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.

Objectives: To develop a robust tablet design for the manufacture of gastro-retentive tablets using fused deposition modelling three-dimensional printing (FDM-3DP) that can provide prolonged gastric residence time with instant floating and minimum influence of process and/or formulation variables. Methods: Three different polymers, such as polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC) and Soluplus were used, separately, for the manufacture of tablets using FDM-3DP. Tablets were designed in a sandwich model that included voids in the internal structure to support buoyancy. Key findings: Fabricated tablets from all polymers were instantly buoyant with no floating lag time. Floating duration was in the order: HPC > Soluplus > PVA which can be explained by the density of the tablets. PVA tablets exhibited significantly (P < 0.05) higher density values (0.86 ± 0.02 mg/mm3) than HPC and Soluplus (0.69 ± 0.03 and 0.72 ± 0.02 mg/mm3, respectively). HPC and Soluplus showed similar zero-order drug release profiles (f2 > 50) and were able to sustain the release of theophylline for 12 h, whereas complete drug release was achieved from PVA tablets after 3 h. Conclusions: Robust gastro-retentive tablets that show instant buoyancy regardless of the polymeric carrier type and composition were successfully manufactured utilising FDM-3DP. This allows for overcoming the restrictions posed by process/formulation parameters on the floatability of gastro-retentive 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.