A molecular understanding of magnesium aluminium silicate - drug, drug - polymer, magnesium aluminium silicate - polymer nanocomposite complex interactions in modulating drug release: Towards zero order release.

This study reports the use of ITC in understanding the thermodynamics occurring for a controlled release system in which complexation has been exploited. In this study, a model drug, propranolol hydrochloride (PPN) was complexed with magnesium aluminium silicate (MAS) and these complexes were used in combination with polyethylene oxide (PEO) as a hydrophilic carrier at various concentrations to sustain the release of PPN. DSC, XRPD, ATR-FTIR and SEM/EDX were successfully used in characterising the produced complexes. 2D- SAXS data patterns for MAS and the produced complexes were shown to be symmetric and circular with the particles showing no preferred orientation at the nanometre scale. ITC studies showed differences between PPN adsorption onto MAS compared with PPN adsorption onto a MAS-PEO mixture. At both temperatures studied the binding affinity Ka was greater for the titration of PPN into the MAS-PEO mixture (5.37E + 04 ± 7.54E + 03 M at 25 °C and 8.63E + 04 ± 6.11E + 03 M at 37 °C), compared to the affinity obtained upon binding between PPN and MAS as previously reported suggesting a stronger binding with implications for the dissolution process. MAS-PPN complexes with the PEO polymer compacts displayed desired manufacturing and formulation properties for a formulator including, reduced plastic recovery therefore potentially reducing the risk of cracking/splitting and on tooling wear, controlled release of PPN at a significantly low (5%) polymer level as well as a zero-order release profile (case II transport) using up to 50% polymer level.

Mechanical and release behaviour of theophylline from matrix tablets containing psyllium powder in combination with grewia polysaccharides.

This study was aimed at investigating the effect of grewia polysaccharides on the mechanical and release properties of tablet matrices containing binary mixtures of the polysaccharide with psyllium. Two grades of grewia polysaccharides (GG and GDS) were extracted and binary mixtures of the polysaccharides with psyllium were formulated into tablet matrices containing theophylline as the model drug. The true, bulk and tapped densities, Carr's compressibility index of the powders and binary composites were determined before tablet compression. Tablet properties (hardness, porosity, and drug release from the matrices) were investigated. The dissolution test was carried out in 0.1 M HCl (pH 1.2) and phosphate buffer (pH 6.8). The results show that GG and GDS produced tablets with good mechanical strength (108.33 N and 95.70 N, respectively) while psyllium produced softer tablets (7.13 N). The combination of psyllium and grewia polysaccharides in the matrices resulted in a significant increase in the mechanical strength of the matrices when compared to matrices containing psyllium alone as the matrix former. The results also showed that GG and GDS reduced the dissolution rate and effectively eliminated the burst release of theophylline from the psyllium matrices at both pHs. The matrices of GG or GDS and the binary mixtures conform to non-Fickian anomalous diffusion with n > 0.45. When overcoming the burst release of drug from matrices such as psyllium, grewia polysaccharides may provide an effective reduction and a more sustained drug release from such matrices.

Real time calorimetric characterisation of clay - drug complex dispersions and particles.

Isothermal titration calorimetry (ITC) along with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) and high-performance liquid chromatography (HPLC) were employed to investigate the process of adsorption of propranolol hydrochloride (PPN) onto magnesium aluminium silicate (MAS) and to characterise the MAS-PPN particles formed upon complexation. The composition of MAS was confirmed by infrared (IR) spectroscopy and a calcimeter. The calorimetric results confirmed the binding between PPN and MAS at various pHs and temperatures. The overall change in enthalpy was found to be exothermic with a comparatively small entropic contribution to the total change in Gibbs free energy. These findings suggest that the binding process was enthalpically driven and entropically unfavourable (lower affinity) suggesting hydrogen bonding and electrostatic interactions dominating the interaction. The variation of pH and temperature did not have a great impact on the thermodynamics of the binding process, as observed from the similarity in enthalpy (ΔH), entropy (ΔS) or Gibbs free energy (ΔG). A slight reduction in the binding affinity (Ka) with varing pH and temperature was however observed. SEM/EDX studies showed the occurrence of changes in the microstructural properties of MAS following complexation which may explain the potential of MAS-PPN complexes for controlled drug release promoting pharmaceutical innovation.

Hydro-alcoholic media effects on theophylline release from sesamum polysaccharide gum matrices.

Concomitant ingestion of alcohol and medications can greatly affect drug plasma concentrations as dose dumping or failure may occur as a result of the fact that formulation excipients may not always be resistant to alcohol. In this study, a natural polysaccharide (Sesamum radiatum gum) (SG) was extracted, characterized and used to formulate sustained release theophylline compacts to study the effect of varying alcohol concentrations (v/v) in dissolution media on drug release from these compacts. X-ray powder diffraction showed that the extracted gum was amorphous in nature with the powder having excellent compaction properties as observed with its compact being significantly harder than those prepared with pure hydroxypropyl methyl cellulose (HPMC) K4M. X-ray microtomography showed that the compacts produced were homogenous in nature, however, swelling studies showed failure of the compacts at the highest concentration of absolute ethanol used (40% v/v). Dissolution studies showed similarity at all levels of alcohol tested (f2 = 57-91) in simulated gastric (0.1 N HCl, pH 1.2) and intestinal fluids (phosphate buffer, pH 6.8) for the HPMC compacts whereas dissimilarity only occurred for the SG compacts at the highest alcohol concentration in both media (f2 = 35). The suitability of SG as a matrix former that can resist alcoholic effects therefore makes it suitable as an alternative polymer with wider applications for drug delivery.

The influence of hydroalcoholic media on the performance of Grewia polysaccharide in sustained release tablets.

Co-administration of drugs with alcohol can affect the plasma concentration of drugs in patients. It is also known that the excipients used in the formulation of drugs may not always be resistant to alcohol. This study evaluates effect of varying alcohol concentrations on theophylline release from two grades of Grewia mollis polysaccharides. X-ray microtomography showed that native polysaccharide formulation compacts were not homogenous after the mixing process resulting in its failure in swelling studies. Removal of starch from the native polysaccharide resulted in homogenous formulation compacts resistant to damage in high alcoholic media in pH 6.8 (40%v/v absolute ethanol). Destarched polymer compacts had a significantly higher hardness (375N) than that of the native polysaccharide (82N) and HPMC K4M (146N). Dissolution studies showed similarity at all levels of alcohol tested (f2=57-91) in simulated gastric media (pH 1.2). The dissolution profiles in the simulated intestinal fluids were also similar (f2=60-94), with the exception of the native polysaccharide in pH 6.8 (40%v/v absolute ethanol) (f2=43). This work highlights the properties of Grewia polysaccharide as a matrix former that can resist high alcoholic effects therefore; it may be suitable as an alternative to some of the commercially available matrix formers with wider applications for drug delivery as a cheaper alternative in the developing world.

Starch-free grewia gum matrices: Compaction, swelling, erosion and drug release behaviour.

Polysaccharides are suitable for application as hydrophilic matrices because of their ability to hydrate and swell upon contact with fluids, forming a gel layer which controls drug release. When extracted from plants, polysaccharides often contain significant quantities of starch that impacts upon their functional properties. This study aimed to evaluate differences in swelling, erosion and drug release from matrix tablets prepared from grewia gum (GG) and starch-free grewia gum (GDS) extracted from the stems of Grewia mollis. HPMC was used as a control polymer with theophylline as a model drug. Swelling, erosion, and in-vitro release were performed in deionized water, pH 1.2 and pH 6.8 media. The Vergnaud and Krosmeyer-Peppas model were used for swelling and drug release kinetics, respectively. However, linear regression technique was used to determine the erosion rate. GDS compacts were significantly harder than the native GG and HPMC compacts. GDS matrices exhibited the fastest erosion and drug release in deionised water and phosphate buffer compared with the GG and HPMC. At pH 1.2, GDS exhibited greater swelling than erosion, and drug release was similar to GG and HPMC. This highlights the potential of GDS as a matrix for controlled release similar to HPMC and GG at pH 1.2 but with a more rapid release at pH 6.8. GDS may have wider application in reinforcing compacts with relatively low mechanical strength.