Development and characterization of glimepiride nanocrystal formulation and evaluation of its pharmacokinetic in rats

Abstract

In this paper, orally nanocrystal capsules were produced using nanocrystal formulations in order to optimize dissolution properties of poorly soluble drug glimepiride and improve its bioavailability. The important preparation variables, such as stabilizers, the power input and the time length of ultrasonication on the mean particle size and polydispersity index were investigated systematically, and the optimal values were 0.2% glimepiride (w/v), 1.2% Lipoid S100, 0.6% PEG 6000 (w/v), 0.6% PVPK 30 (w/v), 500 W and 2 min, respectively. Characterization of glimepiride nanocrystal was carried out by X-ray powder diffractometry, differential scanning calorimetry and scanning electron microscopy. In vitro dissolution test, the nanocrystal-loaded capsules of glimepiride showed an evident increase in dissolution rate compared to micronized and market capsules. The in vivo studies demonstrated that a marked enhancement of bioavailability of nanocrystal-loaded capsules was superior compared to the marketed formulation and microcrystal-loaded capsules, which may reduce the risk of side effect by allowing a reduction in either the dose or its frequency of administration.

A simple and effective method to improve bioavailability of glimepiride by utilizing hydrotropy technique

“…5 illustrated the DSC thermograms of meglumine (5a), glimepiride (5b), GLMP-MU complex (5c) and the physical mixture (5d). The endothermic peak of meglumine and glimepiride appeared at 134°C and 212°C, assigned to their melting point respectively (Du et al, 2013;Aloisio et al, 2014). The obvious shift of endothermic peaks were detected in GLMP-MU complex (5c).…”

“…Concerning the drawbacks associated with the GLMP treatment, the use of suitable strategies to increase its water solubility or gastrointestinal absorption could reduce the undesirable side effects by the administration of lower doses (Aloisio et al, 2013). To overcome these obstacles, a lot of new pharmaceutical technologies, such as inclusion complexes (Ammar et al, 2006a,b), solid dispersions (Ahuja et al, 2007;Mohamed et al, 2012;Pahovnik et al, 2011), cosolvent (Seedher and Kanojia, 2009), self-nanoemulsifying system (Mohd et al, 2014;Shah et al, 2013), nanocrystal (Du et al, 2013;Ning et al, 2011), and micelles (Reven et al, 2010(Reven et al, , 2013Seedher and Kanojia, 2008) have been used for increasing the solubility of glimepiride. Although those technologies improved the solubility of glimepiride to some extent, the improvement of clinical efficacy was not clear or the complex preparation was not suitable for industrial production.…”

“…Chemically it is 1- [[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)-ethyl] phenyl] sulfonyl]-3-trans-(4-methylcyclohexyl) urea ( Fig. 1a) (Salem et al, 2004;Song et al, 2004), and it is a third-generation sulfonylurea oral hypoglycemic agent used for the treatment of patients with type II non-insulin-dependent diabetes mellitus (Ammar et al, 2006a;Du et al, 2013). Preclinical investigation of glimepiride suggested a number of potential benefits over sulfonylurea currently available including lower dosage, rapid onset, longer duration of action and lower insulin C-peptide levels, possibly due to less stimulation of insulin secretion and more pronounced extrapancreatic effects (Ammar et al, 2006a;Song et al, 2004).…”

Development and characterization of lecithin stabilized glibenclamide nanocrystals for enhanced solubility and drug delivery

“…A decrease in AUC may be related to the in vivo properties of NCs. The in vivo properties strongly depend on particle size, shape, surface charge, dissolution rate and nature, and density of coating Du et al, 2013). Considering the particle size, the optimized batch (F1) possessed an average particle size of 155 nm and a distribution of 0.310.…”

Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

“…However, the drawback for the use of GM as oral dosage forms is attributable to its low aqueous solubility (1.6 µg/mL) and slow dissolution rate, which lead to low oral bioavailability. 6,7 Hence many studies have tried to enhance its solubility, and several reports including those where nanocrystals, 8 cosolvency, 9 spray congealing, 10 solid self-nanoemulsify,…”