Adeola O. Adebisi

Gastroretentive microparticles for drug delivery applications

Many strategies have been proposed to explore the possibility of exploiting gastroretention for drug delivery. Such systems would be useful for local delivery, for drugs that are poorly soluble at higher pH or primarily absorbed from the proximal small intestine. Generally, the requirements of such strategies are that the vehicle maintains controlled drug release and exhibits prolonged residence time in the stomach. Despite widespread reporting of technologies, many have an inherent drawback of variability in transit times. Microparticulate systems, capable of distributing widely through the gastrointestinal tract, can potentially minimise this variation. While being retained in the stomach, the drug content is released slowly at a desired rate, resulting in reduced fluctuations in drug levels. This review summarises the promising role of microencapsulation in this field, exploring both floating and mucoadhesive microparticles and their application in the treatment of Helicobacter pylori, highlighting the clinical potential of eradication of this widespread infection.

Lectin-conjugated microspheres for eradication of Helicobacter pylori infection and interaction with mucus.

Using second generation mucoadhesives may enhance targeting antibiotics for eradication of Helicobacter pylori from the stomach for the treatment of peptic ulcer. The aim of this research was to prepare and characterise ethylcellulose/chitosan microspheres containing clarithromycin with their surfaces functionalised with concanavalin A to produce a floating-mucoadhesive formulation. The microspheres were prepared using an emulsification-solvent evaporation method. Particle size, surface morphology, in vitro buoyancy profile, zeta potential, drug entrapment efficiency, in vitro drug release and release kinetics of the particles were determined. Lectin was conjugated to the microsphere surface using two-stage carbodiimide activation and confirmed using FTIR, fluorescence studies and zeta potential measurements. Conjugation ranged from 11 to 15 μg Con A/mg microspheres which represents over 56% efficiency although there was some drug loss during the conjugation process. Conjugation did not have a significant effect on the buoyancy and release of drug from the microspheres using a mucus diffusion model with 53% and 40% of drug released from unconjugated and conjugated microspheres within 12h. Conjugation improved mucoadhesion and interaction with porcine gastric mucin compared to unconjugated microspheres. The buoyancy and improved mucoadhesion of the microspheres provides potential for delivery of clarithromycin and other drugs to the stomach.

Formulation and evaluation of floating mucoadhesive alginate beads for targeting Helicobacter pylori

There are various obstacles in the eradication of Helicobacter pylori infections, including low antibiotic levels and poor accessibility of the drug at the site of the infection. This study describes the preparation and characterisation of novel floating mucoadhesive alginate beads loaded with clarithromycin for delivery to the gastric mucosa to improve the eradication of this microorganism.

Preparation and characterisation of gastroretentive alginate beads for targeting H. pylori

Abstract There are various obstacles in the eradication of Helicobacter pylori (H. pylori) infections including low drug levels due to short gastric residence times and poor accessibility of the drug at the site of the infection. In this study, calcium alginate beads containing metronidazole were prepared by ionotropic gelation with diameters ranging from 2 to 3 mm and bulk densities ranging from 0.11 to 0.23 g/cm3. These beads failed buoyancy tests and released the drug rapidly. The formulation was modified in order to improve floating and modify their drug release profile through addition of oil and coating with chitosan. Upon modification, buoyancy improved and drug release was sustained. This novel formulation will ensure retention for a longer period in the stomach and control the release of drug, ensuring high local drug concentrations, leading to improved eradication of the bacteria.

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions.

This work explores the use of both spray drying and d-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging were also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5μm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (-3.8 versus 0.5nC/g for untreated material and -7.5 versus 3.1nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1-0.3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM.

Modification of drug delivery to improve antibiotic targeting to the stomach

The obstacles to the successful eradication of Helicobacter pylori infections include the presence of antibiotic-resistant bacteria and therapy requiring multiple drugs with complicated dosing schedules. Other obstacles include bacterial residence in an environment where high antibiotic concentrations are difficult to achieve. Biofilm production by the bacteria is an additional challenge to the effective treatment of this infection. Conventional oral formulations used in the treatment of this infection have a short gastric residence time, thus limiting the duration of exposure of drug to the bacteria. This review summarizes the current research in the development of gastroretentive formulations and the prospective future applications of this approach in the targeted delivery of drugs such as antibiotics to the stomach.

Direct imaging of the dissolution of salt forms of a carboxylic acid drug

Graphical abstract Figure. No Caption available. HighlightsDecrease in IDR with an increase in chain length of the counterion observed using UV‐imaging.Developed interfacial area ratio (Sdr) showed significant surface gains for the compacts for IDR determination.Particulates on surface compacts and observed cracks responsible for inflated IDR values.Imaging of surface should be taken into consideration prior IDR determination. ABSTRACT The optimisation of the pharmaceutical properties of carboxylic acid drugs is often conducted by salt formation. Often, the salt with the best solubility is not chosen due to other factors such as stability, solubility, dissolution and bioavailability that are taken into consideration during the preformulation stage. This work uses advanced imaging techniques to give insights into the preformulation properties that can aid in the empirical approach often used in industry for the selection of salts. Gemfibrozil (GEM) was used as a model poorly soluble drug. Four salts of GEM were made using cyclopropylamine (CPROP), cyclobutylamine (CBUT), cyclopentylamine (CPENT) and cyclohexylamine (CHEX) as counterions. DSC, XRD and SEM were used to confirm and characterise salt formation. IDR obtained using UV‐imaging up to 10 min for all the salts showed that an increase in the chain length of the counterion caused a decrease in the IDR. Past the 10 min mark, there was an increase in the IDR value for the CPROP salt, which was visualised using UV‐imaging. The developed interfacial (surface) area ratio (Sdr) showed significant surface gains for the compacts. Full dosage form (capsule) imaging showed an improvement over the GEM for all the salts with an increase in chain length of the counterion bringing about a decrease in dissolution which correlated with the obtained UV‐imaging IDR data.

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

Abstract 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.