Carboxymethylated and acetylated xerogel derivatives of Plectranthus esculentus starch protect Newcastle disease vaccines against cold chain failure.

Developing vaccine stabilizers from local natural sources is desirable especially if the stabilizer would enhance the ability of the antigen to withstand frequent failures in cold chains. The study was undertaken to formulate immunogenic live Newcastle Disease (ND) LaSota vaccines stabilized with modified native starches for use at cold and ambient temperatures and to assess the immunogenicity of the starch stabilized vaccines in vaccinated chickens. Native starch extracted from the tubers of Plectranthus esculentus (Family, Lamiaceae) was modified by carboxymethylation and acetylation/xerogel formation and used as vaccine stabilizers of ND LaSota virus with/without buffers/bulking excipients. Cold Chain Failure (CCF) was simulated by storing the vaccines at 5 ± 2 °C for one month then at 37 ± 1 °C for 96 h. The stability of the samples were evaluated in comparison with peptone stabilized ND vaccines using pH, residual moisture, XRD, reconstitution time, mean embryo infective dose (EID50) and haemagglutination (HA) tests. Haemagglutination inhibition was used to evaluate the efficacy of the vaccines in conferring positive serum antibody titers (≥23 log2) in vaccine-naïve 2-week old broilers that were orally administered a single dose of the vaccines kept at 37 ± 1 °C for 96 h and bled weekly over four weeks. Temperature, pH, moisture content and amorphousness impacted vaccine stability. Peptone stabilized vaccines were significantly less stable and most affected by temperature changes with 1.2log10EID50 loss while buffered/bulked trehalose, carboxymethylated and acetylated/xerogelized starch stabilized vaccines were most stable (0.2-0.5log10EID50 loss in titer) after 96 h in CCF. Buffered trehalose stabilized vaccine (TVB) had lower HA titres than peptone and starch stabilized vaccines containing D-mannitol and Na2HPO4. Antibody titres of vaccinated broilers were between 3.3 ± 1.398 and 8.35 ± 2.678. All the vaccines were immunogenic (HI ≥ 23) and developed HI titres (≥24) considered to be protective. Carboxymethylated and acetylated/xerogel derivatives of P. esculentus starch have a great potential as vaccine stabilizers especially in areas prone to CCF.

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.

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.

Structural characterisation and rheological properties of a polysaccharide from sesame leaves (Sesamum radiatum Schumach. & Thonn.).

A polysaccharide from the leaves of Sesamum radiatum was extracted by maceration in deionized water followed by ethanol precipitation then chemically and physically characterised. Monosaccharide composition and linkages were determined by high performance anion exchange chromatography (HPAEC), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy respectively. Sesamum gum was composed of glucuronic acid, mannose, galactose, and xylose with trace quantities of glucose, rhamnose and arabinose. Proton and (13)C NMR spectroscopy, and linkage analysis revealed a glucuronomannan based structure comprising a backbone of →4)-ß-d-GlcpA-(1→2)-α-d-Manp-(1→ with side-chains of galactose and xylose. Hydrated sesamum gum displayed temperature independent viscoelastic properties with no thermal hysteresis. Intrinsic viscosity was determined to be 3.31 and 4.40dLg(-1) in 0.1M NaCl and deionised water respectively, while the critical concentration was determined to be 0.1% w/v. The characterisation performed in this study will help direct potential applications of this material in foods and pharmaceuticals.

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.