An Overview of Chitosan-Xanthan Gum Matrices as Controlled Release Drug Carriers

Naturally occurring polysaccharides and/or their chemically modified derivatives have been widely investigated in relation to their use as components of controlled release systems for drug delivery. The aforementioned is due, in part, to their distinct properties such as abundant availability and biocompatibility as well as environmental and economic advantages. Chitosan (CS) and xanthan gum (XG) based matrices have received growing scientific/pharmaceutical interest as oral controlled release drug carriers. Herein, recent advances spanning the last two decades in CS-XG based drug delivery systems are reviewed with the emphasis being on oral tablet formulations, due to their versatility as pharmaceutical dosage forms. The mechanism of interaction between CS and XG, by means of computational and experimental approaches, is scrutinized. Results obtained from the literature establish the possibility of fabricating a controlled release drug delivery system based on CS and XG matrices. This can be achieved by monitoring and manipulating the physiochemical properties of the two polymers as well as the experimental variables affecting their drug retardation efficiency, without the need to employ special equipment or sophisticated experimental techniques/methodologies

Effect of protonation state and N-acetylation of chitosan on its interaction with xanthan gum: a molecular dynamics simulation study

Hydrophilic matrices composed of chitosan (CS) and xanthan gum (XG) complexes are of pharmaceutical interest in relation to drug delivery due to their ability to control the release of active ingredients. Molecular dynamics simulations (MDs) have been performed in order to obtain information pertaining to the effect of the state of protonation and degree of N-acetylation (DA) on the molecular conformation of chitosan and its ability to interact with xanthan gum in aqueous solutions. The conformational flexibility of CS was found to be highly dependent on its state of protonation. Upon complexation with XG, a substantial restriction in free rotation around the glycosidic bond was noticed in protonated CS dimers regardless of their DA, whereas deprotonated molecules preserved their free mobility. Calculated values for the free energy of binding between CS and XG revealed the dominant contribution of electrostatic forces on the formation of complexes and that the most stable complexes were formed when CS was at least half-protonated and the DA was ≤50%. The results obtained provide an insight into the main factors governing the interaction between CS and XG, such that they can be manipulated accordingly to produce complexes with the desired controlled-release effect

Low molecular weight chitosan–insulin polyelectrolyte complex: characterization and stability studies

The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs) on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC) consisting of insulin and LMWC in the presence of a Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. Solubilization of insulin-LMWC polyelectrolyte complex (I-LMWC PEC) in a reverse micelle (RM) system, administered to diabetic rats, results in an oral delivery system for insulin with acceptable bioactivity

Influence of Molecular Weight and Degree of Deacetylation of Low Molecular Weight Chitosan on the Bioactivity of Oral Insulin Preparations

The objective of the present study was to prepare and characterize low molecular weight chitosan (LMWC) with different molecular weight and degrees of deacetylation (DDA) and to optimize their use in oral insulin nano delivery systems. Water in oil nanosized systems containing LMWC-insulin polyelectrolyte complexes were constructed and their ability to reduce blood glucose was assessed in vivo on diabetic rats. Upon acid depolymerization and testing by viscosity method, three molecular weights of LMWC namely, 1.3, 13 and 18 kDa were obtained. As for the DDA, three LMWCs of 55%, 80% and 100% DDA were prepared and characterized by spectroscopic methods for each molecular weight. The obtained LMWCs showed different morphological and in silico patterns. Following complexation of LMWCs with insulin, different aggregation sizes were obtained. Moreover, the in vivo tested formulations showed different activities of blood glucose reduction. The highest glucose reduction was achieved with 1.3 kDa LMWC of 55% DDA. The current study emphasizes the importance of optimizing the molecular weight along with the DDA of the incorporated LMWC in oral insulin delivery preparations in order to ensure the highest performance of such delivery systems

Using chitosan and xanthan gum mixtures as excipients in controlled release formulations of ambroxol HCl - in vitro drug release and swelling behavior

Directly compressed matrices were produced using a binary mixture of different chitosan (CH) and xanthan gum (XG) ratios. These hydrophilic excipients were used to control the release of ambroxol HCl. CH and XG were investigated at three ratios of 1:1, 1:4 and 4:1. Mucosolvan LA® was used as a commercially available reference product. The optimal CH to XG ratio was 1:1 and the optimal drug to polymer ratio was 1:3. Matrix erosion, hydration and drug release studies were carried out using a dissolution apparatus (basket method). The release mechanism is also discussed

Application of an excipient made from chitosan and xanthan gum as a single component for the controlled release of Ambroxol

An oral controlled release (CR) matrix system of Ambroxol hydrochloride was developed using a binary hydrophilic polymer mixture of chitosan (CH) and xanthan gum (XG) (1:1 w/w ratio). Two test tablet formulations were prepared using drug to polymer mixture ratios (D:P) of 1:1 and 1:3 (w/w), designated as T1 and T2, respectively. The in vitro drug release data was best fitted to the Higuchi equation. The 1:1 ratio (T1) demonstrated in vitro dissolution similarity with the commercial product, Mucosolvan LA. A preliminary in vivo study was performed using six volunteers. The study was designed to include open, randomized, singledose, three-treatment, six-sequence, crossover (Williams design) under fasting conditions. The data showed that T1 was bioequivalent to Mucosolvan LA ® after the administration of a single 75mg oral dose. Two in vivo, in vitro correlations (IVIVC) were established between Cmax versus the fraction of drug dissolved (FRD) after 4 hours, and AUC versus the ratio of fraction of drug dissolved (FRD) after 10 hours where a multiple point level C correlation of IVIVC was obtained

Development and evaluation of a novel, multifunctional, coprocessed excipient via roller compaction of α-Lactose Monohydrate and Magnesium Silicate

This study investigates co-processing lactose with synthetic amorphous magnesium silicate with the aim of expanding the use of directly compressible excipients based on native lactose. The co-processing was performed using roller compaction. The co-processed excipient was characterized using particle size analysis and compression properties (Kawakita equation). The co-processed excipient demonstrated plastic behavior upon compression, good flowability and crushing strength and a shorter disintegration time. Compatibility between the different ingredients of the co-processed excipient, as well as, between the co-processed excipient and model drugs was tested using Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The interaction between lactose and magnesium silicate proved to be of a physical nature. Formulating this co-processed excipient with Mebeverine HCl and Losartan Potassium as model drugs, indicated its suitability as a single multi-functional excipient. Co-processed lactose with magnesium silicate could be used as a single direct compression excipient for tablet manufacturing

Further investigation on the degree of deacetylation of chitosan determined by potentiometric titration

The degree of deacetylation (DDA) of various low molecular weight chitosan (LMWC) species as the hydrochloride and free base (amine form) was determined by direct and back potentiometric titration, respectively. The DDA values obtained for the chitosan hydrochloride by direct titration were greater than 93% for all oligomers tested (Molecular weight (Mwt) between about 1.3 to 30.0 kDa). However, the DDA values obtained for chitosan amine oligomers using back titration were significantly lower, especially for the relatively high molecular weight (30.0 kDa) chitosan amine oligomers. Furthermore, after using the back titration method, greater DDA values were obtained for the same samples of chitosan amine after the chitosan solution had been heated to 60EC before titration. In addition, the DDA values showed a significant decrease with increased concentration for a given chitosan oligomer. Although the effects of hydration time, ionic strength and method specific behavior were not explicitly studied and therefore cannot be entirely ruled out, the results from this study might be attributed to the conformation of changes of chitosan in solution that lead to more inter/intra attractive forces in the case of chitosan amine. The DDA values obtained by the potentiometric method were also compared with those obtained by the FDUV and IR spectroscopic methods. Thus, subject to the caveats mentioned above, DDA values obtained for chitosan amine by the back titration method should be used with caution since the results are significantly lower than those obtained by direct titration, FDUV spectroscopy or FTIR

A direct compression matrix made from Xanthan gum and low molecular weight chitosan designed to improve compressibility in controlled release tablets

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

Evaluation of Three Chitin Metal Silicate Co-Precipitates as a Potential Multifunctional Single Excipient in Tablet Formulations

The performance of the novel chitin metal silicate (CMS) co-precipitates as a single multifunctional excipient in tablet formulation using direct compression and wet granulation methods is evaluated. The neutral, acidic, and basic drugs Spironolactone (SPL), ibuprofen (IBU) and metronidazole (MET), respectively, were used as model drugs. Commercial Aldactone®, Fleximex® and Dumazole® tablets containing SPL, IBU and MET, respectively, and tablets made using Avicel® 200, were used in the study for comparison purposes. Tablets of acceptable crushing strength (>40 N) were obtained using CMS. The friability values for all tablets were well below the maximum 1% USP tolerance limit. CMS produced superdisintegrating tablets (disintegration time < 1 min) with the three model drugs. Regarding the dissolution rate, the sequence was as follow: CMS > Fleximex® > Avicel® 200, CMS > Avicel® 200 > Dumazole® and Aldactone® > Avicel® 200 > CMS for IBU, MET and SPL, respectively. Compressional properties of formulations were analyzed using density measurements and the compression Kawakita equation as assessment parameters. On the basis of DSC results, CMS co precipitates were found to be compatible with the tested drugs. Conclusively, the CMS co-precipitates have the potential to be used as filler, binder, and superdisintegrant, all-in-one, in the design of tablets by the direct compression as well as wet granulation methods