Tuesday, 16 May 2017

Influence of Several Excipients on Drug Release of Tablets Containing Resveratrol




For pharmaceutical tablet production, there are lots of commercial excipients available. All these excipients influence the drug release of tablet cores in different ways. In this project the influence of Carbopol 71G®, Carbopol 971P®, Fujicalin®, Neusilin US2®, Neusilin UFL2®, Pemulen TR-1®, Pemulen TR-2®, Sepistab ST 200® and Sepitrap 80® on drug release was investigated. Tablets were compressed with resveratrol as a model drug using an eccentric press. Tablets containing 2 wt.% of resveratrol which was mixed with a certain amount of excipient, in addition to 1 wt.% of talc, 1 wt.% magnesium stearate and Ludipress LCE. These products were compared with tablets without any excipients, but with all the other remaining components of the formulation. Drug release was in vitro investigated in dependence of time, according to European Pharmacopoeia (Ph. Eur. 2.9.3). It appeared that drug release depends on the qualities of the pharmaceutical additives. Tablets with Fujicalin® and Sepistab ST 200® exhibit a rapid release and disintegration time, while the other pharmaceutical additives lead to a delayed release (retardation). Drug release kinetics was described by the mathematical model of Korsmeyer-Peppas.


Tablets are the best known and most frequently used pharmaceutical single unit dosage forms. Today more than 40% of all drugs were consumed in tablet form. Tablets could be economically produced by a machine in large quantities. More advantages are the good acceptance of the patients, the possibility for easy transport and storage. The composition of different mixed substances allows to create formulations which releases the drug at the desired location in gastrointestinal tract (GIT). This means that the right combination of excipients tends to result in a less drug amount, which is necessary to achieve the same effects. As a consequence of this, fewer side effects of drug could be expected. Excipients are characterized with their fields of functions as base material, disintegrant, glidant, and lubricant, binder or granulating agent. Binders are used to enhance cohesion of powder particle and increase plasticity of tablets. Glidants and lubricants are flow aids, which improves tablet pressing process. Disintegrants enhance disintegration of tablets in GIT. Fujicalin® includes calciumhydrogenphosphate and dicalcium phosphate anhydrous (DCPA) (Figure 1c). This fillers could be used for direct compression and to receive hard tablets by using only small low compression force. It is a porous product with a low particle size of 115 µm, which is able to adsorb liquid oily substances. Fujicalin® doesn’t act as disintegrant

but improves the decay of tablets. Because of the fact that porousity overcomes tablet pressing, water is enabled to penetrate the tablet faster. Sepistab ST 200® is a commercial excipient based on a mixture of native starch and pregelatinized starch, which act as binder, glidant and disintegrant. Sepitrap 80® is an excipient comprised from polysorbate 80 (Figure 1d) which is derived from polyethoxylated sorbitan and oleic acid. In tablets it works as emulsifier to enhance bioavailability for poorly water soluble drugs. Neusilin® is based on a totally synthetic magnesium aluminometasilicate (Figure 1a). Neusilin US2® is granulate, while Neusilin UFL2® is a powder. These porous products increase flowability of powder mixtures and hardness of resulting tablets [10]. Carbopol 71G NF® and Carbopol 971P NF® are a commercial names for the same type of polyacrylic acid (Figure 1e). While Carbopol 71G NF® exhibits a granular physical form, Carbopol 971P NF® is in powder form. It can be used for direct compressing and leads to extended drug release of resulting tablets. Pemulen® is a cross linked copolymer of acrylic acid and a hydrophobic comonomer with high molecular weight (Figure 1f). Table 1 summarizes all described excipients, with its chemical name. 

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