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

Liqui-Tablet: the innovative oral dosage form using the newly developed Liqui-Mass technology

In this study, an attempt was made to produce Liqui-Tablets for the first time. This was carried out through the compaction of naproxen Liqui-Pellets. The incentive to convert the novel Liqui-Pellet into Liqui-Tablet was due to the array of inherent advantages of the popular and preferred tablet dosage form. The study showed that naproxen Liqui-Tablet could be successfully produced and the rapid drug release rate (100% drug release ~ 20 min) could be achieved under pH 1.2, where naproxen is insoluble. It was observed that the different pH of the dissolution medium affected the trend of drug release from formulations with varying amounts of liquid vehicle. The order of the fastest drug-releasing formulations was different depending on the pH used. The presence of Neusilin US2 showed considerable enhancement in the drug release rate as well as improving Liqui-Tablet robustness and hardness. Furthermore, images from X-ray micro-tomography displayed a uniform distribution of components in the Liqui-Tablet. The accelerated stability studies showed acceptable stability in terms of dissolution profile

Polyvinyl Alcohol/Chitosan single-layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 multi-layered electrospun nanofibers as an ocular matrix for the controlled release of ofloxacin: an in vitro and in vivo evaluation

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0–96 for the nanofibers was 9–20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems

Metronidazole-and amoxicillin-loaded plga and pcl nanofibers as potential drug delivery systems for the treatment of periodontitis: in vitro and in vivo evaluations

The purpose of this study was to prepare poly (D-L) lactide-co-glycolide (PLGA) and poly ε-caprolactone (PCL) nanofibers containing metronidazole and amoxicillin using an electrospinning process as intrapocket sustained-release drug delivery systems for the treatment of periodontal diseases. Scanning electron microscopy showed that the drug containing PLGA and PCL nanofibers produced from the electrospinning process was uniform and bead-free in morphology. The obtained nanofibers had a strong structure and resisted external tension according to the tensiometry results. The cytotoxicity results indicated acceptable cell viability (>80%). Quantification by high-performance liquid chromatography showed almost complete in vitro drug release between 7 and 9 days, whereas 14 days were required for complete drug release in vivo. No significant signs of irritation or inflammatory reaction were detected after three weeks of subcutaneous implantation of nanofibers in the animal models, thus indicating suitable compatibility. The results therefore suggest that the designed nanofibers can be used as potential commercial formulations in the treatment of periodontitis as controlled-release intrapocket drug delivery systems that can increase patient compliance. This is due to their ability to reduce the frequency of administration from three times daily in a systemic manner to once weekly as local delivery

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, pH1.2 and pH6.8 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 pH1.2, 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 pH1.2 but with a more rapid release at pH6.8. GDS may have wider application in reinforcing compacts with relatively low mechanical strengt

Crystal packing arrangement, chain conformation, and physicochemical properties of gemfibrozil amine salts

Salt formation is used to optimize pharmaceutical properties for carboxylic acid drugs but selection can often be empirical. An extended series of salts of the anti-hyperlipidaemia carboxylic acid drug gemfibrozil was prepared using related series of amine counterions to gain a molecular insight into the impact of crystal packing arrangements on their physicochemical properties. With only a few exceptions, the salts had similar crystal packing motifs. Although there was no discernible relationship between melting point of the salt form and the aqueous solubility of the salt across the whole dataset, there were trends within structurally-related series of salts relating increasing melting enthalpy with increasing molecular weight of the counter ion

The dissolution and solid-state behaviours of coground ibuprofen–glucosamine HCl

The cogrinding technique is one of most effective methods for improving the dissolution of poorly water-soluble drugs and it is superior to other approaches from an economical as well as an environmental standpoint, as the technique does not require any toxic organic solvents. Present work explores the role of d-glucosamine HCl (GL) as a potential excipient to improve dissolution of a low melting point drug, ibuprofen (Ibu), using physical mixtures and coground formulations. The dissolution of the poorly soluble drug has been improved by changing the ratio of Ibu:GL and also grinding time. The results also showed that although GL can enhance the solubility of Ibu, it also reduces pH around the Ibu particles which led to poor dissolution performance when the concentration of GL is high. The effect of GL on the solubility of Ibu could be misleading if the pH of the final solution was not measured. Grinding reduced the particle size of GL significantly but in case of Ibu it was less effective. Solid state analysis (XRPD, DSC, and FT-IR) showed that ibuprofen is stable under grinding conditions, but the presence of high concentration of GL in samples subjected to high grinding times caused changes in FT-IR spectrum of Ibu which could be due to intermolecular hydrogen bond or esterification between the carboxylic acid group in the ibuprofen and hydroxyl group in the GL

An investigation into the use of low quantities of functional additives to control drug release from hot melt extruded solid dispersions for poorly soluble drug delivery

The motivation of this study is to demonstrate the practicality of producing slow release and fast release products in a single-step hot melt extrusion (HME) process. HPMCAS as the carrier material showed good potential in monolithic controlled release formulations for the model drug, carbamazepine (CBZ). As binary formulations, CBZ-HPMCAS extrudates showed zero-order release over 24 hours which was accompanied by the swelling of the extrudates. A range of functional excipients was used at low quantities to modulate the release rate. The release rates of the HME extrudates could be either accelerated by the incorporations of low quantities (5% w/w) of soluble additives or further sustained by adding lipid excipient, Gelucire 50/13. Clear phase separations of the soluble additives including crosscarmellose sodium, sodium starch glycolate, maltodextrin and lactose in the extrudates led to higher interior porosity and quicker erosion in comparison to the binary extrudates. The phase separated Gelucire in the extrudates led to the substantial swelling of the extrudates and resulted in further prolonged drug release. This study provided clear formulation strategies for modulating the drug release rate from controlled release formulation prepared directly by single-step HME. In addition, this research work also evaluates for the first time HME extrudates simultaneous swelling and drug release using this UV imaging technique. The whole dose cell of this instrumentation is utilised to provide insights into the dissolution process of solid dispersions prepared by HME