentioned above are:

a) Both approaches increase the time needed for drug concentration to enter the therapeutic window because rate of absorption in most NDDS is slower that conventional dosage forms and

b) Amount of drug to be incorporated into the NDDS so that drug can be delivered at the estimated/calculated rate to maintain drug concentrations for the requisite time. The first problem is generally solved by giving a conventional or rapidly releasing dose (loading dose) of the drug in order to quickly reach the desired concentration, followed by maintaining the levels via the NDDS.

Acknowledgement:
I would like to express my gratitude to my beloved professor Vijaya Ratna madam who helped me in bringing out the pharmacokinetic blogs.

References:

1. Pharmacokinetics in Drug discovery and development by Ronald D. Schoenwald; Basic principles pg nos- 7-10
2. Integrated Pharmacology 2nd edition by Walker, Hoffmann,Curtis,Sutter,Clive; Pharmacokinetics pg nos- 50,51

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