Preparation and Characterization of Tablet Formulation based on Solid Dispersion of Glimepiride and Poly(ester amide) Hyperbranched Polymer

Abstract

The feasibility of incorporating a solid dispersion containing poorly soluble antidiabetic drug glimepiride and poly(ester amide) hyperbranched polymer into a tablet using a direct-compression tabletting technique was investigated. Tablet cores were additionally coated with hydroxypropyl methylcellulose phthalate in order to protect the extremely hygroscopic solid dispersion from atmospheric moisture. Preliminary stability studies show that glimepiride, which is in amorphous form within solid dispersion, is chemically stable, even if tablets are exposed to elevated temperature and/or moisture. In-vitro dissolution studies show some impact of storage conditions on the tablet cores disintegration time and, consequently, drug release rate. Glimepiride solubility also deteriorates somewhat, most probably due to its partial recrystallization. Storage conditions much less affect the physical stability of coated tablets, which was ascribed to reduced tablet hygroscopicity due to the presence of protecting coating. The hyperbranched polymers are rather new and complex macromolecules. Therefore, we addressed also the biocompatibility of hyperbranched polymer, i.e., its impact on haemolysis of the red blood cells. The concentration required for the haemolytic effect on the red blood cells is around 100-times higher than its expected gastrointestinal luminal concentration, which makes the occurrence of hyperbranched polymer mediated cytotoxicity very unlikely.

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

“…An attempt to tailor and customize excipients by modifying the functional groups which could be potentially used in ASD formulations has also been reported (157). In some other studies, more unconventional excipients were explored to investigate their potential use in oral pharmaceutical formulations, with limited reports on their inclusion in amorphous dosage forms (113,158–160). The excipients used in these cases were added for many different reasons, not only to provide amorphous stability (i.e.…”

“…The duration also varied significantly, with stability studies lasting from 24 h to two years (73,74,81,82,84,86,88,92,93,104,105,109,110,113,115,116,118,120,123,124,126,127,129,130,132,134,135,139,143,146,149,153,158,166,169,172,175,176). While most of the studies did not mention the container used for the physical stability test, a few specified, for example, whether a closed or open container was used (88,92,113,123,132,146). Of these six articles that mentioned whether closed or open container was used, only one specifically reported the type of container used (i.e.…”

“…Of these six articles that mentioned whether closed or open container was used, only one specifically reported the type of container used (i.e. high density polyethylene bottle) in the stability study (132) whereas the remaining studies mentioned only that tube (88), airtight brown vial (92), vial (113), sealed aluminum strip (123) or sealed glass container (146) was used. These large variations in the design of stability studies make direct comparison impossible, since the stability profile obtained is specific only for the stability method employed.…”

“…In the reviewed articles, no specific method was used in the investigation of amorphous solubility and dissolution behavior, even though different pharmacopoeia methods provide general guidance on how they should be performed. Ninety-two of the 101 studies reported solubility and dissolution studies (71–74,77–79,81–92,95,97–107,109–111,113–119,121,123,124,126–133,135–139,141–154,156,157,160,161,166,168–176). The USP in vitro dissolution type II apparatus was the most commonly used instrument (67%), followed by the USP type I apparatus (6%), while the remaining 27% used various other apparatuses, including modified versions of the USP type I only (148) or paired with confocal Raman microscopy (98), USP types I and II apparatus (72), USP type IV (152), closed loop of USP types II and IV (152), a perspex flow cell (73,142), a rotary mixer (131), a Chinese pharmacopoeia type III apparatus (118), an in-house miniaturized USP type II apparatus (175), Sirius T3 apparatus (146), μFLUX dissolution-permeation apparatus (141), Raman UV-Vis flow cell system (99), a centrifuge (88), high throughput screening using a 96-well plate (82,115,157), Wood’s apparatus (99,137), an orbital shaking incubator (156), and another shake-flask method (171) (Fig.…”

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.…”