Drug Formulation
A:Phenobarbital 100 mg = 5 ml as solution in Myvacet 9-08; B: Phenobarbital 100 mg = 25 ml as suspension, extemporaneously prepared with an aqueous suspension vehicle C: Phenobarbital 100 mg tablet

. Volunteers
The study protocol and written informed consent were approved by the local Institutional Review Board. Seven healthy male volunteers (mean age: 32 yr; mean weight: 75 kg) gave their written consent to participate.

Study-design
On three occasions separated by a 4-week time interval each subject received one of the preparations of phenobarbital. At 8 o'clock in the morning after an overnight fast the drugs were administered to the volunteers with 200 ml of water. No beverages and food were allowed for two hours postdose. All subjects stayed in the hospital for at least 8 h after administration of the phenobarbital. Blood samples were taken 0, 0,25, 0,5 0,75, 1, 2, 3, 4, 5, 6, 8, 24 and 48 hr after intake of the medication.

Analysis of Phenobarbital
A sensitive and validated HPLC method was used for the analysis of phenobarbital.

Pharmacokinetic Parameters
From the individual serum concentration-versus-time curves Cmax and Tmax were determined. For each curve AUC0-48 was calculated by the linear trapezoidal method.

Statistical Analysis
After logarithmical transformation the values for Cmax and AUC0-48 were subjected to an analysis of variance (ANOVA). Values for Tmax were also statistically analyzed.

Other than some mild transient drowsiness no adverse reactions were reported. Most volunteers disliked the taste of phenobarbital in Myvacet 9-08.

Figure 1 shows the serum concentration-versus time profiles of one subject during the initial 10 h after administration of the medication.
Figure 1

Table 1 summarizes the mean pharmacokinetic parameters of phenobarbital after administration of the three preparations.
Table 1

Table 2 shows the statistical analysis on Cmax and AUC0-48. All three oral dosage forms of phenobarbital are bioequivalent.
Table 2

The results of the statistical analysis of Tmax of phenobarbital from the doasge froms are shown in Table 3.
Table 3

Previous pharmacokinetic studies in healthy volunteers showed, that phenobarbital administered as a tablet has almost complete bioavailability. Literature is sparse on the pharmacokinetics after oral administration of a suspension. Our study has demonstrated, that the suspension and the tablet are bioequivalent. The individual data show, that in most subjects the absorption of phenobarbital from the suspension is faster than from the tablet with a smaller Cmax and AUC0-48. Besides the disadvantages of using a suspension, for patients who find it difficult to swallow tablets, the formulation of the suspension of phenobartbital as we studied it, could be a good alternative.

For drugs with a low aqueous solubility microemulsions or self-emulsifying drug delivery systems may be considered as a formulation for oral administration. We showed, that phenobarbital dissolved in Myvacet 9-08 and formulated without addition of an emulsifier, has a good oral absorption profile and is bioequivalent to a tablet and the suspension. Myvacet 9-08 might prove to be an excellent vehicle to enhance the intestinal absorption of a co-formulated drug, therefore it should be studied with other drugs with a known bioavailability problem.

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