Formulation Interactions

The reasons why individuals differ in their responsiveness to drugs in medical products are manifold, and include age, gender, genetics, disease, and drugs given concomitantly. 

The focus of interaction studies has changed from ad hoc observational studies to rationally designed studies. Depending on the structural and physicochemical characteristics and on animal and human in vitro data, selective in vivo studies are performed. Based on the results of such studies the risk of clinically relevant interactions may be predicted. As a result, essential informa- 

While formulation interactions often are subject to in vitro investigations, the section below presents a particular example of an in vivo formulation interaction study (CPMP/EWP/QWP/1401/98 2002) a potential interaction of a drug in medical practice frequently given concomitantly with another drug (i.e. both mixed in a syringe) was subject to a clinical study which is illustrated below. For the purposes of simplicity, the description is limited to the collection, handling, and interpretation of pharmacokinetic data although clearly safety and pharmacodynamic parameters were also studied. 

The design of a typical formulation interaction study is presented below. 

Pharmacokinetics of HMR1964 (insulin glulisine) syringe-mixed versus simultaneosly injected 0.1 lU/kg HMR1964 (insulin glulisine) and 0.2 lU/kg NPH insulin in healthy subjects using the euglycemic clamp technique. 

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D Fleisher, C Li, Y Zhou, L-H Pao, A Karim. Drug, meal and formulation interactions influencing drug absorption after oral administration. Clin Pharmaco-kin 36 233-254, 1999. 

Cosmetic applications, lactic acid in, 14 125 Cosmetic emulsions, 10 129 Cosmetic formulations, interaction with skin, 24 158... 

In the same spirit as that of the extraction of small-particle interactions, it is possible to specialize the general expression for the interaction of planar half-spaces in order to formulate interactions between point particles and substrates (see Fie. LI.44). 

Peart, J. Orban, J.C. McGlynn, P. Redmon, M.P. Sargeant, C.M. Byron, P.R. MDI electrostatics valve and formulation interactions that really make a difference. In Respiratory Drug Delivery VIII, Dalby, R.N., Byron, P.R., Peart, J., Parr, S.J., Eds. Davis Horwood International Raleigh, NC, 2002 223-230. 

C. Connection with the Semiclassical Formulation Interaction Representation and Coherent States... 

More recent proposals discussed for evaluating bioequivalence are based on approaches termed Individual Bioequivalence and Population Bioequivalence. The average bioequivalence approach focuses only on the comparison of population averages (p, p ) of a bioequivalence metric of interest and not on the variances of the metric for the T and R products. The individual bioequivalence approach not only compares the population averages (pj, p ), but also assesses the within-subject variability (o t, o r ) as well as the subject-by-formulation interaction (Od ). The population bioequivalence approach is designed to assess the total variability, i.e., within- and between-subject variability (o, Oxr ) of the pharmacokinetic parameter (metric) in the population. The individual and population bioequivalence... 

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