A Direct Compression Matrix Made from Xanthan Gum and Low Molecular Weight Chitosan Designed to Improve Compressibility in Controlled Release Tablets

Abstract

The subject of our research is the optimization of direct compression (DC), controlled release drug matrices comprising chitosan/xanthan gum. The foregoing is considered from two main perspectives; the use of low molecular weight chitosan (LCS) with xanthan gum (XG) and the determination of important attributes for direct compression of the mixtures of the two polymers. Powder flow, deformation behaviour, and work of compression parameters were used to characterize powder and tableting properties. Compression pressure and LCS content within the matrix were investigated for their influence on the crushing strength of the tablets produced. Response surface methodology (RSM) was applied to determine the optimum parameters required for DC of the matrices investigated. Results confirm the positive contribution of LCS in enhancing powder compressibility and crushing strength of the resultant compacts. Compactibility of the XG/LCS mixtures was found to be more sensitive to applied compression pressure than LCS content. LCS can be added at concentrations as low as 15% w/w to achieve hard compacts, as indicated by the RSM results. The introduction of the plasticity factor, using LCS, to the fragmenting material XG was the main reason for the high volume reduction and reduced porosity of the polymer mixture. Combinations of XG with other commonly utilized polymers in controlled release studies such as glucosamine, hydroxypropyl methylcellulose (HPMC), Na alginate (ALG), guar gum, lactose and high molecular weight (HMW) chitosan were also used; all the foregoing polymers failed to reduce the matrix porosity beyond a certain compression pressure. Application of the LCS/XG mixture, at its optimum composition, for the controlled release of two model drugs (metoprolol succinate and dyphylline) was examined. The XG/LCS matrix at 15% w/w LCS content was found to control the release of metoprolol succinate and dyphylline. The former preparation confirmed the strong influence of compression pressure on changing the drug release profile. The latter preparation showed the ability of XG/LCS to extend the drug release at a fixed rate for 12 h of dissolution time after which the release became slightly slower.

Understanding the Performance of a Novel Direct Compression Excipient Comprising Roller Compacted Chitin

“…P k , which represents the pressure needed to reduce (a) into half its initial value, is the most important Kawakita parameter to be tested. This is due to the fact that it represents how hard the granules are, and therefore, their ability to be used in direct compression applications [27]. The data in Figure 6 shows that the P k values of compacted raw chitin powder were the highest amongst all three types of samples.…”

Applications of polymer blends in drug delivery

“…However, in general, most direct compression and granulation processes would be considered to be particulate level blends given the size of their constituent particles. A relevant example from the recent literature describes the use of 90-250 μm particle size range chitosan and xanthan gum blends for use as a direct compression matrix [69]. In this case, the polymer blend is clearly at the particulate level given its particle size range and the use of a direct compression process which does not involve size reduction of the powders.…”

Study of Different Chitosan/Sodium Carboxymethyl Cellulose Proportions in the Development of Polyelectrolyte Complexes for the Sustained Release of Clarithromycin from Matrix Tablets

“…Natural anionic polymers have been extensively used for the development of PECs [ 5 , 6 , 7 , 8 ]. However, anionic cellulose derivatives such as hypromellose phthalate [ 4 ] and carboxymethyl cellulose sodium [ 9 ] show greater control of the molecular weight and the number of carboxylic groups (COO − ).…”

“…The degree of substitution, which is determined by the number of carboxymethyl groups per unit of CMC, has been widely studied and is one of the main factors affecting its physicochemical behavior [ 9 , 10 ]. Recent studies have shown that the development of matrix tablets containing mixtures of CS and anionic polymers self-assemble during the compression process [ 6 , 7 ].…”