Improvement of Dissolution and Hypoglycemic Efficacy of Glimepiride by Different Carriers

Abstract

Abstract. Effects of tromethamine (Tris), polyvinylpyrrolidone (PVP-K25), and low molecular weight chitosan (LM-CH) on dissolution and therapeutic efficacy of glimepiride (Gmp) were investigated using physical mixtures (PMs), coground mixtures, coprecipitates (Coppts) or kneaded mixtures (KMs), and compared with drug alone. Fourier transform infrared spectroscopy, differential scanning colorimetry, and X-ray diffractometry were performed to identify any physicochemical interaction with Gmp. Surface morphology was examined via scanning electron microscopy. The results of Gmp in vitro dissolution revealed that it was greatly enhanced by Coppt with Tris or PVP-K25 and KM with LM-CH at a drug to carrier ratio of 1:8. Gmp amorphization by PVP-K25 and LM-CH was a major factor in increasing Gmp dissolution. Being basic, Tris might increase the pH of the microdiffusion layer around Gmp particles improving its dissolution. Formation of water-soluble complexes suggested by solubility study may also explain the enhanced dissolution. Capsules were prepared from Coppts and KM 1:8 drug to carrier binary systems and also with Tris PMs. In vivo, the hypoglycemic efficacy of Gmp capsules in rabbits increased by 1.63-, 1.50-, and 1.46-fold for 1:8 Coppts with Tris or PVP-K25 and KM with LM-CH respectively, compared with Gmp alone. Surprisingly, the response to Tris PM 1:20 capsules was 1.52-fold revealing statistically insignificant difference to that of Tris Coppt 1:8 (1.63 fold). As a conclusion, dissolution enhancement and hypoglycemic potentiation by 1:20 PM of Gmp/Tris, being simple and easy to prepare, may enable development of a reduced-dose and fast-release oral dosage form of Gmp.

Self-nanoemulsifying drug-delivery systems for potentiated anti-inflammatory activity of diacerein

“…Dissolution efficiency (DE) was calculated as percentage of the area under the dissolution curve to time t to that of the rectangle representing 100% dissolution at the same time. 37,38 Relative dissolution rate (RDR) was estimated as percentage dissolved Dcn from each binary system either SNEDDS or PM to that of the drug alone at the same time. 38,39…”

“…37,38 Relative dissolution rate (RDR) was estimated as percentage dissolved Dcn from each binary system either SNEDDS or PM to that of the drug alone at the same time. 38,39…”

“…An amorphous drug is expected to dissolve at a faster rate than a crystalline form, due to its high energy. 38,39 With regard to carrier concentration, the effects of the carriers differed. Generally, an increase in Glc concentration from drug:carrier weight ratio 1:1 to 1:10 significantly (P,0.05) enhanced Dcn release, except with 1:2 SNEDDS ( Figure 5B), as reflected by mean DE 30 values (Table 2), whereas, physical mixing of Dcn with increased concentrations of TPGS from 1:1 to 1:10 drug:carrier ratio resulted in an insignificantly different Dcn release ( Figure 5C), as suggested by DE 30 estimates in Table 2.…”

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

“…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.…”

Glimepiride-Loaded Nanoemulgel; Development, In Vitro Characterization, Ex Vivo Permeation and In Vivo Antidiabetic Evaluation

“…The major problem associated with GMP is its poor aqueous solubility. To overcome this problem, many studies have been conducted to enhance the solubility of GMP by using a cyclodextrin inclusion complexation [11].…”