Carbamazepine: A clinical biopharmaceutical study

Abstract

In a biopharmaceutical study of carbamazepine, the F-CBZ, DAK preparation, which contained small particles with minor variation in size, had a more rapid dissolution rate than Tegretol, which contained larger particles of more variable size. Accordingly, carbamazepine had a more rapid absorption rate from F-CBZ, DAK than from Tegretol in a comparative absorption test involving single-dose administration of 200 mg to 8 healthy volunteers. The clinical significance of the difference in absorption rates for the steady state levels of carbamazepine and carbamazepine-10,11-epoxide, and the frequency of side-effects in relation to tablet intake, were evaluated in a double-blind, randomized, double-dummy cross-over trial of 35 days' duration, in 21 well-adjusted epileptic patients. 9 patients were treated with Tegretol alone and 12 with Tegretol combined with other antiepileptic drugs. A lower steady state plasma level of carbamazepine was found at 08.00 h during treatment with F-CBZ, DAK in comparison with Tegretol. The difference was small. There was no difference in the type and frequency of side-effects or seizures between the 2 preparations. The frequency of epileptic fits was not correlated with the plasma level of carbamazepine or the epoxide. Side-effects, however, had a tendency to be correlated with the concentration of the epoxide. Thus, the particle size influenced the absorption rate of carbamazepine, without having a significant correlation wih the frequency of side-effects. The difference in the minimum plasma level of carbamazepine between treatments with the two preparations was modest, and appeared to be without clinical significance.

Dissolution and relative bioavailability of two carbamazepine preparations for children with epilepsy

“…1). The extent of dissolution found here for the 200 mg tablets of the proprietary (about 87%) was higher than the range of values (65-75'Y") reported by Dam et al (1981). Fig.…”

“…The absence of a dissolution test for carbamazepine tablets from the monographs of the British Pharmacopoeia (BP) and United States Pharmacopeia (USP) necessitated establishing dissolution criteria. However, Dam et al(1981) used 1 L of 0.1 M HCI as the dissolution media, so this was adopted. The amount of carbamazepine which dissolved in 1 L of 0.1 M HCI at 37°C during 120 min was determined using a 6 place Copley Dissolution Station coupled via a Watson Marlow 10-head peristaltic pump to a Beckman DU65 ultraviolet/visible spectrophotometer fitted with a 10 mm flowthrough cell.…”

Influence of Polymorphic Form, Morphology, and Excipient Interactions on the Dissolution of Carbamazepine Compacts

“…[4][5][6][7] In the past 20 years, investigations of CBZ have focused on the in vitro dissolution behavior and in vivo bioavailability of the drug where dissolution tests were employed in most studies. 5,[8][9][10][11][12][13][14] It was found that different CBZ forms have different physico-chemical properties 7,[15][16][17] and dissolution profiles with CBZ dihydrate (DH) showing the slowest dissolution rate and solubility (approximately two thirds of that of CBZ form III). 4 Also, dissolution testing of different sources of marketed CBZ tablets stored at varying temperature and humidity conditions has been carried out.…”

Controlled Release Carbamazepine: Cognitive Side Effects in Patients with Epilepsy

“…The serum concentration of CBZ is characterized by rapid absorption and a short half-life, leading to considerable fluctuation of the level between doses (Dam et al, 1981;Sillanpaa, 1981;Neuvonen, 1985). This implies that cognitive defects may be restricted to the limited periods of peak times: short periods with high serum concentration, sometimes even in the toxic range.…”