International Journal of Pharmaceutics, 72 (1991) 79- 86 Elsevier Science Publishers B.V. ADONIS 0378517391002096 79 IJP 02408 Predictive modelling of the behaviour of a controlled release buflomedil HC1 formulation using scintigraphic and pharmacokinetic data C.G. Wilson 1, N. Washington 1, J.L. Greaves a, C. Washington 2, I.R. Wilding 2, T. Hoadley 3 and E.E. Sims 3 1 Department of Physiology & Pharmacology, Medical School, Queen's Medical Centre, Nottingham NG7 2UH (U.K.), 2 Department of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD (U.K.) and 3 Abbott Laboratories, International Development Centre, Queenborough, Kent MEl l 5EL (U.K.) (Received 22 December 1990) (Accepted 5 February 1991) Key words: Buflomedil HC1; Gamma scintigraphy; Pharmacokinetics; Gastrointestinal transit; Computer modelling Summary A combined scintigraphic and pharmacokinetic study was carried out in seven healthy subjects to evaluate the effect of meal size on the behaviour of an oral controlled release preparation of buflomedil HCI (600 mg). Micronised resin radiolabelled with 111 In was incorporated into the tablets which were administered to subjects after either a light (646 kJ) or a heavy (3327 kJ) breakfast in a randomised cross-over study. The gastrointestinal transit of the formulation, and the buflomedil serum concentrations were monitored for 25 h following administration of the tablets. The mean gastric residence times (+ SD) of the formulation after the heavy and light breakfasts were 6.2 + 2.3 and 2.2+0.2 h, respectively (p < 0.01; Wilcoxon Signed Rank test), however, transit through the small intestine was unaffected by the meal size. Complete disintegration of the tablet occurred in the large intestine in all cases, apart from in one subject where disintegration occurred in the small intestine after administration with a heavy breakfast. The peak serum drug concentration occurred at 4 h following a light meal (1.87 + 0.53/.tg m1-1) and at 6 h following the heavy meal (2.16 + 1.0/~g ml-1). The area under the serum-concentration time curve was 21.7 + 8.1/.tg m1-1 h for the light meal and 24.8 + 10.5 /~g ml- 1 h for the heavy meal. The transit data and the in vivo release rates of the radioactive marker from the tablet were used in a computer simulation to demonstrate that the observed serum concentrations could result from predominantly small intestinal absorption of the drug with a smaller contribution from colonic absorption. Introduction Buflomedil hydrochloride (Loftyl®, Lofton® and Bufedil®, Abbott Laboratories) is a vasoactive Correspondence." C.G. Wilson, Department of Physiology & Pharmacology, Medical School, Queen's Medical Centre, Not- tingham NG7 2UH, U.K. drug which improves perfusion in the impaired microcirculation of the peripheral and central vascular beds. The mode of action is not fully understood but the drug is known to exert a non-specific antagonism on a-adrenoceptors and is a weak calcium-channel antagonist. The normal 0ral dosage regimen is 450-600 mg per day, usually administered in two to four di-