The influence of fillers on theophylline release from clay matrices

Abstract: The objectives of this study were to investigate the suitability of magnesium aluminium silicate (MAS) (Veegum®) to control drug release of a model drug, theophylline, from tablet matrices. To this end, the performance of three commonly used fillers namely: lactose, microcrystalline cellulose (Avicel PH102; MCC), and pre-gelatinized starch, Starch 1500 PGS), were evaluated against Veegum®. The physico-mechanical properties of the tablet matrices were studied along with dissolution studies to determine the effect of single or binary mixtures of the excipients on the drug release pattern. A DSC hydration methodology was also employed to characterize the states of water present in the tablet matrices and to determine any impact on drug release. Formulations containing MAS alone produced compacts with the lowest hardness (4.5 kp) whereas formulations containing MCC alone produced the hardest tablets (17.2 kp). Dissolution studies suggested that matrices containing MAS alone released the theophylline quickest as compared to lactose, MCC or PGS. It was difficult to establish a trend of the bound and free water states in the tablet matrices; however the formulation containing only MAS had the highest bound water at 29 %. The results therefore show that theophylline does not interact with MAS. As such the dominant factor in controlling drug release using MAS requires interaction or intercalation with a cationic drug. In the absence of this however, other excipients can play a role in controlling drug release. Keywords: Veegum, clay matrices, DSC hydration, Magnesium aluminium silicate, filler

Solid state characterization and rheological properties of native and modified Bambara groundnut (Vigna subterranean) starches

This study was designed to determine the suitability of native, pregelatinized and carboxymethylated Vigna subterranean (Bambara nut) starches for pharmaceutical applications, through their characterization by means of physicochemical, rheological, thermal, morphological and instrumental spectroscopic methods. The native starch was extracted from Bambara nut, after which it was used to prepare both pregelatinized and carboxymethylated forms. Microscopy revealed increased in granular size on modification. Both pregelatinized and carboxymethylated Bambara starches had better flow properties and swellability compared to the native starch. Native Bambara starch had greater tendency to retrogradation, was more sensitive to heat and heat change, these were alleviated by both pregelatinization and carboxymethylation. DSC confirmed that carboxymethylated Bambara starch was the most thermally stable starch. Presence of functional groups and crystallinity were established by FTIR and XRD, respectively. Native and modified Bambara starches can be used as locally and readily available alternative excipients in pharmaceutical formulations

Formulation and evaluation of floating mucoadhesive alginate beads for targetingHelicobacter pylori

Objectives: There are various obstacles in the eradication of Helicobacter.pylori (H. 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 (CMN) for delivery to the gastric mucosa to improve the eradication of this micro-organism. Methods: Calcium alginate beads were prepared by ionotropic gelation. The formulation was modified through addition of oil and coating with chitosan in order to improve floating, mucoadhesion and modify drug release. Key findings: SEM confirmed the sphericity of the beads with X-ray microtomography (XμMT) showing the 3D structure of the beads with the layered internal structure of the bead and the even distribution of the drug within the bead. This formulation combined two gastro-retentive strategies and these formulations produced excellent in vitro floating, mucoadhesive and drug release characteristics. Enhanced stability of the beads in phosphate buffer raises a potential for the modified formulations to be targeted to regions of higher pH within the gastrointestinal tract with a higher pH. Drug release from these beads was sustained through an unstirred mucin layer simulating in vivo conditions under which the H. pylori resides in the gastric mucosa. Conclusions: This novel formulation will ensure retention for a longer period in the stomach than conventional formulations and control drug release, ensuring high local drug concentrations, leading to improved eradication of the bacteria

The use of various organic solvents to tailor the properties of Ibuprofen-glucosamine HCl solid dispersions

A fast release dosage form is desirable to improve the absorption of poorly water soluble drugs. Ibuprofen (IBU) is a BCS class II drug that exhibits poor dissolution rate in the gastrointestinal (GI) tract. The aim of the present study is to use various organic solvents to prepare solid dispersions of IBU in the presence of glucosamine HCl (GL), which acts as a carrier to enhance the dissolution of ibuprofen. Different ratios of ibuprofen and glucosamine were dissolved in various organic solvents to obtain the solid dispersions of ibuprofen-glucosamine mixtures. The physic-chemical/solid state analysis of the samples investigated using SEM, DSC, FT-IR and XRPD, particle size analysis and in vitro dissolution studies showed that the type of solvent has a big influence on the dissolution. Ibuprofen-glucosamine solid dispersions obtained from acetone produced better dissolution compared to that of other organic solvents. The effect of water in binary mixtures of acetone or ethanol was also investigated and the results showed that when the ratio of acetone to water was 75:25, the highest dissolution was obtained. Solid state analysis ruled out any chemical interaction between the dug and carrier even in the presence of various organic solvents which indicates a good stability of the solid dispersions to enhance the dissolution rate of ibuprofen. It was also investigated via XRPD analysis that the ibuprofen retained its crystallinity without any adverse effect on the dissolution rates

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 infectio

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

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. Read More: http://informahealthcare.com.libaccess.hud.ac.uk/doi/abs/10.3109/02652048.2013.80584

Solid state characterization and rheological properties of native and modified Bambara groundnut (Vigna subterranean) starches

This study was designed to determine the suitability of native, pregelatinized and carboxymethylated Vigna subterranean (Bambara nut) starches for pharmaceutical applications, through their characterization by means of physicochemical, rheological, thermal, morphological and instrumental spectroscopic methods. The native starch was extracted from Bambara nut, after which it was used to prepare both pregelatinized and carboxymethylated forms. Microscopy revealed increased in granular size on modification. Both pregelatinized and carboxymethylated Bambara starches had better flow properties and swellability compared to the native starch. Native Bambara starch had greater tendency to retrogradation, was more sensitive to heat and heat change, these were alleviated by both pregelatinization and carboxymethylation. DSC confirmed that carboxymethylated Bambara starch was the most thermally stable starch. Presence of functional groups and crystallinity were established by FTIR and XRD, respectively. Native and modified Bambara starches can be used as locally and readily available alternative excipients in pharmaceutical formulations

Agitation Sequence and Ionic Strength on In-Vitro Drug Release from Hypromellose –The Influence of Compaction Force

The evaluations of the systematic effects of agitation and ionic strength and its impact on tablet compression force on the drug release from a gel forming matrix were the objectives of this study. To achieve this, two model drugs namely, theophylline and diltiazem HCl were formulated with hydroxypropyl methyl cellulose into matrix tablets and the drug release in a range of pHs 1.2-7.5 was evaluated using the automated USP type III Bio-Dis Varian. The effects of agitation were investigated at 10, 20 and in an ascending and descending order in the vials. Agitation had a profound effect on the drug release from the K100LV tablet matrices. Ionic strength was investigated using NaCl as the ionic strength regulator. A range of 0-0.4 M ionic strengths were studied. It was noticed that an increase in the compression of the tablet matrices for the K100LV theophylline and diltiazem HCl tablet matrices resulted in a significant difference in their drug release profiles both in the agitation sequence and with the influence of ionic concentration strength. The K100M tablet matrices for the theophylline and diltiazem HCl on the other hand were generally unaffected. This investigation also highlights the importance of controlling drug release in the desired dissolution medium as agitation could significantly influence the drug release resulting in a possible toxicity or making drug not available at the required site. Keywords: HPMC, theophylline, diltiazem hydrochloride, ionic strength, agitation, compression, USP III Bio-Di

Solid state characterization and rheological properties of native and modified Bambara groundnut (Vigna subterranean) starches

This study was designed to determine the suitability of native, pregelatinized and carboxymethylated Vigna subterranean (Bambara nut) starches for pharmaceutical applications, through their characterization by means of physicochemical, rheological, thermal, morphological and instrumental spectroscopic methods. The native starch was extracted from Bambara nut, after which it was used to prepare both pregelatinized and carboxymethylated forms. Microscopy revealed increased in granular size on modification. Both pregelatinized and carboxymethylated Bambara starches had better flow properties and swellability compared to the native starch. Native Bambara starch had greater tendency to retrogradation, was more sensitive to heat and heat change, these were alleviated by both pregelatinization and carboxymethylation. DSC confirmed that carboxymethylated Bambara starch was the most thermally stable starch. Presence of functional groups and crystallinity were established by FTIR and XRD, respectively. Native and modified Bambara starches can be used as locally and readily available alternative excipients in pharmaceutical formulations