Preparation and Evaluation of Sustained-Release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding

Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading. © 2012 American Association of Pharmaceutical Scientists.

Hydrogels as drug-delivery platforms:Physicochemical barriers and solutions

The properties of hydrogels, in particular their high biocompatibility and water sorption uptake, make hydrogels very attractive in drug delivery and biomedical devices. These favorable features of hydrogels are compromised by certain structural limitations such as those associated with their low mechanical strength in the swollen state. This review highlights the most important challenges that may seriously affect the practical implementation of hydrogels in clinical practice and the solutions that may be applied to overcome these limitations. © 2012 Future Science Ltd.

Electrically-responsive anti-adherent hydrogels for photodynamic antimicrobial chemotherapy

The loading of the photosensitisers meso-Tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP), methylene blue (MB) and IMP with sodium dodecyl sulphate (SDS) into and release from hydrogels composed of the polyelectrolyte poly(methyl vinyl ether-co-maleic acid) crosslinked in a 2:1 ratio with PEG 10,000 were investigated as a potential rapid photodynamic antimicrobial chemotherapy (PACT) treatment for infected wounds using iontophoresis as a novel delivery method. Photosensitiser uptake was very high; (% TMP uptake; 95.53-96.72%) (% MB uptake; 90.58-93.26%) and was PMVE/MA concentration independent, whilst SDS severely limited TMP uptake (5.93-8.75%). Hydrogel hardness, compressibility and adhesiveness on the dermal surface of neonate porcine skin increased with PMVE/MA concentration and were significantly increased with SDS.

The ionic conductivities of the hydrogels increased with PMVE/MA concentration. Drug release was PMVE/MA concentration independent, except for drug release under iontophoteric conditions for MB and TMP (without SDS). In just 15 min, the mean% drug concentrations released of TMP, TMP (with SDS) and MB using an electric current ranged from 22.30 to 64.72 mu gml(-1), 6.37-4.59 mu gml(-1) and 11.73-36.57 mu gml(-1) respectively. These concentrations were in excess of those required to induce complete kill of clinical strains of meticillin-resistant Staphylococcus aureus and Burkholderia cepacia. Thus these results support our contention that the iontophoteric delivery of IMP and MB using anti-adherent, electrically-responsive, PEG-crosslinked PMVE/MA hydrogels are a potential option in the rapid PACT treatment of infected wounds. (c) 2012 Elsevier B.V. All rights reserved.

Investigation of swelling and network parameters of poly(ethylene glycol)-crosslinked poly(methyl vinyl ether-co-maleic acid) hydrogels

The influence of poly(ethylene glycol) (PEG) plasticiser content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether-co-maleic acid) was investigated using thermal analysis, swelling studies, scanning electron microscopy (SEM) and attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy. FTIR spectroscopy revealed a shift of the C{double bond, long}O peak from 1708 to 1731 cm, indicating that an esterification reaction had occurred upon heating, thus producing crosslinked films. Higher molecular weight PEGs (10,000 and 1000 Da, respectively), having greater chain length, producing hydrogel networks with lower crosslink densities and higher average molecular weight between two consecutive crosslinks. Accordingly, such materials exhibited higher swelling rates. Hydrogels crosslinked with a low molecular weight PEG (PEG 200) showed rigid networks with high crosslink densities and, therefore, lower swelling rates. Polymer:plasticizer ratio alteration did not yield any discernable patterns, regardless of the method of analysis. The polymer-water interaction parameter (?) increased with increases in the crosslink density. SEM studies showed that porosity of the crosslinked films increased with increasing PEG MW, confirming what had been observed with swelling studies and thermal analysis, that the crosslink density must be decreased as the M of the crosslinker is increased. Hydrogels containing PMVE/MA/PEG 10,000 could be used for rapid delivery of drug, due to their low crosslink density. Moderately crosslinked PMVE/MA/PEG 1000 hydrogels or highly crosslinked PMVE/MA/PEG 200 systems could then be used in controlling the drug delivery rates. We are currently evaluating these systems, both alone and in combination, for use in sustained release drug delivery devices. © 2008 Elsevier Ltd. All rights reserved.

Influence of a pore-forming agent on swelling, network parameters, and permeability of poly(ethylene glycol)-crosslinked poly(methyl vinyl ether-co-maleic acid) hydrogels:Application in transdermal delivery systems

We characterized hydrogels, prepared from aqueous blends of poly(methyl vinyl ether-co-maleic acid) (PMVE/MA) and poly(ethylene glycol) (PEG 10,000 Daltons) containing a pore-forming agent (sodium bicarbonate, NaHCO ). Increase in NaHCO content increased the equilibrium water content (EWC) and average molecular weight between crosslinks (M ) of hydrogels. For example, the %EWC was 731, 860, 1109, and 7536% and the M was 8.26, 31.64, 30.04, and 3010.00 × 10 g/mol for hydrogels prepared from aqueous blends containing 0, 1, 2, and 5% w/w of NaHCO , respectively. Increase in NaHCO content also resulted in increased permeation of insulin. After 24 h, percentage permeation was 0.94, 3.68, and 25.71% across hydrogel membranes prepared from aqueous blends containing 0, 2, and 5% w/w of NaHCO , respectively. Hydrogels containing the pore-forming agent were fabricated into microneedles (MNs) for transdermal drug delivery applications by integrating the MNs with insulin-loaded patches. It was observed that the mean amount of insulin permeating across neonatal porcine skin in vitro was 20.62% and 52.48% from hydrogel MNs prepared from aqueous blends containing 0 and 5% w/w of NaHCO . We believe that these pore-forming hydrogels are likely to prove extremely useful for applications in transdermal drug delivery of biomolecules. © 2012 Wiley Periodicals, Inc.

Physical characterisation and component release of poly(vinyl alcohol)-tetrahydroxyborate hydrogels and their applicability as potential topical drug delivery systems

Poly(vinyl alcohol)-tetrahydroxyborate (PVA-THB) hydrogels are dilatant formulations with potential for topical wound management. To support this contention, the physical properties, rheological behaviour and component release of candidate formulations were investigated. Oscillatory rheometry and texture profile analysis were used at room temperature and 37 °C. Results showed that it was possible to control the rheological and textural properties by altering component concentration and modifying the type of PVA polymer used. Hydrogels made using PVA grades with higher degrees of hydrolysis displayed favourable characteristics from a wound healing perspective. In vitro release of borate and PVA were assessed in order to evaluate potential clinical dosing of free species originating from the hydrogel structure. Component diffusion was influenced by both concentration and molecular weight, where relevant, with up to 5% free PVA cumulative release observed after 30 min. The results of this study demonstrated the importance of poly(vinyl alcohol) selection for ensuring appropriate gel formation in PVA-THB hydrogels. The benefits of higher degrees of hydrolysis, in particular, included lower excipient release and reduced bioadhesion. The unique physical characteristics of these hydrogels make them an appealing delivery vehicle for chronic and acute wound management purposes.

Preliminary clinical assessment of polyvinyl alcohol-tetrahydroxyborate hydrogels as potential topical formulations for local anesthesia of lacerations

The aim of this study was to assess a novel semisolid material as a potential topical drug delivery system for acute laceration. The objectives were to correlate physical characterization data using rheologic studies and to compare with clinical assessment of performance in an emergency department (ED).

Quantification of singlet oxygen generation from photodynamic hydrogels

Recently, we described a series of novel porphyrin-impregnated hydrogels capable of producing microbicidal singlet oxygen (1O2) on photoactivation. Indirect assessment of the efficacy of 1O2 production from such hydrogels has been previously described using microbiological techniques, but here we report a novel, direct method of quantification. Anthracene-9,10-dipropionic acid (ADPA) is known to irreversibly form an endoperoxide on reaction with 1O2, causing photobleaching of its absorbance band at approximately 378 nm. Here, the reaction of this probe is exploited in a novel way to provide a simple, inexpensive, and convenient measurement of 1O2 generation from the surface of porphyrin-incorporated photosensitising hydrogels, with the ability to account for effects due to hydrogel porosity. Ingress of the probe into the materials was observed, with rates of up to 3.83 x 103 s-1. This varied by up to 200-fold with material composition and surface modification. Rates of 1O2 generation in these porphyrin-incorporated hydrogels, after compensating for ADPA ingress, ranged from 1.86x103 – 5.86x103 s-1. This work demonstrates a simple and straightforward method for direct 1O2 quantification from porous materials, with general utility.