Complete bioavailability and lack of food‐effect on pharmacokinetics of gliclazide 30 mg modified release in healthy volunteers

Abstract

A new modified release (MR) formulation containing 30 mg of gliclazide was developed to obtain a better predictable release of the active principle and to allow once-daily dosing regimen. An absolute bioavailability study was carried out to characterise the performance of the new formulation and the food-effect was also investigated in a separate study. Both studies were single dose, randomised, open label, two way cross over studies with a wash out period between doses. For the bioavailability study, each volunteer received 30 mg of gliclazide given either as a 1 h intravenous infusion or as a 30 mg MR tablet. For the food-effect study, the treatment was given either fasted or 10 min after the start of a standardised Melander breakfast. Blood samples were collected up to 72 h after administrations and plasma samples assayed for gliclazide concentrations using a reverse-phase HPLC method with UV detection. Mean absolute bioavailability of gliclazide was 97% and ranged between 79 and 110% showing complete absorption. A similar moderate to low variability was observed after IV and oral administration showing the MR formulation did not add to the overall variability which is solely due to the disposition parameters, in particular metabolism of gliclazide. No significant difference was observed in t(max), t(1/2z), C(max) and AUC of gliclazide after administration of the 30 mg MR tablet under fasted and fed conditions. In conclusion, after single oral administration of a 30 mg MR tablet, gliclazide was completely absorbed both under fasted and fed conditions. A consistent and optimal release of gliclazide from this formulation leads to a low to moderate overall variability of its pharmacokinetic parameters. Diamicron 30 mg MR can be given without regards to meals i.e. before, during or after breakfast.

Development of a Dissolution Method for Gliclazide Modified-Release Tablets Using USP Apparatus 3 with <i>in Vitro–in Vivo</i> Correlation

“…Thus, it suggests a possible excipient effect on the solubility and dissolution rate of GLZ MR tablets, especially in acidic media. In addition, this observation is in agreement with reports from Harrower 8) and Delrat et al 9) that suggested that the dissolution of GLZ MR tablets is controlled by the formulation. This information was an important guide for the composition of the dissolution pH steps in our study.…”

“…33) However, the MR tablets of the GLZ were formulated with a hydrophilic matrix to obtain a more consistent and less pH-dependent release. 8,9) Dissolution Studies Using USP Apparatuses 1 and 2 To date, a single official dissolution method for GLZ is described for IR tablets in the British Pharmacopoeia. 30) The method recommends the use of USP2 at 100 rpm and 900 mL of PBS (pH 7.4).…”

“…9) The drug absorption was estimated using the numerical deconvolution method from Wagner-Nelson 16,25,31) (Eq. 1).…”

“…6,7) To improve its availability, modified-release (MR) tablets of the drug were formulated with a hydrophilic matrix to obtain a more consistent and less pH-dependent release profile of the active pharmaceutical ingredient over a 24 h period. 8,9) The formulation can be administered before, during or after meals. 8,9) Dissolution is an important tool to evaluate the quality of dosage forms, to guide drug development and can also be applied to bioequivalence studies.…”

“…8,9) The formulation can be administered before, during or after meals. 8,9) Dissolution is an important tool to evaluate the quality of dosage forms, to guide drug development and can also be applied to bioequivalence studies. 10,11) During the development of a dissolution method, the in vitro parameters such as the presence of surfactants, pH, ionic strength and media volume should be evaluated.…”