Physicochemical and drug diffusion analysis of rifampicin containing polyethylene glycol-poly(epsilon-caprolactone) networks designed for medical device applications

This study reports the physicochemical and drug diffusion properties of rifampicin containing poly(epsilon-caprolactone) (PCL)/polyethylene glycol (PEG) networks, designed as bioactive biomaterials. Uniquely, the effects of the states of both rifampicin and PEG and the interplay between these components on these properties are described. PCL matrices containing rifampicin (1-5%, w/w) and PEG 200 (0-15%, w/w) were prepared by casting from an organic solvent (dichloromethane). The films were subsequently characterized in terms of their thermal/thermorheological, surface and tensile properties, biodegradation and drug diffusion/release properties. Incorporation of PEG and/or rifampicin significantly affected the tensile and surface properties of PCL, lowering the ultimate tensile strength, % elongation at break, Young modulus and storage and loss moduli. Both in the absence and presence of PEG, solubilisation of rifampicin within the crystalline domains of PCL was observed. PEG was present as a dispersed liquid phase. The release of rifampicin (3% loading) was unaffected by the presence of PEG. Similarly the release of rifampicin (5%) was unaffected by low concentrations of PEG (5-10%) however, at higher loadings, the release rate of rifampicin was enhanced by the presence of PEG. Rifampicin release (10% loading) was enhanced by the presence of PEG in a concentration dependent fashion. These observations were accredited to enhanced porosity of the matrix. In all cases, diffusion-controlled release of rifampicin occurred which was unaffected by polymer degradation. This study has uniquely illustrated the effect of hydrophilic pore formers on the physicochemical properties of PCL. Interestingly, enhanced diffusion controlled release was only observed from biomaterials containing high loadings of PEG and rifampicin (5, 10%), concentrations that were shown to affect the mechanical properties of the biomaterials. Care should therefore be shown when adopting this strategy to enhance release of bioactive agents from biomaterials. (C) 2011 Elsevier B.V. All rights reserved.

An examination of the thermorheological and drug release properties of zinc tetraphenylporphyrin-containing thermoresponsive hydrogels, designed as light activated antimicrobial implants

This study describes the thermorheological, mechanical and drug release properties of novel, light-activated antimicrobial implants. Hydrogels, based on N-isopropylacrylamide (NIPAA) and hydroxyethyl methacryl ate (HEMA) and either devoid of or containing zinc tetraphenylporphyrin, were prepared by free radical polymerisation and characterised using oscillatory rheometry and texture profile analysis. Drug release was studied at both 20 and 37 degrees C. Hydrogels containing NIPAA exhibited a sol-gel temperature (Tin), which increased as the proportion of HEMA increased and was

Mucoadhesive, syringeable drug delivery systems for controlled application of metronidazole to the periodontal pocket: In vitro release kinetics, syringeability, mechanical and mucoadhesive properties

Novel mucoadhesive formulations containing hydroxyethylcellulose (HEC; 3 and 5%, w/w) or Carbopol (3 and 5%, w/w), polycarbophil (PC; 1 and 3%, w/w) and metronidazole (5%, w/w) at pH 6.8 were designed for the treatment of periodontal diseases. Each formulation was characterised in terms of hardness, compressibility, adhesiveness and cohesiveness (using Texture Profile Analysis), drug release, adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode) and, finally, syringeability (using the texture analyser in compression mode). Drug release from all formulations was non-diffusion controlled. Drug release was significantly decreased as the concentration of each polymeric component was increased, due to both the concomitant increased viscosity of the formulations and, additionally, the swelling kinetics of PC following contact with dissolution fluid. Increasing the concentrations of each polymeric component significantly increased formulation hardness, compressibility, adhesiveness, mucoadhesion and syringeability, yet decreased cohesiveness. Increased product hardness, compressibility and syringeability were due to polymeric effects on formulation viscosity. The effects on cohesiveness may be explained both by increased viscosity and also by the increasing semi-solid nature of products containing 5% HEC or Carbopol and PC (1 or 3%). The observations concerning formulation adhesiveness/mucoadhesion illustrate the adhesive nature of each polymeric component. Greatest adhesion was noted in formulations where neutralisation of PC was maximally suppressed. For the most part, increased time of contact between formulation and mucin significantly increased the required force of detachment, due to the greater extent of mucin polymer hydration and interpenetration with the formulations. Significant statistical interactions were observed between the effects of each polymer on drug release and mechanical/mucoadhesive properties. These interactions may be explained by formulatory effects on the extent of swelling of PC. In conclusion, the formulations described offered a wide range of mechanical and drug release characteristics. Formulations containing HEC exhibited superior physical characteristics for improved drug delivery to the periodontal pocket and are now the subject of long-term clinical investigations. (C) 1997 Elsevier Science B.V.